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Biomedical subjects

K Kogawa

Publications and source records attributed to K Kogawa.

At least 55 records · Page 3Linked to original sources
PubMed1997

Insulin resistance in non-obese, non-insulin-dependent diabetic patients with diabetic nephropathy.

To investigate the association between insulin resistance and diabetic nephropathy, peripheral insulin sensitivity indices (M/I values) were evaluated via euglycemic-hyperinsulinemic clamp in 45 non-obese, non-insulin-dependent diabetic (NIDDM) subjects. The patients were divided into four groups: 18 with normoalbuminuria (urinary albumin excretion rate [AER] < 30 mg/24 h, stage I), 10 with microalbuminuria (30 < or = AER < or = 300 mg/24 h, stage II), seven with overt proteinuria (AER > 300 mg/24 h, stage III), and 10 with uremia (serum creatinine levels > 2.0 mg/dL, stage IV). There were no significant differences in age, body mass index (BMI), fasting plasma glucose, or hemoglobin A1c (HbA1c) among the four groups. No significant difference in M/I values was seen between stage I and stage II (6.30 +/- 0.73 and 5.95 +/- 0.85 mg/kg/(min per microU/mL) x 100, respectively). M/I values in the stage I and stage II groups were strongly correlated with BMI (r = -.790, P = .0001 and r = -.785, P = .007, respectively). M/I values in the stage III group (4.53 +/- 0.51) were lower than in the stage I group, although not significantly so. M/I values in the stage IV group (3.16 +/- 0.37) were significantly lower than in the stage I group (P = .025). In multiple regression analysis with a model in which age, sex, BMI, HbA1c, and creatinine clearance (Ccr) were included as independent variables, BMI and Ccr were demonstrated to be significant and independent contributors to insulin sensitivity indices as the dependent variable (beta = -0.716 and beta = 0.272, respectively, R2 = .564, P < .0001). In conclusion, the present cross-sectional study demonstrated in non-obese NIDDM patients with nephropathy that microalbuminuria did not affect peripheral insulin resistance, but uremia did, as in nondiabetic patients, and that the peripheral insulin resistance was significantly contributed to by the degree of obesity and uremia.

Adult↗
PubMed1997

Long-term survival and differentiation of human peripheral blood CD34+ cells in SCID mice.

Human peripheral blood progenitor cells (PBPC) are currently used as a source of hematopoietic reconstitution by autologous transplantation after myeloabrative chemotherapy for malignancies. PBPC would also be useful for allogeneic transplantation since the collection of PBPC is much safer than that of bone marrow stem cells (BM). For allogeneic transplantation, it is imperative to confirm that PBPC contains self-renewable stem cells that can sustain a long lasting hematopoiesis. In the present study, we examined the reconstitution of human hematopoiesis in severe combined immunodeficiency (SCID) mice by transplanting peripheral blood CD34+ cells in which the neo gene was transduced as a marker. In 2 of 4 mice receiving PB-CD34+ cell transplantation, the neo gene appeared as early as 4 weeks and lasted as long as 24 weeks in all DNA preparations of bone marrow, peripheral blood and spleen cells from the SCID mice, while in 2 of 4 mice receiving BM-CD34+ cell transplantation, although the neo gene also lasted as late as 24 weeks, it did not appear as early as in the mice receiving PB-CD34+ cell transplantation. A similar observation was noted in clinical trials, i.e. the white blood cell and platelet recovered earlier by transplantation of PBPC than of BM. In mice who had the neo gene, we were also able to demonstrate by FACS the presence of human lineage specific antigen in the cells as late as 24 weeks after transplantation with PB-CD34+ cells, and the presence of human IgG in the sera 10 weeks after transplantation. These findings indicate that PB-CD34+ cells contain long-term repopulating stem cells which undergo differentiation in SCID mice.

Animals↗
PubMed1997

Intrarenal hemodynamic abnormalities in diabetic nephropathy measured by duplex Doppler sonography.

Intrarenal hemodynamics were studied by duplex Doppler sonography in 112 inpatients with type II diabetes mellitus (DM; 65 males, 47 females, 58 +/- 13 years old). The resistive index (RI) and pulsatility index (PI) of the interlobar arteries were calculated. The patients were divided into four groups: group I consisted of patients with urinary albumin excretion (UAE) < 20 micrograms/min (N = 42), group II with 20 < or = UAE < 200 (N = 28), group III with UAE > or = 200 (N = 25), and group IV with serum creatinine > or = 1.5 mg/dl (N = 17). Both RI and PI values in groups II, III, and IV were significantly higher than those in the controls (age- and sex-matched healthy persons, N = 37; P < 0.001), and those in group IV were significantly higher than those in groups I, II, and III (P < 0.0001). Multiple regression analysis revealed that RI values in DM patients were significantly affected by creatinine clearance, age, and duration of diabetes (R2 = 0.554, P < 0.0001). When intima-medial thickness (IMT) of the femoral and carotid arteries were measured by B-mode ultrasonography, RI values were significantly correlated with both the femoral and carotid arterial IMT. These results demonstrate that intrarenal hemodynamic abnormalities are present in type II DM patients with nephropathy, and that intrarenal hemodynamics are affected by decreased glomerular function and also probably by advanced arteriosclerosis.

Aged↗
PubMed1997

Transient erythrophagocytosis in Diamond-Blackfan anemia.

We report on a 4-month-old Japanese infant girl with Diamond-Blackfan anemia (DBA) as shown by congenital macrocytic pure red cell hypoplasia with marked reduction of erythroid precursors in bone marrow, reticulocytopenia, increased fetal hemoglobin, and elevated adenosine deaminase activity in peripheral blood. She responded poorly to conventional doses of corticosteroids, however, with high-dose corticosteroids she responded with reticulocytosis and an elevation of hemoglobin level above 12 g/dL. Erythrophagocytosis was noted during the tapering period of prednisone when her hemoglobin level declined to 7.6 g/dL and reticulocyte level to 0.4%. At that time, the erythrophagocytosis was noted in about 60% of marrow histiocytes. These findings were not observed prior to or during the high dose prednisone therapy. We speculate that one of the causes of pure red cell aplasia and reticulocytopenia in DBA is mediated by erythrophagocytosis.

Bone Marrow↗
PubMed1997

Effect of polymorphism of apolipoprotein E and angiotensin-converting enzyme genes on arterial wall thickness.

We examined the association between the polymorphism of the apolipoprotein E (apoE) and the ACE genes and the intima-media thickness (IMT) of the carotid and femoral arteries measured using ultrasonography. The values of IMT of each artery were significantly higher in NIDDM patients (n = 356) than in control subjects (n = 235). The E4 allele or the D allele did not affect clinical characteristics, including age, fasting plasma glucose, total cholesterol, HDL cholesterol, LDL cholesterol, or blood pressure, in NIDDM or control subjects. No difference in the carotid IMT value was noted among the apoE genotypes in control or diabetic subjects. The carotid IMT was significantly higher in diabetic patients with the DD genotype (1.200 +/- 0.586 mm) than in those with the II genotypes (0.990 +/- 0.364 mm). Neither the E4 allele nor the D allele affected the femoral IMT in control or diabetic subjects. Multiple regression analysis demonstrated that the carotid IMT of NIDDM patients was associated with age, the D allele, and LDL cholesterol but not with the E4 allele, whereas that of control subjects was associated with age, sex, systolic blood pressure, LDL cholesterol, and HDL cholesterol, inversely. These results suggested that the E4 allele was not associated with the carotid or femoral IMTs, but that the D allele was statistically associated with carotid IMT in NIDDM patients but not control subjects. However, since the association was weak (2.3% explanatory power), its biological significance remains to be determined.

Adolescent↗
PubMed1996

Angiotensin-converting enzyme gene polymorphism is associated with carotid arterial wall thickness in non-insulin-dependent diabetic patients.

BACKGROUND: The insertion/deletion (I/D) polymorphism of the ACE gene has been shown to be associated with cardiovascular disease in healthy subjects as well as in patients with non-insulin-dependent diabetes mellitus (NIDDM). We investigated the relationship between the ACE gene polymorphism and the wall thickness of both carotid and femoral arteries in NIDDM patients. METHODS AND RESULTS: We measured the intimal plus medial thickness (IMT) of both carotid and femoral arteries using high-resolution B-mode ultrasonography in 288 Japanese NIDDM patients (160 men, 128 women). No significant differences among the three genotypes were found with respect to age, sex, duration of diabetes, body mass index, blood pressure, plasma glucose, hemoglobin AIC, total cholesterol, triglycerides, HDL cholesterol, or cigarette-years. Plasma ACE levels were strongly associated with I/D polymorphism, with an additive effect of the D alleles. The carotid IMT of the patients carrying the D allele (DD+ID genotype) was significantly higher than that of the patients not carrying the D allele (II genotype) (P = .037), whereas the femoral IMT was not affected by the I/D polymorphism. Multiple regression analysis demonstrated that the risk factors for carotid IMT of patients with NIDDM were age, non-HDL cholesterol, and D allele of the ACE gene (R2 = .155, P < .0001). CONCLUSIONS: The D allele of the ACE gene may be a risk factor for the development of wall thickening of the carotid but not the femoral artery in NIDDM patients.

Adolescent↗
PubMed1996

The epidemiology of human calicivirus/Sapporo/82/Japan.

Based on genome analysis of the RNA-dependent RNA polymerase region, it has been proposed that human caliciviruses (HuCV) can be classified into at least three genogroups: genogroup I is represented by Norwalk virus (NV), genogroup II by Snow Mountain agent (SMA) and genogroup III by HuCV/Sapporo/82/Japan (HuCV/Sa/82/J) virus. HuCV/Sa/82/J strain is genetically unique and more closely related to animal caliciviruses than are other known HuCVs, such as NV and SMA. HuCV/Sa/82/J strain was detected in four outbreaks of HuCV gastroenteritis occurring between 1977 and 1982 in an infant home in Sapporo. The HuCVs detected from these four outbreaks all showed a typical "Star of David" configuration by electron microscopy (EM), and they were identical antigenically and genetically. This strain has also been detected in other prefectures in Japan, as well as in the USA, UK, Saudi Arabia and Kenya. Seroepidemiological studies have shown a worldwide distribution of this virus, including Japan, USA, UK, Southeast Asia, Canada, China and Kenya. This virus has been circulating in Sapporo for at least 19 years (1977-1995). HuCV/Sa/82/J strain is thought to be one of the common causes of viral gastroenteritis worldwide. The HuCV/Sa/82/J strain has been detected mainly in infants. Age-related prevalence of antibody to this strain also shows that infections commonly occur in children less than 5 years old, although viruses in the NV and SMA genogroups commonly infect adults. The pattern of acquisition of antibodies to strain HuCV/Sa/82/J is similar to that of other common viral infections. HuCV/Sa/82/J strain is unique virologically and clinically among caliciviruses.

Age Factors↗
PubMed1996

Establishment of high- and low-invasion clones derived for a human tongue squamous-cell carcinoma cell line SAS.

Distant-organ metastasis and regional lymph node metastasis are still the major cause of mortality of oral-cavity squamous-cell cancer (SCC). However, only a few studies have been undertaken to elucidate the mechanism of invasion and metastasis of oral SCC. In this study, we attempted to establish human oral SCC clones with different invasiveness, defined by endothelial cell monolayer assay, which can be used for the study of invasion and metastasis of oral SCC. We established five clones from the human oral SCC cell line SAS by a limiting-dilution method. Two distinct clones, SAS-L1 with very low invasive potential and SAS-H1 with very high invasive potential, were picked out by rat lung endothelial cell monolayer assay. The number of SAS-H1 that penetrated the rat lung endothelial cell monolayer was six fold higher than the number of SAS-L1. There were no differences of metalloproteinase production and cell adhesiveness to Matrigel of SAS-L1 and SAS-H1. However, SAS-H1 exhibited a higher migration ability than SAS-L1. This pair of clones would be a useful experimental model to help in the study of the invasiveness of human oral SCC.

Basement Membrane↗
PubMed1996

Dot blot hybridization with a cDNA probe derived from the human calicivirus Sapporo 1982 strain.

A dot blot hybridization assay was developed for detection of human calicivirus/Sapporo/82/J (HuCV/Sa/82) or strains closely related to HuCV/Sa/82 in stool specimens. The cDNA derived from the RNA-dependent RNA polymerase (RDRP) region of HuCV/Sa/82 was used as a positive probe and the pBR322 DNA as a negative control probe. Both probes were labeled with digoxigenin and the products of hybridization reaction were detected with an anti-digoxigenin antibody-alkaline phosphatase conjugate. This assay was specific for HuCV/Sa/82 and for HuCV antigenically related to HuCV/Sa/82. The lower limit of sensitivity of this assay was estimated to be about 10(5) physical particles or 10 pg of cDNA, similar to that of the previously developed ELISA for HuCV. In 1273 stool specimens obtained from children with acute gastroenteritis in Sapporo, Japan, 110 (8.6%) contained small round structured viruses by EM and 23 (1.8%) were positive for HuCV antigenically related to HuCV/Sa/82 by either the hybridization assay or ELISA. A higher positive rate was obtained with the dot blot assay (21%) than by ELISA (10%), suggesting that the dot blot assay either detects HuCV more broadly than the ELISA or detects HuCV covered with fecal antibodies which interrupt antigen-antibody reactions in the ELISA. Negative results for detection of Norwalk virus (NV) cDNA and feline calicivirus (FCV) RNA by both this assay and the ELISA indicated that the HuCV/Sa/82 strain is distinct antigenically and genetically from NV and FCV.

Acute Disease↗
PubMed1996

Outbreaks of nosocomial rotavirus gastro-enteritis in a paediatric ward.

UNLABELLED: Faecal samples were collected from patients with gastro-enteritis during two winter seasons on a paediatric ward. Three outbreaks of nosocomial rotavirus gastro-enteritis were identified by latex agglutination and the virus strains were characterized by polyacrylamide gel electrophoresis of the genome nucleic acid and by subgrouping and serotyping enzyme-linked immunosorbent assays (ELISA). One outbreak was caused by serotype 1 rotavirus, one by serotype 2 and the remaining outbreak was caused by a mixture of serotypes 1 and 4. Identical electrophoretic patterns of the rotavirus genome in each outbreak combined with the ELISA results indicate that these three outbreaks were hospital-acquired cases. The index cases in the three outbreaks were community-acquired and one of two index cases in the second outbreak was hospital-acquired. On each occasion, susceptible roommates were easily infected from the index cases and then cross-infection occurred in the paediatric ward. Possible vehicles were the medical staff, especially doctors, parents of infected patients and infected patients who were moved to other rooms. One patient who had been treated with a series of antitumour therapies excreted rotaviruses in faeces for a long time period and probably played a role as a source of the outbreak. Moreover, some patients still excreted rotaviruses in their normal stool 1 week after recovery from gastro-enteritis. These findings indicate that continual examination of stool samples for rotaviruses until they are negative may be important to prevent the spread of rotavirus infection. CONCLUSION: Nucleic acid analysis and serotyping ELISA are useful tools for analyzing nosocomial rotavirus gastro-enteritis and important to prevent the spread of rotavirus infection in institutions.

Child↗
PubMed1996

The fumagillin analogue TNP-470 inhibits DNA synthesis of vascular smooth muscle cells stimulated by platelet-derived growth factor and insulin-like growth factor-I. Possible involvement of cyclin-dependent kinase 2.

The effect of an angiogenesis inhibitor, TNP-470, on DNA synthesis and its underlying signaling cascades stimulated by platelet-derived growth factor (PDGF)-BB and insulin-like growth factor (IGF)-I were examined in bovine vascular smooth muscle cells (SMCs). PDGF-BB (10 ng/mL)- and IGF-I (100 ng/mL)-stimulated increase in DNA synthesis was completely abolished by simultaneous treatment with TNP-470 (1.0 ng/mL). TNP-470 had no effects on PDGF receptor autophosphorylation or early signal transduction, such as activation of mitogen-activated protein kinase and immediate early gene expression. PDGF-BB induced an increase in mRNA levels of cyclin D1, cyclin-dependent kinase (cdk) 4, and cdk2, as well as the activity of cdk2, which preceded the G1/S boundary, as estimated by the kinetics of DNA synthesis. The PDGF-BB-induced activation of cdk2 was inhibited by TNP-470, which was correlated with decreased cdk2 mRNA levels. In contrast, TNP-470 had no or less marked effect on cyclin D1 and cdk4 mRNA levels induced by PDGF-BB. TNP-470 also inhibited a much smaller increase in cdk2 mRNA levels and activation stimulated by IGF-I. In conclusion, TNP-470 potently inhibits DNA synthesis of SMCs, and this inhibition is associated with decreased levels of cdk2 mRNA and activity.

Animals↗
PubMed1995

Superoxide dismutase in SAS human tongue carcinoma cell line is a factor defining invasiveness and cell motility.

This article describes an apparent inverse relationship between cell motility and intracellular Cu-Zn superoxide dismutase (SOD) activity of two human squamous carcinoma-derived clones, SAS-H1 with high invasiveness and SAS-L1 with low invasiveness. Clone SAS-H1 exhibited significantly greater motility than SAS-L1 but had significantly lower levels of intracellular Cu-ZnSOD than SAS-L1 cells. We then transfected Cu-ZnSOD antisense cDNA into SAS-L1 to reduce the intracellular Cu-ZnSOD activity. Antisense cDNA transfected SAS-L-AS clones had lower Cu-ZnSOD activity than control vector-transfected SAS-L-Neo clones, and this was associated with increased motility. Invasiveness of SAS-H1 and SAS-L-AS1 was enhanced by superoxide treatment, while the invasiveness of SAS-L1 was unaffected. These findings indicate that intracellular SOD is involved in cell motility by virtue of its action in scavenging superoxide in the cells.

Base Sequence↗
PubMed1995

T-cell mediated polyclonal B-cell activation in a case of B-cell lymphoma associated with polyclonal hypergammaglobulinemia.

The mechanism of abnormal immunoglobulin production in non-Hodgkin's lymphoma is still poorly understood. We report a case of B-cell type non-Hodgkin's lymphoma associated with marked elevated polyclonal hyper-gammaglobulinemia (serum IgG was 7598 mg/dl; IgM, 455 mg/dl). We conducted a mixed lymphocyte culture test using peripheral lymphocytes obtained from the patient and a healthy volunteer. After co-culture with the patient's CD3+ cells, not only the patient's CD3- cells but also control CD3- cells produced greater amounts of IgG and IgM. Elevated IL-6 was also detected from the patient's CD3+ cells. This strongly suggests that B-lymphoma cells stimulate CD3+ cells to produce IL-6 and hence activate normal CD3- cells.

B-Lymphocytes↗
PubMed1995

Histopathological evaluation of gastric mucosal environments in peptic ulcer using the endoscopic 5-point gastric biopsy method.

Although a strong association has been established between chronic Helicobacter pylori infection and peptic ulcers, the role of H. pylori is not necessarily causative because there are many patients infected with H. pylori who do not develop peptic ulcer. Therefore, we studied the relationship between the gastric mucosal environment and the development of peptic ulcers. We examined 165 endoscopic biopsy specimens from the gastric mucosa of 33 patients with peptic ulcers using the 5-point gastric biopsy method. The follow-up biopsies done within 3 weeks were well correlated with the first biopsy samples. We also reviewed the clinicohistopathological findings of 2250 endoscopic biopsy specimens from 450 patients with active gastric and/or duodenal ulcers. Over 90% of the patients with duodenal ulcer, with or without gastric ulcer, had no fundic gland atrophy, and a high incidence of intestinal metaplasia and pyloric mucosal atrophy was found in the patients with gastric ulcer. These findings suggest that patients with concomitant active gastric and duodenal ulcers exhibit severe atrophic changes in the antral mucosa but not in the fundic mucosa.

Adult↗
PubMed1994

Suppressive effect of recombinant human Cu, Zn-superoxide dismutase on lung metastasis of murine tumor cells.

The inhibitory effect of recombinant human Cu++Zn++superoxide dismutase (rhSOD) on metastasis of tumor cells in the mouse was investigated. In an experimental pulmonary metastasis model employing Meth A cells as inoculum, significant inhibition of metastasis was obtained by intravenous pre- and post-administration of rhSOD. An inhibitory effect of rhSOD was also observed in a spontaneous pulmonary metastasis model with 3LL cells as the inoculum. rhSOD was not observed to have any significant effects on the platelet-aggregating activity of tumor cells, the adhesiveness of tumor cells to vascular components (endothelial cells, laminin and type-IV collagen), or the growth of tumor cells either in vitro or in vivo. However, rhSOD suppressed invasion of Meth A and 3LL cells into Matrigel (an artificially reconstituted basement membrane of collagen, laminin and heparan sulfate) in the presence of hypoxanthine and xanthine oxidase, in vitro producers of superoxide. Thus, the present study shows that rhSOD is able to inhibit both experimental and spontaneous pulmonary metastasis, possibly through the suppression of tumor cell invasion into the extracellular matrix.

Animals↗
PubMed1994

Efficacy of rhesus rotavirus vaccine MMU-18006 against gastroenteritis due to serotype 1 rotavirus.

We conducted a clinical trial of rhesus rotavirus vaccine MMU-18006 (RRV, serotype 3) to assess the immunogenicity, transmissibility and booster effect of this vaccine in a welfare nursery in Sapporo, from September 1986 to October 1988. After the trial, in March 1989, an outbreak of gastroenteritis due to a wild strain of serotype 1 rotavirus (RV-1) occurred in the study population. Infants were divided into three groups based on vaccination history: five booster vaccinees, 18 one-dose vaccinees and 18 control infants who did not receive vaccine. There was a significant relationship between asymptomatic infection and higher levels of preoutbreak antibody titres against KU (serotype 1) but not RRV. Significant protection from rotavirus illness was observed both in the booster vaccine group and in the one-dose vaccine group but not in the control group. Rotavirus-specific serum IgA immune response was considered to be one of the indicators of recent rotavirus infection, and did not correlate with resistance to rotavirus illness. Our results revealed that protection from rotavirus illness was serotype-specific and that previous rotavirus infection, including vaccination, was important to induce the heterotypic immune response, and that ageing or booster inoculation of RRV might play a role in the protection against serotype 1 rotavirus infection. From our findings, a booster administration was thought to be important to induce effective heterotypic immunity and should be included in a future rotavirus vaccine trial to obtain sufficient protection against four major serotypes of rotavirus.

Antibodies, Viral↗
PubMed1994

Bone marrow transplantation for erythroleukemia: a case report.

A 2 year old girl was diagnosed as having erythroleukemia (EL; M6 according to the French-American-British classification). After one course of low-dose cytosine arabinoside (Ara-C), complete remission was obtained. After three courses of low-dose Ara-C for consolidation, allogeneic bone marrow transplantation was performed from HLA-identical sibling. The course of post-transplantation was uneventful. Two years after transplantation, she continues to have durable engraftment and remission. In children with EL, conventional chemotherapy appears to be inadequate for producing durable long-term disease-free survival. Bone marrow transplantation should be considered in children with EL, in cases where suitable donors are available.

Bone Marrow Transplantation↗