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Background It is well-known that cerebral and ocular vessels are highly sensitive to changes in the partial pressure of CO 2 (P ET CO 2 ). However, it is unclear whether there are regional differences in the magnitude of the vascular response to CO 2 (CO 2 reactivity) in various vessels of a single individual, and whether there is a relationship in the CO 2 reactivity of specific vessels between different individuals. Methods We compared the CO 2 reactivity of the superior mesenteric artery (SMA), middle cerebral artery (MCA), retinal artery (RA), and retinal and choroidal vessels (RCV) during a 3-min inhalation of CO 2 -rich air (5%) in 70 subjects. Results The blood flow velocities in the MCA, RA, and RCV significantly increased by 21 ± 2% (mean ± SE), 9 ± 1%, and 7 ± 2%, respectively ( P < 0.05) during hypercapnia, whereas that in the SMA did not change significantly (−17 ± 11%). The CO 2 reactivity–the relative change in blood flow to a given change in P ET CO 2 –was significantly greater in the MCA (2.2 ± 0.2%/mmHg) than in the RA and RCV (0.9 ± 0.1%/mmHg and 0.8 ± 0.2%/mmHg, respectively). There was a weak correlation in the CO 2 reactivity only between RA and RCV ( r = 0.43, P < 0.05). Conclusion These findings indicate that the CO 2 reactivity can vary even in cerebral and ocular vessels, although the correlation is weak. [ABSTRACT FROM AUTHOR]

The present paper made the heat balance equation (HBE) for nude or minimally clad subjects a linear function of mean skin temperature ( t) by applying new equations for sweating efficiency ( η) and thermoregulatory sweat rate ( S). As the solution of the HBE, the equation predicting t was derived and used for a heat strain scale of subjects. The η was proportional to the reciprocal of S/ E ( S, sweat rate; E maximum evaporative capacity) and the S was proportional to t with a parameter of the sweating capacity of the subject. The errors of predicted t from observations due to the approximation of η were examined based on experimental data conducted on eight young male subjects. The value of errors of t was −0.10 ± 0.42 °C (mean ± sample standard deviation (SSD)). We aim to apply the predicted t of a subject at a level of sweating capacity as a heat strain scale of a function of four environmental factors (dry- and wet-bulb temperatures, radiation, and air velocity) and three human factors (metabolic rate, sweating capacity, and clothing (≤0.2clo)). [ABSTRACT FROM AUTHOR]

This paper applies the heat balance equation (HBE) for clothed subjects as a linear function of mean skin temperature ( t) by a new sweating efficiency ( η) and an approximation for the thermoregulatory sweat rate. The equation predicting t in steady state conditions was derived as the solution of the HBE and used for a predictive heat strain scale. The heat loss from the wet clothing (WCL) area was identified with a new variable of 'virtual dripping sweat rate VDSR' ( S). This is a subject's un-evaporated sweat rate in dry clothing from the regional sweat rate exceeding the maximum evaporative capacity, and adds the moisture to the clothing, reducing the intrinsic clothing insulation. The S allowed a mass balance analysis of the wet clothing area identified as clothing wetness ( w). The w was derived by combining the HBE at the WCL surface from which the evaporation rate and skin heat loss from WCL region are given. Experimental results on eight young male subjects wearing typical summer clothing, T-shirt and trousers verified the model for predicting t with WCL thermal resistance ( R) identified as 25 % of dry clothing ( R). [ABSTRACT FROM AUTHOR]

Purpose: To assess the diagnostic performance of diffusion-weighted magnetic resonance (MR) imaging (DWI) for prostate cancer detection, using different b-values.Methods: A total of 201 patients who underwent MR imaging before total prostatectomy were evaluated. MR images were independently assessed by three radiologists. Three combinations of sequences were separately evaluated, as follows: group 1 [T2-weighted images (T2WI) alone], group 2 (T2WI and DWI with a b-value of 1,000 s/mm2), group 3 (T2WI and DWI with a b-value of 2,000 s/mm2). Whole-mount-section histopathological examination was the reference standard. Areas under the receiver operating characteristic curve (AUCs) and diagnostic performance parameters were determined.Results: The sensitivity, specificity, and AUC for the detection of prostate cancer were as follows: 52.2%, 80.7%, and 0.694 in group 1; 61.2%, 82.6%, and 0.755 in group 2; 73.2%, 89.7%, and 0.842 in group 3. Group 3 achieved the highest diagnostic performance, followed by group 2 (P<0.05). In the transition zone, the specificity was lower (P<0.001) for group 2 (82.2%) than for group 1 (86.2%).Conclusion: The addition of diffusion-weighted images with a b-value of 2,000 s/mm2 to T2WI can improve the diagnostic performance of MR imaging in prostate cancer detection. [ABSTRACT FROM AUTHOR]

We carried out instrumental neutron activation analysis (INAA) as well as k0-based prompt gamma-ray analysis ( k0-PGA) to measure the amount of the elements in onions and studied whether the onions collected from different sites can be categorized based on the elemental concentration profile. Six elements (Na, Mg, Cl, K, Ca, Mn) and 3 elements (B, S, Cl) were measured by INAA and PGA in the onions grown in two districts, Hokkaido and Saga, in Japan, respectively. After principal component analysis, it was found that Cl was an important element to feature the producing districts of onions. [ABSTRACT FROM AUTHOR]

We present chemometric study to identify the provenance of agricultural product, beef. Combination of instrumental neutron activation analysis (INAA) and prompt gamma-ray analysis ( k0-PGA) were performed to determine 10 elements, C, H, N, S, Sm, Br, Mg, Na, K, Cl, nondestructively. We measured elemental profiles in beef samples produced from different districts in Japan, Australia and USA. In the case of PGA, k0-method was employed to determine the elemental concentrations. There was a difference in elemental profiles between Japanese black cattle beef and that produced in USA through principal component analysis (PCA). However, Holstein beef of Japan and that of Australia was not sufficiently grouped by the PCA modeling with the elemental data set. This is the first study to identify the provenance of beef through elemental analysis. [ABSTRACT FROM AUTHOR]

Using time-differential perturbed-angular-correlation technique, hyperfine fields at 99Tc (←99Mo) in the Mo layers in polyimide/Fe (10 nm)/[Mo ( t Mo)/Fe (2.0 nm)]120, where t Mo is in the range between 0.4 and 1.5 nm, were measured at room temperature. The values of the magnetic hyperfine field at the Mo/Fe interface were extracted. Its dependence on the Mo layer thickness suggests that the oscillatory interlayer exchange coupling is due to conduction electron spin polarization in the Mo layer, which in turn is produced via an RKKY-type mechanism. [ABSTRACT FROM AUTHOR]

We have established a new method for allogeneic pancreatic islet (PI) transplantation: relatively low doses of irradiation followed by simultaneous transplantation of PIs and bone marrow cells (BMCs) via the portal vein (PV). In the present study, we have compared this method with intra-bone marrow (IBM)-bone marrow transplantation (BMT), and with a combination of both methods. Streptozotocin (STZ)-induced diabetic-recipient rats, Fischer 344 (F344, RT1Al, RT1Bl), were irradiated 1 day before transplantation. PIs of Brown Norway rats (BN, RT1An, RT1Bn) were transplanted into the liver of the diabetic F344 rats via the PV. BMCs from BN rats were injected into the recipients' bone marrow (IBM), PV or intravenously (IV) or by a simultaneous combination of PV plus IBM (PV+IBM). We compared graft survival among the groups of ‘9 Gy+IBM’(10/10 accepted), ‘9 Gy+PV’(7/10 accepted), ‘9 Gy+IV’(0/7 accepted), ‘9 Gy+PV+IBM’(8/8 accepted), ‘8.5 Gy+IBM’(4/9 accepted), ‘8.5 Gy+PV’(0/7 accepted), ‘8.5 Gy+IV’(0/7 accepted), ‘8.5 Gy+PV+IBM’(9/12 accepted), ‘8 Gy+IBM’(2/10 accepted) and ‘8 Gy+PV+IBM’(2/8 accepted). As we reported previously, PV-BMT is more effective in inducing the acceptance of allogeneic PIs than IV-BMT. However, IBM-BMT requires less pretreatment than PV-BMT. (PV+IBM)-BMT was found to be the most effective in inducing the acceptance of allogeneic PIs. These results suggest that allogeneic PI-transplantation in conjunction with (PV+IBM)-BMT could become a viable strategy.Bone Marrow Transplantation (2006) 38, 657–664. doi:10.1038/sj.bmt.1705500; published online 2 October 2006 [ABSTRACT FROM AUTHOR]

Wnt signalling plays a critical role in the development of cancer. Recent studies indicate that Wnt signalling is negatively regulated by secreted Wnt antagonists such as secreted frizzled related proteins (sFRPs) and Dickkopfs (Dkks). We compared Dkk family expression levels in normal prostate and prostate cancer cells and found a reduction in Dkk-3 expression in cancer cells. Ectopic expression of Dkk-3 inhibited colony formation in LNCaP and PC3 prostate cancer cell lines and inducible expression of Dkk-3 reduced LNCaP cell proliferation. Moreover, small interfering RNA-mediated downregulation of Dkk-3 enhanced cell cycle progression in untransformed RWPE-1 prostate epithelial cells. Immunohistochemical analysis revealed that Dkk-3 is expressed in a subset of normal prostate gland acini and that Dkk-3 expression is reduced in prostate tumours, particularly those with a high Gleason grade, suggesting a role for Dkk-3 in postmitotic differentiation. Consistent with this, depletion of Dkk-3 disrupted acinar morphogenesis of RWPE-1 cells in a three-dimensional cell culture model. Our results are consistent with the loss of Dkk-3 expression resulting in impairment of glandular structure and uncontrolled prostate epithelial cell (PrEC) proliferation, both of which are crucial for prostate cancer progression.Oncogene (2006) 25, 6528–6537. doi:10.1038/sj.onc.1209661; published online 5 June 2006 [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Proinsulin C-peptide is involved in several biological activities. However, the role of C-peptide in vascular smooth muscle cells is unclear. We therefore investigated its effects, in vascular smooth muscle cells in high-glucose conditions. Methods: Rat aortic smooth muscle cells were cultured with 5.5 or 20 mmol/l glucose with or without C-peptide (1 to 100 nmol/l) for 3 weeks. Proliferation activities, the protein expression of platelet-derived growth factor (PDGF)-beta receptor, the phosphorylation of p42/p44 mitogen-activated protein (MAP) kinases, and glucose uptake were measured. Results: The proliferation activities increased approximately three-fold under high-glucose conditions (p«0.05). C-peptide suppressed hyperproliferation activities that were induced by high glucose. This happened in a dose-dependent manner from 1 to 100 nmol/l of C-peptide. C-peptide (10 and 100 nmol/l) inhibited the increased protein expression of PDGF-beta receptor and the phosphorylation of p42/p44 MAP kinases that had been induced by high glucose (p«0.05). Furthermore, 100 nmol/l of C-peptide augmented the impaired glucose uptake in the high-glucose conditions. Conclusions/interpretation: These observations suggest that C-peptide could prevent diabetic macroangiopathy by inhibiting smooth muscle cell growth and ameliorating glucose utilisation in smooth muscle cells. C-peptide may thus be a novel agent for treating diabetic macroangiopathy in patients with type 1 and type 2 diabetes. [ABSTRACT FROM AUTHOR]

Duodenogastric reflux (DGR) was assessed in patients surgically treated for choledochal cyst, with emphasis on two different biliary reconstruction methods: Roux-en-Y hepaticojejunostomy (HJ) and hepaticoduodenostomy (HD). Gastric bile monitoring with the Bilitec device revealed excessive DGR in patients in the HD group. Endoscopic findings demonstrated mild to moderate gastric mucosal erosion in patients after HD. In contrast, neither DGR nor gastritis was found in patients after HJ. This preliminary study suggests that HJ, rather than HD, should be recommended as a method of biliary reconstruction for pediatric patients with choledochal cyst. Careful observation of DGR should be continued in patients who have undergone HD. [ABSTRACT FROM AUTHOR]

This study aimed to assess the clinical usefulness of magnetic resonance cholangiopancreatography (MRCP) as a postoperative diagnostic tool in children with choledochal cysts. Magnetic resonance cholangiopancreatography was performed postoperatively in 19 patients and image quality was compared with that obtained by intravenous cholangiography spiral computed tomography (IVC-SCT). While the detectability by MRCP was inferior to that by IVC-SCT, MRCP highly (84.2%) depicted the anastomotic site together with the reconstructed bowel and intrahepatic bile ducts. Magnetic resonance cholangiopancreatography also clearly delineated the postoperative condition of pancreaticobiliary maljunction (PBM), residual distal common bile duct, common channel, and pancreatic duct. Since MRCP is noninvasive and requires neither radiation exposure nor a contrast agent, and is useful for detecting both anastomosis and pancreatico-biliary ducts around PBM, MRCP might be superior to IVC-SCT as an imaging technique for outpatient clinics performing long-term follow-up studies in children with choledochal cysts. [ABSTRACT FROM AUTHOR]

Most tumour cells are sensitive to TRAIL-induced apoptosis, but not normal cells; thus, cancer therapy using TRAIL is expected clinically. Several tumour cells are resistant to TRAIL-induced apoptosis, and various mechanisms of such resistance were reported in individual cases. In this study, we established a TRAIL-resistant glioma cell line, which completely lacked TRAIL receptors. In addition, this tumour cell line had wild-type p53 tumour-suppressive gene, suggesting new mechanisms for tumour cells to expand and escape from immune surveillance. The present study further explored the mechanisms that determine the sensitivity to TRAIL. We show that genotoxic agents such as cisplatin, doxorubicin and camptothecin, in addition to UV radiation, can induce TRAIL-R2 on the cell surface of TRAIL receptor-negative tumour cells. Newly synthesised TRAIL-R2 is functional, so apoptosis is effectively induced by TRAIL, but it is significantly inhibited by constitutive expression of dominant-negative p53. In addition, apoptosis induced by pretreatment of genotoxic agents and additional stimulation of TRAIL is efficiently inhibited by either antagonistic anti-TRAIL-R2 antibody or pan-caspase inhibitor z-VAD-FMK. Taken together, these findings suggest that resistance to TRAIL by lack of TRAIL receptors on glioma is restored by genotoxic agents, which support the new strategies for tumour killing by TRAIL-bearing cytotoxic cells in combination with genotoxic treatment. [ABSTRACT FROM AUTHOR]

We present autopsy findings in a patient with a dissecting aneurysm of the vertebral artery causing subarachnoid haemorrhage. We sectioned the artery longitudinally and compared it with the angiogram, which showed the “pearl-and-string”. Histological examination showed a pseudoaneurysm covered by adventitia alone, forming the “pearl”. Internal elastic lamina and media were destroyed, and haematoma extended in the subadventitial space of the wall of the pseudoaneurysm. Media thickened by haematoma caused the “string”, narrowing the parent artery. Alcian blue staining showed that stratified internal elastic lamina in the aneurysm and the parent artery, had undergone marked mucoid degeneration, which may have been responsible for the dissection. [ABSTRACT FROM AUTHOR]

Cytotoxicity of Ni ions on three fibroblasts such as L929, Balb/3T3 clone A31 and MC3T3–E1 were examined by cell count (CC) and Neutral Red assay (NR). Three cells were incubated for 6 days in 1 ml DME medium containing Ni ions which ranged from 0 to 2 mM/l. The results clarified that Ni ions had dose-dependent cytotoxicity. L929 possessed the largest TC50 values (the amount of Ni ion that caused 50% cell death or 50% cell viability) of 0.12 mM/l (CC) and 0.32 mM/l (NR), and Balb/3T3 clone A31 had the least values of 0.05 mM/l (CC) and 0.09 mM/l (NR), whilst MC3T3–E1 had the intermediate values of 0.08 mM/l (CC) and 0.15 mM/l (NR). The dissolution of Ni ions from Ni-containing metallic restorations must be lower than these concentration levels so that body tissues might not be severely damaged. © 2001 Kluwer Academic Publishers [ABSTRACT FROM AUTHOR]

Aims/hypothesis. The protein kinase C (PKC), platelet-derived growth factor (PDGF) and polyol pathway play important parts in the hyperproliferation of smooth muscle cells, a characteristic feature of diabetic macroangiopathy. The precise mechanism, however, remains unclear. This study investigated the relation between polyol pathway, protein kinase C and platelet-derived growth factor in the development of diabetic macroangiopathy. Methods. Smooth muscle cells were cultured with 5.5 or 20 mmol/l glucose with or without an aldose reductase inhibitor, epalrestat, or a PKC-β specific inhibitor, LY333 531. Protein kinase C activities, the expression of PKC-βII isoform and PDGF-β receptor protein, free cytosolic NAD+:NADH ratio, the contents of reduced glutathione, and proliferation activities were measured. Results. Smooth muscle cells cultured with 20 mmol/l glucose showed statistically significant increases in protein kinase C activities, the expression of PKC-βII isoform and PDGF-β receptor protein, and proliferation activities, compared with smooth muscle cells cultured with 5.5 mmol/l glucose. Although epalrestat and LY333 531 inhibited protein kinase C activation induced by glucose to the same degree, the effects of epalrestat on proliferation activities and expression of the PDGF-β receptor were more prominent than those of LY333 531. Epalrestat improved the glucose-induced decrease in free cytosolic NAD+:NADH ratio and reduced glutathione content, but LY333 531 did not. The increased expression of membranous PKC-βII isoform was normalized by epalrestat. Conclusion/interpretation. These observations suggest that polyol pathway hyperactivity contributes to the development of diabetic macroangiopathy through protein kinase C, PDGF-β receptor, and oxidative stress, and that an aldose reductase inhibitor has a therapeutic value for this complication. [Diabetologia (2001) 44: 480–487] [ABSTRACT FROM AUTHOR]

Using a new method based on pulse dye densitometry, circulating blood volume (BV) was measured without direct sampling in patients undergoing open-heart surgery, and the effects of phosphodiesterase (PDE) III inhibitor administration during cardiopulmonary bypass (CPB) were evaluated. Sixteen patients scheduled for elective coronary artery bypass grafting were randomly assigned to the PDE III inhibitor group or control group. BV was determined before CPB, and immediately, and 4 and 12 h after operation. After declamping of the aorta, the PDE III inhibitor amrinone (1 mg/kg) was infused as a single bolus into the venous reservoir in the PDE III inhibitor group. BV decreased significantly soon after the operation in the control group. It did not decrease in the PDE III inhibitor group (48.6 ± 44 and 60.6 ± 8.0 ml/kg for the control and PDE III inhibitor groups, respectively). Four hours after surgery and beyond no significant changes in BV were observed in either group. The body fluid balance was negative in both groups. In conclusion, a single administration of PDE III inhibitor during CPB was found to sustain BV soon after operation and, therefore, is useful for postoperative management of open-heart surgery. [ABSTRACT FROM AUTHOR]

The ultrastructures of the upper surface layer of rat articular cartilage were studied with our “in vivo cryotechnique” followed by freeze-substitution method for scanning electron microscopy (SEM) or transmission electron microscopy (TEM). Rat hip or knee articular cartilage was quickly frozen by the in vivo cryotechnique with liquid isopentane-propane cryogen (−193°C), and surface areas of some frozen specimens were freeze-fractured with a scalpel in liquid nitrogen. They were freeze-substituted and freeze-dried, ion-sputtered, and then observed in SEM. Other frozen specimens were routinely freeze-substituted and embedded in epoxy resin for TEM. Many globular structures were detected in the thick upper surface layer that had not been revealed by the conventional fixation methods. Their sizes were reduced by Triton X-100 treatment, and their localization was also detected in synovial fluid, as revealed by SEM. Such globular lipid-like structures in the upper surface layer of hip or knee articular cartilage might contribute to joint lubrication. [ABSTRACT FROM AUTHOR]

Background: CO2 pneumoperitoneum provides a new surgical environment to treat malignant disease. The purpose of this study was to investigate the influence of CO2 pneumoperitoneum during laparoscopic surgery on cancer cell growth.Methods: WiDr human colon cancer cells were incubated for 3 h under the following two conditions: 100% CO2 at 10 mmHg, and 95% air/5% CO2 (control). Cell proliferation was assessed by the WST-1 assay and BrdU assay. Tumor growth was assessed by subcutaneous injection into 20 nude mice. Cellular damage was measured by lactate dehydrogenase (LDH) assay.Results: The number of WiDr cells under pneumoperitoneal conditions decreased in the first 24 h. However, no significant difference was observed in the proliferation rate and tumor growth of the viable cells. LDH release of the CO2 pneumoperitoneal group was higher than that of the controls.Conclusions: Our data indicate that CO2 pneumoperitoneum does not promote cancer cell proliferation but instead has a toxic effect on cancer cells. [ABSTRACT FROM AUTHOR]

Aims/hypothesis. Although increased polyol pathway activity has been implicated in the pathogenesis of diabetic microangiopathy, the relation with diabetic macroangiopathy remains unclear. Galactose feeding is known to stimulate the polyol pathway and to develop abnormalites similar to those in diabetic microangiopathy. Our study was conducted to investigate whether an activation of polyol pathway by long-term treatment with galactose produced morphological changes in coronary arteries of dogs and the effect of an aldose reductase inhibitor, epalrestat, was also studied.¶ Methods. Dogs received either normal chow or chow containing 30 % galactose with or without epalrestat given orally (20 or 50 mg · kg–1). After 44 months, morphometric analyses of coronary arteries were carried out and the galactitol contents in aortas were measured.¶ Results. The ratio of areas of the intimal layer to those of the medial layer, an indicator of intimal thickening, was statistically significantly increased in galactose-fed dogs compared with control dogs. Galactose-fed dogs had a remarkable accumulation of galactitol in their aortas. These morphological and biochemical deficits were reduced by treatment with epalrestat.¶ Conclusion/ interpretation. This report morphologically shows diabetes-like macrovascular abnormalities in galactosaemic animals, suggesting that polyol pathway hyperactivity is closely related to the development of diabetic macroangiopathy, which could be prevented by aldose reductase inhibition. [Diabetologia (1999) 42: 1404–1409] [ABSTRACT FROM AUTHOR]

A primary xanthomatous tumor is very rare in the central nervous system (CNS). Here we report the case of a fibroxanthoma arising from the dura mater of the cerebrum that demonstrated no systemic disease or metabolic abnormalities. A 19-month-old, otherwise healthy boy was found to have an enlarged head. Magnetic resonance imaging demonstrated a left occipital dural mass lesion and an enlarged left cerebral hemisphere with ipsilateral ventricular enlargement. Subtotal removal of the tumor was performed through the left parieto-occipital craniotomy. The tumor was composed of a central fibrous portion, a peripheral xanthomatous area, and a boundary. The peripheral area of the tumor showed abundant uniform xanthomatous cells with a thin fibrous stroma and the mass was diagnosed as fibroxanthoma involving the dura. This may represent a distinct category of tumor, which is different from the previously reported cases of fibrous xanthoma and fibrous histiocytoma. Intracranial xanthomatous tumors may be heterogeneous in their origin and histological features. However, further studies are needed to elucidate their clinical features, biological behavior, and optimal treatment strategies. [ABSTRACT FROM AUTHOR]

An exceedingly rare case of prenatally diagnosed cystic neuroblastoma (NB) is described. Prenatal ultrasonography at 28 weeks' gestation revealed a cystic right suprarenal mass that measured 15 × 17 mm in diameter. The mass increased parallel to fetal size until it was 41 × 44 mm in diameter at 39 weeks' gestation. Magnetic resonance imaging performed prenatally and after delivery showed two different intracystic intensities with fluid levels, suggesting intracystic hemorrhage. The patient underwent a right adrenalectomy at 20 days of age, and the resected tumor was diagnosed as a poorly-differentiated ganglioneuroblastoma. Eight months after surgery, the patient is generally healthy with no evidence of recurrence. We reviewed 25 additional cases of prenatally diagnosed adrenal cystic NB and examined the clinical features of this rare entity. [ABSTRACT FROM AUTHOR]

We describe a 22-year-old man with Crohn's ileocolitis accompanied by intestinal stenosis and ileovesical fistula in whom laparoscopically-assisted surgery was successfully performed after thorough nutritional therapy. Laparoscopic procedures are characterized by minimal access and minimal invasion, features which can contribute to the early recovery of patients who undergo surgery. It is suggested that laparoscopic (or laparoscopically-assisted) surgery after strict nutritional therapy can be effective in the treatment of patients with Crohn's disease who have intestinal complications. [ABSTRACT FROM AUTHOR]

Four children, who were treated for supratentorial primitive neuro-ectodermal tumours between 1986 and 1995 at Kyushu University Hospital, are here presented. The initial characteristic symptoms and signs of these patients included vomiting and headache, followed by motor weakness. All patients underwent direct surgery for their tumours while 2 also received a course of postoperative radio-therapy. After these treatments, 3 died within 4 months after diagnosis, whereas one infant, who underwent a total removal of the tumour but had no adjuvant therapy, is still alive after a follow-up period of 4 years. Most of the tumour cells of these 4 cases were poorly differentiated neuro-ectodermal cells, but some also showed variable differentiation along the glial and/or neuronal lines. While such differentiation had no impact on the clinical course of the patients, the malignant potential as assessed by the percentage of MIB1-positive cells showed a good correlation with the clinical features; the 3 cases with a rapid clinical course had MIB1 staining indices of more than 2%, and one case, who survived more than 4 years, had the same indices of 0.2% as found in benign tumours. Although “PNETs” of Hart and Earl share certain clinical features, they may be a group of tumours heterogeneous in their origins, histogenesis, and biological behaviours. [ABSTRACT FROM AUTHOR]

The effect of an analogue of l-carnitine, propionyl- l-carnitine, on the electroretinogram, motor nerve conduction velocity and nerve blood flow was determined in rats with streptozotocin-induced diabetes, and was compared with the effects of insulin alone or combined therapy. Oral administration of propionyl- l-carnitine (3 g/kg daily for 4 weeks) significantly increased caudal nerve motor conduction velocity and sciatic nerve blood flow in diabetic rats. There were no differences in the effects of insulin (8-10 U daily for 4 weeks), propionyl- l-carnitine and combined therapy. Although propionyl- l-carnitine significantly shortened the peak latency of the electroretinogram b-wave in diabetic rats, its effect was far weaker than that of insulin or combined therapy, with combined therapy producing the greatest improvement. These effects of propionyl- l-carnitine were accompanied by a decrease of serum lipid levels, an increase of the sciatic nerve carnitine content, and no changes of the tissue (nerve and retinal) sorbitol and myo-inositol concentrations. In contrast, insulin significantly reduced the tissue sorbitol content and markedly increased myo-inositol. These findings suggest that propionyl- l-carnitine may improve diabetic neuropathy and retinopathy without influencing the polyol pathway, and that this beneficial effect may be mediated through the amelioration of microcirculation and tissue carnitine content, thus probably increasing fatty acid oxidation. [ABSTRACT FROM AUTHOR]

The pathophysiology of Hirschsprung's disease has not been fully elucidated but is known to have a neurogenic basis. In recent years, new neural proteins and peptides have been discovered and our aim in this study was to use immunocytochemistry to investigate their involvement in the neuronal abnormalities associated with this condition. Large bowel samples from 9 children undergoing surgery for Hirschsprung's disease were compared with those taken from 8 children with other gastrointestinal diseases but no aganglionosis. Immunocytochemistry was carried out using antibodies to a wide range of neuron specific proteins and peptides. Examination of sections immunostained for the general neuronal markers, protein gene product 9.5, neuron specific enolase and neurofilament triplet proteins, allowed rapid identification of aganglionic segments. Nerves containing vasoactive intestinal polypeptide/peptide histidine methionine (VIP/PHM), galanin, substance P, somatostatin, met-enkephalin or calcitonin gene-related peptide (CGRP) showed a marked reduction in all layers of the aganglionic bowel. However, scattered VIP/PHM immunoreactive fibres were also found in the hypertrophied nerve bundles. In contrast with these reduced peptide-containing nerves, fibres displaying NPY immunoreactivity showed a marked increase in all aganglionic segments, particularly in the circular muscle where few are found normally. Our findings shed further light on the neurobiology of aganglionic bowel and suggest that immunostaining of neural proteins and the peptide NPY can aid rapid histopathological diagnosis of congenital aganglionosis. [ABSTRACT FROM AUTHOR]

The morphological alteration of gut-associated lymphoid tissue (GALT) induced by long-term absence of dietary stimulation was investigated. Male Wistar rats weighing ∼230 g were maintained with total parenteral nutrition (TPN). Control rats were allowed to have the same amount of the solution orally. After two weeks, the morphological alteration of GALT was examined. Although no significant difference in weight gain was noted between the two groups, the area comprised by Peyer's patches was decreased in TPN rats. The number of transported lymphocytes and the ratio of helper T (T) cells to suppressor/cytotoxic T (T) cells in intestinal lymph were lowered after TPN treatment. In an immunohistochemical study of the rat ileum, the number of T cells and the T/T ratio were decreased both in the intraepithelial spaces and in the lamina propria of TPN rats. The percentage of interleukin-2 receptor-positive cells and the number of IgA-containing cells in the lamina propria were significantly reduced in TPN rats. These results suggest that dietary stimulation might play a role in the maintenance of GALT function and morphology. [ABSTRACT FROM AUTHOR]

Copyright of International Orthopaedics is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of International Orthopaedics is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

An insulin-dependent diabetes mellitus (IDDM)-susceptibility gene (IDDM13) has recently been mapped to a region of distal chromosome 2q, which is syntenic to the region of mouse chromosome 1 containing a murine susceptibility gene for IDDM, Idd5. To determine the contribution of this region to IDDM disease susceptibility further and to narrow the region for positional cloning of susceptibility genes, we have studied the association of distal chromosome 2q with IDDM in the genetically distinct Japanese population. A 137 mobility unit (mu) allele at D2S137 locus was significantly associated with IDDM (odds ratio 1.92, p = 0.0016). Other markers, D2S301 and D2S143, located in the same region were not associated with IDDM, indicating that IDDM13 is in linkage disequilibrium with D2S137, but not with D2S301 or D2S143. The association of D2S137 with IDDM was observed in patients lacking one of two high risk HLA alleles, DQB1 * 0303 and DQB1 * 0401, but not in patients with either of these alleles. The frequency of high risk HLA alleles was significantly lower in patients with the susceptible allele at D2S137, suggesting that IDDM13 contributes to IDDM susceptibility in subjects without high risk genotypes at IDDM1. Demonstration of allelic association of D2S137 with IDDM localizes IDDM13 in the close vicinity (< 2 centiMorgans) of D2S137, greatly facilitating fine structure mapping and positional cloning of IDDM13. [Diabetologia (1998) 41: 228–232] [ABSTRACT FROM AUTHOR]

An insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme (ACE) gene has repeatedly been shown to be associated with ischaemic heart disease, but the association of this genetic marker with diabetic microangiopathy is controversial. To assess the association of the genotypes with the development of diabetic nephropathy or retinopathy, we performed a meta-analysis of data from the literature, using Mantel-Haenszel method followed by the Breslow-Day test for assessing homogeneity among data. In a total of 4773 diabetic patients from 18 studies with ( n = 2495) and without ( n = 2278) renal complications, the D allele was significantly associated with diabetic nephropathy ( p < 0.0001) in a dominant model (summary odds ratio 1.32, 95 % confidence interval: 1.15 to 1.51). There was no significant evidence against homogeneity of the odds ratios ( χ 2 = 18.9, 20 df; p = 0.53). The association was significant both in non-insulin-dependent ( p < 0.005) and in insulin-dependent diabetes mellitus ( p < 0.05). Likewise, in a total of 2010 diabetic patients with ( n = 1008) and without ( n = 1002) retinopathy, there was no association of the I/D polymorphism with diabetic retinopathy. These data suggest that the ACE I/D polymorphism affects the risk for diabetic nephropathy, but not for diabetic retinopathy. [Diabetologia (1998) 41: 47–53] [ABSTRACT FROM AUTHOR]

The mouse ob gene and its human homologue OB have recently been cloned. The mutations in the ob gene are known to be associated with extreme obesity. The relationship between the human OB gene and disease, however, is largely unknown due to the lack of suitable markers within or adjacent to the OB gene. To obtain informative markers, we searched for simple tandem repeat polymorphisms in the genomic sequence of the human OB gene and identified a novel tetranucleotide repeat in the 3′ flanking region. Fifteen alleles were detected in this marker with a heterozygosity of 0.85 and polymorphism information content of 0.83, indicating a highly informative nature of this marker. Two-point linkage mapping in two Centre Etude Polymorphisme Humaine (CEPH) reference families suggested that this marker is located in the interval between D7S514 and D7S530, the same interval where the OB gene is located (recombination fractions with D7S514 and D7S530 were 0.026 and 0.034, respectively). Although allele frequency distributions of this marker did not differ between 84 control subjects and 69 NIDDM patients, there was a tendency to higher body weight in control subjects with class I/class I genotype than in those without this genotype (68.8 ± 11.1 vs 60.8 ± 10.3 kg, p = 0.05). The highly polymorphic nature of this marker and its location in the OB gene makes this marker useful for linkage studies of the OB gene with a number of phenotypes, such as obesity, non-insulin-dependent diabetes mellitus, hypertension and the insulin resistance syndrome. [Diabetologia (1996) 36: 1398-1401] [ABSTRACT FROM AUTHOR]

A possible pathogenic mutation in the Β3-adrenergic-receptor gene (Trp64Arg) has been reported to be associated with an earlier age of onset of non-insulin-dependent diabetes mellitus (NIDDM) and clinical features of the insulin resistance syndrome in Pima Indian, Finnish and French subjects. Since marked heterogeneity has been reported in the association of mutations of candidate genes with NIDDM between Japanese and other ethnic groups, we investigated the association of Trp64Arg with NIDDM in Japanese subjects. The allele frequency of the mutation (Arg) was slightly, but not significantly, higher in NIDDM than in control subjects (70 out of 342 alleles [20.5%] vs 40 out of 248 [16.1%], respectively, p>0.2). When our data were combined with those of Pima Indian and Finnish subjects, however, the Arg/Arg genotype was significantly associated with NIDDM as compared with the other two genotypes ( p<0.005, relative risk [RR] 2.13, 95% confidence interval [CI] 1.28-3.55). The Arg allele was also associated with NIDDM ( p<0.05, RR 1.27, 95% CI 1.06-1.52). Japanese subjects homozygous for the mutation had a significantly higher body mass index (mean ± SD∶25.5±3.9 kg/ m) than heterozygotes (22.6±4.1, p<0.05) and normal homozygotes (22.8±3.8, p<0.05). NIDDM patients homozygous for the mutation tended to have an earlier age of onset of NIDDM than those with other genotypes. These data suggest that the Trp64Arg mutation not only contributes to weight gain and age-at-onset of NIDDM but is also associated with susceptibility to NIDDM. [ABSTRACT FROM AUTHOR]

The NSY (Nagoya-Shibata-Yasuda) mouse was established as an inbred strain of mouse with spontaneous development of diabetes mellitus, by selective breeding for glucose intolerance from outbred Jcl∶ICR mice. NSY mice spontaneously develop diabetes mellitus in an age-dependent manner. The cumulative incidence of diabetes is 98% in males and 31% in females at 48 weeks of age. Neither severe obesity nor extreme hyperinsulinaemia is observed at any age in these mice. Glucose-stimulated insulin secretion was markedly impaired in NSY mice after 24 weeks of age. In contrast, fasting plasma insulin level was higher in male NSY mice than that in male C3H/He mice (545±73 vs 350±40 pmol/l, p<0.05, at 36 weeks of age). Pancreatic insulin content was higher in male NSY mice than that in male C3H/He mice (76±8 vs 52±5 ng/mg wet weight, p<0.05, at 36 weeks of age). Morphologically, no abnormal findings, such as hypertrophy or inflammatory changes in the pancreatic islets, were observed in NSY mice at any age. These data suggest that functional changes of insulin secretion in response to glucose from pancreatic beta cells may contribute to the development of non-insulin-dependent diabetes mellitus (NIDDM) in the NSY mouse. Although insulin sensitivity was not measured, fasting hyperinsulinaemia in NSY mice suggests that insulin resistance may also contribute to the pathogenesis of NIDDM. Since these findings are similar to the pathophysiologic features of human NIDDM patients, the NSY mouse is considered to be useful for investigating the pathogenesis and genetic predisposition to NIDDM. [ABSTRACT FROM AUTHOR]

The formation of α plates during isothermal aging of a Cu-26.7 wt pct Zn-4.0 wt pct Al alloy at 150 °C to 350 °C follows thermally activated incubation kinetics. Early stage α plates possess an ordered 18R or 9R long-period stacking order (LPSO) crystal structure, with antiphase domain boundaries running continuously across the interface. The plates also exhibit invariant plane strain (IPS) crystallography consistent with calculations of the phenomenological theory of martensite crystallography (PTMC). The ordered LPSO structure and IPS crystallography are gradually annealed out only after extended aging as the structure changes to the equilibrium disordered face-centered cubic (fcc) one. High-resolution transmission electron microscopy (TEM) analyses reveal that early stage α plates have straight coherent interfaces. Prolonged aging induces misfit dislocations at the interface and causes the interface to protrude into the parent phase. Although microanalytical analyses indicate that a composition difference exists between the α plates and the parent matrix, solute depletion was observed at neighboring defects. These observations support the proposed transformation mechanism that the α plates nucleate at solute depleted defects through a shear mechanism and that subsequent plate growth is then controlled by a diffusional process. [ABSTRACT FROM AUTHOR]

Recently, hepatocyte nuclear factor-1 α (HNF-1 α, which is encoded by the TCF1 gene) mutations were reported in a subset of patients with maturity onset diabetes of the young (MODY3). We studied the contribution of TCF1 to genetic susceptibility to common non-insulin-dependent diabetes mellitus (type 2) in Japanese subjects by investigating allelic association with type 2 diabetes use of three markers. We also studied the frequency of the G191D mutation, the only mutation of TCF1 reported so far in late-onset type 2 diabetes. A total of 356 subjects were studied. There were no significant differences in allele frequency of the three markers between patients with type 2 diabetes and control subjects. A G191D mutation was not found in the subjects studied, giving a frequency of less than 0.4% in common type 2 diabetes. The lack of association of type 2 diabetes with three markers in and near TCF1 suggests that mutations in TCF1 derived from a limited number of founders are not a major cause of common type 2 diabetes even in the genetically homogeneous Japanese population. The data also indicate that the G191D mutation in TCF1 plays little, if any, role in susceptibility to common type 2 diabetes in the Japanese. [ABSTRACT FROM AUTHOR]

Metal ion incorporation into N-methyl-5,10,15,20-tetrakis(4-sulfonatophenyl)porphine (N-CHTSPP) has been shown to be much faster than that for non-methylated porphyrins such as 5,10,15,20-tetrakis(4-sulfonatophenyl)porphine (TSPP). We have proposed a kinetic method, utilizing differential rate of metal ion incorporation into N-CHTSPP, for the determination of submicrogram amounts of copper(II) and zinc(II) in serum. [ABSTRACT FROM AUTHOR]

Both Beckwith-Wiedemann syndrome (BWS) and hemihypertrophy (HH) have been recognized to be overgrowth syndromes associated with an increased risk of cancer. We report an infant with hepatoblastoma associated with both BWS and HH in whom high serum alpha-fetoprotein (AFP) levels persisted even after complete tumor resection with no tumor recurrence. This phenomenon might be partly due to the nature of the proliferative disease. It is important to recognize that in some infants with BWS prolonged high serum AFP levels mimic the existence of a tumor, and that treatment should be based not only on AFP measurement, but also on repeated radiologic imaging. [ABSTRACT FROM AUTHOR]

Postoperative intussusception of the appendiceal stump is a rare complication of appendicectomy. We report an infant who developed an intussusception of the appendiceal stump 2 days following an appendicectomy performed during a right inguinal herniotomy as a day case. The intussusception was diagnosed on ultrasonography and was to be treated laparoscopically, but spontaneous reduction occurred during induction of general anesthesia. [ABSTRACT FROM AUTHOR]

Conservative treatment was performed for 60 trigger thumbs (19 right, 17 left, 12 bilateral) in 48 children (19 boys, 29 girls); the age at initial diagnosis ranged from 0 to 48 months old (mean 26 months). In this approach, only passive exercise of the affected thumb was performed by the mother. As a result, two patients (two thumbs) dropped out of treatment. Fifty-six thumbs out of 58 showed a satisfactory result (96%). Sixteen thumbs (in stage 2) and eight thumbs (in stage 3) showed completely recovery. Four thumbs (in stage 3) have not yet improved. In conclusion, we suggest that conservative treatment is effective for trigger thumbs in stage 2, while surgical therapy was thought to be indicated for stage 3 before the age of 3 years to avoid flexion deformity. [ABSTRACT FROM AUTHOR]

Unlabelled: Funnel-type intraluminal duodenal diverticulum (windsock web) is a rare congenital malformation. A 4-year-old boy with vomiting and abdominal pain for several weeks was referred to the hospital. A plain abdominal X-ray on admission disclosed a double bubble sign. Abdominal echography and CT disclosed a foreign body lodged in the alimentary tract. After the foreign body was removed with a fibrescope, endoscopy showed a stenotic descending portion where the foreign body was located. An upper gastro-intestinal contrast study demonstrated a post-bulbar duodenal stenosis with a barium-filled pear-shaped sac in the descending portion of the duodenum. Surgical exploration was done under the diagnosis of windsock web of the duodenum. A simple excision of the web at its base was carried out. A hole 7 mm in diameter was found at the edge of the web. The microscopic appearance of the resected specimen was characterized by the duodenal mucosa with an extensive chronic inflammation lining both sides of the diverticulum and the lack of muscular layer of mucosa.Conclusion: If an ingested material is not excreted in the stool, possible clogging in the intestinal tract should always be considered and a further intensive examination is warranted. [ABSTRACT FROM AUTHOR]

We report a 45-year-old woman with a meningioma which was in contact with only the pituitary stalk on MRI. As the pituitary stalk has no dura mater, we suggest this tumour may have originated from the arachnoid membrane of the pituitary stalk. Though some reports have shown that meningiomas can arise from sites lacking a dural component, this is the first report of a meningioma originating from the pituitary stalk. [ABSTRACT FROM AUTHOR]

A possible pathogenic mutation in the glucagon receptor gene causing a Gly to Ser change at codon 40 (Gly40Ser) was reported to be associated and linked with non-insulin-dependent diabetes mellitus (NIDDM), in France and Sardinia, Since the frequency of the mutation (Gly40Ser), about 5% in the French population of familial NIDDM and 8% in randomly chosen diabetic patients in Sardinia, was much higher than that of any of the previously reported mutations in candidate genes, it is important to clarify whether the contribution of this mutation to NIDDM is universal. In this study, we investigated the association of this mutation with diabetes mellitus in a large number of Japanese diabetic patients (383 NIDDM and 53 insulin-dependent diabetic patients) by polymerase chain reaction-restriction fragment length polymorphism analysis. None of the Japanese diabetic patients showed Gly40Ser mutation and the association of this mutation with NIDDM was significantly different ( p<4·10 vs French, p<3·10 vs Sardinian by Fisher's exact test). The results not only indicate that the mutation plays little, if any, role in susceptibility to diabetes in Japan, but also indicate the genetic heterogeneity in NIDDM and further emphasize the importance of studies on genetic susceptibility to NIDDM and other complex traits in different ethnic groups. [ABSTRACT FROM AUTHOR]

A case of choledochal cyst (CC) antenatally diagnosed at 29 weeks' gestation is reported. Rapid enlargement of the cyst soon after delivery resulted in complete gastric outlet obstruction (GOO). The lesion was treated by external drainage as a temporary maneuver, with delayed cyst excision and hepaticoduodenostomy at the hepatic hilum performed at 81 days of age. Surgical treatment of CC in early infancy has been reported to be safe and effective. However, delayed primary excision would be an alternative procedure, especially in rare cases showing rapid enlargement resulting in GOO, since this choice has the potential advantage of allowing weight gain and improved nutritional status without risking interim complications due to the drainage procedure. [ABSTRACT FROM AUTHOR]

A 7-year-old boy who presented with a painful left hemiscrotal mass was diagnosed with acquired lymphangioma of the scrotum. Chronic friction from a cast for Perthes' disease might have been the cause of sudden enlargement of a congenital lymphangioma of the scrotum. Magnetic resonance imaging (MRI) was useful for preoperative diagnosis and determining the extent of the scrotal lesions. Total excision of the mass leaving the overlying skin was successfully performed. The clinical significance of MRI for preoperative diagnosis and planning surgical resection of this lesion is discussed. [ABSTRACT FROM AUTHOR]

Anal canal duplication is an extremely rare abnormality. Two cases in children are reported; in both cases, the orifice of the duplicate tubular structure was located just behind the normal anus and ran along the posterior side of the anal canal without communication with the anorectum. Complete removal of the duplication was performed through a perineal approach. Histology revealed a squamous lining with a smooth-muscle component around the cavity, with mucus-secreting transitional epithelium. Anal ducts with apocrine secretion and lymphocyte infiltration were also observed. The postoperative clinical courses were uneventful with satisfactory anal function. We collected nine similar cases from the literature. The term "anal canal duplication" is proposed based on common clinical features and pathology. [ABSTRACT FROM AUTHOR]

To understand human evolution it is critical to clarify which adaptations enabled our colonisation of novel ecological niches. For any species climate is a fundamental source of environmental stress during range expansion. Mammalian climatic adaptations include changes in size and shape reflected in skeletal dimensions and humans fit general primate ecogeographic patterns. It remains unclear however, whether there are also comparable amounts of adaptation in humans, which has implications for understanding the relative importance of biological/behavioural mechanisms in human evolution. We compare cranial variation between prehistoric human populations from throughout Japan and ecologically comparable groups of macaques. We compare amounts of intraspecific variation and covariation between cranial shape and ecological variables. Given equal rates and sufficient time for adaptation for both groups, human conservation of non-human primate adaptation should result in comparable variation and patterns of covariation in both species. In fact, we find similar amounts of intraspecific variation in both species, but no covariation between shape and climate in humans, contrasting with strong covariation in macaques. The lack of covariation in humans may suggest a disconnect in climatic adaptation strategies from other primates. We suggest this is due to the importance of human behavioural adaptations, which act as a buffer from climatic stress and were likely key to our evolutionary success. [ABSTRACT FROM AUTHOR]