Biomedical subjects
Publications and source records attributed to Y Hamada.
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.
A 36-year-old Japanese male, who 7 years previously had been diagnosed as having an ependymoma in the left parietal region, had received surgery, chemotherapy and radiotherapy. He later developed a rapid growth of multiple skin lesions on his back and extremities, which coincided with a regrowth of the tumor. Postmortem examination revealed that the ependymoma showed anaplastic transformation and necrosis; however, no malignancy was observed in the extracranial organs. The skin lesions were histologically diagnosed as seborrheic keratoses. We have, therefore, diagnosed the patient as having Leser-Trélat sign associated with anaplastic ependymoma.
The neurofibromatosis 2 (NF2) gene-encoded protein, named merlin, may function as a molecular linkage connecting cytoskeleton and plasma membrane. Merlin is thought to play a crucial role as a tumor suppressor not only in hereditary NF2-related tumors, but also in sporadic tumors such as schwannomas, meningiomas and gliomas. Using a merlin-expression vector system, we raised specific antiserum against merlin. We observed the intracellular distribution of merlin in cultured glioma cells, and further investigated merlin expression in 116 human brain tumors. Immunofluorescence microscopy revealed that merlin was localized beneath the cell membrane and concentrated at cell-to-cell adhesion sites, where actin filaments are densely associated with plasma membrane. By immunohistochemistry, none of the schwannomas from either NF2 patients or sporadic cases showed any immunoreactivity, while normal Schwann cells of cranial nerves were immunopositive. In meningiomas, merlin expression was frequently seen in the meningothelial subtype (8/10, 80%), but no expression could be detected in either the fibrous or the transitional variant. Most normal astrocytes were negative; however, reactive astrocytes often expressed merlin. Glioblastomas and anaplastic astrocytomas were found to be strongly positive, and focal positive staining was observed in fibrillary and pilocytic astrocytomas. Thus, the loss of merlin appears to be integral to schwannoma formation and the differential pathogenesis of meningioma subtypes. However, merlin alterations do not appear to play a critical role in either the tumorigenesis or malignant transformation of neoplastic astrocytes.
We reviewed 95 consecutive patients with cervical spinal cord injury admitted within 2 days of injury and treated nonoperatively, to elucidate the relationship between neurological deterioration and the white blood cell count in the first 4 days after injury. The count for 14 patients who had neurological deterioration was 13.2 +/- 3.2 x 10(9)/l, and that for 81 patients who had no deterioration was 11.0 +/- 3.1 x 10(9)/l. None of 19 patients whose highest white blood cell count was less than 9 x 10(9)l deteriorated, while 14 of 76 patients whose count was 9 x 10(9)/l or more deteriorated. These results suggest that the white blood cell is important in the secondary pathological changes after mechanical injury to the spinal cord.
In an animal model of human non-insulin dependent diabetes mellitus (NIDDM), Otsuka Long-Evans Tokushima Fatty (OLETF) rats were fed with sucrose for 8 weeks to obtain severe hyperglycemia. The effects of sucrose administration on peripheral nerve functions, motor nerve conduction velocity (MNCV) and coefficient of variance of R-R interval (CVR-R), were investigated with concomitant measuring of sciatic nerve blood flow (SNBF), ADP-induced platelet aggregation and polyol content in the sciatic nerves. The effects of an aldose reductase inhibitor, TAT, on these parameters were also studied. Administration of sucrose to OLETF rats caused significant body weight reduction and remarkable hyperglycemia. Sucrose-fed OLETF rats demonstrated significantly delayed MNCV, decreased CVR-R, reduced SNBF and increased platelet aggregation activity to ADP. Sorbitol and fructose accumulation, and myo-inositol depletion in sciatic nerves were observed only in sucrose-fed OLETF rats. These abnormalities were all ameliorated by the treatment with TAT. These observations suggest that the sucrose-fed OLETF rat is a useful animal model for studying the pathogenesis of diabetic neuropathy in human NIDDM, and that an aldose reductase inhibitor is a useful therapeutic agent for the treatment of diabetic neuropathy.
BACKGROUND: Neurofibromatosis-2 (NF2) is an autosomal dominant disorder in which patients typically show bilateral acoustic tumors, and they are usually diagnosed histopathologically as schwannomas. The nerve of origin of a schwannoma is often demonstrated on the periphery along the capsule but not penetrating the substance of the tumor. However, there is a possibility that NF2 schwannomas and solitary schwannomas differ from participation in nerve components. METHODS: In this study, the authors noted the relationship between the tumor and the original nerves. To detect whether there were embedded nerves in the tumor, immunohistologic staining using neurofilament and myelin basic protein antibodies was performed on 6 NF2 schwannomas and 17 non-NF2 schwannomas. RESULTS: Four of five NF2 schwannomas had embedded nerves and one of four, which was considered to be the early stage of the tumor occurrence, remarkably embedded original nerves. On the other hand, embedded nerves were not seen in non-NF2 schwannomas. CONCLUSIONS: The authors concluded that the NF2 schwannomas tend have original nerves embedded in the tumor substance, which may be based on the difference of the motility of tumor cells, and the authors believe that it is difficult to remove NF2 schwannomas while preserving the original nerve.
4-Hydroxy-2-nonenal (HNE), one of the major products of lipid peroxidation, inactivated the rate-limiting enzymes (from animal sources) of the glycolytic pathway and the pentose phosphate pathway when incubated at 37 degrees C for 1 h in the absence of glutathione (GSH). The HNE concentration for half-maximal inactivation of 6-phosphofructokinase (PFK) and glyceraldehyde-3-phosphate dehydrogenase was 3-10 microM; and that value for pyruvate kinase, glucose-6-phosphate dehydrogenase, and hexokinases I and II was 0.15-0.6 mM. In the presence of 5 mM GSH, however, only PFK, irrespective of the source (muscle, liver, or erythrocyte), was inactivated by 40-50% when incubated with 0.1 mM HNE for 1 h. Even PFK was not inactivated in the presence of both GSH and its substrate, ATP (2 mM). Glycolysis in human erythrocytes was not affected by treatment of cells with 0.1 mM HNE at 37 degrees C for 30 min. The results suggest that HNE, at concentrations observable under physiological and pathological conditions, hardly affects glycolysis in cells.
A putative pathogenic mutation in the beta3-adrenergic receptor gene (Trp64Arg) has been reported to be associated with higher diastolic blood pressure as well as clinical features of the insulin resistance syndrome and an earlier onset of non-insulin-dependent diabetes mellitus (NIDDM) in Pima Indians and Finns. Because essential hypertension is reported to be associated with insulin resistance, we studied the mutation in Japanese patients with essential hypertension to clarify associations of this mutation with hypertension, insulin resistance, and basal adrenergic state in hypertensive subjects. The allele frequency of the mutation (Arg) in patients with essential hypertension was similar to that in control subjects (35 of 202 alleles [17.3%] v 27 of 146 [18.5%], respectively, P > .7). Insulin sensitivity measured by hyperinsulinemic euglycemic glucose clamp and plasma norepinephrine and epinephrine levels were also similar in hypertensive subjects with and without the mutation. These data suggest that Trp64Arg mutation in the beta3-adrenergic receptor gene does not play a major role in susceptibility to essential hypertension or in insulin resistance and basal adrenergic state in hypertension.
The relative timings of impulses caused by two neurons can be studied using cross-correlation techniques or the related techniques of the joint peristimulus-time histogram and the time-dependent correlation function. Analysis of the relative timings of several related neurons is important to the study of the dynamics, since we consider functional connectivity to be partially related to the dynamics. Functional connectivity changes of short duration reflect physiological functions rather than changes of synaptic connections. The relative timings of impulses are considered to reflect functional connectivity. Using the joint impulse configuration scatter diagram (JICSD) proposed by Perkel, a time-dependent scatter diagram (TDSD) is calculated to analyze the change of functional connectivity. The JICSD displays the long-time average of relative timings of impulses or the functional connectivity of three interconnected neurons. We generated JICSDs for short durations and we subsequently generated TDSDs by arranging JICSDs in chronological order. The change of a "snowflake pattern" of each JICSD was interpreted in terms of change of the functional connectivity. We propose a method for analyzing the changing functional connectivity among three neurons.
This paper describes the efficacy of utilizing Tumor Necrosis Factor-alpha (TNF) as a detectable parameter of acute rejection after bone allografts. The authors used a bone-joint allograft model, transferring vascularized allograft knee joints across a major histocompatibility barrier, using three groups of rats divided into controls, non-immunosuppressed, and immunosuppressed with cyclosporine. The paper supplies preliminary information suggesting that TNF may be a marker for early bone-joint allograft rejection.
Both glucagon and glucagon-like peptide-1 (GLP-1) play an important role in the regulation of nutrient homeostasis. In this study, the tissue distributions of the expression of receptor genes for glucagon and GLP-1 were examined. Expression of glucagon receptor gene was detected in liver, kidney, ileum and pancreatic islets but not in brain. In contrast, expression of GLP-1 receptor gene was detected in brain, pancreas and pancreatic islets but not in liver, kidney, or ileum. To investigate the existence and characteristics of glucagon and GLP-1 receptors on pancreatic beta cells, expression of the receptor genes and translational regulation of the expression of the receptor genes by glucose were analyzed in a mouse pancreatic beta cell line, MIN6 cells. In the cDNA pool of MIN6 cells, both glucagon and GLP-1 receptor genes were identified and showed higher expression level in MIN6 cells cultured under high glucose condition than in those cultured under low glucose condition. These results suggest that glucagon and GLP-1 receptor genes are expressed in pancreatic beta cells and their expression is upregulated by glucose.
A case associated with insulin-dependent diabetes mellitus (IDDM), rheumatoid arthritis (RA), and autoimmune thyroid disease (AITD) was reported. A high titer of anti-glutamic acid decarboxylase antibody (GAD) and a positive islet cell antigen were observed. The patient's human leukocyte antibody (HLA) haplotype was a homozygote of DQA1*0301, DQB1*0401, and DRB1*0405. Because this haplotype was in linkage disequilibrium with DPB1*0501, an allele associated with AITD in Japanese patients, the patient was homozygous for alleles susceptible to IDDM, RA, and AITD. A specific HLA haplotype susceptible to several autoimmune disease may result in the development of IDDM, RA, and AITD.
OBJECTIVE: In recent years, dural arteriovenous fistulas (DAVFs) have been primarily thought to be acquired lesions, formed after sinus thrombosis. The pathogenesis of DAVF, however, is still controversial. We have studied histopathological aspects of DAVFs in resected specimens obtained from nine patients, to obtain clues to the pathogenesis of DAVFs. METHODS: Histological comparison was made among nine DAVF cases and five control cases without venous sinus disease. In addition, the relationship between the clinical course and histological aspects was investigated. RESULTS: The essential abnormality found was a connection between the dural arteries and the dural veins within the venous sinus wall, through small vessels averaging approximately 30 microns in diameter. By using several staining methods, we confirmed that the vessels were part of the venous system; we named these dilated venules "crack-like vessels." CONCLUSIONS: The development of abnormal communications between dural arteries and dural veins (crack-like vessels) is regarded as the essential part of the pathogenesis of DAVFs, and sinus thrombus is not thought to be an essential lesion of DAVFs. It might be postulated that sinus hypertension caused by stenocclusive disease of the venous sinuses triggers the development of fistulous connections between arteries and veins in the dural wall, which may result in increasingly dilated venules and the formation of DAVFs.
We studied the stability of our cementless acetabular component (socket) with 3 spikes in 65 joints of 65 patients who were followed for over 5 years. In 1 case, there was osteolysis around the femoral component (stem) but not around the socket. The movement of the socket and the radiolucent line was observed in 11 cases of osteoarthritis with acetabular hypoplasia (a mean of 43 degrees of the sharp angle) and 3 cases with rapidly destructive coxarthrosis. We could obtain favorable stability in 50 patients, including 38 with osteoarthritis (a mean of 41 degrees of the sharp angle), 8 with aseptic necrosis, 2 with rapidly destructive coxarthrosis, and 2 with rheumatoid arthritis. Our socket is very effective in preventing osteolysis and is expected to provide more stable mechanical stability by arranging an insertion angle (35 degrees of the optimal open angle and 10 degrees of the anteversion angle) and a full bone graft in osteoarthritic patients.
To investigate the role of increased polyol pathway activity and hemodynamic deficits in the pathogenesis of diabetic retinopathy in non-insulin-dependent diabetes mellitus (NIDDM), Otsuka Long-Evans Tokushima fatty (OLETF) rats, an animal model of human NIDDM, were given water with or without 30% sucrose and some of them were fed laboratory chow containing 0.03% cilostazol, an anticoagulant, or 0.05% [5-(3-thienyl)tetrazol-1-yl] acetic acid monohydrate (TAT), an aldose reductase inhibitor, for 8 wk. Long-Evans Tokushima Otsuka (LETO) rats were used as nondiabetic controls. The peak latencies of oscillatory potentials of the electroretinogram in sucrose-fed OLETF rats were significantly prolonged compared with those in OLETF rats without sucrose feeding and LETO rats. There was a marked increase in platelet aggregability and a significant decrease in erythrocyte 2,3-diphosphoglycerate in sucrose-fed OLETF rats. Cilostazol significantly improved these parameters without changes in retinal levels of sorbitol and fructose. TAT, however, ameliorated all of these parameters. These findings confirm that the sucrose-fed OLETF rat is a useful animal model of retinopathy in human NIDDM and suggest that cilostazol improved diabetic retinopathy by modifying vascular factors, not by altering polyol pathway activity.
A possible pathogenic polymorphism in the gene for the G subunit of the glycogen-associated regulatory form of protein phosphatase 1 (PP1 G subunit), causing an Asp-to-Tyr substitution at codon 905 (Asp905Tyr), has been reported to be associated with insulin resistance and hypersecretion of insulin in the white population. Since marked heterogeneity has been reported in the association of mutations of candidate genes with essential hypertension between Japanese and other ethnic groups, we investigated the association of Asp905Tyr with essential hypertension in Japanese subjects. The frequency of the Tyr allele in Japanese control subjects (0.70) was much higher than that in the Danish population (0.10, P<1x10(-8)), indicating that the Tyr allele, previously reported as a rare variant in white subjects, is a common allele in our population. The genotype distribution in Japanese hypertensive patients (n=109; Asp/Asp=0.09, Asp/Tyr=0.39, Tyr/Tyr=0.52) was not significantly different (chi2=0.7, df=2, P>.6) from that in normotensive control subjects (n=148; Asp/Asp=0.12, Asp/Tyr=0.36, Tyr/Tyr=0.52). Among subjects with different PP1 G subunit genotypes, there was no difference in blood pressure, serum cholesterol, plasma glucose and insulin levels, and glucose disposal rate estimated by the euglycemic hyperinsulinemic clamp test. These data indicate that the Asp905Tyr polymorphism of the PP1 G subunit is not associated with essential hypertension, nor with insulin resistance and/or hyperinsulinemia in Japanese patients with essential hypertension, suggesting that the polymorphism plays little if any role in susceptibility to insulin resistance or hypertension.
OBJECTIVE: To clarify the effects of glycemic control on the level of 3-deoxyglucosone (3-DG), a reactive dicarbonyl compound, in plasma from diabetic patients. RESEARCH DESIGN AND METHODS: Fasting plasma samples were collected from 15 healthy volunteers and 27 patients with NIDDM. Samples were collected from six poorly controlled patients before and after improved glycemic control for at least 2 months. Plasma 3-DG was determined by high-performance liquid chromatography (HPLC) as a 2,3-diaminonaphthalene derivative. We observed the relationship of 3-DG levels with plasma glucose or HbA1c levels and examined changes in 3-DG levels after glycemic control in the six patients. RESULTS: Plasma 3-DG was significantly more increased in diabetic patients than in nondiabetic control subjects (31.8 +/- 11.3 vs. 12.8 +/- 5.2 ng/ml, means +/- SD, P < 0.001), but there was an approximately threefold difference in 3-DG levels among diabetic patients. 3-DG levels were well correlated with plasma glucose (r = 0.56, P < 0.005) and HbA1c levels (r = 0.74, P < 0.001) in diabetic patients. The improvement of hyperglycemia in six patients resulted in a significant decrease in 3-DG (35.2 +/- 13.2 vs. 21.3 +/- 3.4 ng/ml, P < 0.05). CONCLUSIONS: The results indicate that the plasma glucose level is a predominant determinant of the plasma 3-DG level in diabetic patients and good glycemic control would be important to reduce this reactive metabolite.
A 6-day-old female presented with vomiting and an abdominal mass. At laparotomy, a pyloroduodenal duplication cyst was enucleated from the pyloric region. Of the diagnostic studies performed, IV cholangiography with spiral computed tomography and an upper gastrointestinal barium study were useful in the preoperative differential diagnosis.