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Angiomyofibroblastoma (AMF) is a rare benign mesenchymal neoplasm that arises in the pelviperial region.A patient presented with a painless mass in the right vulva. Under the preoperative diagnosis of Bartholin cyst, she underwent a simple tumor excision. Pathological examination revealed an AMF. Immunohistochemical examination showed that tumor cells were positive for estrogen receptor, progesterone receptor, vimentin, and CD34. She has been with no evidence of local recurrence for ten months after surgery.AMF of the vulva is a distinctive mesenchymal tumor that is curable with a simple excision.

To evaluate the usefulness of the combination of serum prostate-specific antigen (PSA) and cancer volume in biopsy specimens as markers to predict the extent of prostate cancer.Of patients presenting at our hospital with urinary symptoms suggesting prostatic disease, 311 (median age 70 years, range 42-88) with either nodules in the prostate detected by digital rectal examination or with elevated serum PSA levels (2.0 ng/mL) underwent systematic biopsy; 69 had prostate cancer. The cancer volume in the biopsy specimens was examined pathologically by measuring the percentage of the biopsy core involved with cancer, the length of cancer tissue per biopsy core and the percentage of cancer in the biopsy specimen. The relationship of serum PSA level, cancer volume in the biopsy specimen and the extent of disease was examined.The volume of cancer in the biopsy specimens increased with increasing serum PSA concentration and the incidence of skeletal metastasis. The number of patients with extraprostatic disease or bony metastasis was significantly higher for these Japanese patients with a serum PSA of10 ng/mL. All six patients with a positive bone scan and who had a serum PSA level of10 ng/mL had a larger volume of cancer in their biopsy specimens. Among patients who underwent radical prostatectomy and pelvic lymphadenectomy, the incidence of extraprostatic disease increased with the value of each biopsy variable. Among patients with similar serum PSA levels, those showing higher values for the biopsy variables also showed extraprostatic disease. Among those with extraprostatic disease, seminal vesicles were involved by cancer in four of six patients with40% positivity in the biopsy cores,1.5 mm of cancer per biopsy core or20% cancer in the biopsy specimens. Lymph node metastasis was found in four of five patients with serum PSA levels of20 ng/mL and a large cancer volume in the biopsy specimen.These results indicate that a combination of serum PSA level and cancer volume in the biopsy specimen could be useful markers for predicting the extent of prostate cancer.

The transition of low-grade endometrial stromal sarcoma (ESS) to high-grade ESS remains a rare clinical event.A patient presented with abdominal pain and abnormal genital bleeding. She underwent a supracervical hysterectomy with bilateral salpingo-oophorectomy, omentectomy, and resection of peritoneal disseminated lesions. Pathological examination revealed low-grade ESS in the uterus and omentum. Immunohistochemical examination showed immunoreactivity for CD10 and Ki-67 (MIB1) in the uterus and omentum. However, estrogen receptor, progesterone receptor, alpha-SMA, desmin, h-caldesmon, and CAM5-2 were negative. P53 immunoreactivity was noted only in the omental lesion. Despite performing six courses of adjuvant chemotherapy, she recurred in the abdomen. She underwent ileostomy and resection of peritoneal disseminated lesions. Pathology showed high-grade ESS in the recurrent lesion of the ileum, which was characterized by severe cytologic atypia, high mitotic index, multifocal necrosis, increased Ki-67 index, and immunoreactivity for p53.Although rare, the transition of low-grade ESS to high-grade ESS may occur and suggests the worsening of the prognosis. Pathological examination and immunohistochemistry are useful for the diagnosis of the transition of low-grade ESS to high-grade ESS.

A superoxide dismutase derivative (SM-SOD) that circulates and is bound to albumin with a half-life of 6 h was injected intraperitoneally into rats before exhaustive treadmill running to study its antioxidant scavenging capacity in the plasma and soleus and tibialis muscles. The exercise induced a marked increase in xanthine oxidase activity in plasma and an increase in thiobarbituric acid-reactive substances in the plasma as well as in the soleus and tibialis muscles of nonadministered rats immediately after the exercise. The immunoreactive content and activity of both SOD isoenzymes (Cu,Zn-SOD and Mn-SOD) of the nonadministered rats increased in the soleus and tibialis muscles immediately after running. SM-SOD treatment definitely attenuated the degree of the increase in thiobarbituric acid-reactive substances and xanthine oxidase in all samples examined immediately after exercise. Glutathione peroxidase activity significantly increased in the soleus muscle of nonadministered rats 1 day after running, whereas catalase activity remained unchanged throughout the experimental period. These results suggest that a single bout of exhaustive exercise induces oxidative stress in skeletal muscle of rats and that this oxidative stress can be attenuated by exogenous SM-SOD.

Objective To determine the usefulness of transrectal ultrasound (TRUS) and systematic biopsy by correlating these Results with pathological findings after radical prostatectomy. Patients and methods Pre-operative TRUS examination combined with the findings on systematic biopsy in 15 patients (mean age 70.6 years, range 57-87) who underwent radical prostatectomy between October 1992 and February 1994 were compared retrospectively to the histological features of whole mount sections of the surgical specimens. Results In all cases, the tumour was visualized as a hypoechoic area on the sonogram. In addition, in six of 15 cases the tumour was localized in an isoechoic area which was examined before the operation by systematic biopsy. In this series, a systematic biopsy before operating detected tumour grade and localization of the tumour in 14 and 15 patients, respectively. The positive predictive value of capsular penetration and seminal vesicle invasion on the sonogram was 0.71 and 1.00, respectively, while sensitivity was 1.00 and 0.33, respectively. Five of seven patients with findings of capsular penetration on the sonogram revealed capsular penetration in the resected prostate, whereas, of three patients with pathologically detected seminal vesicle invasion, only one had findings of seminal vesicle invasion by ultrasonography. The serum prostate specific antigen level of all three patients was more than 30 ng/mL. Moreover, in this series of 15 patients TRUS detected the precise stage in 11 patients. In the remaining four patients, two were overstaged and two were understaged. Tumours with hypoechogenicity were of higher grade and larger than tumours with isoechogenicity. AH tumours with hypoechogenicity were palpable and all with isoechogenicity were not. Conclusions TRUS combined with a systematic biopsy was useful in predicting tumour grade, exact location and capsular penetration. However, it was not useful for determining tumour stage or predicting seminal vesicle invasion of prostate cancer. TRUS-guided seminal vesicle biopsy must be performed in patients with a serum prostate specific antigen of more than 30 ng/mL.

We examined the effects of a 9-week exercise training (TR) in Wistar male rats, beginning at 4 weeks of age, on the density of endothelial cells (ECs) in epididymal white adipose tissue (WAT) and the mRNA expression of angiogenic factors in adipose tissue stromal vascular fraction (SVF) cells. The number of ECs and mRNA expressions were assessed by lectin staining and real-time reverse transcriptase-polymerase chain reaction, respectively. Compared with control (CR) rats, TR rats gained weight more slowly and had significantly lower final weight of WAT due to the reduction in the size and the number of adipocytes. TR significantly increased the number of ECs per square millimeter and per adipocyte (1.37- and 1.23-fold, respectively) in WAT. This is probably because the number of adipocytes is fewer while the number of ECs is constant in the WAT of TR rats, because the regression line of TR rats for adipocyte number-dependent EC number was shifted toward the left without significant differences in the slopes between groups. TR also induced the upregulation of mRNA expression of vascular endothelial growth factor (Vegf)-A and Vegf-receptor-2 in SVF cells, thereby retaining a constant number of ECs in the WAT.

Immunoregulatory states induced by i.p. inoculation with the metazoan parasite Echinococcus multilocularis in the murine system were investigated. Proliferative responses and IL-2 production induced by Con A in spleen cells from BALB/c mice were significantly depressed at an early stage after infection with E. multilocularis protoscoleces (PSC). Addition of plastic-adherent cells from normal syngeneic mice to the nonadherent spleen cells from infected mice did not restore the depressed Con A responsiveness. On the other hand, exogenous IL-2 reconstituted completely the proliferative responses to Con A. Flow cytometry analysis revealed that CD4- CD8+ cells with a low density of CD8 Ag (CD8dull cells) increased in spleens from infected mice 2 weeks after inoculation. Addition of the spleen cell subpopulation containing the CD8dull cells, but not that depleted of the CD8dull cells, to normal spleen cells resulted in marked suppression of the Con A responses. These findings suggest that the CD8dull cells detected in spleens of mice inoculated with E. multilocularis PSC may play a key role in the suppressive regulation of immune responses. The relevance of the immune suppression seen in the early stages of experimental infection with E. multilocularis PSC to the eventual establishment of a host-parasite relationship is discussed.

Experiments were carried out to analyze the binding sites on human cells for highly purified retroviral protein p15E isolated from Feline Leukemia Virus, Rickard Strain. Binding of 125I-labeled p15E was tested with surfaces of human peripheral blood lymphocytes and 3 cell lines, Raji, MOLT-4, and U-937. 125I-labeled p15E showed specific binding to human peripheral blood lymphocytes. In addition, all of the cell lines tested showed binding of 125I-labeled p15E. Using U-937 cells, we characterized the interaction between p15E and the surface of these cells, and showed that the binding was specific by the following 3 different sets of evidence: (i) in equilibrium binding experiments, 18,000 binding sites with a dissociation constant of 2 x 10(-9) M were present on U-937 cells; (ii) trypsin or N-glycanase treatment decreased the binding sites of 125I-labeled p15E; and (iii) by affinity chromatography using p15E or BSA Sepharose columns, the isolated membranes of 125I-labeled U-937 cells previously treated with Triton X-100 showed a significantly higher binding to the p15E column than to the BSA column.

Aim It is generally accepted that endurance exercise increases the expression of peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha), which governs the expression of oxidative metabolic enzymes. A previous report demonstrated that the regulation of mitochondrial protein expression in skeletal muscles in response to cold exposure depends on muscle fibre type. Cold exposure and endurance exercise are both metabolic challenges that require adjustments in mitochondrial energy metabolism, we hypothesized that the exercise-induced increase in oxidative enzymes and PGC-1alpha expression is higher in fast-type than in slow-type muscle. Methods Female ICR mice were individually housed in cages equipped with running wheel for 1, 2, 4, 6 or 8 weeks. The soleus, plantaris (PLA) and tibialis anterior (TA) muscles were then prepared from each mouse. The expression levels of PGC-1alpha, mitochondrial proteins and GLUT4 were evaluated by Western blotting. Results The expression level of PGC-1alpha was increased only in the PLA muscle. Furthermore, the expression levels of all mitochondrial proteins and GLUT4 in the PLA muscle were increased. In the TA muscle, although there was no increase in PGC-1alpha expression, the expression levels of mitochondrial proteins and GLUT4 were increased. Conclusions These results suggest that muscle type-specific responses occur during endurance exercise, and that the increase in PGC-1alpha expression is not the only factor that promotes oxidative capacity as a result of endurance exercise.

We explore the role of phonons in the volume behavior of an itinerant electron ferromagnet by taking into account the close relation between phonon and magnetic properties. From a model numerical calculation we find that phonon contribution to thermal expansion can be negative in the ferromagnetic state of a metal.

Skeletal muscle is highly adaptable, being capable of undergoing changes in its structural and functional properties in response to physiological stimuli. The fast-to-slow muscle fiber-type transition is evoked by increased motor nerve activity. Recently, the calcineurin (CaN) signaling pathway has been implicated in the transcriptional regulation of slow muscle fiber genes. Here we investigated the effect of treatment with a CaN-specific inhibitor, FK506, on skeletal muscle fiber-type transition in functionally overloaded muscles. The overloaded plantaris muscle showed fast-to-slow muscle fiber type transition, i.e., a decrease in myosin heavy chain (MHC) IIb, an increase in MHCIIa+d/x, and new expression of MHCI. In the FK506-administered group, however, overload-induced muscle fiber-type transition was completely prevented. We have demonstrated, therefore, that the CaN signaling pathway is required for fast-to-slow skeletal muscle fiber-type transition. Furthermore, we also confirmed that the protein expression levels of downstream effectors of CaN signaling exhibit a transient increase in the early phase of the overloaded condition.

Summary 1. We investigated the effect of intermittent exposure to hypobaric hypoxia on the ability of neutrophils to generate ·O2–. 2. Seven male volunteers were exposed intermittently to hypobaric hypoxia, equivalent to an altitude of 4500 m, for 7 successive days. Peripheral blood samples were collected before and after the 2 h course of hypobaric hypoxia on days 1 and 7 and neutrophils were subjected to a chemiluminescence assay for ·O2– production. 3. On day 1, 2 h exposure to hypobaric hypoxia induced granulocytosis (P

There is increasing concern about the potential neurotoxic effects of exposure to methylmercury for the 6 million people living in the Amazon, even in regions situated far away from the gold mines (garimpos), considered to be the major source of mercury pollution. In November 1998, a spot investigation on mercury contamination was conducted in three fishing villages (Barreiras, Rainha, and Sao Luiz do Tapajos) on the Tapajos River, an effluent of the Amazon, situated several hundred kilometers downstream from the gold-mining areas. A total of 132 fishermen and their families volunteered for the current study. As was anticipated, the total mercury levels in the head hair collected from the fishing villages were relatively high (14.1-20.8 ppm on the average) and the number of subjects with a high total mercury level over 10 ppm (the least upper bound of a normal value) was 103 (78.0%) in total, along with various symptoms, thereby suggesting wide mercury contamination in the Tapajos River basin. Moreover, in view of the absence of other diseases (e.g., alcoholism or malaria), a high intake of fish containing a methylmercury level, and high hair mercury levels in addition to the various symptoms such as sensory disturbance (especially glove-and-stocking type, which is characteristic of Minamata disease), tremor, failure in two-point discrimination, and slight balancing failure, several subjects examined were diagnosed with mild Minamata disease. The findings obtained suggest, thus, that the mercury pollution in the Amazon should be crucially observed for head hair mercury level and health in a much broader region.

Extracellular superoxide dismutase (EC-SOD) concentration was measured in sera from 141 patients with 20 forms of infantile diseases including IDDM, SLE and epilepsy, 31 healthy children (controls), and 21 healthy young men by an enzyme-linked immunosorbent assay using a polyclonal antibody against human lung EC-SOD. Serum from patients with IDDM and fever of unknown origin had a significantly (p0.05) lower concentration of EC-SOD than control serum. Part of sera from patients with the seven forms of diseases (SLE, viral infections, epilepsy, nephrosis, hyperthyroidism, hepatic disease, and Reye syndrome), on the other hand, had a greatly high concentration of EC-SOD, albeit not statistically significant. This SOD isoenzyme profile appears to be specific to each pediatric disease.

The fatigue strength of a nickel-base superalloy, Inconel 718, was investigated at room temperature under an ultrasonic frequency (1 9.5 kHz) loading in ambient air environment. The endurance (S-N) data show that fatigue strength was enhanced at ultrasonic frequency as compared to those at conventional frequencies. Small crack initiation and propagation behavior was observed during the fatigue progress at both ultrasonic fatigue and conventional rotary bending fatigue. The effect of frequency on the fatigue fracture mechanism was examined from a microscopic viewpoint.

The aim of this study was to investigate the influence of acute cold exposure on the mRNA expression and immunoreactivity of superoxide dismutase (SOD) isoenzymes [Mn-SOD, Cu,Zn-SOD, and extracellular-SOD (EC-SOD)] in different tissues from lean and obese (ob/ob) mice at 10 months of age. The animals were kept at 10 degrees C for 3 h, with the colonic temperature in obese mice declining progressively during the cold stress, but not in lean mice, probably because of a strong tendency to atrophy of the brown adipose tissue (BAT) in obese mice. In the expression of mRNAs for lean mice, acute cold exposure led to a significant increase only in Mn-SOD in testes, but a significant decline in Cu,Zn-SOD in kidney and in Mn-SOD and EC-SOD in white adipose tissue (WAT), as well as in all SOD isoenzymes in lung and BAT. In obese mice, the mRNA level of Mn-SOD in heart and gastrocnemius muscle was significantly decreased following the cold exposure, whereas that of EC-SOD in testes was significantly increased. These changes, however, were not always accompanied by those in the corresponding protein levels; for example, the significant decreases in the expression of mRNAs for the three SOD isoenzymes in lung and BAT from lean mice did not result in any changes in the respective isoenzyme protein levels. These results suggest that, except for testes, a cold-exposure period of 3 h down-regulates SOD isoenzymes at the transcriptional process especially in lean mice, but is not long enough to induce their protein synthesis. It seems likely, thus, that, despite a marked decrease in colonic temperature, acute exposure to cold has less effect on SOD isoenzymes in obese mice as compared with those in normal lean siblings.

A 22-year-old man, in first complete remission of acute myelogenous leukemia, developed a high grade B cell lymphoma 19 months after an allogeneic bone marrow transplant (allo-BMT) from an HLA-identical unrelated donor. Biopsy of a cervical lymph node revealed a lymphoma that was negative for Epstein-Barr virus-encoded small nuclear RNAs (EBERs) in situ hybridization. Genotypic analyses identified the lymphoma to be of donor origin, and there was no evidence of the Epstein-Barr virus (EBV) DNA in the lymphoma by Southern blot analysis. The lymphoma went into complete remission, following four courses of combination chemotherapy, but relapsed after a month and the patient died of congestive heart failure. The patient was thought to be persistently immunosuppressed 11 months after cessation of immunosuppressants, and the lymphoma was thought to be induced by one or more factors other than EBV.

The proportion of cells with a high density of ED2 (ED2high cells) in peritoneal cells from old rats was significantly lower than that from young rats. The expression of major histocompatibility complex class II (MHC class II) molecules, the antigen presentation, production of interleukin (IL)-1beta and IL-6, and nuclear factor-kappaB activity in ED2high cells were markedly higher than those in cells with a low density of ED2 (ED2low cells), although no significant difference was observed in the expression of MHC class II molecules and the antigen presentation between ED2high cells from young and old rats. Meanwhile, basal corticosterone concentration in serum and glucocorticoid (GC) receptor mRNA expression in peritoneal cells increased significantly in old rats. The proportion of ED2high cells was increased by adrenalectomy in young rats. Furthermore, nuclear translocation of GC receptor was observed in ED2low cells, whereas GC receptor was detected in cytoplasmic extracts from ED2high cells. These results suggest that the decrease in functional ED2high macrophages with age results in the age-associated decline of immune responses, which is regulated, in part, by the basal GC concentration.

Our previous study has shown that chronic hindlimb suspension leads to an increase in both the thermogenic capacity and the activity in brown adipose tissue (BAT) of adult rats (Yamashita, H., Ohira, Y., Wakatsuki, T., Yamamoto, M., Kizaki, T., Oh-ishi, S., Sato, Y. and Ohno, H. (1995). J. Appl. Physiol. 78: 384-387). In order to examine if unloading also increases the BAT activity in rat pups, the hindlimbs in the suspended pups were unloaded by tail suspension beginning on postnatal day 4 and suspended until day 21. The thermogenic activity (which was assessed by guanosine 5'-diphosphate binding to BAT mitochondria) was markedly lower in 21-day-old suspended pups than in 21-day-old control pups, although there was no difference in uncoupling protein 1 (UCP1) content or UCP1 mRNA expression in the BAT mitochondrial fraction between both pups. Likewise, there was no disparity in either adrenal or thymus mass between the control and suspended pups throughout the experiment. These results suggest that, in contrast to adult rats, chronic hindlimb suspension leads to a decrease in the thermogenic activity in BAT of rat pups possibly for reason that pups are less susceptible to the stress of unloading.

The blood pressure of the rat is influenced by the dietary restriction of calcium. Since the vasomotor activities may be affected by calcium restriction, we measured vasoconstriction as well as endothelium-dependent and endothelium-independent relaxation responses in isolated aortic rings of the Wistar rat. Compared with the control rat fed a normal diet (1.04% calcium), the femur mineral density was significantly reduced in the rat fed the low-calcium (0.01%) diet for one month (LC1M) or for three months (LC3M). Although neither LC1M nor LC3M changed Cmax (the maximum constriction induced by phenylephrine) in aortic rings without endothelium, LC3M, but not LC1M, significantly increased CD50 (the dose of phenylephrine inducing 50% of Cmax). On the other hand, the low-calcium diet did not change Cmax and CD50 in rings with intact endothelium. Thel low-calcium diet showed no significant change in the vasorelaxation responses to acetylcholine (Ach) or sodium nitroprusside (SNP). Cyclic GMP production stimulated by Ach or SNP was not affected by calcium restriction. These results suggest that an insufficient calcium supply for three months, attenuates alpha-adrenoceptor-mediated vasoconstriction in the normotensive rat but vasorelaxation responses to Ach or SNP are not affected.

The effect was investigated of running training on the thermogenic activity of brown adipose tissue (BAT) in rats. The exercised rats were trained on a rodent treadmill for 5 days per week and a total of 9 weeks. After the training, a significantly lower rate of increase in body weight was found, suggesting some training effect, whereas the training failed to induce a decrease in BAT mass. As previously reported (Yamashita, Yamamoto et al., 1993), there was also a markedly lower expression of uncoupling protein (UCP) mRNA in BAT from trained rats; nevertheless, no definite effect of the running training was noted on either UCP content or guanosine 5'-diphosphate binding in the mitochondria recovered from BAT. The results obtained suggest that running training has no overt effect on the thermogenic activity of BAT in rats.

Ageing is usually accompanied by a decline in immune and neuroendocrine functions. To elucidate the mechanisms underlying age-related immunosuppression, the functions and surface phenotypes of peritoneal cells in the monocyte/macrophage lineage from old mice were investigated. The role of glucocorticoids (GC) in the immunomodulation was also examined. Proliferative responses of spleen cells from control mice stimulated with concanavalin A (Con A) were significantly suppressed by adding peritoneal exudate cells from old mice. Flow cytometry analysis revealed that the proportion of MAC-1+ cells with a high density of type II or type III receptor for the Fc portion of IgG (Fc gamma RII/IIIbright cells) was increased markedly in the periotoneal exudate cells from old mice. The prominent suppressor activity for Con A responses of control spleen cells was found in the Fc gamma RII/IIIbright cells, whereas MAC-1+ cells with a low density of Fc gamma RII/III (Fc gamma RII/IIIdull cells) did not suppress the Con A responses. On the other hand, both the basal corticosterone concentrations in serum and the mRNA expression for GC receptor in peritoneal exudate cells increased significantly in old mice. Furthermore, the proportion of Fc gamma RII/IIIbright cells in peritoneal exudate cells from old mice was normalized on administration of the GC antagonist RU 38,486 (mifepristone). These results suggest that the increase in basal corticosterone concentrations in old mice induces the generation of Fc gamma RII/IIIbright suppressor cells, possibly leading to the immune-suppressive state.

The current study was undertaken to investigate the effect of swimming training on the antioxidant enzyme system in kidney of young and old mice. Both young and old mice, aged 2 and 26 months old, respectively, were divided into the sedentary and swimming-trained groups. The trained mice underwent a 6-week swimming program (1 h/day, 5 days/week) in water at 35-36 degrees C. Cu,Zn-superoxide dismutase (Cu,Zn-SOD) activity was significantly decreased with aging but was not influenced by swimming training, such changes being similar to those noted for catalase activity rather than for glutathione peroxidase activity. After swimming training Mn-SOD activity increased significantly only in old mice but was unaffected by aging. Although neither aging nor swimming training had overt effect on the expression of Cu,Zn-SOD mRNA, the immunoreactive Cu,Zn-SOD content in young mice decreased significantly after the training. Meanwhile, Mn-SOD mRNA expression in old mice was reduced by half after swimming training, accompanied by a significant decrease in its immunoreactive content; unexpectedly, however, Mn-SOD content in young mice did not parallel its mRNA expression. These findings suggest that the antioxidant enzyme system in mouse kidney trends to be down-regulated with aging, and that swimming training fails to attenuate such reduced levels of the antioxidant enzymes.

Brown adipose tissue (BAT) of obese animals is generally in a relatively atrophied and thermogenically quiescent state. The aim of the current study was to investigate the effect of swimming training on BAT activity in lean and obese (ob/ob) mice. The trained mice underwent a 6-week endurance swimming training (1 h/day, 5 days/week) in water at 35-36 degrees C. The swimming training significantly increased BAT mass and its protein content in both the lean and obese mice, suggesting hypertrophy. After swimming training, the amounts of protein and guanosine 5'-diphosphate binding in the mitochondria recovered from BAT of both mice increased significantly as compared with the respective sedentary groups, whereas the uncoupling protein (UCP) content increased significantly only in lean mice. After swimming training, the level of UCP mRNA expression did not change substantially in lean mice but appeared to increase in obese mice. The results obtained here suggest that swimming training leads to an increase in the nonshivering thermogenesis of obese mice in addition to lean mice.

The effects of acute and chronic physical exercise on the sensitivity of isolated aorta to norepinephrine were investigated. After chronic exercise, the EC50 values for norepinephrine increased 3.1-fold and 2.3-fold in endothelium-intact and in endothelium-denuded aorta, respectively. The attenuated sensitivity of aorta to norepinephrine after chronic exercise was still evident in endothelium-denuded aorta, but to a lesser extent than in endothelium-intact aorta. After acute exercise, in control rats, the EC50 values increased 7.8-fold and 5.4-fold in endothelium-intact and endothelium-denuded aorta, respectively. The attenuated sensitivity of aorta to norepinephrine after an acute exercise was still evident in endothelium-denuded aorta. In trained rats, the EC50 values increased 2.3-fold and 2.6-fold in endothelium-intact and endothelium-denuded aorta, respectively. Thus, acute exercise was less effective in trained than in control rats. No significant difference in 60 mM KCl-induced tension between control and trained rats was observed with or without endothelium after acute and chronic exercise. The results suggest that levels of endothelium-dependent releasing factor may increase in response to norepinephrine after acute and chronic exercise. In addition, the attenuated sensitivity of aorta to norepinephrine after acute and chronic exercise may also result from the change(s) in the receptor sites. However, the degree of desensitization caused by acute exercise was less in the rats adapted to chronic exercise than in the sedentary control rats.

To elucidate the role of norepinephrine (NE) in the hyperplasia of brown adipose tissue (BAT), we investigated the effects of NE on the expression of fibroblast growth factor-2 (FGF-2) in rat brown adipocyte primary culture and on capillary growth in an in vitro angiogenesis model in which microvascular fragments and brown adipocyte precursor cells isolated from rat BAT were grown in coculture. NE significantly increased the number of brown adipocyte precursor cells. The NE effect on cell proliferation was greatly inhibited by anti-FGF-2-specific antibody. Likewise,NE considerably increased the levels of FGF-2 mRNA and the antigen in brown adipocyte primary culture. The ability of NE to stimulate the expression of FGF-2 mRNA was blocked by actinomycin D or was inhibited partly by propranolol. Moreover, NE considerably increased the in vitro capillary growth and the level of FGF-2 antigen in the coculture. These results suggest that NE is a crucial factor to mediate FGF-2 production, in part via the beta-adrenergic receptor, in rat brown adipocytes and to stimulate the cell proliferation and capillary growth in BAT by an autocrine/paracrine mechanism.

Immunoregulatory states in acute cold-stressed or cold-acclimatized mice were investigated. When male C57BL/6 mice were exposed to environmental temperature of 5 degrees for 24 hr (acute cold stress), the spleen cells showed depressed proliferative responses to stimulation with concanavalin A (Con A) or lipopolysaccharide (LPS) compared with control mice (reared at 25 degrees). The proportion of Thy-1.2+ cells increased significantly in spleens from these acute cold-stressed mice. The Con A responses of T-enriched cells from acute cold-stressed mice were restored to the normal level by adding plastic-adherent cells from control mice. Further, adherent cells from acute cold-stressed mice markedly suppressed the Con A responses of control spleen cells. Thus, the plastic-adherent cells appeared to be responsible for the suppressed Con A responses. On the other hand, proliferative responses to Con A or LPS were elevated in spleen cells from mice exposed to 5 degrees for 3 weeks (cold acclimatization). A significant decrease of Thy-1.2+ cells was detected in these spleens. It was shown that the enhanced proliferative responses were attributable to functional alterations of the plastic adherent cell population but not to those of lymphoid cell population. These findings indicate that the low or high responsiveness of spleen cells to Con A observed in cold-stressed or cold-acclimatized mice, respectively, may be due to a mechanism including the contrary modulations of functions of cells of mononuclear phagocyte lineage.

The effect of insulin on the hyperplasia of brown adipose tissue (BAT) was investigated using the primary culture of rat brown adipocyte precursor cells (RBAC). Results showed insulin to significantly increase the number of RBAC, but not bovine capillary endothelial cells, in the presence of fetal bovine serum. Insulin also increased the expression of basic fibroblast growth factor (bFGF) mRNA and the related protein in the primary culture of RBAC. In addition, insulin enhanced the capillary growth in an in vitro angiogenesis model in which microvascular fragments and RBAC isolated from rat BAT were grown in coculture. The level of bFGF-related protein in the coculture was higher in the presence of insulin than in the absence of insulin. These findings suggest that insulin may play an important role in the proliferation as well as in the differentiation of brown adipocytes, with resulting hyperplasia of BAT (including the formation of new capillaries) through increased production of bFGF in brown adipocytes.

A 32-year-old man was admitted after bone marrow transplantation because of hematochezia. He had history of chronic graft-versus-host disease (GVHD) of the skin and the liver, and cytomegaloviral pneumonia. Barium enema and colonoscopy showed multiple colon ulcers in the ascending and transverse colon. This feature is very rare in chronic GVHD and resembles the feature in autoimmune disease such as periarteritis nodosa. Thus, this ulceration is thought to be caused by vasculitis due to an autoimmune reaction in chronic GVHD.

The aim of the present study was to determine whether heat acclimation increases whole-body sensitivity to insulin. Male Wistar rats were kept at 34 degrees C for 2 weeks (HA group). Warm-acclimated rats (WA group) at 25 degrees C served as controls. The glucose infusion rate (GIR) was assessed as an index of in vivo insulin sensitivity, using a hyperinsulinemic euglycemic clamp technique. Moreover, the 125I-insulin binding capacity to purified insulin receptor preparations from m. gastrocnemius of rats after 1, 7, or 14 days of heat exposure was examined. Mean GIR values of HA group were slightly higher than those of WA group, but not significant. The great deviation of the HA group, however, appeared to exist. About half of HA rats showed markedly high GIR values (p0.01 vs. WA group). Mean GIR value of the remaining HA rats were significantly (p0.05) lower than those of the WA group. Likewise, the binding capacity to 125I-insulin was not significantly different among the periods of time of heat exposure, and the deviation went on increasing from 1 to 14 days. These results suggest that there is a wide individual difference between the changes in glucose metabolism under heat exposure. In view of such results, there appears to be a great need for further studies on the factors affecting the variation of insulin action.

Total retropubic prostatectomy was performed on 31 patients with prostatic cancer (median age; 70 years). The accuracy of staging was 55% (17 patients). In 11 patients (35%) the staging had been underestimated, and in 3 patients (10%) overestimated. The pathological stage and grade were stage B in 14 patients, stage C in 4 patients, stage D1 in 13 patients (pN1; 8 patients, pN2; 5 patients), well differentiated adenocarcinoma (WDA) in 8 patients moderately differentiated adenocarcinoma (MDA) in 7 patients, and poorly differentiated adenocarcinoma (PDA) in 16 patients. The WDA were all stage B, and 85% of the PDA were stage D1. The positive surgical margin rate was 21% in stage B, 50% in stage C, 85% in stage D1, 13% in WDA, 43% in MDA, and 75% in PDA. Five of the patients died, and the causes of death were prostatic cancer in 2 patients (pN2/PDA), and others in 3 patients (1 patient; stage B/PDA, 2 patients; pN2/PDA). The 5-year survival rate (Kaplan-Meier) was 84% on the whole, 83% for stage B, 100% for stage C, 83% for stage D1, 100% for WDA, 100% for MDA, 71% for PDA, 86% for pN0, 100% for pN1, and 38% for pN2.

Addition of protoscoleces (PSC) of Echinococcus multiocularis suppressed proliferative responses in spleen cells stimulated with concanavalin A (Con A) on day 3 of culture. The suppression was not observed in the spleen cell population depleted of CD8+ cells but observed in the population depleted of CD4+ cells, suggesting the involvement of the CD8+ T cells in the apparent suppression. Indeed, flow cytometry analysis revealed that the proportion of CD8+ cells markedly increased in the Con A cultures containing PSC. Furthermore, when spleen cells were co-cultured with PSC alone, marked increase in the proportion of CD8+ cells as well as B220+ cells was observed. Addition of these increasing CD8+ cells suppressed the proliferative responses of fresh spleen cells stimulated with Con A. These findings suggest that the low responsiveness of spleen cells to Con A on day 3 of culture in the presence of PSC is attributable to an active suppressor mechanism including CD8+ T-suppressor cells generated by stimulation with PSC.

Renal biopsies and kidneys from 111 adult patients with segmental sclerosing glomerular lesions were put into different morphological groups by pathologists unaware of clinical findings. 'Overload changes' (n = 11) were large glomeruli with hilar lesions. Ten of these patients had reduced renal mass. In the 'glomerular tip lesion' (n = 10) there were changes at the tubular origin in otherwise normal glomeruli. All patients in this group had the nephrotic syndrome, completely responsive to steroids. 'Mesangial hypercellularity with diffuse segmental changes at the glomerular tip', corresponding to 'early classical focal segmental glomerulosclerosis' (n = 18), differed from the glomerular tip lesion in that glomeruli were larger and hypercellular. Most patients with this classification had the nephrotic syndrome, several were given additional immunosuppression, and less than half had complete remission. 'Diffuse multiple segmental lesions', corresponding to 'late classical focal segmental glomerulosclerosis' (n = 16), presented usually with the nephrotic syndrome, and most of these patients had no response to immunosuppression. Unlike most other groups, in 'focal segmental sclerosing lesions' (n = 56) there were genuinely focal lesions, not in every glomerulus. Most patients had asymptomatic proteinuria. Pathological study is able to classify segmental lesions that would often be grouped as 'focal segmental glomerulosclerosis' into types with different pathogenesis, clinical findings, appropriate treatment, response to treatment, and prognosis.

A multi-centre controlled trial of prednisone in the nephrotic syndrome in adults was run by the Medical Research Council between 1962 and 1966. Sections of renal biopsies and necropsy kidneys from the trial had been kept. These were restained 25 years later with periodic acid-methenamine silver and examined for the glomerular tip lesion, an abnormality of the kidney described after the trial in patients with the nephrotic syndrome. The glomerular tip lesion was found in material from 10 patients, representing 7% of 150 patients with the nephrotic syndrome and glomerulonephritis. In the trial, seven had been classified as minimal-change nephropathy and three as proliferative glomerulonephritis. Detailed follow-up was limited but it was known that two patients died shortly after presentation, not, apparently, from progression of the glomerular disorder; that none of the others had progressed to renal failure, at least for the duration of follow-up of the trial, 2-4 years; and that those classified as minimal-change nephropathy appeared to have behaved clinically as though they had minimal-change nephropathy. These findings show that at least one adult series of minimal-change nephropathy has contained cases of the glomerular tip lesion but that clinically this may not be an important error as the conditions behave similarly. A more important error may be to call the glomerular tip lesion a proliferative glomerulonephritis, which may lead the clinician to withhold steroids.

A multi-centre controlled trial of prednisone in the nephrotic syndrome in adults was run by the Medical Research Council between 1962 and 1966. Sections of renal biopsies and necropsy kidneys from the trial had been kept. These were restained 25 years later with periodic acid-methenamine silver and examined for the glomerular tip lesion, an abnormality of the kidney described after the trial in patients with the nephrotic syndrome. The glomerular tip lesion was found in material from 10 patients, representing 7% of 150 patients with the nephrotic syndrome and glomerulonephritis. In the trial, seven had been classified as minimal-change nephropathy and three as proliferative glomerulonephritis. Detailed follow-up was limited but it was known that two patients died shortly after presentation, not, apparently, from progression of the glomerular disorder; that none of the others had progressed to renal failure, at least for the duration of follow-up of the trial, 2-4 years; and that those classified as minimal-change nephropathy appeared to have behaved clinically as though they had minimal-change nephropathy. These findings show that at least one adult series of minimal-change nephropathy has contained cases of the glomerular tip lesion but that clinically this may not be an important error as the conditions behave similarly. A more important error may be to call the glomerular tip lesion a proliferative glomerulonephritis, which may lead the clinician to withhold steroids.

Renal biopsies and kidneys from 111 adult patients with segmental sclerosing glomerular lesions were put into different morphological groups by pathologists unaware of clinical findings. 'Overload changes' (n = 11) were large glomeruli with hilar lesions. Ten of these patients had reduced renal mass. In the 'glomerular tip lesion' (n = 10) there were changes at the tubular origin in otherwise normal glomeruli. All patients in this group had the nephrotic syndrome, completely responsive to steroids. 'Mesangial hypercellularity with diffuse segmental changes at the glomerular tip', corresponding to 'early classical focal segmental glomerulosclerosis' (n = 18), differed from the glomerular tip lesion in that glomeruli were larger and hypercellular. Most patients with this classification had the nephrotic syndrome, several were given additional immunosuppression, and less than half had complete remission. 'Diffuse multiple segmental lesions', corresponding to 'late classical focal segmental glomerulosclerosis' (n = 16), presented usually with the nephrotic syndrome, and most of these patients had no response to immunosuppression. Unlike most other groups, in 'focal segmental sclerosing lesions' (n = 56) there were genuinely focal lesions, not in every glomerulus. Most patients had asymptomatic proteinuria. Pathological study is able to classify segmental lesions that would often be grouped as 'focal segmental glomerulosclerosis' into types with different pathogenesis, clinical findings, appropriate treatment, response to treatment, and prognosis.

Certain retroviral envelope proteins and peptides have been shown to be highly immunosuppressive. Recently, we have demonstrated that a synthetic 17 amino acid peptide (CKS-17*) homologous to a highly conserved region in the transmembrane portion of the envelope of several human or animal retroviruses suppresses the production of human interferon-gamma (IFN gamma) by human peripheral blood leukocytes (PBL). In the present investigation, we studied the role of exogenous IL-1 or IL-2, and IL-1 plus IL-2 on the suppressive action of CKS-17* in the production of IFN gamma. The results showed that preculture of PBL with CKS-17* reduced the production of IFN gamma in a dose-dependent manner. The addition of IL-1 or IL-2 reduced, in part, this suppression of IFN gamma production. Full abrogation of the inhibition attributable to CKS-17, however, occurred only when PBL precultured with CKS-17* were recultured with staphylococcus enterotoxin A (SEA) together with exogenous IL-1 plus IL-2. These results show that the inhibition of IFN-gamma production by CKS-17* is reversible. The findings indicate that cytokines can modulate certain of the immunosuppressive actions attributable to retroviruses or their components and suggest that some cytokines influence immunosuppressive consequences of retroviral infection.

SUMMARY The effect of the administration of a xenogeneic anti-idiotype antibody (anti-Id33) to a cross-reactive idiotype (Id33) present on anti-dsDNA antibody was examined in 6-week-old (NZB/NZW) F1 (BWF1) female mice. The administration of anti-Id33 led to a transient reduction in immunoglobulins expressing Id33, followed by a rise at 30 and 34 weeks that was significantly higher than in untreated mice (P

Recently it was found by Manosa et al. and Sidov et al. that phonon Gruneisen constants, γ D , associated with longitudinal acoustic phonon become negative in Invar systems. In this paper we discuss why γ D can become negative in an Invar, and how it would vary with temperature.

By treating the roles of electrons and phonons on the same footing, we numerically calculate thermal expansion coefficient of an itinerant electron ferromagnet for both T T c and T > T c with a simple model of the electronic density of 1758 0727 states, and find thermal phonons to play a crucial role in the Invar behavior.

Effects of acute cold stress (5 degrees C for 24 h) on the functions of peritoneal macrophages and the mechanisms for controlling host homeostasis were investigated in mice. Phagocytic activity and expression of the cell surface adhesion molecule CD11b/CD18 were markedly increased in peritoneal exudate cells by acute cold stress. These alterations were attributable to an increased number and phenotypical changes of adherent cells from acute cold-stressed mice. On the other hand, a lipopolysaccharide-induced activity of src-family tyrosine kinase Fgr, an expression of interleukin-1beta (IL-1 beta) mRNA, and a bioactivity of IL-1 in the culture supernatants of adherent cells from acute cold-stressed mice were markedly lower than those from control mice. A time course study revealed that the number of adherent cells in peritoneal exudate cells was markedly increased in mice exposed to cold for 24 h but returned to normal numbers when mice were exposed to cold for 72 h. DNA fragmentation and Annexin-V(+) cells were observed in peritoneal exudate cells from acute-cold stressed mice. Thus, cold stress activated macrophages but these macrophages were destined to be eliminated by apoptosis.