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Background Uncomplicated hyperglycaemia is a common presentation in the emergency department (ED). Rapid glucose control is associated with the risk of iatrogenic hypoglycaemia. We sought to determine the safety of a rapid glucose control protocol delivered in a 24-h emergency department observation unit (OU). Methods This is a retrospective chart review of patients admitted to the OU for hyperglycaemia where the assessing clinician deemed there was no other reason for medical admission apart from hyperglycaemia; and that the patient could be safely discharged provided their hyperglycaemia was adequately treated. The rapid glucose control protocol consists of 4–6 hourly glucose monitoring and insulin injections according to a sliding scale. We report the demographics, reduction in glucose values and the incidence of hypoglycaemia in the OU. We also determine the rate of discharge from OU and the rate of hospital admission at 30 days. Results We included 101 patients. The mean age was 53.5 years (95% CI 50.4–56.6) and 64% of patients were male. The mean HbA1c value was 12.8% (95% CI 12.3–13.3). The mean admission and discharge glucose values were 27.2 (95% CI 26.3–28.1) and 13.9 (95% CI 13.2–14.6) mmols/l respectively. There was no incidence of hypoglycaemia in the OU. We successfully discharged 90.1% of the patients from the OU, of which 3 (3.3%) patients were admitted to the hospital within 30 days of discharge. Conclusion ED OU is a safe location to deliver effective management for patients presented with uncomplicated severe hyperglycaemia.

In anesthetized rats, in addition to marked pressor response, intense cerebral compression (ICC) by mechanical means produced a transient but marked bradycardia, a late tachycardia and a terminal bradycardia to cardiac arrest. Changes of ST or J junction and T wave in ECG were observed during the tachycardia. Ventricular extrasystoles were consistently observed during the tachycardiac but only occasionally during the bradycardiac phase. The effects of acute adrenalectomy, decerebration, vagotomy and spinal transection on the cardiac responses have been evaluated. It was found that: 1) These cadiac changes were independent of the higher centers or catecholamines release from the adrendals. 2) The initial bradycardia was mediated through direct vagal activation rather than baroceptor reflex action. 3) The late tachycardia with changes of ST, J and T wave and ventricular extrasystoles was principally produced through sympathetic activation. The vagal mechanism was not important.

Enteritis is a serious problem for patients having received abdominal radiation. This study was to investigate whether zinc affected intestinal injury induced by the radiation. ICR mice were divided randomly into three groups and treated with one of three different compounds. Two of the compounds contained zinc (gluconate and amino acid chelated with bovin prostate extract) and one was water. One week after receiving the treatment, they were irradiated with 6 or 10 Gy at the abdominal region. One, 2, and 4 weeks after the irradiation the animals were sacrificed to examine the histological changes in the intestinal mucosa. The apoptotic cell numbers were found to be significantly higher after irradiation. The number of the apoptotic cells increased with increasing radiation doses. In this study we found that zinc appears to have the capability to lower the occurrence of apoptosis in the intestinal mucosa, thus protecting intestinal mucosa from injuries. Based on this finding, it would be reasonable to suggest that zinc could be used as food supplements in patients with cancer receiving radiotherapy in a hope to reduce radiation induced toxicity.

We have previously demonstrated that intra-hippocampal injection of corticotrophin-releasing factor improved memory retention of an inhibitory avoidance learning in rats; while the electrophysiological effects corticotrophin-releasing factor produces on hippocampal neurons are largely uncharacterized. In the present study, we found that corticotrophin-releasing factor injected into the dentate gyrus of hippocampus produced a dose-dependent and long-lasting enhancement in synaptic efficacy of these neurons, as measured by an increase in the amplitude and slope of population excitatory postsynaptic potentials, as well as the amplitude of population spike. The onset of corticotrophin-releasing factor-induced potentiation was slow. It was observed approximately 40-60 min after corticotrophin-releasing factor administration and lasted for more than 5 h. This effect of corticotrophin-releasing factor was blocked by pretreatment with the cyclase-adenosine-3,5-monophosphate (cAMP) inhibitor Rp-adenosine-3,5-cyclic monophosphothiolate triethylamine (Rp-cAMPS) and partially blocked by the N-methyl-D-aspartate receptor antagonist MK-801. Further, pretreatment with corticotrophin-releasing factor receptor antagonist dose-dependently diminished tetanization-induced long-term potentiation, and corticotrophin-releasing factor and tetanic stimuli had an additive effect on hippocampal neuron excitation. Moreover, direct injection of corticotrophin-releasing factor increased cAMP level in the dentate gyrus. These results together suggest that corticotrophin-releasing factor-induced potentiation simulates the late phase of tetanization-induced long-term potentiation and cAMP seems to be the messenger mediating this effect. Moreover, corticotrophin-releasing factor-induced potentiation and long-term potentiation may share some similar mechanisms, and corticotrophin-releasing factor is probably involved in the neural circuits underlying long-term potentiation. Thus, corticotrophin-releasing factor may play an important role in modulating synaptic plasticity in the hippocampus.

The intercellular lipid lamellae of the stratum corneum (SC) is believed to provide the permeability barrier of the epidermis. Previous functional studies have demonstrated an increase in the transepidermal water loss (TEWL) after long-term use of topical corticosteroids (TCS): however, direct morphological confirmation of this barrier abnormality is still lacking. The aim of this study was to determine whether any abnormality could be detected in the structure of the SC intercellular lipid lamellae in patients after long-term TCS. Atrophic skin and untreated normal skin of 10 patients after long-term TCS were examined by transmission electron microscopy using ruthenium tetroxide-fixed tissue for the multilamellar lipid sheets of SC, and oil red O stain for neutral lipids of the SC. Layers of the SC were evaluated by 0.1% methylene blue stain after alkaline expansion, and TEWL was measured by Evaporimeter EP1. The TCS-treated atrophic skin had fewer layers of horny cells, mean 9.4 layers, than the normal control skin, 18 layers (P < 0.001) and increased TEWL of 21.3 g/m2 compared with the control skin TEWL of 6.7 g/m2 (P < 0.01). The mean neutral lipid content of the SC was also significantly lower (P < 0.001). Moreover, ultrastructural studies revealed a marked decrease in both the numbers of intercellular lipid lamellae of SC and membrane-coating granules of stratum granulosum in the atrophic skin. These results suggest that the diminution in the SC intercellular lipid lamellae and SC cell layers play an important part in the pathogenesis of barrier dysfunction after long-term use of TCS.

Instillation of cold water into the urinary bladder has been used as a diagnostic test to evaluate neurogenic dysfunctions of the lower urinary tract (LUT). This study examined the effects of cold stimulation on the LUT of urethan-anesthetized rats. Urinary bladder pressure and external urethral sphincter (EUS) electromyogram (EMG) were recorded during cystometrograms in which body- or room-temperature saline was infused continuously into the bladder and voided through the urethra. Subsequent infusion of cold saline (6-8 degrees C) into the bladder increased by approximately 100% the duration and amplitude of supraspinal reflex bladder contractions, increased baseline bladder pressure, increased the pressure threshold for inducing micturition, and increased EUS EMG activity. Blocking EUS activity by transecting the pudendal nerves or by administering a neuromuscular blocking agent markedly reduced or eliminated the effect of cold stimulation. Capsaicin pretreatment suppressed the effect of cold stimulation. It is concluded that cold temperatures stimulate capsaicin-sensitive C fiber bladder afferents that reflexly activate the EUS, producing detrusor and sphincter dyssynergia and increasing urethral outlet resistance. This in turn increases the amplitude and duration of bladder contractions during voiding.

A rapid method for the production of a glass-insulated microwire electrode is described. A microwire was threaded into a glass capillary which was then pulled on a vertical pipette puller. A conical tip of the microwire was formed when the strongly heated glass capillary broke together with the wire in it. A tight seal of the glass-insulated microwire electrode between the glass and the metal was accomplished with silicone glue. The manufactured electrode performed consistently at different immersion depths, and yielded stable recordings of single units in the cerebral cortex and the medulla of rats. The strength and low impedance characteristics of the glass-insulated microwire electrode may make it useful for the recording of single units in deep brain structures. Furthermore, the electrode can be easily combined with another glass micropipette to form a dual recording-injection microelectrode unit.

This study was undertaken to dynamically examine the effects of ethanol on the striatal dopaminergic transmission, in terms of N-methyl-D-aspartate (NMDA)-evoked dopamine release and dopamine uptake. In the striatum of urethane-anesthetized Sprague-Dawley rats, extracellular dopamine was measured using in vivo electrochemical detection coupled with a nafion-coated carbon fiber working electrode. Micro-ejection of NMDA evoked a transient dopamine release from the dopamine-containing nerve terminals in striatum. Local application of ethanol by pressure ejection did not elicit significant changes in spontaneous dopamine release. However, with ethanol pretreatment, the time course of NMDA-induced dopamine release was markedly prolonged while the magnitude and the rate of clearance were significantly reduced. These effects were compared to those of nomifensine, a dopamine uptake blocker. Nominfensine pretreatment was found to augment the time course of NMDA-evoked dopamine release analogous to those by ethanol pretreatment. Furthermore, pretreatment with ethanol did not increase the time course parameters of dopamine signals if dopamine releases were induced by co-application of NMDA and nominfensine. These data suggest that in addition to the attenuation of NMDA-evoked dopamine release, ethanol inhibits dopamine uptake in a similar fashion to that observed with nomifensine in situ in the striatum. Indeed, ethanol altered the uptake of exogenous dopamine from the extracellular space of striatal cortex. The time course of dopamine signals was prolonged and the rate of clearance was reduced after ethanol treatment. Taken together, our data demonstrate that ethanol simultaneously inhibits NMDA-evoked dopamine release and dopamine uptake in the striatum, suggesting the importance of the interplay between release and uptake in ethanol effects on striatal dopaminergic transmission.

The distribution and reactivity of vasomotor sites in the ventrolateral (VLM) and dorsomedial medulla (DMM) of stroke-prone spontaneously hypertensive rats (SHRSP), spontaneously hypertensive rats (SHR), and Wistar-Kyoto rats (WKY) were compared. Rats were anesthetized with alpha-chloralose and urethan. Baroreceptor denervation and vagotomy were performed. L-Glutamate (Glu, 10 mM, 30 nl) was microinjected into the DMM or VLM to identify vasoactive sites. The extent and the patterns of distribution of these sites in the three strains of rats were similar. The dose-response curve of the vasoactive site was studied with 1–500 pmol of Glu. The maximum responses of blood pressure and renal sympathetic activity were larger and threshold doses of Glu were lower in hypertensive rats. The significance of the differences among the strains was analyzed before and after adjustment for baseline pressure or activity. Most of the differences were statistically significant before baseline adjustment. After baseline adjustment, many differences between the SHRSP and the WKY remained significant. However, the only significant difference detected between the SHR and the WKY was the threshold dose for eliciting renal sympathetic change in the caudal VLM. These results suggest that there may be a general increase in excitability of the vasomotor neurons in the medulla of the hypertensive rats.

Gastric interposition was performed and prospectively studied in 9 patients with esophageal cancer, 1 patient with esophageal neurofibroma and 5 with corrosive esophageal stricture. The postoperative follow-up periods were between 6 to 68 months with a mean of 28.6 months. The subjects were then endoscopically reviewed. Twelve of them were macroscopically normal. The others exhibited signs of inflammation and hyperemia. Mucosal biopsies were obtained at the upper and lower third of the graft. The histologic findings were compared with those of the preoperative specimens. Among the 15 post-operative specimens, only minute histologic changes were seen. Three patients whose proximal grafts showed inflammatory signs revealed congestion. Another 2 patients exhibited granulocyte infiltration in the mucosa of the distal third. The mucosal structure of the remaining 10 patients was similar to that of the preoperative graft. In conclusion, the macroscopic and microscopic changes were few and minimal although there were alterations in function, physiology and location of the stomach.

This study evaluated the role of the micronucleus (MN) in liver fine needle aspiration (FNA) cytology.Histological features of 75 cases of hepatocellular carcinoma (HCC), of which 25 were well differentiated, 37 moderately differentiated and 13 poorly differentiated, and 58 benign hepatic lesions (total, 133 cases) were correlated with MN expression observed in FNA smears reported as benign (n =40), atypical (n = 14), suspicious (n = 30) and malignant (n =49).Stepwise increases in the MN score (0.4 ± 0.6, 1.2 ± 1.3, 6.3 ± 4.2 and 14.8 ± 8.8) correlated with the degree of cytological abnormality: benign, atypia, suspicious and malignant, respectively. The mean MN scores for well-, moderately and poorly differentiated HCC were 5.4 ± 2.2, 11.5 ± 4.5 and 24.9 ± 9.1, respectively, which was significantly different between malignant and suspicious (P0.0001), between suspicious and atypical (P= 0.008) but not between atypical and benign. The MN scores differed significantly between all degrees of differentiation of HCC and between the HCC and benign hepatic lesions (P0.0001). High sensitivity, specificity and accuracy of liver FNA for diagnosing HCC (96%, 98%, and 96%, respectively) were obtained at a cutoff of three for the MN score.The MN score is an effective HCC biomarker and has a good potential use as an ancillary tool for diagnosing HCC using FNA cytology.

A mixture of allogeneic and autologous microskin grafts (10:1 expansion ratio) were transplanted and overlain with Biobrane, on to full-thickness skin wounds (8.0 x 5.0 cm in size) in 16 rabbits. They were divided into two groups: in group I, the expansion ratio of both allo- and autograft was 20:1; in group II, the expansion ratio of allo- and autograft was 15:1 and 30:1 respectively. On day 9, all wounds of group I and II were almost completely resurfaced with neoepithelium. There was no serious rejection reaction within the neoepithelium and the wounds were maintained completely resurfaced after day 9. There were scales on the epithelialized wound which were more numerous in group II than in group I. Histological examination revealed that these wounds were resurfaced with well-differentiated epithelium which contained two different histological patterns. They were identified as the survived transplanted allogeneic and autologous microskin grafts, each having their own characteristic histological features and different sex chromosome. Thus both the largely expanded allogeneic and autologous microskin grafts could proliferate together and contribute to the resurfacing of the wound. With this method, the rabbit skin wound could be resurfaced completely after the ninth postoperative day with markedly minimized amounts of autologous and allogeneic grafts.

In 65 cats anesthetized with chloralose (40 mg/kg) and urethane (400 mg/kg), the effects of electrical stimulation and microinjection of sodium glutamate (0.25 M, 100–200 nl) in the pressor areas in the rostral brain stem on the evoked L5 ventral root response (EVRR) due to intermittent stimulation of sciatic afferents were compared to stimulating the dorsomedial (DM) and ventrolateral (VLM) medulla. In general, stimulating these rostral brain stem pressor areas including the diencephalon (DIG) and rostral pons (RP) produced increases in systemic arterial pressure (SAP). In most of the cases (85%) there were associated changes in the EVRR, predominantly a decrease in EVRR (72%). Stimulation of the midbrain (MB, principally in the periaqueductal grey) produced decreases in SAP and EVRR. Decreases in EVRR was observed in 91% of the DM and VLM stimulations in which an increase in SAP was produced. This EVRR inhibition was essentially unaltered after acute midcollicular decerebration. Increases in EVRR were also observed and occurred more often in the rostral brain stem than in the medulla. Since changes of both EVRR and SAP could be reproduced by microinjection of Glu into the cardiovascular-reactive areas of the brain stem, this suggests that neuronal perikarya in these areas are responsible for both actions. On some occasions, Glu induced changes in EVRR but not in SAP. This effect occurred more frequently in the rostral brain stem than in the medulla. The present data suggest that separate neuron population exist in the brain stem for the integration of SAP and spinal reflexes. These neurons are relatively dispersed from DIC to RP but are in close proximity to one another in the medulla. Rostral structures also contain more neurons responsible for augmenting spinal reflexes.

In 65 cats anesthetized with alpha-chloralose and urethane, the effects of insulin on cardiovascular responses to stimulation of various structures in the brain stem were studied. The threshold dose of insulin injected intravenously that produced systemic hypoglycemia was 5-10 U/kg. Subthreshold hypoglycemic doses of insulin were used intracerebroventricularly (0.25 U/kg) or intracerebrally (2 mU in 200 nl). Sixty minutes after intravenous insulin, when serum glucose concentrations decreased from 158 to 43 mg/100 ml, pressor responses to stimulation of the periaqueductal gray of midbrain (PAG), locus coeruleus (LC), dorsal medulla (DM), ventrolateral medulla (VLM), and parvocellular reticular nucleus (PVC) decreased significantly. Depressor and bradycardiac response to stimulation of paramedian reticular nucleus or dorsal motor nucleus of vagus (DMV) decreased significantly as well. Thirty minutes after intracerebroventricular insulin, pressor responses of PAG, DM, and the bradycardiac response of DMV decreased significantly. Thirty minutes after intracerebral insulin, pressor responses and renal nerve activities of LC (but not PAG), VLM, DM, and PVC decreased significantly. A similar but faster onset (5 min) of depression of cardiovascular responses on stimulating the LC, VLM, DM, and PVC was observed in another six acutely midcollicular-decerebrate cats recovered from halothane anesthesia. These findings suggest that insulin directly inhibits the vasomotor structures of the brain stem and decreases the pressor responses to stimulation.

To investigate the interaction between cardiovascular (CV)-reactive areas in the brain stem and urinary bladder (UB) motility, 48 adult cats of either sex were anesthetized intraperitoneally with alpha-chloralose (40 mg/kg) and urethan (400 mg/kg). The changes of UB motility and systemic arterial blood pressure (SAP) were produced by microinjection of sodium glutamate (0.5 M, 100-200 nl) into the pressor, depressor, or vagobradycardiac areas of the brain stem. Stimulation of these CV-reactive areas increased or decreased UB motility. Areas that produced an increase in UB motility listed in decreasing order of effectiveness are locus ceruleus-parabrachial nucleus in the pons, dorsal medulla, dorsal motor nucleus of vagus, and ventrolateral medulla. Areas eliciting a decrease in UB motility listed in decreasing order are gigantocellular tegmental field, parvocellular reticular nucleus, and ambiguus nucleus. Stimulation of other pressor sites in medulla also increased UB motility. Activation of the paramedian reticular nucleus, which consistently produced depressor responses, and activation of raphe nuclei, which produced depressor or pressor responses, consistently decreased UB motility. The integrity of the vagus nerve was not essential for the UB response to brain stimulation. These findings indicate that neuronal mechanisms for controlling UB and CV functions coexist at many sites in the brain stem. At those sites that commonly produce changes in UB motility, the type of UB response (excitation or inhibition) was in the same direction as the change of SAP. However, at some sites responses were inverse. It is not known whether the responses of the UB and CV system are controlled by common or separate populations of neurons at these sites.

Either intact rats, sham-operated rats, or rats with lesions of the paramedian reticular nucleus (PRN) were exposed to cold (2 degrees C) or heat (36 degrees C) stress and their locomotor activity responses and striatal dopamine (DA) release were compared. At room temperature (22 degrees C), results analyzed revealed significant effects in the PRN-lesioned rats: increases in locomotion (including both horizontal and vertical motion), direction of turnings (including both clockwise and anticlockwise) or striatal DA release. In both the intact rats and the sham-operated rats, either cold or heat stress increased the locomotion, the direction of turnings and the striatal DA release. The increases in both vertical motion and striatal DA release following cold or heat stress were attenuated by PRN lesions. The data suggest that a PRN-striatal DA link existing in rat's brain which affects both the spontaneous and the thermal stress induced locomotor activities.

Allogeneic microskin grafts (expansion ratio of 10:1), overlain with Biobrane, were applied to 30 rabbits. There were two groups. In group I, the allogeneic donor microskin grafts were transplanted without specific management. In group II, the donor skin was treated with ultraviolet (312 nm) irradiation to depress Langerhans cells immediately before the transplantation. Histological examination of these grafted wounds in the early stage showed that these micrografts proliferated actively with increased mitotic figures and became regularly stratified under the conditions provided by the Biobrane. By day 9, these wounds in group I were almost resurfaced with neoepithelium. In group II, the rate of regeneration of the neoepithelium was slower than those of group I. Subsequently there was rejection with moderate mononuclear infiltration, hydropic degeneration and satellite necrosis of basal and suprabasal keratinocytes, and local destruction of epithelium. Grossly these reactions caused 'melting' of the neoepithelium and resulted in raw areas. These rejections were more severe about 2 weeks after transplantation and then subsided gradually. Mild cellular infiltration continued to prevent the formation of rete ridges and the dermoepidermal junction was smooth at all times. Langerhans cells could not be found in these grafted wounds using OKT-6 and S100 stain. In spite of the destruction caused by these rejections in both groups, 25 wounds were completely resurfaced with well-differentiated neoepithelium by day 21. This study revealed that the transplanted allogeneic microskin grafts could proliferate to form neoepithelium and resurface the skin wounds of rabbits.

The neural and nonneural factors contributing to maintain the hemodynamic status in 14 to 16 weeks old stroke prone spontaneously hypertensive rats (SHRSP) and spontaneously hypertensive rats (SHR) were compared with those of the age matched normotensive Wistar Kyoto (WKY) rats under chloralose-urethane anesthesia. The ascending aortic blood flow, arterial blood pressure and heart rate were measured under resting condition, ganglionic blockade by hexamethonium, 5 mg/kg i.v. and maximum vasodilation by hexamethonium and 0.07 mg/kg nitroprusside. The neural component (hexamethonium blockable component) was the major factor in the maintenance of resting blood pressure and total peripheral resistance index (TPRI) in the above three strains of rats. In contrast, the residual component after hexamethonium and nitroprusside administrations was the most important controlling factor for cardiac index (CI). In SHRSPs, the neural component of TPRI and residual component of CI were both significantly higher than those of WKYs by 75% and 47%, respectively. In SHRs, the residual component of CI was 52% higher than that of WKYs. These results suggest that both the increased neural component of TPRI and nonneural component of CI are important contributing factors for the blood pressure increase in the early stage of established hypertension in SHRSPs. On the other hand, in the age matched SHRs, the most important contributing factor for hypertension is the increased nonneural component of CI. Considering the differences between these two strains of hypertensive rats, the neural component of TPRI is the major factor responsible for the different levels of hypertension in SHRSPs and SHRs.

SUMMARY 1. The inhibitory effects produced by activation of the medial region of caudal medulla on activities of the left and right cardiac sympathetic, vagus and greater splanchnic nerves were studied in chloralose-urethane anaesthetized cats. 2. Electrical stimulation of the medial region produced an 80–92% inhibition of the sympathetic nerve activities, and a 45% and 58% inhibition of the left and right cardiac vagal nerve activities, respectively. There were no significant differences between effects elicited in the left and right autonomic nerves. Similar but smaller inhibitory effects were produced by micro-injection of sodium glutamate (0.5 mol/L) or DL-homocysteic acid (50 mmol/L) to the same medullary sites. 3. These data suggest that neurons residing in the medial medullary region exert strong inhibitory effects on autonomic nerve activities. Since the vasculature is principally innervated by sympathetic nerves, inhibition of sympathetic nerve activities might be the principal factor responsible for the depressor effects caused by activation of the medial region of caudal medulla. The heart is innervated both by sympathetic and parasympathetic nerves. Thus, their simultaneous inhibition during activation of the medial region elicits only a weak and variable inhibition of the heart.

Malignant mixed müllerian tumor (MMMT) is a rare tumor in females and extragenital MMMT is even more so. We report a patient with MMMT primarily in the mesentery with synchronous ovarian cancer. In the English literature, 42 cases of extragenital MMMT have been reported other than the presented case, and this is only the second MMMT arising from the mesentery. Furthermore, among the cases reviewed, MMMTs tend to be associated with synchronous or metachronous colonic cancer or gynecologic tumors originating from the müllerian duct, including ovarian tumors, fallopian tube cancer, endometrial cancer, cervical cancer, and serous carcinoma of the peritoneum (14 out of 43 patients; 32.6%). The risk factors for MMMT include obesity, nulliparity, exogenous estrogen, and long-term tamoxifen use. The prognosis of MMMT is catastrophic and the treatment is based on the experience of those of uterine sarcomas, which is composed of operation, radiotherapy and chemotherapy.

Perivascular epithelioid cell tumours (PEComas) are a family of tumours including classic angiomyolipoma, lymphangioleiomyomatosis, and clear epithelioid cell tumours reported under a variety of names such as epithelioid angiomyolipoma, pulmonary and extrapulmonary clear cell sugar tumour, and PEComa. Our previous comparative genomic hybridization study of PEComas demonstrated recurrent chromosomal aberrations including deletions on chromosome 16p, where the TSC2 gene is located. In this study, we focused on the alteration of chromosome 16p, including TSC2. We collected ten sporadic and two tuberous sclerosis complex-associated PEComas, as well as 14 sporadic classic hepatic and renal angiomyolipomas (AMLs) as controls. We used 16 microsatellite markers distributed along chromosome 16p to test for allelic imbalances on chromosome 16p and at TSC2, and two markers for TSC1. Furthermore, we carried out immunohistochemical staining for phospho-p706K, phospho-AKT, and phospho-S6 to evaluate the effect of TSC2 alterations on the mTOR signalling pathway. Loss of heterozygosity (LOH) was found in 11 PEComas and involved the region of the TSC2 locus in seven. Six classic angiomyolipomas had allelic changes at chromosome 16p. Microsatellite instability was detected in two PEComas. The incidence of genetic aberrations was significantly higher in the PEComa group. Only one PEComa showed LOH at the TSC1 locus. Eleven PEComas and 13 AMLs revealed elevated phospho-p70S6K accompanied by reduced phospho-AKT. Five PEComas and eight classic angiomyolipomas were positive for phospho-S6. The phosphorylation profile indicates functional activation of the mTOR pathway through a disrupted TSC1/2 complex. Our observations of frequent deletion of TSC2 and the mTOR signalling pathway provide evidence that the oncogenetic lineage of PEComa, as a distinct TSC2-linked neoplasm, is similar to that of angiomyolipoma.

A stimulation of the gigantocellular tegmental field (FTG) in the medulla oblongata often increases systemic arterial blood pressure (SAP) and decreases heart rate (HR). We investigated if the cardioinhibitory/depressor areas, including the nucleus ambiguus (NA), the dorsal motor nucleus of vagus (DMV) and the caudal ventrolateral medulla (CVLM), underlied the functional expression of FTG neurons in regulating cardiovascular responses. In 73 chloralose-urethane anesthetized cats, the HR, SAP and vertebral nerve activity (VNA) were recorded. Neurons in the FTG, NA, DMV and CVLM were stimulated by microinjection of sodium glutamate (25 mM Glu, 70 nl). To study if the NA, DMV, and CVLM relayed the cardioinhibitory messages from the FTG, 24 mM kainic acid (KA, 100 nl) was used as an excitotoxic agent to lesion neurons in the NA, DMV or CVLM. We found that the cardioinhibition induced by FTG stimulation was significantly reduced by KA lesioning of the ipsilateral NA or DMV. Subsequently, a bilateral KA lesion of NA or DMV abolished the cardioinhibitory responses of FTG. Compared to the consequence of KA lesion of the DMV, only a smaller bradycardia was induced by FTG stimulation after KA lesion of the NA. The pressor response induced by Glu stimulation of the FTG was reduced by the KA lesion of the CVLM. Such an effect was dominant ipsilaterally. Our findings suggested that both NA and DMV mediated the cardioinhibitory responses of FTG. The pressor message from the FTG neurons might be partly working via a disinhibitory mechanism through the depressor neurons located in the CVLM.

1. Cats were anaesthetized with urethane (1100-1200 mg/kg, i.p.), supplemented with halothane inhalation during surgery. Responses in terms of systemic arterial pressure, mean systemic arterial pressure(MSAP), heart rate, mean blood flow of the common carotid artery and femoral artery, amplitude and frequency of vocalizations, thoracic-abdominal contractions and limb movements were recorded. 2. Microinjection of N-methyl-D-aspartate (NMDA; 20 mmol/L, 200 nL) into the pretentorial periaqueductal grey (PAG) produced two classes of response: (i) cardiovascular responses and vocalization; and (ii) cardiovascular responses without vocalization. 3. For class 1 responses, five types of vocalization concomitant with pressor (VPR) or depressor (VDPR) responses were observed: (i) type 1 VDPR and VPR, elicited in the rostral and caudal part of the dorsal PAG, produced vocalization of slight hissing, with or without limb movement, moderately increased flow of the common carotid and slightly increased flow of the femoral arteries; (ii) types 2 and 3 VPR, elicited in the dorsolateral and intermediate-lateral PAG, produced hissing-howling and growling, increased respiratory movement, with or without repetitive burst limb movements or stretching of paws, slightly decreased common carotid artery flow and inconsistent changes (increased or decreased slightly) in femoral artery flow; (iii) type 4 VPR, elicited in the dorsomedial and intermediate-medial PAG, produced meowing-crying but without limb movements, common carotid artery flow was increased, but the femoral artery flow was slightly decreased or increased markedly; and (iv) type 5 VPR, elicited in the ventromedial PAG, produced meowing-screaming with or without limb movements, common carotid artery flow increased moderately and femoral artery flow increased markedly. Vocalization was loud and wild in type 4 and 5 responses. 4. For class 2 responses, two types of responses were observed: (i) a pressor response (PR) alone, elicited in the dorsolateral and intermediate-lateral PAG, produced inconsistent changes in common carotid and femoral artery flow, which increased, decreased or underwent no change; and (ii) a depressor response (DPR) elicited in the ventrolateral PAG produced moderate increases of common carotid and femoral artery flow. 5. The reduction of resistance in the femoral artery was more prominent (P < 0.05) in type 1 VDPR than in DPR. Similar changes occurred in the femoral artery among types 3 (P < 0.05) and 5 VPR (P < 0.005) and PR. In addition, the frequency of vocalization was significantly positively correlated with the increase in MSAP (P < 0.05) and mean common carotid and femoral artery flow (both P < 0.01) in all types of VPR. 6. These results suggest the presence of neurons involved in the expression of defence reactions in a longitudinal, complicated functional organization in the entire PAG column. In particular, NMDA stimulation of the medial, dorsal and dorsolateral PAG may elicit five different types of defence reactions, expressed by various forms of cardiovascular alterations concomitant with vocalization responses.

The aim of the present study was to examine the relationship between the lateral tegmental field (FTL), a cardioinhibitory area, with other cardioinhibitory areas, i.e., the ambiguus nucleus (NA) and the dorsal motor nucleus of vagus (DMV) and the caudal ventrolateral medulla (CVLM), a vasopressor inhibitory area. In 55 cats anesthetized with chloralose (40 mg/kg) and urethane (400 mg/kg), the cardiovascular responses of heart rate (HR), systemic arterial blood pressure (SAP) and vertebral nerve activity (VNA) were recorded. The FTL, NA, DMV and CVLM were identified first by stimulation (rectangular pulses in 80 Hz, 0.5 ms, 50-100 microA) and then confirmed by microinjection of sodium glutamate (Glu, 0.25M, 70 nl). In studying the influence of NA, DMV, or CVLM lesion on the Gluinduced responses in FTL, kainic acid (KA, 24 mM, 100 nl) was microinjected into the NA, DMV or CVLM. FTL stimulation produced an average decrease of HR by 55%. After KA lesioning of the ipsilateral NA or the DMV, the decreased HR induced by FTL was significantly diminished. After subsequent lesion of the contralateral DMV or NA, the bradycardia of FTL was abolished. The reduction of resting HR was more intense after lesioning the NA than DMV and with the left side more than that of the right side. These studies suggest that the cardioinhibitory responses of FTL are mediated through both NA and DMV with predominance of the former, while the hypotensive effect of FTL is mediated through CVLM. The precise pathway responsible for the FTL-induced bradycardia and hypotension is to be determined.

A 36-year-old woman had suffered from epigastric fullness for half a year. A splenic mass was found by ultrasonography. She was treated with splenectomy. Inflammatory pseudotumor of the spleen was diagnosed pathologically. This benign tumor in the spleen is extremely rare. To our knowledge, only 67 cases had been reported in the literature. Recognition of this rare entity is important because it may mimic splenic malignancy clinically and radiographically.

The difference of prognosis in patients with the same WHO grade of astrocytic tumors suggests that such tumors comprise a heterogeneous group in biological behavior. The correlation between p53 immunoreactivity and prognosis has often been reported but remains controversial. From the perspective of clonal expansion of p53 immunopositive cells, the distribution patterns of p53 immunoreactivity can be divided into four types: negative, scattered, focally clustered, and diffusely clustered. The survival rate was evaluated by classifying the p53 immunoreactivity into two groups: the significantly immunopositive patterns (focally and diffusely clustered types) and the significantly immunonegative patterns (negative and scattered types). The survival analysis showed a highly significant difference between these two patterns within the same WHO grade of astrocytic tumors (p = 0.0185). Our studies demonstrate that the distribution patterns of p53 immunoreactivity, which reflect the trends of clonal expansion of p53 immunopositive cells, are significantly valuable in predicting the prognosis of patients with the same WHO grade of astrocytic tumors.

Antigen-specific cancer immunotherapy and antiangiogenesis have emerged as two attractive strategies for cancer treatment. An innovative approach that combines both mechanisms will likely generate the most potent antitumor effect. We tested this approach using calreticulin (CRT), which has demonstrated the ability to enhance MHC class I presentation and exhibit an antiangiogenic effect. We explored the linkage of CRT to a model tumor antigen, human papilloma virus type-16 (HPV-16) E7, for the development of a DNA vaccine. We found that C57BL/6 mice vaccinated intradermally with CRT/E7 DNA exhibited a dramatic increase in E7-specific CD8(+) T cell precursors and an impressive antitumor effect against E7-expressing tumors compared with mice vaccinated with wild-type E7 DNA or CRT DNA. Vaccination of CD4/CD8 double-depleted C57BL/6 mice and immunocompromised (BALB/c nu/nu) mice with CRT/E7 DNA or CRT DNA generated significant reduction of lung tumor nodules compared with wild-type E7 DNA, suggesting that antiangiogenesis may have contributed to the antitumor effect. Examination of microvessel density in lung tumor nodules and an in vivo angiogenesis assay further confirmed the antiangiogenic effect generated by CRT/E7 and CRT. Thus, cancer therapy using CRT linked to a tumor antigen holds promise for treating tumors by combining antigen-specific immunotherapy and antiangiogenesis.

The pathophysiology of nasal polyps remains unclear, but recent work suggests that many cytokines are produced in nasal polyps (NPs) and that they may play various important roles in the pathogenesis of NPs. Transforming growth factor-beta 1 (TGF-beta 1), secreted by many inflammatory cells, is a potent inducer of myofibroblasts. Myofibroblasts express alpha-smooth muscle actin (alpha-SMA) and a source of extracellular matrix (ECM). In this study, we investigated a potential link between inflammation and the growth process in human NPs. Sixteen patients who were affected by NPs and who had undergone functional endoscopic sinus surgery were included in this study. Nasal mucosa of inferior turbinate (NM) of 10 patients who had received rhinoplasty or turbinectomy for other disease was used as the control. alpha-SMA and TGF-beta 1 were detected using immunohistochemistry and the number of labeled cells were counted (alpha-SMA and TGF-beta 1 indices). The expression of alpha-SMA and TGF-beta 1 indices found in NPs and NM was compared using Student's t-test. In our study, alpha-SMA and TGF-beta 1 indices were found to be significantly higher in nasal polyps than in nasal mucosa. TGF-beta 1 produced by inflammatory cells can influence the development of myofibroblasts which in turn can induce extracellular matrix accumulation and, therefore, TGF-beta 1 plays a important role in the formation of nasal polyps.

The HER-2/neu proto-oncogene amplification or oncoprotein overexpression is an important prognostic factor and a predictive factor for resistance to endocrine therapy and adjuvant chemotherapy in breast cancers. Moreover, it is an entry criterion in the assessment of patients for whom Herceptin (Trastuzumab) treatment is considered. The overexpression rate of HER-2/neu oncoprotein has been identified in 10% to 40% of human breast cancers. In Taiwan, a higher grade of pathobiologic characteristics of familial breast cancer was also noted than that found in the non-familial group. It is worthwhile to evaluate whether the overexpression is more frequent in familial breast cancers. Fifty-six familial and 111 non-familial breast cancers were studied between 1990 and 1999 to assess both the overexpression of HER-2/neu oncoprotein immunohistochemically and the correlation with the histological type, grade and stage of breast carcinoma. The overexpression rate is higher in the familial breast cancer group (50.0%) when compared with non-familial breast cancer group (36.9%), which did not prove to be statistically significant (P = 0.1068). However, when the infiltrating ductal carcinomas of both groups are compared, it is statistically significant (52.3% vs. 33.7%, P = 0.0429). Overexpression correlated with node status and histological grade of infiltrating ductal carcinomas in non-familial and overall breast cancers. It also correlated with nuclear pleomorphism and mitotic counts, but not tubule formation or tumor size. All 3 cases of Paget's disease revealed overexpression, whereas all 12 cases of mucinous and one case of metaplastic carcinoma and one case of medullary carcinoma were negative. The overexpression rate was higher both in familial and non-familial intraductal carcinomas (57.1% vs. 73.3%, P = 0.4716). No statistical difference was identified between the 2 subsets. A case of infiltrating ductal carcinoma combined with intraductal carcinoma revealed heterogeneous staining in the component of ductal carcinoma in situ, while the invasive component did not. This suggests that overexpression decreases within individual tumors as they evolve from in situ to invasive lesioins. The HER-2/neu may imply a different role in intraductal carcinoma, Paget's disease and invasive duct carcinoma. Although the overexpression rate of HER-2/neu oncoprotein of familial breast cancer was not significantly higher than that of the non-familial group, it is appropriate to evaluate the rate of HER-2/neu overexpression according to the histological type of breast cancers from familial breast cancer and non-familial breast cancer. The prognoses will be needed for future evaluation.

Certain domains of bacterial toxins have been shown to facilitate translocation from extracellular and vesicular compartments into the cytoplasm. This feature represents an opportunity to enhance class I presentation of exogenous antigen to CD8(+) T cells. We investigated this notion by creating a novel fusion of the translocation domain (domain II) of Pseudomonas aeruginosa exotoxin A (ETA(dII)) with a model tumor antigen, human papillomavirus type 16 E7, in the context of a DNA vaccine. Our in vitro studies indicated that cells transfected with ETA(dII)/E7 DNA or dendritic cells pulsed with lysates containing ETA(dII)/E7 protein exhibited enhanced MHC class I presentation of E7 antigen. Vaccination of mice with ETA(dII)/E7 DNA generated a dramatic increase in the number of E7-specific CD8(+) T cell precursors ( approximately 30-fold compared with wild-type E7 DNA) and converted a less effective DNA vaccine into one with significant potency against human papillomavirus type 16 E7-expressing murine tumors via a CD8-dependent pathway. These results indicate that fusion of the translocation domain of a bacterial toxin to an antigen may greatly enhance vaccine potency.

The purpose of this study is to evaluate whether there are pathobiologic differences and differences in overall rates survival between familial and non-familial breast cancer patients in Taiwan. A retrospective study was performed evaluating 76 familial breast cancer patients in 69 families, which included two BRCA1 related cases and six BRCA2 related cases. Patients were compared with 425 non-familial sporadic cases. Familial breast cancer patients had similar ages and stages as non-familial patients (mean, 46.6 years vs 48.9 years, p = 0.306). However, the familial breast cancer patients with BRCA1 and BRCA2 related cases presented at lower stages (p = 0.034) and younger ages than non-familial patients (mean, 45.1 years vs 48.9 years P = 0.042). The occurrence of infiltrating ductal carcinoma and lobular carcinoma in situ was not significantly different in the two groups. Mucinous carcinoma was represented with 6.7% (4/76) and 1.3% (1/76) medullary carcinoma. The overall grade of familial breast cancer, including BRCA1 and BRCA2 related cases in 8 infiltrating ductal carcinoma, was significantly higher than that of controls. The mean follow up was 4.5 years for familial breast cancers. Five- and 10-year overall survival rates were 69% and 61% for those with a family history, compared with 86% and 64% for those in the control group (p = 0.644). There were no statistically significant differences in disease-free survival rates between the two groups at 5 or 10 years (69% vs 78% in 5 years; 48% vs 58% in 10 years) (p = 0.862). Despite the younger ages and earlier stages at presentation in familial breast cancer patients with BRCA1 and BRCA2 related cases, the familial breast cancer patients had higher grade patholobiologic characteristics, but similar prognoses when compared with sporadic breast cancer patients. Owing to the limited number of familial cases in this study, more cases and longer follow up are needed.

Nitric oxide (NO) is involved in cardiovascular regulation and sympathetic nerve activity of the central nervous system (CNS). The nucleus tractus solitarius (NTS) is important to cardiovascular regulation. However, the physiological role of NO in cardiovascular regulation effecting through the NTS remains unclear. The purpose of this study is to investigate the effect of NO measured by in vivo voltammetry on the cardiovascular responses in NTS induced by N-methyl-D-aspartate (NMDA) in anesthetized cats. Extracellular NO concentration was monitored through a Nafion- and porphyrin-coated carbon fiber electrode, which has previously been demonstrated sensitive and selective to NO responses. Microinjection of NMDA into NTS elicited a dose-dependent decrease in cardiovascular responses associated with NO release. Following the dose-response curve, a dose of 3 nmol of NMDA was selected. Microinjection of NMDA into NTS produced depressor responses and NO release. These responses in NTS to NMDA were attenuated by pretreatment with a competitive antagonist, 2-amino-5-phosphonopentanoat (AP-5, 1 nmol), and methylene blue (MB, 1 nmol), an inhibitor of guanylate cyclase. These results suggest that NO is formed from NMDA activation in NTS and that NO diffuses out of neurons into the nearby target neurons to produce depressor response and NO release through cyclic guanosine monophosphate (cGMP) formation. In conclusion, NO mediates depressor response consequent to activation of NMDA receptors in neurons of NTS.

Middle ear cholesteatoma has a remarkable invasive activity accompanied by destruction of ossicles and temporal bone. Its aggressive growth and high tendency to recur have impact on the postoperative care of the patients. Proliferating cell nuclear antigen (PCNA) is a 36 KDa DNA-delta-polymerase-associated protein whose level of synthesis has been found to correlate directly with rates of cellular proliferation. In this present study, we used ABC (avidin-biotin complex) technique and monoclonal antibody to PCNA to evaluate the expression of PCNA in 37 cases of cholesteatoma epithelium and 21 cases of normal postauricular skin. The rate of PCNA-positive cells in basal, parabasal, and upper layer of cholesteatoma epithelium tissue is 78% (29 cases), 68% (25 cases), and 41% (15 cases). In each layer of the postauricular skin tissue is 71% (15 cases), 67% (14 cases) and 34% (7 cases). No statistical difference of expression of PCNA-positive cells exists between each layer of cholesteatoma epithelium and normal postauricular skin; however, a tendency of higher PCNA-positive cells in cholesteatoma epithelium was observed. Immunohistochemical method of PCNA has the advantages of spatial architecture preservation, the relative simplicity of the methodology and the rapid acquisition of results. Although the etiology and histopathology of the growth pattern and osteolytic activity of cholesteatoma are unclear, information on cell kinetics may assist in cholesteatoma classification and may help predict the risk of recurrence and bone destruction. The results of this report indicate that cholesteatoma has a similar proliferative activity to the normal postauricular skin, and cholesteatoma itself is not a real tumor, despite its clinical behavior, which is similar to neoplastic cells. It is necessary to further study whether the cell kinetic information we obtained from the PCNA immunohistochemical analysis provides a valuable tool in accessing the prognosis of the cholesteatoma.

Various types of brain tumors may cause hemorrhage. The purpose of the study was to examine the clinical relevance of tumor hemorrhage and the hemorrhagic mechanism from the pathologic viewpoint. We retrospectively reviewed 761 consecutive brain tumor cases according to clinical, operative, and pathologic records. Pituitary adenomas and recurrent tumors were excluded. Twenty-seven patients (17 men and 10 women, mean age, 50 years) with brain tumor hemorrhage were identified, resulting in an incidence of 3.5%. In 632 cases of primary brain tumors, there were 15 cases with hemorrhage, resulting in an incidence of 2.4%. There were 12 cases of brain tumor hemorrhage in 129 patients with metastatic tumors, for an incidence of 9.3% Among hemorrhagic cases, 63.0% of patients presented with acute onset of clinical deterioration. In 72.7% of gliomas with hemorrhage, hematoma appeared within the tumor, and 75% of metastatic brain tumors with hemorrhage were intracerebral hemorrhages around the borders of the tumors. The highest hemorrhage rate for primary brain tumors occurred in pilocytic astrocytomas, while the highest hemorrhage rates in secondary tumors occurred in metastatic thyroid papillary carcinomas and hepatocellular carcinomas. In our pathology study, increasing intratumor vascularization with dilated, thin-walled vessels and tumor necrosis were the most important mechanisms of hemorrhage.

Herein we are reporting a case of simultaneous occurrence of renal and pancreatic foreign body granuloma due to retained gauze. The different imaging features of the two lesions make correct preoperative diagnosis difficult. Foreign body granulomas due to retained surgical gauze or sponges should be considered in patients who have previous histories of operations and who also have a mass in the surgical bed. Simultaneous occurrence of foreign body granuloma away from primary surgical field is also possible.

The role of p53 gene mutations in the formation or progression of human astrocytic tumors is controversial. We studied the distribution pattern of p53 immunoreactivity and analyzed p53 gene mutations to define the significance of p53 gene mutations in astrocytoma tumorigenesis or malignant progression. Twenty-three astrocytic tumors were evaluated with immunohistochemistry, single-strand conformation polymorphism (SSCP) analysis, and sequence analysis. We also searched MEDLINE to collect data on p53 gene mutation frequencies in astrocytic tumors in order to evaluate the association of p53 mutations and tumor grade. Strong immunoreactivity with a diffuse clustering pattern was found in three of five glioblastomas and seven of 12 anaplastic astrocytomas. Three of four low-grade astrocytomas were immunonegative. The p53 immunopositive cells in the only positively staining low-grade astrocytoma in our study appeared sparsely scattered. The results of immunostaining suggested that clonal expansion was associated with astrocytoma progression. Mutations of the p53 gene were detected in four of the 23 astrocytomas (one glioblastoma and three anaplastic astrocytomas). In the genetic data analysis, 76 of 367 astrocytomas had p53 gene mutations. A significantly greater p53 gene mutation frequency was found in anaplastic astrocytomas or glioblastomas than in the low-grade astrocytomas. The results of these immunohistochemical and genetic studies support the view that p53 gene mutation is associated with the malignant progression from low-grade to high-grade astrocytomas rather than with tumor initiation or promotion.

Hemorrhage of juvenile pilocytic astrocytomas is very rare. However, it is clinically important because a high probability of a fatal outcome exists if hemorrhage occurs outside the optic nerve. Hemorrhage of a hypothalamic juvenile pilocytic astrocytoma has been reported only once, from an autopsy examination. We present a successfully managed case. The patient, a 34-year-old man, presented with sudden loss of consciousness. Computed tomography (CT) and magnetic resonance imaging demonstrated an exophytic hypothalamic tumor with a hemorrhage. Craniotomy with total removal of the tumor and the hematoma was performed. Histopathologic examination revealed that the tumor was a juvenile pilocytic astrocytoma. Brain CT examination 18 months later revealed no evidence of tumor recurrence. The patient was well, without neurologic deficit, and had a normal social life as of the last follow-up examination 22 months after craniotomy.

We have previously demonstrated that intra-hippocampal injection of corticotrophin-releasing factor improved memory retention of an inhibitory avoidance learning in rats; while the electrophysiological effects corticotrophin-releasing factor produces on hippocampal neurons are largely uncharacterized. In the present study, we found that corticotrophin-releasing factor injected into the dentate gyrus of hippocampus produced a dose-dependent and long-lasting enhancement in synaptic efficacy of these neurons, as measured by an increase in the amplitude and slope of population excitatory postsynaptic potentials, as well as the amplitude of population spike. The onset of corticotrophin-releasing factor-induced potentiation was slow. It was observed approximately 40-60 min after corticotrophin-releasing factor administration and lasted for more than 5 h. This effect of corticotrophin-releasing factor was blocked by pretreatment with the cyclase-adenosine-3,5-monophosphate (cAMP) inhibitor Rp-adenosine-3,5-cyclic monophosphothiolate triethylamine (Rp-cAMPS) and partially blocked by the N-methyl-D-aspartate receptor antagonist MK-801. Further, pretreatment with corticotrophin-releasing factor receptor antagonist dose-dependently diminished tetanization-induced long-term potentiation, and corticotrophin-releasing factor and tetanic stimuli had an additive effect on hippocampal neuron excitation. Moreover, direct injection of corticotrophin-releasing factor increased cAMP level in the dentate gyrus. These results together suggest that corticotrophin-releasing factor-induced potentiation simulates the late phase of tetanization-induced long-term potentiation and cAMP seems to be the messenger mediating this effect. Moreover, corticotrophin-releasing factor-induced potentiation and long-term potentiation may share some similar mechanisms, and corticotrophin-releasing factor is probably involved in the neural circuits underlying long-term potentiation. Thus, corticotrophin-releasing factor may play an important role in modulating synaptic plasticity in the hippocampus.

Molecular pathology may play an important role in predicting the tumor prognosis, particularly p53, epidermal growth factor receptor (EGFR), and c-erbB-2. We investigated six variables (age, sex, histopathological grade, p53, EGFR, and c-erbB-2) to identify the role of such factors in predicting the outcome of patients with supratentorial astrocytic tumors. Thirty-seven tumors were studied including 9 well-differentiated astrocytomas (WHO grade 2), 19 anaplastic astrocytomas (WHO grade 3), and 9 glioblastomas multiforme (WHO grade 4). In univariate analysis, no statistical significance was found for the prognostic value of the sex (p = 0.2188), age (p = 0.5530), p53 immunostain (p = 0.2194), and c-erbB-2 immunostain (p = 0.4203). A significant correlation with the prognosis was found with respect to the histopathological grade (p = 0.0049) and EGFR expression (p = 0.0284). In multivariate analysis, the histopathological grade was shown to be significant independent variable (p = 0.0152). In WHO grade 2 and 3 astrocytomas, expression of p53 or EGFR was associated with poorer patient outcome. In glioblastomas, expression of p53 was also associated with poorer prognosis. Our studies suggested that conventional histological assessment of supratentorial astrocytic tumors remains the best guide to prognosis. Although no statistical significance was found between the immunostains and survival in variant grades of astrocytomas, there was a trend between p53 or EGFR proteins expression and the decrease of survival time.

The cardiac and vascular components of the baroreceptor reflex in spontaneously hypertensive rat (SHR) and stroke-prone spontaneously hypertensive rat (SHRSP) were compared against their counterparts in normotensive Wistar Kyoto rat (WKY). SHR, SHRSP and WKY of 12-16 weeks old were chronically instrumented for intra-arterial recording of blood pressure. Intravenous injections of phenylephrine and nitroprusside were used to challenge their baroreflex. The products of blood pressure change and the half time required for the pressure to return to the control value were used as the quantitative estimation of the blood pressure stabilizing capability. The cardiac component of the baroreflex was obtained from the change in the blood pressure stabilizing capability after blockade of beta and muscarinic receptors by atenolol and atropine, respectively. The vascular component was obtained by subtracting the cardiac component from the total stabilizing capability which was the difference after blockade with a ganglionic transmission blocker, hexamethonium. We found the cardiac component of the baroreflex of the hypertensive rats was significantly less sensitive than that of the WKY. In contrast, the vascular component of the baroreflex of the three strains did not differ significantly. Therefore, we concluded that the 12-16 week old SHRs were able to maintain a stable blood pressure due to the intact vascular component of the baroreflex.

In this study, we developed a differential integrator unit containing a window discriminator (WPI-121) and three integrators (sample/hold, Gould) to characterize the difference in spikes involved in sympathetic vertebral nerve activity (VNA) and integrated VNA (Int. VNA) during stimulation of the dorsomedial (DM) and rostral ventrolateral (RVLM) medullar. The upper level (UL) in the window discriminator was set at a value, 80% of the VNA amplitude above the zero. The low level (LL) was set at a value 10% above the zero. The number of VNA spikes above the UL in the window discriminator was defined as Fa, while the number of VNA spikes within the UL and LL as Fw. In 26 cats anesthetized with urethane and alpha-chloralose, results showed that electrical stimulation and microinjections of glutamate (Glu, 0.25 M, 50 nl) or glycine (Gly, 1.0 M, 50 nl) at the same point in DM or RVLM increased both systemic arterial pressure (SAP) and Int. VNA. However, the increase of Int.VNA on DM stimulation was contributed by increases of both Fa and Fw, while on RVLM stimulation the increase of Int.VNA was mainly contributed by the increase of Fa, against a decrease of Fw. As compared to Glu, stimulation of DM by Gly produced more increase in Fw, while stimulation of RVLM by Gly produced more decrease in Fw. During RVLM stimulation the VNA was usually transferred to a huge synchronized oscillation. These findings suggest that although stimulations of the sympathetic-pressor neurons in DM and RVLM produce similar increases in SAP and VNA, the nature of these neurons is different.

Adenocarcinoma of the prostate commonly metastasizes to the lymph nodes and bones, with occasional visceral deposits, however, metastasis to the brain is rare. A case of prostatic carcinoma with brain metastasis presenting as a tumor hemorrhage is reported. The pertinent literature is also reviewed.

Muscle damage in the legs of male Wistar rats after exposure to high-dose radiation was evaluated by observations of biopsied tissue made with light and transmission electron microscopy. Both legs of about 40 mature male Wistar rats were exposed to 80 Gy 6 MV X rays from a linear accelerator given in 40 fractions of 2 Gy. At intervals starting from the first day to 12 months after irradiation, serial muscle biopsies were obtained by sacrificing the rats on different days according to the experimental design. The irradiated gastrocnemius muscle displayed a progressive structural change that began immediately after the completion of the exposures. Morphological changes in irradiated muscles were characterized by hemorrhage, lymphocytic infiltration and obvious vascular destruction. Increased amounts of collagen between the muscle fibers were present even at 12 months after irradiation. There were significant changes in the number, size and structure of mitochondria in the muscle cells from the first day until 1 year after irradiation. Even 12 months after the final exposure, no recovery of muscle tissue was seen by light and transmission electron microscopy.

Therapeutic ultrasound has been used in the treatment of osteoarthritis for the relief of symptom and improvement of functional status. In recent study, we found that ultrasound enhances cartilage repair in experimental early stage osteoarthritis, and prevents deteriorative changes in later stages. In the present study, we further investigate the bioeffects of ultrasound on cartilage matrix of experimental arthritis. Fifty-four rats with three different degrees of papain induced osteoarthritis classified by 99m-Tc pertechnetate bone scan were collected for ultrasound treatment. The changes in their arthritic severity after sonication treatment and two months after treatment were measured using 99m-Tc bone scan. The histopathological changes were evaluated through light microscope after disarticulation sections (H.E. stain), and the changes in mucopolysaccharide density in cartilage matrix were measured using a Optimas scanner analyzer after Alcian blue staining. The results showed that the density of mucopolysaccharide rose in the initial stage of induced arthritis, and decreased progressively in the later stage. The density of mucopolysaccharide increased upon complete sonication more for the treated rats than for the controls, and this was closely related with the improvement in histopathological findings, but inversely with the changes in arthritic severity. In conclusion, therapeutic ultrasound enhances mucopolysaccharide synthesis of arthritic cartilage, and results in the repair of arthritic cartilage in the early stage of induced arthritis and the prevention of deteriorative changes in later stages.

To investigate the histological effect of therapeutic ultrasound on arthritic cartilage of rats with various severities of induced osteoarthritis.Twenty-seven rats with 3 different stages (Grade I, II, III) of papain induced knee arthritis received 7 min pulse sonication treatment, 3 times/week for 4 weeks. Another 27 rats with the same severity of induced arthritis were studied as controls. The severity of arthritis and related histopathological changes of articular cartilage were evaluated by bone scan and histological findings with hematoxylin and eosin stain."Severity indexes" based on bone scan decreased after sonication treatment in each study group. Histopathological findings indicated marked cartilage repair in the early stage of induced arthritis (Grade I). However, progressive cartilage damage present in untreated Grade II, III induced arthritis was significantly reduced after sonication.Therapeutic ultrasound enhances cartilage repair in the early stage, and has the effect of arresting further deteriorative damage in the later stage of induced arthritis.

Tumorigenesis is the result of sequential or multiple genetic alterations. The overexpression or amplification of various oncogenes in diverse human brain tumors have been observed. While numerous studies on the immunohistochemical demonstration of EGFR-overexpression have been reported, little has been found in the literature about the c-erbB-2 protein in human astrocytic tumors. In the present study, we evaluated the expression of EGFR and c-erbB-2 protein in 33 astrocytic tumors with immunohistochemistry. According to the World Health Organization brain tumor classification, the study included 9 low-grade astrocytomas (grade 2), 15 anaplastic astrocytomas (grade 3), and 9 glioblastomas multiforme (grade 4). The positive EGFR immunoreactivity was detected in 28 (85%) of 33 tumors. The expression of EGFR increased with the grade of malignancy in low-grade astrocytomas (67%), anaplastic astrocytomas (87%), and glioblastomas (100%). For the expression of c-erbB-2 protein, 17 (51.5%) of 33 tumors were positive immunostain, including 3 low-grade astrocytomas (37.5%), 9 anaplastic astrocytomas (81.8%), and 5 glioblastomas (62.5%). Different degrees of immunoreactivity for c-erbB-2 protein were found in variant grades of astrocytomas. However, the positive immunostain of EGFR displayed moderate or strong reactivity. The coexpression of EGFR and c-erbB-2 protein was found in 17 (15.5%) of 33 tumors. The results emphasize that the overexpression of EGFR parallels astrocytoma progession and higher frequency of c-erbB-2 immunoreactivity was seen in snaplastic astrocytomas and glioblastomas than in low-grade astrocytomas.

The role of paramedian reticular nucleus (PRN), a structure effecting sympathetic inhibition, in the development of hypertension was investigated in young spontaneously hypertensive rats (SHR) and two age-matched normotensive rats, Wistar-Kyoto (WKY) and Sprague-Dawley rats (SD). Three different experimental manipulations, including electrical-lesioning, sham-operated and intact control, were performed in SHR, WKY and SD rats 7 weeks after birth. In the control groups, the systolic arterial blood pressure (SABP) of SHR increased abruptly from 160 mmHg to 230 mmHg from the 6th to 13th week after birth, whereas those of WKY and SD maintained a normal range of SABP. In the lesioned groups, a hypotension and/or bradycardia was evoked by electrical stimulation to verify the location of PRN. Following the verification, a direct current was delivered to lesion the PRN in situ. The effect of PRN lesioning on the subsequent development of hypertension was illustrated by comparing SABP in three experimental groups of age-matched conscious SHR, WKY and SD during 8-13 weeks after birth. We found that the average SABP in the lesioned SHR was consistently elevated and was not significantly different from those of the sham-operated and the control. In contrast, in the normotensive rats, there was no significant increase in SABP within the three experimental groups, i.e., the average SABP of the lesioned, the shamed-operated and the control group maintained a normal range. Our results support the contention that the hypertension of SHR developed within 6-13 weeks after birth. In addition, the sympatho-inhibitory mechanism of PRN was not directly related to the development of hypertension.

The intercellular lipid lamellae of the stratum corneum (SC) is believed to provide the permeability barrier of the epidermis. Previous functional studies have demonstrated an increase in the transepidermal water loss (TEWL) after long-term use of topical corticosteroids (TCS): however, direct morphological confirmation of this barrier abnormality is still lacking. The aim of this study was to determine whether any abnormality could be detected in the structure of the SC intercellular lipid lamellae in patients after long-term TCS. Atrophic skin and untreated normal skin of 10 patients after long-term TCS were examined by transmission electron microscopy using ruthenium tetroxide-fixed tissue for the multilamellar lipid sheets of SC, and oil red O stain for neutral lipids of the SC. Layers of the SC were evaluated by 0.1% methylene blue stain after alkaline expansion, and TEWL was measured by Evaporimeter EP1. The TCS-treated atrophic skin had fewer layers of horny cells, mean 9.4 layers, than the normal control skin, 18 layers (P0.001) and increased TEWL of 21.3 g/m2 compared with the control skin TEWL of 6.7 g/m2 (P0.01). The mean neutral lipid content of the SC was also significantly lower (P0.001). Moreover, ultrastructural studies revealed a marked decrease in both the numbers of intercellular lipid lamellae of SC and membrane-coating granules of stratum granulosum in the atrophic skin. These results suggest that the diminution in the SC intercellular lipid lamellae and SC cell layers play an important part in the pathogenesis of barrier dysfunction after long-term use of TCS.

In a rabbit model, transplantation of largely expanded microskin grafts (expansion ratio 25 X) were studied. In Group I, the autologous microskin grafts were transplanted onto the full-thickness skin defect on the back of a rabbit and were overlaid with Biobrane. In Group II, the autologous microskin grafts were mixed with allogeneic microdermal substance (expansion ratio 25 X) before the transplantation. The percentage of re-epithelialized area to the total grafted wound was analyzed by means of computerized planimetric analyses of photographs of the grafted wounds on days 11 and 13. Biopsies of the grafted wounds were done. On day 11, the mean percentage of Group I was 72.4% and that of Group II was 82.7%. On day 13, they were 82.3% in Group I and 92.3% in Group II. In Group II, the allogeneic dermal tissue did not cause obvious rejection in the neoepithelium. Histological features showed the existence of allogeneic dermal tissue in the grafted wound. The adding of largely expanded allogeneic dermal substance to autologous microskin grafts in Group II provided better circumstances than that in Group I for re-epithelialization of autologous mciroskin grafts.