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Biomedical subjects

A Kawakami

Publications and source records attributed to A Kawakami.

At least 91 records · Page 5Linked to original sources
PubMed1999

Serum levels of leptin and changes during the course of recovery from diabetic ketoacidosis.

Secretion of leptin, the obese gene product, is stimulated by insulin and glucocorticoids and reduced by fasting. In subjects with diabetic ketoacidosis (DKA), severe insulinopenia and prolonged fasting might cause a decrease in serum leptin levels, and subsequent insulin therapy would reverse the decrease. Otherwise, some other confounding factors, neither insulin nor fasting, might affect serum leptin levels in patients with DKA. The present study was undertaken to address these issues. Eleven patients with type 1 diabetes mellitus (seven males and four females, aged 44+/-6 years, mean +/- SEM), admitted to Jichi Medical School Hospital presenting DKA, were studied during the therapeutic period. Thirty-five sex-, age- and body mass index-matched healthy subjects served as controls. Serum leptin levels at the hospitalization were significantly greater than those of the matched control subjects (5.5+/-1.0 vs. 3.2+/-0.3 microg/l, P < 0.01). After the start of therapy with a small dose of short-acting insulin and a large volume of fluid infusion, serum leptin concentrations further increased to 10.6+/-3.6 microg/l at 24 h, and thereafter the concentrations gradually decreased and normalized at the discharge (3.3+/-0.7 microg/l, day 24+/-4). The peak levels at 24 h were significantly higher than the levels at the discharge (P < 0.05), and also +77+/-34% higher than those at the hospitalization (P < 0.005). Serum cortisol levels (1830+/-200 nmol/l) were markedly elevated at hospitalization. These results indicate that serum leptin levels are increased even under insulinopenia and fasting in the patients with DKA. Such a finding may be associated with marked hyperglycemia or enhanced secretion of glucocorticoid hormone, although the exact mechanisms remain to be elucidated. We speculate that leptin may serve as a stress peptide in DKA, but further analysis is necessary to explore a physiological role of leptin in DKA.

Adolescent↗
PubMed1999

Acute relapsing encephalopathy mimicking acute necrotizing encephalopathy in a 4-year-old boy.

A 4-year-old boy showed two episodes of encephalitis/encephalopathy involving disturbed consciousness, convulsion, and paresis associated with the elevated levels of protein and myelin basic protein of the cerebrospinal fluid. MRI studies of the brain revealed symmetrical lesions in the brain stem and thalami at the first episode, and additional lesions were found in the cerebellum involving both the gray and white matter in the second episode. The intensities of MRI lesions were low in T I and high in T2. These episodes were followed by an elevation of the anti-viral antibody titers, for influenza A virus during the first episode and for adenovirus during the second. In the second episode, intravenous methylprednisolone therapy resulted in rapid improvement of his neurological signs.

Brain↗
PubMed1999

Regulation of the chitinase gene expression in suspension-cultured rice cells by N-acetylchitooligosaccharides: differences in the signal transduction pathways leading to the activation of elicitor-responsive genes.

Expression patterns of chitinase transcripts induced by N-acetylchitooligosaccharide elicitor were analyzed by northern blot hybridization in order to reveal a signal transduction pathway leading to the activation of class I chitinase genes (Cht-1 and Cht-3), which may play an important role in producing N-acetylchitooligosaccharide elicitor. The transcription level of both genes was enhanced in response to N-acetylchitooligosaccharides larger than pentaose at subnanomolar concentrations. These structure and dose dependencies were consistent not only with those for a 75 kDa high-affinity binding protein for N-acetylchitooligosaccharide elicitor in the plasma membrane, but also with other series of cellular responses including phytoalexin production and the expression of elicitor-responsive genes (EL2, EL3). Therefore, the elicitor signal to evoke these cellular responses including the activation of the chitinase genes could be common and transmitted into cells through the 75 kDa protein. However, the signal transduction pathway for the activation of the chitinase gene appeared to diverge from those for the other elicitor-responsive genes shortly after the signal perception. It was shown that the induction of chitinase expression by N-acetylchitooligosaccharide would require protein phosphorylation, but not de novo protein synthesis. The oxidative burst was demonstrated not to be necessary for transcriptional induction of the all four elicitor-responsive genes (Cht, PAL, EL2, EL3) by N-acetylchitooligosaccharide.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1999

Association of CTLA-4 polymorphism with positive anti-GAD antibody in Japanese subjects with type 1 diabetes mellitus.

OBJECTIVE: CTLA-4, expressed on activated T cells, is thought to be a negative regulator of T cell function. Its gene (2q33) may confer genetic susceptibility to type 1 diabetes mellitus (IDDM12). The present study was undertaken to clarify the role of CTLA-4 gene polymorphism in Japanese subjects with type 1 diabetes and its effect on their clinical features. SUBJECTS AND METHODS: In 117 Japanese subjects with type 1 diabetes, the CTLA-4 exon 1 polymorphism (49 A/G) was defined by PCR-RFLP analysis. Anti-GAD antibodies (GAD-Ab) and fasting serum C-peptide were also determined. 141 healthy age- and sex-matched subjects served as controls. RESULTS: The frequency of each polymorphism was not different between the type 1 diabetic subjects and the controls; AA 21, AG 42 and GG 54 for the diabetic subjects, and AA 22, AG 47 and GG 72 for the controls. The frequency of the GG genotype was higher in the diabetic subjects with positive GAD-Ab (greater than 8 U/ml) (67%) than in the GAD-Ab negative subjects (39%) (P < 0.05). The prevalence of positive GAD-Ab declined with the duration of diabetes. In the diabetic subjects with disease duration of less than 5 years (n = 40), the frequency of the GG genotype was also higher in the GAD-Ab positive subjects (71%) (P < 0.05). In the analysis of all the diabetic subjects, there was a strong association between positive GAD-Ab and beta cell function (P < 0.0001). CONCLUSIONS: There was no evidence that the CTLA-4 exon 1 polymorphism (49 A/G) confers genetic susceptibility to type 1 diabetes mellitus in our case-control study in Japanese subjects. However, the frequency of positive GAD-Ab was higher in the GG subjects. CTLA-4 polymorphism might contribute to the clinical heterogeneity of type 1 diabetes mellitus in Japanese subjects.

Abatacept↗
PubMed1999

Induction of cyclooxygenase-2 in human synovial cells by beta 2-microglobulin.

BACKGROUND: Prostaglandins (PGs) are important mediators of inflammation in arthritis. We evaluated the role of the cycloxygenase-2 (COX-2) enzyme, which regulates PG biosynthesis, in osteoarthropathy associated with hemodialysis-associated amyloidosis (HAA) by characterizing COX-2 expression in beta 2-microglobulin-treated human synovial cells. METHODS: We examined the effects of beta 2-microglobulin (beta 2m), a major constituent protein of amyloid fibrils in HAA, on the COX-2 protein and mRNA expression in human synovial cells using Western blot and reverse transcriptase-polymerase chain reaction. RESULTS: beta 2m selectively increased the biosynthesis of COX-2 protein and induction of COX-2 mRNA in a dose-dependent manner. Immunoabsorption of beta 2m-containing media by anti-beta 2m-specific antibody abrogated beta 2m-mediated COX-2 expression on synovial cells. On the other hand, dexamethasone markedly suppressed the induction of COX-2 protein and mRNA in beta 2m-stimulated synovial cells. CONCLUSIONS: Our results suggest that induction of COX-2 expression by beta 2m may be an important component of the inflammatory process in hemodialysis-associated osteoarthropathy.

Blotting, Western↗
PubMed1999

High-fluence blue light stimulates transcription from a higher plant chloroplast psbA promoter expressed in a cyanobacterium, Synechococcus (sp. strain PCC7942).

High-fluence white and blue light, but not red light, enhanced transcription of the barley chloroplast psbA promoter when heterologously expressed as a lacZ transcriptional fusion in the cyanobacterium, Synechococcus sp. strain PCC7942. Analysis of Arabidopsis thaliana phytochrome mutants, phyAphyB and hy2, indicated that a distinct blue phototransduction pathway stimulates psbA expression. The evolutionary implications of these findings are discussed.

Arabidopsis↗
PubMed1999

Survey of 222Rn concentrations in the air of a tunnel located in Nagano City using the solid-state nuclear track detector method.

The survey of 222Rn concentration in the air of tunnels constructed during World War II has been performed using a solid-state nuclear track detector technique. For the practical application of this technique to the determination of 222Rn concentrations in air, some basic properties were experimentally examined on the cellulose nitrate film, Kodak LR 115 type II. The calibration coefficient of the cellulose nitrate film used is determined from a correlation between the 222Rn concentration in air and the observed number of perforated etched tracks for widespread radon concentrations. The slope of the linear relationship observed yields a calibration coefficient of (0.00209 +/- 0.00018) tracks cm(-2) (Bq m(-3) h)(-1). From the survey of 222Rn concentration in the air of tunnels, the concentration of several thousand Bq m(-3) was observed at the inner most area of the tunnel, and the seasonal variation was clearly observed. The exponential distribution of radon concentration as a function of distance from the openings of the tunnel suggests that the radon concentration in the tunnel is basically governed by diffusion and mixing of radon gas with air.

Air Pollutants, Radioactive↗
PubMed1999

HTLV-I associated Sjögren's syndrome is aetiologically distinct from anti-centromere antibodies positive Sjögren's syndrome.

OBJECTIVE: To investigate whether Sjögren's syndrome (SS) with anti-HTLV-I antibodies is aetiopathologically distinguishable from SS without these antibodies, the study compared prevalence of autoantibodies in serum samples of SS patients with or without anti-HTLV-I antibodies. METHODS: The test group included 135 patients with primary SS and 97 patients with secondary SS. Serum samples of the patients were examined for the presence of anti-nuclear antibodies (ANA), anti-SS-A/Ro antibodies, anti-SS-B/La antibodies, anti-centromere antibodies (ACA), and anti-HTLV-I antibodies. RESULTS: Anti-HTLV-I antibodies were detected in 25.0% of primary SS patients and in 29.2% of secondary SS patients. There were no significant differences in the mean age, sex, values of asparate aminotransferase, alanine aminotransferase, alkaline phosphatase, serum complements and IgG between HTLV-I seropositive and seronegative SS patients. The rheumatoid factor, ANA, anti-SS-A/Ro, and anti-SS-B/La antibodies in serum samples of SS patients were detected in 60.0%, 84.0%, 51.9%, and 12.0%, respectively. There was no significant difference in the prevalence of these antibodies between HTLV-I seropositive and seronegative SS patients. Using the indirect immunofluorescence test, 14.2% showed a discrete speckled staining pattern. All serum samples contained significant amounts of ACA determined by enzyme linked immunosorbent assay. These antibodies were detected in only 4% of HTLV-I seropositive SS patients but were present in 19.9% of HTLV-I seronegative SS patients. Furthermore, the prevalences of anti-SS-A/Ro and anti-SS-B/La antibodies in serum samples of ACA positive patients were significantly lower than those in ACA negative SS patients. CONCLUSION: These results suggest that SS patients with anti-SS-A/Ro or anti-SS-B/La antibodies, or both, might be aetiopathologically distinct from SS patients with ACA. HTLV-I might be involved in the pathogenesis of SS in a subset of patients with anti-SS-A/Ro or anti-SS-B/La antibodies, or both, but not SS patients with ACA.

Aged↗
PubMed1999

Expression of mitogen activated protein kinases in labial salivary glands of patients with Sjögren's syndrome.

OBJECTIVE: The expression of CD40 and CD40 ligand (CD40L) in mononuclear cells (MNCs) infiltrating the salivary glands of patients with Sjögren's syndrome (SS) has recently been reported. This study determined the expression of mitogen activated protein kinase (MAP kinase) superfamilies, which act as downstream effector molecules of CD40, in MNCs infiltrating labial salivary tissues in SS patients. METHODS: Six HTLV-I seronegative SS patients and 10 HTLV-I seropositive patients including five HTLV-I associated myelopathy (HAM) patients were examined. The expression of MAP kinase superfamilies in labial salivary glands was examined by immunohistochemistry containing the mirror section technique. RESULTS: Both active forms of c-Jun N-terminal kinase (JNK) and p38 were found in salivary infiltrating MNCs of SS patients. Only minimal expression of the active form of extracellular signal regulated kinase (ERK) was observed in these tissues, however, co-expression of active JNK and active p38 was confirmed by the mirror section technique. Furthermore, these protein kinases were co-expressed in CD40(+) MNCs. No difference in expression levels of active JNK and p38 was found in patients who were positive or negative for anti-HTLV-I antibody. CONCLUSION: These results indicate that JNK and p38, but not ERK, function as downstream effector molecules of CD40 in salivary infiltrating MNCs in SS patients, and suggest that these molecules may be involved in the pathological process of chronic sialadenitis in SS.

Adult↗
PubMed1999

PAX6 expression in the developing human eye.

AIMS: To investigate the changes in PAX6 expression in the developing human eye. METHODS: Six developing human eyes from 6 to 22 weeks' gestation were evaluated. Frozen sections were immunohistochemically stained with monoclonal antibody to chick Pax6 (amino acids 1-223). To verify antibody specificity, western blot analysis was carried out using cell lysates from P19 cells transfected with the human PAX6 gene. RESULTS: Western blot analysis demonstrated that the antibody reacted to human PAX6 protein. Positive immunostainings for PAX6 were seen in the surface ectoderm, lens vesicle, inner and outer layers of the optic cup, and optic stalk at 6 weeks, and in the corneal epithelia and conjunctiva, lens, and non-pigmented ciliary epithelia from 8 to 22 weeks. In the retina, positive cells were seen in the entire retina from 8 to 10 weeks, and were restricted to the ganglion cell layer and the inner and outer portions of the inner nuclear layer after 21 weeks. CONCLUSIONS: PAX6 is expressed on the surface and neuroectoderms at an early stage, then in the differentiating cells in the cornea, lens, ciliary body, and retina through development. PAX6 may play a role in determining cell fate in the morphogenesis of various human ocular tissue.

Antibody Specificity↗
PubMed1999

Immunologically-related or incidental coexistence of diabetes mellitus and Graves' disease; discrimination by anti-GAD antibody measurement.

Coexistence of diabetes mellitus and Graves' disease may be classified into either an immunologically-related or an incidental phenomenon. It has been reported that anti-GAD antibody (GAD-Ab) persists at high levels for longer duration in subjects with type 1 diabetes and Graves' disease, whereas the prevalence of positive GAD-Ab (1.5%) in 131 non-diabetic subjects with Graves' disease was comparable to that in normal subjects (0.3%, P=0.2012). Thus, GAD-Ab might be a marker of the immunologically-related coexistence of the two diseases. To test this hypothesis, we investigated characteristics of Japanese subjects having both diseases according to the presence or absence of GAD-Ab. Sixty-one patients having diabetes mellitus and Graves' disease (24 men, 37 women, aged 53+/-2 years old, mean +/- SE) were consecutively registered between 1993-1997. The patients were divided into two groups of 14 GAD-Ab positive and 47 negative subjects. In the GAD-Ab positive subjects, earlier (32+/-3 years old) and abrupt onset (86%) of diabetes and insulin dependency (64%) were documented, as would be expected from the features of type 1 diabetes. Graves' disease often preceded diabetes (57%), presenting typical manifestations (79%). In contrast, older (45+/-2 years old, P=0.0031) and gradual onset (87%, P<0.0001) of diabetes, non-insulin dependency (74%, P<0.0001), and masked manifestations of Graves' disease (57%, P=0.0214) were common in the negative subjects. Precedence of diabetes dominated in these subjects (43%, P=0.0109). Immunological studies showed less frequent HLA-DR 2 locus (0%, P<0.02) in the GAD-Ab positive subjects. There was also a trend of higher frequency of HLA-DQA1*03 allele and of lower frequency of DQA1*01 allele in these subjects. Allelic frequency of cytotoxic T lymphocyte antigen 4 (CTLA-4) differed between the positive and negative subjects (P=0.0432). There were distinct clinical and immunological differences between the GAD-Ab positive and negative subjects having both diabetes mellitus and Graves' disease. The present results indicate that GAD-Ab measurement could draw a distinction between the immunologically-related and incidental coexistence of the two diseases.

Abatacept↗
PubMed1999

Successful treatment of adult-onset Henoch-Schönlein purpura nephritis with high-dose immunoglobulins.

A 26-year-old woman was admitted for the evaluation of edema and massive proteinuria. She had a history of purpura of the lower extremities, abdominal pain and melena. Laboratory investigations showed hypoalbuminemia, hypercholesterolemia and proteinuria of over 10 g/day. Renal biopsy showed moderate proliferative glomerulonephritis with mesangial immunoglobulin A (IgA) deposition. She was diagnosed as having Henoch-Schonlein purpura nephritis. Oral prednisolone, dipyridamole and intravenous heparin treatment were not effective. Steroid pulse therapy induced a partial improvement of proteinuria to 2-3 g/day. High-dose intravenous immunoglobulin (i.v.-IG) treatment was introduced and a dramatic improvement of proteinuria was noted. I.v.-IG should be fully considered in patients with steroid-resistant Henoch-Schonlein purpura nephritis.

Adult↗
PubMed1999

Endogenous glucose production and glucose effectiveness in type 2 diabetic subjects derived from stable-labeled minimal model approach.

Insulin sensitivity, glucose effectiveness, and endogenous glucose production (EGP) during stable-labeled, frequently sampled insulin-modified intravenous glucose tolerance test (FSIGT) were evaluated by a single-and two-compartment minimal model combined with nonparametric deconvolution in eleven nonobese Japanese type 2 diabetic patients. Four patients were treated with sulfonylureas, and the remaining seven with diet therapy alone. None had diabetic retinopathy and microalbuminuria. Their fasting glucose level was 117+/-7 mg/dl (mean +/- SE), and HbA1c was 6.6+/-0.3%. Age-, sex-, and BMI-matched subjects with normal glucose tolerance served as control subjects. Plasma insulin response to the stimuli and insulin sensitivity indexes (S(I), S(I)*, and S(I)2* were derived from a minimal model and single- and two-compartment-labeled minimal models) were impaired in the type 2 diabetic patients. The combined ability of glucose, per se, to increase its own uptake and suppress EGP (glucose effectiveness [SG]), which was derived from kinetic analysis of plasma glucose by a minimal model, was significantly lower in the type 2 diabetic patients (0.0132+/-0.0015 vs. 0.0203+/-0.0022; P<0.05). However, the ability of glucose, per se, to stimulate glucose uptake, assessed as S(G)* and S(G)2* from the kinetic analysis of labeled glucose by single- and two-compartment minimal model, was not impaired in those patients. EGP of the type 2 diabetic patients as a whole was suppressed to the level similar to that of the control subjects despite a higher plasma glucose level throughout FSIGT. When EGP in the diabetic subjects was analyzed, considering their recent glycemic control, the initial suppression was blunted in the patients with higher HbA1c levels. In conclusion, glucose mass action to stimulate glucose uptake remains near-normal in the lean Japanese type 2 diabetic patients of this study, whereas ability of glucose to suppress EGP is impaired in the patients with recent hyperglycemia. This blunted suppression of EGP might be one of the conspirators for decreased S(G) in subjects with type 2 diabetes.

Adult↗
PubMed1999

Are nonproper chopstick holders clumsier than proper chopstick holders in their manual movements?

To examine the working hypothesis that a lack of childhood training in the fine-detailed finger movements illustrated by learning to use chopsticks properly as a child has later rendered such individuals clumsier in the execution of other more adult-like motor movements, four experiments were conducted. Groups of proper and nonproper users (both males and females) performed a task of picking up rice grains (Exp. 1), a pin-down task (Exp. 2), a task of unfastening nuts from bolts (Exp. 3), and a knot-tying task (Exp. 4). Only on the rice-grain transfer task and the knot-tying task, proper chopstick users showed better performance than nonproper users. On the pin-down task and the nuts-and-bolts task, no difference was found between groups. These results suggest that there is no clear evidence to support the hypothesis that a lack of early training for proper chopstick use makes such individuals more clumsy as adults in at least some motor movements.

Adult↗
PubMed1999

Expression of CD40/CD40 ligand and Bcl-2 family proteins in labial salivary glands of patients with Sjögren's syndrome.

Lymphocytes infiltrating the salivary glands of patients with Sjögren's syndrome (SS) are activated and resist apoptosis. We determined the role of interactions between CD40 and CD40 ligand (CD40L) in these infiltrating lymphocytes on B-cell differentiation and expression of Bcl-2 family proteins. Ten human T-cell leukemia/lymphoma virus-I (HTLV-I)-seronegative and eight HTLV-I-seropositive SS patients were examined in the present study. Immunohistochemistry was performed to examine the expression of CD3, CD20, PCA-1, CD40, CD40L, Bcl-2, Bax, and Bcl-x on T and B lymphocytes infiltrating labial salivary glands of SS patients. We also examined the expression of CD40 and CD40L on peripheral blood lymphocytes of the same patients by using flow cytometry. CD40L was not expressed on peripheral blood lymphocytes of SS patients. Peripheral blood B cells but not T cells expressed CD40. In contrast, >50% of mononuclear cells, including T and B cells infiltrating the glands, expressed CD40. In addition, a clear expression of CD40L in both infiltrating T cells and B cells, and that of PCA-1, was also demonstrated. Surprisingly, the expression of Bcl-2 and Bcl-x was colocalized with that of CD40 determined by mirror section technique. Bcl-x was also abundantly expressed on infiltrating mononuclear cells, but, Bax expression was relatively less than that of Bcl-2 or Bcl-x. The expression of the above molecules was not different between HTLV-I-seronegative and HTLV-I-seropositive SS patients. Our results indicate that CD40/CD40L pathways could be augmented in salivary glands of SS patients, inducing B-cell differentiation to PCA-1 + plasma cells. Immunohistochemical analysis also suggests that signaling through CD40 by means of CD40L increases the expression of Bcl-2 as well as Bcl-x in infiltrating lymphocytes, providing the resistance against apoptosis. Our findings were commonly observed in SS patients irrespective of HTLV-I seropositivity.

Aged↗