Search PubMed⌕ Search

Biomedical subjects

I Kobayashi

Publications and source records attributed to I Kobayashi.

At least 145 records · Page 8Linked to original sources

Simultaneous analysis of serum immunoglobulins in patients with M protein using cellulose acetate membrane isoelectric focusing.

We developed a method for the simultaneous analysis of microheterogeneity of human serum IgG, IgA, IgM, IgD, and IgE, and serum protein pattern using cellulose acetate membrane isoelectric focusing, and analyzed in 11 healthy subjects and 67 patients with M protein (17 cases of multiple myeloma [MM] and 50 cases of monoclonal gammopathy of undetermined significance [MGUS]). Using this method, bands indicating the microheterogeneity of each immunoglobulin could clearly be detected.Among healthy subjects, the detected IgG, IgA, and IgM bands did not vary, but the detected IgE and IgD bands did vary. Therefore, IgA, IgM, and IgG were selected for comparison of serum immunoglobulins in MM and in MGUS. In the IgA-type M protein group, normal IgM and IgG bands were decreased in MM patients compared to MGUS patients, while the M band and other bands were increased in MM patients compared to MGUS patients, but the differences between the two groups were not significant. In the IgG-type M protein group, normal IgM, IgA, and IgG were significantly decreased in MM patients compared to MGUS patients. We examined the changes in electrophoretic pattern in six MM patients and eight MGUS patients with IgA-type M protein after neuraminidase treatment. The width of the M band in MM patients with IgA-type M protein decreased with neuraminidase treatment. On the other hand, the width of the M band in MGUS patients with IgA-type M protein increased with neuraminidase treatment. We concluded that the decrease of the normal immunoglobulins in MM patients with IgG type M protein could be detected by this method, and IgA type of M protein binding sugar chain were different between MM and MGUS patients.

Blood Proteins↗

Spontaneous Enantiomeric Resolution in a Fluid Smectic Phase of a Racemate.

Right- and left-handed homochiral domains segregate in a fluid smectic phase of the racemic (R*,S*)-beta-Me-TFMHPOBC analogue shown. This CF(3)-containing liquid crystalline compound exhibits an electrooptic response in a homogeneous cell, although no macroscopic dipole is expected to exist. Moreover, the homeotropic cells of this material exhibit striped domains, which are associated with fine stripes having two opposite tilt senses with respect to the predominant stripes.

Journal Article↗

Aortoduodenal fistula arising from the dilatation of a knitted Dacron graft: report of a case.

A fatal aortoduodenal fistula occurred in a 72-year-old man who underwent a repair of an abdominal aortic aneurysm 16 years previously with a 20 x 10 mm bifurcated knitted Dacron graft. The aortic part of his bifurcated graft had dilated to 40 mm in diameter, with a discrepancy of 20 mm in the diameter between the graft and infrarenal aorta. The fourth portion of the duodenum adhered to the left side of the anastomosis, where the aortoenteric fistula had occurred. We believe that the graft dilatation was the cause of the anastomotic failure, although other factors such as atherosclerotic degeneration of the host aorta should also be considered. Knitted Dacron grafts that have been implanted for more than 10 years should therefore be monitored carefully because they have an inherent tendency to dilate, especially those manufactured before 1981.

Aged↗

Identification of an autoimmune enteropathy-related 75-kilodalton antigen.

BACKGROUND & AIMS: We have previously reported a 75-kilodalton autoantigen specific to X-linked autoimmune enteropathy (AIE) associated with tubulonephropathy. The aim of this study was to identify the autoantigen. METHODS: Complementary DNA (cDNA) clones were isolated by immunoscreening a human duodenal cDNA-expression library with serum from a patient with AIE. RESULTS: cDNA encoding the 75-kilodalton antigen (AIE-75) was identified. The composite nucleotide sequence of the cDNA for AIE-75 was 2214 base pairs long and encoded 552 amino acids. The genomic sequence of AIE-75 was found in Sequence DataBank, which consisted of 21 exons and was located on the chromosome 11p14.3. Recombinant AIE-75 specifically reacted with sera from 3 of 4 unrelated patients with AIE but not with 58 control sera. AIE-75 was predominantly distributed in the epithelial cells of the luminal surface and the upper half of the crypts of the intestine and in the proximal renal tubulus. Similarity searches revealed that the AIE-75 cDNA sequence was an authentic form of several colon cancer-related cDNAs of unknown function. The deduced amino acid sequence contained 3 conserved PSD-95/Dlg/ZO-1 (PDZ) domains. CONCLUSIONS: AIE-75 is a PDZ domain-containing protein expressed in the differentiated epithelial cells of the intestine and kidney and may be involved in protein-protein interaction. The identification of the autoantigen may prove useful in the approach to the pathogenesis of this poorly understood disease.

Amino Acid Sequence↗

Heat stress aggravates viral myocarditis in mice.

While a beneficial effect of hyperthermia on viral infection has been hypothesized, there are no data on viral myocarditis in vivo. To investigate whether hyperthermia might attenuate the course or severity of viral myocarditis, we studied the pathological changes in a murine model of viral myocarditis. C3H mice were inoculated i.p. with the encephalomyocarditis virus (500 pfu). They were anesthetized and heated to a body temperature of 42.5+/-0.2 degrees C for 30 min. The latter was performed 4 hr before (n=28, HB) or 4 hr after (n=28, HA) the viral inoculation; results were compared with nonheated, infected controls (n=30, Cont). Cardiac viral titers were recorded on day 3, and the body weight (BW), heart weight (HW) and pathological changes were recorded on days 5 and 10. The incidence of spontaneous mortality on day 10 was significantly higher in the HA group (all deaths occurring by day 7 post-inoculation) as compared with the HB (35%) or Cont (18%) groups. Viral titers in the HA group (n=4) were significantly (P<0.05) higher than those in the Cont (n=7) or HB (n=7) groups (4.11+/-0.54 vs 3.01+/-0.44 and 3.23+/-0.45 LogTCID50/mg, respectively). On day 5, the HW, the BW/HW ratio, and the severity of myocardial necrosis were all significantly higher in the HA than in the Cont and HB groups. To confirm the effect of hyperthermia on the expression of heart shock protein (HSP), immunohistochemical staining was done in the virus-infected hearts. The nucleus and cytoplasm of the injured myocardium in the HA group strongly expressed HSP70, whereas the HB and Cont groups were negative for this protein. In conclusion, induction of hyperthermia after viral inoculation aggravated the viral-induced myocardial necrosis and increased the mortality rate in a murine model of viral myocarditis and induced myocardial heat shock protein 70.

Animals↗

Running exercise increases tumor necrosis factor-alpha secreting from mesenteric fat in insulin-resistant rats.

Tumor necrosis factor-alpha (TNF-alpha) is an important mediator of insulin resistance in obese subjects, through its overexpression in fat tissue. However, how exercise can modify the expression of TNF-alpha is controversial. We examined TNF-alpha in adipose tissue using an animal model of insulin resistance that was produced by feeding rats a diet high in sucrose. The rats were allocated to one of three groups: those receiving a starch-based diet (control group): those fed a high-sucrose diet (sucrose-fed group): and those fed a high-sucrose diet and given wheel exercise (exercised group). The animals were allowed to eat and drink ad lib for 4 or 12 weeks (4 wk: control n=7, sucrose-fed n=7, exercised n=10; 12 wk: control n=5, sucrose-fed n=5, exercised n=9). The voluntary wheel exercise was initiated with the feeding of the high-sucrose diet. The rats in the exercise groups ran 15 +/- 3 km/week. We showed that 12-week voluntary running exercise significantly (P<0.05) increased both TNF-alpha protein (5-fold) and mRNA (1.4 fold) in the mesenteric fat of insulin-resistant rats compared to non-exercised sucrose-fed mice. Accordingly, in exercised group, plasma glucose (124 +/- 9 mEq/L vs 141 +/- 11 mEq/L). and free fatty acid (0.98 +/- 0.07 mEq/L vs 1.4 +/- 0.05 mEq/L) concentrating in portal vein blood were reduced compared to sucrose-fed group. The amounts of fatty tissue both in mesenteric and subcutaneous tissues were significantly (P<0.05) decreased through running exercise. We consider that up-regulation of TNF-alpha in mesenteric fat may be a compensatory mechanism for the reduction of fatty acid in adipose tissues and this change could control metabolic homeostasis during exercise to modulate a hyperinsulinemic state.

Adipose Tissue↗

Increased severity of viral myocarditis in mice lacking lymphocyte maturation.

The role of lymphocytes in the pathogenesis of viral myocarditis is controversial. To better understand how lymphocyte maturation controls a virus-induced myocarditic process, a murine model of viral myocarditis was utilized. Encephalomyocarditis virus (EMCV) was inoculated intraperitoneally into three kinds of mice; virus-susceptible C57BL/6, virus-resistant 129/SV and recombination activity gene (RAG)-2 knockout 129/SV mice. The RAG2 participate in the maturity of T and B lymphocytes. Survival rate, heart weight (HW), HW to body weight (BW) ratio, viral genome, cardiac inflammation and myocardial necrosis were evaluated after EMCV (500 plaque forming unit/mouse) inoculation. On post-inoculation day 10, the survival rate of C57BL/6, 129/SV and RAG2 knockout mice were 42, 90 and 0%, respectively. Myocardial viral titer was significantly (P<0.05) higher in C57BL/6 and RAG2 knockout mice than in 129/SV mice. In situ hybridization demonstrated the EMCV genome in the myocardium of RAG2 knockout and C57BL/6 mice, but not in 129/SV mice. At day 8, HW and HW/BW ratios were elevated (P<0.05) in RAG2 knockout mice as well as C57BL/6 mice compared with 129/SV mice. Myocardial necroses were more severe in RAG2 knockout mice than in wild-type 129/SV mice. In conclusion, matured lymphocytes protect the development of viral myocarditis which includes viral replication and myocardial apoptosis.

Animals↗

Hormone replacement therapy in postmenopausal women with essential hypertension increases circulating plasma levels of bradykinin.

Hormone replacement therapy (HRT) reduces the incidence of cardiovascular disease (CVD) in postmenopausal women (PMW). Recently, it has been reported that HRT declines angiotensin converting enzyme (ACE) activity, which may be one of the factors protecting against CVD. We measured the plasma levels of bradykinin, which would be expected to increase because the bradykinin-degrading enzyme (kinase II) is the same as ACE. Treatment with conjugated estrogens (0.625 mg/day) and medroxyprogesterone (2.5 mg/ day) was given for 3 months as HRT to 19 hypertensive and 19 normotensive PMW. Plasma bradykinin and ACE activity levels were measured at baseline and after 3 months of HRT. The plasma levels of ACE activity in both the hypertensive and normotensive PMW were significantly reduced by HRT. The plasma levels of bradykinin in the hypertensive PMW were significantly increased by HRT, whereas the administration of HRT tended to increase plasma levels of bradykinin in the normotensive PMW. The increased bradykinin levels with a concomitant decrease of plasma ACE activity by HRT in hypertensive PMW seem to be beneficial for reducing the risk of CVD.

Aged↗

Shaping the genome--restriction-modification systems as mobile genetic elements.

A restriction enzyme gene is often linked to a modification methylase gene the role of which is to protect a recognition site on DNA from breakage by the former. Loss of some restriction-modification gene complexes leads to cell death through restriction breakage in the genome. Their behavior as genomic parasites/symbionts may explain the distribution of restriction sites and clarify certain aspects of bacterial recombination repair and mutagenesis. A comparison of bacterial genomes supports the hypothesis that restriction-modification gene complexes are mobile elements involved in various genome rearrangements and evolution.

Bacteria↗

The distribution of BrdU- and TUNEL-positive cells during odontogenesis in mouse lower first molars.

This study investigated the minute distribution of both proliferating and non-proliferating cells, and cell death in the developing mouse lower first molars using 5-bromo-2'-deoxyuridine (BrdU) incorporation and the terminal deoxynucleotidyl transferase-mediated deoxyuridine-5'-triphosphate (dUTP)-biotin nick end labeling (TUNEL) double-staining technique. The distribution pattern of the TUNEL-positive cells was more notable than that of the BrdU-positive cells. TUNEL-positive cells were localized in the following six sites: (1) in the most superficial layer of the dental epithelium during the initiation stage, (2) in the dental lamina throughout the period during which tooth germs grow after bud formation, (3) in the dental epithelium in the most anterior part of the antero-posterior axis of the tooth germ after bud formation, (4) in the primary enamel knot from the late bud stage to the late cap stage, (5) in the secondary enamel knots from the late cap stage to the late bell stage, and (6) in the stellate reticulum around the tips of the prospective cusps after the early bell stage. These peculiar distributions of TUNEL-positive cells seemed to have some effect on either the determination of the exact position of the tooth germ in the mandible or on the complicated morphogenesis of the cusps. The distribution of BrdU-negative cells was closely associated with TUNEL-positive cells, which thus suggested cell arrest and the cell death to be essential for the tooth morphogenesis.

Animals↗

Reduced production of nitric oxide during haemodialysis.

OBJECTIVE: To examine the influence of systemic nitric oxide (NO) synthesis on blood pressure in patients with chronic renal failure undergoing haemodialysis, since nitric oxides are susceptible to renal excretion or are dialysed, a different indicator that is unaffected by renal function, such as the level of exhaled NO was evaluated. We examined the levels of the endogenous NO before and after a haemodialysis session. DESIGN AND METHODS: We evaluated the serum concentrations of nitrite/nitrate and the rate of nitric oxide release into exhaled air in 10 patients with hypertension who were receiving maintenance haemodialysis. RESULTS: The serum concentrations of nitrite/nitrate before haemodialysis were significantly higher than those in 10 normal controls (183 +/- 151 microM vs 42 +/- 17 microM, P < 0.05). These levels decreased significantly by the end of haemodialysis (42 +/- 26 microM). Because the amount of nitric oxide in the deepest expirate correlated well with the duration of exhalation, we were able to derive the rate of release of NO. The rate of NO release was 0.034 +/- 0.012 nmol/sec before haemodialysis, similar to that in normal controls (0.031 +/- 0.013nmol/sec). The rate was significantly reduced after dialysis (0.023 +/- 0.010 nmol/sec) (P < 0.05). The mean pre-dialysis mean blood pressure (109 +/- 11 mm Hg) and the post-dialysis blood pressure (106 +/- 9 mm Hg) were the same. CONCLUSIONS: These data indicate that NO production does not appear to have a critical role in control of arterial blood pressure across haemodialysis in patients with chronic renal failure.

Adult↗

Ratio of factor V activities in PT and APTT assays as a new diagnostic marker of lupus anticoagulant.

Lupus anticoagulant (LA) is an antibody that interferes with phospholipid-dependent coagulation tests. We investigated the usefulness of the ratio of factor V activity determined by the Simplastin auto test (PT assay) to factor V activity determined by the Platelin Excel LS test (APTT assay) for detection of LA in plasma samples obtained from 276 patients with haematological and non-haematological disorders and 73 healthy subjects. This ratio was significantly higher in the 15 LA-positive (4.82 +/- 3.34) than in samples from healthy subjects (1.09 +/- 0.10) and was > 1.4 in 10 of the remaining 261 patient samples. The ratio was particularly low in the 54 samples from warfarin-treated patients. These findings suggest that determination of this ratio may be useful as a routine laboratory test for detection of LA. This test requires no specific antigens and can be applied in patients receiving anticoagulants such as warfarin and heparin.

Adult↗

Influence of transfusion-transmitted virus infection on the clinical features and response to interferon therapy in Japanese patients with chronic hepatitis C.

Recently, the genome of a novel DNA virus, transfusion-transmitted virus (TTV), was cloned from the plasma of a blood donor who had an elevated aminotransferase level but no serological markers of known hepatitis viruses. In this study, we investigated the influence of TTV infection on the clinical features and response to interferon (IFN) therapy in patients with chronic hepatitis C. We studied 247 patients who had received a 16- or a 24-week course of IFN-alpha therapy. The serum of these patients was analysed for TTV DNA using a hemi-nested polymerase chain reaction and TTV was detected in 114 patients (46%). No significant differences were found with respect to clinical features (gender, age, liver-related biochemical tests, hepatitis C virus (HCV) genotype and serum HCV RNA levels) between the patients who were positive for TTV DNA and those who were negative for TTV DNA. The fibrosis score was higher in TTV-positive patients (2.1 +/- 1.1) than in TTV-negative patients (1.7 +/- 1.1, P = 0.023). The biochemical sustained-response rate was 25% in TTV-positive patients and 25% in TTV-negative patients (not significant). A sustained HCV clearance rate was achieved in 26% of TTV-positive patients and in 22% of TTV-negative patients (not significant). TTV DNA clearance after IFN therapy was observed in 36 of 69 patients (52%) for whom stored serum samples were available. The disappearance of TTV DNA had no effect on the biochemical response to IFN therapy. In conclusion, TTV co-infection is frequently observed in Japanese patients with chronic hepatitis C. In chronic hepatitis C, TTV does not modify the clinical features or the response to IFN.

Adolescent↗

Relationship between atrioventricular delay, QT interval and cardiac function in patients with implanted DDD pacemakers.

QT interval may change when cardiac function is improved by optimizing the atrioventricular the (AV) delay. The relationship between AV delay, QT interval and cardiac function in patients with implanted DDD pacemakers was studied in 12 patients (aged 71+/-12 SD years) with complete or high degree AV block. Cardiac output (CO) was measured using a Swan-Ganz catheter or by continuous Doppler echocardiography. The pacing rate was fixed at 70-80/min to eliminate the influence of heart rate. The AV delay was prolonged stepwise by 30 ms starting from 90 ms. All measurements were performed after 5 min of pacing. When the AV delay was prolonged, the CO and QT interval gradually increased and reached a peak, and then decreased. When the CO was increased from the minimum to the maximum value by optimizing the AV delay, the QT interval was significantly prolonged from 440+/-40 to 456+/-39 ms (P<0.002). The CO increased from 5.5+/-2.5 to 6.0+/-2.5 l x min(-1) (P<0.002) when the AV delay was changed, during which the QT interval was prolonged from the minimum to the maximum value. There was a significant positive correlation between the optimal AV delay at which CO was maximal (161+/-33 ms) and the optimal AV delay predicted from the maximum QT interval (167+/-29 ms, r=0.85, P<0.001). In conclusion, the optimal AV delay can be predicted from the QT interval.

Adult↗

Reduction of leptin precedes fat loss from running exercise in insulin-resistant rats.

Serum concentrations of leptin, a hormone secreted into the circulation by adipocytes, correlate with body mass index. Circulating of leptin is thought to signal the brain in patients with hyperinsulinemia, a condition reported to be preventable and testable by exercise training. In the present experiments, sucrose-fed rats had reduced concentrations of leptin in portal venous blood after 4 weeks of nonforced wheel-running exercise (1.1 +/- 0.1 vs. 6.2 +/- 1.8 ng/mL, in nonexercised sucrose-fed rats, P < 0.05). Mesenteric and subcutaneous fat stores were similar between groups. After 12 weeks of exercise, portal vein levels of leptin concentrations (5.2 +/- 2.1 vs. 9.9 +/- 0.8 ng/mL, P < 0.05) and mesenteric and subcutaneous fat all were reduced in the exercise group. These results suggest that short-term running exercise reduces circulating leptin before any reduction of adipose mass, and this reduction in the concentration of leptin available to its receptors has beneficial effects on the metabolism of fat and carbohydrates.

Adipose Tissue↗

Magnolol inhibits leukotriene synthesis in rat basophilic leukemia-2H3 cells.

We have observed an inhibitory action of magnolol on the production of leukotriene (LT) C4 and LTB4, important lipid mediators in allergy and inflammation. IgE- and A23187-stimulated production of LTC4 and LTB4 was measured by radio-immunoassay (RIA) in the absence or presence of various concentrations of magnolol in intact rat basophilic leukemia (RBL)-2H3 cells. Magnolol dose-dependently inhibited synthesis of LTC4 and LTB4. Magnolol inhibited the IgE-mediated increase of intracellular calcium ion concentration, resulting in the inhibition of cytosolic phospholipase A2 (cPLA2) and possibly 5-lipoxygenase (5-LO), both calcium ion-dependent enzymes. In cell-free studies magnolol inhibited LTC4 synthase activity. LTA4 hydrolase activity was only inhibited at the higher concentration (2.5 x 10(-5)M). These results indicate that magnolol inhibits production of LTs by inhibiting PLA2, 5-LO, LTC4 synthase and LTA4 hydrolase which are essential for LT-synthesis. Magnolol may have anti-allergic effect by blocking LT-synthesis.

Animals↗

Effect of DNA sequence divergence on homologous recombination as analyzed by a random-walk model.

A point connecting a pair of homologous regions of DNA duplexes moves along the homology in a reaction intermediate of the homologous recombination. Formulating this movement as a random walk, we were previously successful at explaining the dependence of the recombination frequency on the homology length. Recently, the dependence of the recombination frequency on the DNA sequence divergence in the homologous region was investigated experimentally; if the methyl-directed mismatch repair (MMR) system is active, the logarithm of the recombination frequency decreases very rapidly with an increase of the divergence in a low-divergence regime. Beyond this regime, the logarithm decreases slowly and linearly with the divergence. This "very rapid drop-off" is not observed when the MMR system is defective. In this article, we show that our random-walk model can explain these data in a straightforward way. When a connecting point encounters a diverged base pair, it is assumed to be destroyed with a probability that depends on the level of MMR activity.

DNA↗