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Biomedical subjects

T Kawamura

Publications and source records attributed to T Kawamura.

At least 73 records · Page 4Linked to original sources
PubMed2001

Characteristics of recurrent hepatocellular carcinoma in Japan and our surgical experience.

A nationwide survey conducted by the Liver Cancer Study Group of Japan showed that approximately 85%-90% of recurrences of hepatocellular carcinoma (HCC) were in the remnant liver, and that the location of the intrahepatic recurrence was widely distributed throughout the entire liver, with 30%-40% of the recurrences on the side opposite the primary tumor, beyond Cantlie's line. In our experience, about 70% of the recurrences were seen within 2 years after surgery, and the survival rate tended to be lower as the period from the primary surgery to the recurrence was shorter. To achieve longer survival in patients with HCC, one of the most important issues is, therefore, how to prevent and control intrahepatic recurrence after surgery. Although, according to the nationwide survey, repeat hepatectomy has been performed in only 1.6% of all patients with intrahepatic recurrence, we have experienced 28 patients with repeat hepatic resection. The 1-, 3-, and 5-year survival rates from the time of re-resection were 93%, 59%, and 47%, respectively, and survival rates from the time of the initial surgery were 85% at 3 years, 62% at 5 years, and 53% at 8 years. In particular, in patients with a second primary cancer from multicentric carcinogenesis, the 5-year survival rate after the re-resection was approximately 80%. These results suggested that repeat hepatectomy should be recommended for selected patients.

Adult↗
PubMed2001

Peptide-specific cytotoxicity of T lymphocytes against glutamic acid decarboxylase and insulin in type 1 diabetes mellitus.

Cytotoxic T lymphocytes (CTL) against pancreatic beta-cells probably play a major role in the etiology of type 1 diabetes mellitus (DM). CTLs recognize a complex formed between MHC class I and antigenic peptides fragments derived from intracellular processing of proteins. However, the exogenous peptides, which show strong affinities to MHC class I, can be presented. In this study, we focused on the cytotoxic activity of peripheral lymphocytes in patients with type 1 DM against the peptides of glutamic acid decarboxylase (GAD) and insulin, which can bind MHC class 1 A24. Lymphocytes were isolated from peripheral blood of 12 type 1 DM patients and eight healthy control subjects. The effector cells were cultured with peptides, IL-2 and IL-7, restimulated weekly by autologous antigen presenting cells, which were cultured with IL-4 and GM-CSF. On day 21, CTL activities of cultured effector cells were tested against autologous EB-blast cells as target cells pulsed with the stimulating peptides using 51Cr release assay. The results showed that cytotoxicity against insulin peptide binding to MHC class I A24 was observed in lymphocytes of four out of ten patients with type 1 DM. The mean cytotoxicity was 46.0% of the maximum release. The antibody against HLA-class I inhibited this effect. Cytotoxicity against GAD peptide which bind MHC class I A24 was not observed in seven patients. None of healthy controls showed cytotoxicity against GAD or insulin peptides was observed. This is the first report describing the cytotoxic activity of CD8+ T lymphocytes against insulin in type 1 DM.

Adolescent↗
PubMed2001

Beta(3)-adrenergic receptor gene variant is associated with upper body obesity only in obese Japanese-American men but not in women.

We investigated gender differences in the relationships between the Trp64Arg variant of the beta(3)-adrenergic receptor (AR) gene in obesity and insulin resistance in nondiabetic subjects. In 476 nondiabetic Japanese-Americans (M/F=204/272), the Trp64Arg variant of the beta(3)-AR gene was examined. The presence or absence of the Trp64Arg mutation was examined in DNA separated from leukocytes in peripheral blood using the PCR-RFLP method. The frequency of abnormal allele of the beta(3)-AR gene was 0.18 for males and 0.17 for females, almost the same as the reported values in Japanese. There was no difference in the frequency of the beta(3)-AR gene variant between obese and non obese subjects for each gender. However, among obese males (body mass index > or =24.2 kg/m(2)), with the beta(3)-AR gene mutation, the waist-to-hip ratio, fasting insulin, 2-h insulin, total insulin, and HOMA, an index of insulin resistance, were all significantly higher than obese males without the mutation. In females, the index of obesity, insulin resistance, or lipid metabolism did not differ significantly between the subjects with or without the beta(3)-AR gene variant either in the obese and non-obese group. We suggest that the beta(3)-AR gene variant is not important as an obesity-inducing factor in Japanese. However, in males, when obesity becomes obvious, the beta(3)-AR gene variant is considered to influence the enhancement of insulin resistance, in association with visceral obesity.

Aged↗
PubMed2001

cDNA of a novel mRNA expressed predominantly in mouse kidney.

We examined embryonic carcinoma (EC) cells for a potential prototype molecule of C3, the third component of complement. PCR primers, corresponding to the base sequence derived from the C3 cDNA of several species, were used for PCR amplification of the EC cell cDNA. All the PCR products obtained had the same sequence and showed no sequence homology to C3. Subsequently, cDNA clones were isolated from a mouse liver cDNA library using the PCR product as a probe. Unexpectedly, neither the base sequence of the cDNA clones nor the amino acid sequence deduced from the cDNA showed homology to C3, although partial homology was observed to a number of sequences from EST databases. We designated this new clone NCU-G1. Northern hybridization experiments revealed that NCU-G1 is expressed constitutively not only in the mouse fetus but also in various mouse tissues, and is most abundant in the kidney cortex.

Amino Acid Sequence↗
PubMed2001

Molecular characterisation of glutamate dehydrogenase gene defects in Japanese patients with congenital hyperinsulinism/hyperammonaemia.

Congenital hyperinsulinism and hyperammonaemia (CHH) is caused by dysregulation of glutamate dehydrogenase (GDH). We characterised the GDH gene in two Japanese patients with CHH. Patient 1 showed late-onset and mild hypoglycaemic episodes and mild hyperammonaemia, compared with patient 2. In GDH activity of lymphoblasts, patient 1 showed twofold higher basal GDH activity than control subjects and mild insensitivity for GTP inhibition. Patient 2 showed severe insensitivity for GTP inhibition, and similar allosteric stimulation by ADP in the controls. Genetic studies identified heterozygous and de novo L413V and G446D mutations in patients 1 and 2, respectively. COS cell expression study confirmed that both mutations were disease-causing gene. The insensitivity for GTP inhibition in L413V and G446D was emphasised in COS cell expression system as a result of the dosage effect of mutant GDH gene. L413V showed less impairment of GDH than G446D based on biochemical and genetic results, which was consistent with the clinical phenotype. Based on the structure of bovine GDH, G446D was located in GTP binding site of pivot helix and its surroundings, while L413V was located in alpha-helix of antenna-like structure. These different locations of mutations gave different effects on GDH enzyme. The antenna-like structure plays an important role in GDH activity.

Animals↗
PubMed2001

Smoking and drinking habits as risk factors for hearing loss in the elderly: epidemiological study of subjects undergoing routine health checks in Aichi, Japan.

In order to determine the risk factors for hearing loss in the elderly, a total of 496 subjects with bilateral hearing loss and 2807 age-matched persons without hearing disturbance were recruited from the participants in an automated multiphasic health screening examination, and their lifestyle and medical data were analysed. Current smokers showed a significantly increased risk of hearing loss compared with non-smokers (odds ratio after adjustment for sex, age, and potential confounders=2.10 (1.53-2.89)), while heavy drinkers did not show an increased risk compared to non-drinkers. Our findings might provide some clues for the primary prevention of age-related hearing loss.

Aged↗
PubMed2001

Intensive generation of NK1.1- extrathymic T cells in the liver by injection of bone marrow cells isolated from mice with a mutation of polymorphic major histocompatibility complex antigens.

Whether intermediate TCR (TCRint) cells and natural killer T (NKT or NK1.1+TCRint) cells are extrathymically generated remains controversial. This arises from the fact that there are few of these T cells in athymic nude mice and neonatally thymectomized mice. However, when athymic mice were provided with appropriate microenvironments or stimulation, many TCRint cells (mainly NK1.1-) were found to arise in the liver. NKT cells are known to be positively selected by monomorphic major histocompatibility complex (MHC) -like antigens (e.g. CD1d). This is true even if they are CD4+. In other words, a MHC class I-like antigen is restricted to CD4 antigen. This rule is somewhat different from that seen in conventional T cells (i.e. the restriction of class II with CD4 and that of class I and CD8). In the case of NK1.1-TCRint cells, they were selected by polymorphic MHC antigens, but their MHC restriction to CD4 or CD8 antigen was incomplete. This was revealed by experiments of bone marrow transfer with class I (bm 1) or II (bm 12) disparity. Depending on the disparity, a unique cytokine profile in sera was detected. These results suggest that the development of T lineage lymphocytes and MHC restriction to CD4 and CD8 might have occurred in parallell as a phylogenic event, and that NK1.1- extrathymic T cells (i.e. NK1.1-TCRint) are at an intermediate position between NKT cells and conventional T cells in phylogeny.

Aging↗
PubMed2001

Size of the population of CD4+ natural killer T cells in the liver is maintained without supply by the thymus during adult life.

Given that there are few natural killer T (NKT) cells in the liver of athymic nude mice and in neonatally thymectomized mice, it is still controversial whether all NKT cells existing in the liver are supplied by the thymus or if some such cells develop in the liver. To determine whether or not NKT cells are consistently supplied from the thymus during adult life, thymectomy was conducted in mice at the age of 8 weeks. Interestingly, the proportion and number of CD4+ NKT cells increased or remained unchanged in the liver after adult thymectomy and this phenomenon continued for up to 6 months after thymectomy. The administration of alpha-galactosylceramide induced severe cytopenia (due to apoptosis) of CD4+ NKT cells in the liver on day 1, but subsequent expansion of these NKT cells occurred in thymectomized mice similar to the case in normal mice. However, in thymectomized mice given lethal irradiation (9.5 Gy) and subsequent bone marrow transfer, the population of CD4+ NKT cells no longer expanded in the liver, although that of CD8+ NKT cells did. These results suggest that thymic CD4+ NKT cells, or their progenitors, may migrate to the liver at a neonatal stage but are not supplied from the thymus in the adult stage under usual conditions. CD8+ NKT cells can be generated in the liver.

Animals↗
PubMed2001

Ganglioside as an endogenous growth suppressor for glomerular mesangial cells.

BACKGROUND: Glomerular mesangial cells potentially secrete many growth-modulating substances that could regulate mesangial cell proliferation. To date, however, the properties of such factors have not been fully evaluated. METHODS: For that purpose, conditioned medium (CM) from mesangial cells was used for cross-feeding experiments. Cell proliferation was evaluated by 3H-thymidine incorporation assay and direct cell counting. The growth-regulatory molecule was further characterized using biochemical techniques. RESULTS: Cross-feeding this CM to mesangial cells in vitro, despite stimulation with platelet-derived growth factor (PDGF), effectively suppressed the cells' synthesis of DNA in a dose-dependent manner. The inhibitory substance derived from mesangial cells was less than 3 kD in molecular mass, was heat stable, and was insensitive to proteinase K. After neuraminidase digestion, this inhibitory activity was lost. These data indicated that the inhibiting substance bore the typical features of gangliosides, which are multifunctional glycolipids that reside in cell membrane. Gangliosides were abundant in the CM from mesangial cells, as detected by metabolic radiolabeling and thin-layer chromatography (TLC). This result suggested that mesangial cells constitutively shed gangliosides. The growth suppressive activity in the CM was blunted when mesangial cells were pretreated with the ganglioside synthesis inhibitor d-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol-HCl (d-threo-PDMP; 20 micromol/L) in accordance with the decreased ganglioside content in cells. Finally, gangliosides isolated from CM of mesangial cells suppressed PDGF-induced DNA synthesis of mesangial cells. CONCLUSIONS: These results suggest that mesangial cells constitutively shed gangliosides that then suppress the division of these cells in an autocrine-like manner.

Animals↗
PubMed2001

Corpora amylacea replace the hippocampal pyramidal cell layer in a patient with temporal lobe epilepsy.

A 39-year-old woman, with a 23-year history of medically intractable seizures of the complex partial type, underwent a left anterior temporal lobectomy and hippocampectomy. Histologic examinations revealed a massive occurrence of corpora amylacea, neuronal loss, and gliosis in the pyramidal cell layer of the hippocampus. The distribution of corpora amylacea in this case was quite distinctive and unlike the patterns of "nonspecific" corpora amylacea formation seen in aging or other neurodegenerative conditions. The pathogenetic aspects of the accumulation of these peculiar bodies are discussed in relation to hippocampal sclerosis.

Adult↗
PubMed2001

Gln27Glu variant of the beta2-adrenergic receptor gene is not associated with obesity and diabetes in Japanese-Americans.

The beta(3)-adrenergic receptor (AR) gene variant (Trp64Arg) has been reported to be associated with obesity and insulin resistance in humans. However, this association remains controversial. We investigated the relationships between the beta(2)-AR gene variant (Gln27Glu) and obesity, insulin resistance, and serum lipids in Japanese-Americans. The frequency of an abnormal Gln27Glu allele in the beta(2)-AR gene in 652 subjects was 0.092 in males, 0.077 in females, and 0.084 overall, markedly lower than the previously reported value of 0.4 in Caucasian men and women. In both males and females, there were no differences in the indices of obesity, insulin resistance, and serum lipid levels between the subjects with and without the beta(2)-AR gene (Gln27Glu) variant in patients with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), or diabetes (DM). The frequency of the beta(2)-AR gene (Gln27Glu) variant tended to increase with worsening of glucose tolerance, but the differences were not statistically significant. Furthermore, there were no differences in the frequency of the beta(2)-AR gene variant in either males or females with obesity (body mass index [BMI], > or = 25.2). Even in Japanese-Americans, who have a more westernized life style than Japanese, the association of the beta(2)-AR gene (Gln27Glu) variant with the parameters of obesity, insulin resistance, and serum lipid level has yet to be clarified. We conclude that the beta(2)-AR gene (Gln27Glu) variant might not be an important factor for obesity or IGT in Japanese subjects.

Aged↗
PubMed2001

Resolving obstructive hydrocephalus from AVM.

Obstructive hydrocephalus with deterioration of consciousness from a ruptured arteriovenous malformation (AVM) requires urgent decompression, but also vigilance during the preoperative stage in case of rare spontaneous resolution.

Child↗
PubMed2001

Primary Ki-1 lymphoma in the central nervous system.

Large cell anaplastic malignant lymphoma with Ki-1 (CD30) antigen is a new entity among human non-Hodgkin's malignant lymphomas according Updated Kiel Classification and is also a very rare subtype in primary central nervous system (CNS) malignant lymphomas. The precise clinical characteristics and the significance of Ki-1 antigen have yet to be clarified. The authors herein report a case of Ki-1 positive primary T-cell CNS malignant lymphoma. A 49-year-old man presented with multiple mass lesions in the brain on MRI. Immunohistochemical investigations of biopsy specimens from the superior medullary velum revealed a large cell anaplastic T-cell lymphoma positive for Ki-1 antigen. After administering extensive chemo-radiotherapy, the patient has survived for more than 42 months after the onset of symptoms.

Cerebellar Neoplasms↗
PubMed2001

Japanese and Western diet and risk of idiopathic sudden deafness: a case-control study using pooled controls.

BACKGROUND: One of the proposed aetiological mechanisms for idiopathic sudden deafness is vascular disease. However, it is not known whether traditional cardiovascular risk factors, such as particular dietary factors, are associated with this condition. METHODS: A case-control study using pooled controls was conducted in Japan to investigate the relationship between idiopathic sudden deafness and diet. An m:n matched-pairs method was used to obtain age-, gender- and residential district-matched controls from a nationwide database of pooled controls. Food intake was assessed from a self-administered usual food frequency questionnaire that asked about intake of 35 foods (including four drinks). Participants were classified according to the frequency of intake of Western foods and the frequency of intake of traditional Japanese foods. Subgroup analyses were performed using audiometric subtypes of idiopathic sudden deafness. RESULTS: Data were obtained for 164 cases and 20,313 controls. An increased risk of sudden deafness was observed among participants who frequently consumed Western foods (OR = 1.82, 95% CI : 1.14--2.89), and a decreased risk of this condition was observed among participants who frequently consumed Japanese foods (OR = 0.52, 95% CI : 0.33--0.82). A direct association of sudden deafness with Western food intake was evident for flat-type hearing loss. CONCLUSIONS: This study suggests that a largely Western diet might be a risk factor for idiopathic sudden deafness, a traditional Japanese diet might be a preventive factor for this condition, or both. These findings are consistent with the hypothesis that vascular factors are an important cause of idiopathic sudden deafness, although the possibility of residual confounding by unmeasured confounders such as socioeconomic status cannot be ruled out.

Audiometry↗
PubMed2001

Pulmonary intravascular lymphoma complicated with Pneumocystis carinii pneumonia: a case report.

We report a case of intravascular lymphoma (IVL) complicated with Pneumocystis carinii pneumonia (PCP). A 65-year-old male complaining of dyspnea and dementia was diagnosed to have pulmonary IVL by transbronchial lung biopsy. Concomitantly, deoxyribonucleic acid sequence specific to Pneumocystis carinii was detected in bronchoalveolar lavage fluid by polymerase chain reaction. Differential responses to the sequential treatments for PCP and IVL implied that increased serum lactate dehydrogenase (LDH) was due to PCP, whereas hypoxemia and dementia were due to IVL. Although pulmonary IVL and PCP share many clinical presentations, exact diagnosis is essential for their successful treatment.

Aged↗
PubMed2001

Association of vitamin D receptor gene polymorphism with periodontal diseases in Japanese and Chinese.

We examined whether polymorphisms in the vitamin D receptor (VDR) gene are associated with the incidence of adult periodontitis (AP) and early-onset periodontitis (EOP) in case-controlled studies of Japanese and Chinese subjects. Restriction fragment length polymorphisms in the VDR gene detected by digestion with Taq I were found to be significantly associated with the occurrence of AP or EOP, suggesting that the VDR genotype a risk factor for periodontitis.

Adult↗
PubMed2001

Renal protective effects of chronic exercise and antihypertensive therapy in hypertensive rats with chronic renal failure.

OBJECTIVES: Patients with chronic renal failure are restricted to mild physical activity and tend to a lack of exercise. However, there have been few reports regarding the influence of chronic exercise on the progression of renal disease. Similarly, there are few animal models concerned with the effect of exercise training on improving renal function. Therefore, we assessed the renal effects of moderate chronic treadmill exercise in a remnant kidney model of spontaneously hypertensive rats (SHR) with chronic renal failure. We also assessed the effects of exercise and antihypertensive therapy on renal function. DESIGN AND METHODS: Eight-week-old SHR were subjected to 5/6 nephrectomy by removal of the left kidney and excision of two-thirds of the right kidney. The rats were divided into four groups: (i) no exercise (Non-EX); (ii) moderate exercise with treadmill running (20 m/min, 0 grade incline for 60 min) (EX); (iii) EX with an angiotensin converting enzyme (ACE) inhibitor, enalapril (2 mg/kg per day, i.p.); and (iv) EX with an angiotensin receptor antagonist, losartan (5 mg/kg per day, i.p.), for 4 weeks. RESULTS: Chronic EX significantly attenuated the increase in proteinuria (P < 0.01) and significantly protected against increases in the index of glomerular sclerosis (IGS). Both enalapril and losartan with EX significantly decreased blood pressure (P < 0.001), and further decreased the IGS. In the stepwise multiple regression analysis, only antihypertensive drug remained in the model as a significant predictor of IGS (P < 0.0001). In contrast, exercise, antihypertensive drug and mean systolic blood pressure (weeks 1-4) remained in the model as a significant predictors of mean proteinuria (weeks 1-4) (all P < 0.0001). CONCLUSIONS: These results suggest that exercise does not worsen renal function and has renal-protective effects in this model of rats. Moreover, the antihypertensive therapy has additional renal-protective effects in this model of rats.

Angiotensin Receptor Antagonists↗