Biomedical subjects

Y Kitagawa

Publications and source records attributed to Y Kitagawa.

At least 19 recordsLinked to original sources

PubMed1997

Insulin gene region contributes to genetic susceptibility to, but may not to low incidence of, insulin-dependent diabetes mellitus in Japanese.

In the Caucasian population, it has been demonstrated that the insulin gene (INS) region contains the insulin-dependent diabetes mellitus locus (IDDM2). In the Japanese population, however, there has been no report demonstrating the contribution of IDDM2 to the pathogenesis of IDDM. We conducted an association study of IDDM in a large number of Japanese subjects with multiple polymorphisms in INS region. We found a significant association of the INS region with IDDM. Alleles positively associated with IDDM in INS region were the same as those positively-associated with IDDM in Caucasian population, although positively-associated alleles are very common (allele frequencies > 0.9) in the Japanese general population. These data suggest that IDDM2 is involved in the genetic susceptibility to IDDM in Japanese. The high frequencies of disease-associated alleles in the general population suggest that IDDM2 locus is not responsible for the low incidence of IDDM in Japanese.

DNA, Satellite↗

PubMed1997

Distinct roles of mouse laminin beta1 long arm domains for alpha1beta1gamma1 trimer formation.

Mouse embryonal carcinoma F9 cells expressing partial mouse laminin beta1 covering either the C-terminal end (delta beta1S) or the whole (delta beta1L) of the long arm were established to study the assembly and interchain disulfide-bonding of beta1 to endogenous laminin alpha1 and gamma1. Both delta beta1S and delta beta1L were disulfide-bonded to gamma1 but only delta beta1L gamma1 dimer formed a disulfide-bonded alpha1 delta beta1L gamma1 trimer which was actively secreted into the medium. Meanwhile, in the cells producing delta beta1S gamma1 dimer, the level of endogenous alpha1 beta1 gamma1 was reduced but the level of monomeric alpha1 was increased, suggesting that alpha1 was recruited to trimer formation with the delta beta1S gamma1 dimer without disulfide-bonding. This shows that the delta beta1S gamma1 dimer can associate with alpha1 but not support the disulfide-bonding at the N-terminus of the long arm of alpha1. While control cells secrete neither monomeric alpha1 nor the beta1gamma1 dimer into the medium, the delta beta1S gamma1 producing cells probably do as alpha1 delta beta1 gamma1 trimer. We thus propose that the N- and C-termini of the long arm of laminin beta1 have distinct roles for trimer formation.

Animals↗

PubMed1997

Antibodies to glutamic acid decarboxylase in Japanese diabetic patients with secondary failure of oral hypoglycaemic therapy.

Some patients with non-insulin-dependent (Type 2) diabetes mellitus (NIDDM) are positive for antibodies to glutamic acid decarboxylase (anti-GAD), which have been shown to be a useful marker for the diagnosis and prediction of insulin-dependent (Type 1) diabetes mellitus (IDDM). Anti-GAD positive NIDDM patients tend to develop insulin deficiency. We investigated the prevalence of anti-GAD in 200 NIDDM with secondary failure of oral hypoglycaemic therapy (SF) and 200 NIDDM well controlled by diet and/or sulphonylurea agents (NSF). Twenty-two of 200 (11%, p < 0.05) SF patients and 6 of 200 (3%) NSF patients were anti-GAD positive. The positive. The positive rate for anti-GAD was as high as 23.8% in the non-obese and insulin deficient SF patients. The SF patients with anti-GAD tended to be non-obese and to have an impaired release of endogenous insulin. The internal before development of secondary failure was not associated with the presence of anti-GAD in this study. In conclusion we found that anti-GAD was positive in as many as 11% of the SF patients, suggesting that autoimmune mechanisms may play an important role in the pathogenesis of secondary failure or sulphonylurea therapy.

Analysis of Variance↗

PubMed1997

Effect of mechanical deformation on structure and function of polymorphonuclear leukocytes.

The present studies were designed to test the hypothesis that mechanical deformation of polymorphonuclear leukocytes (PMN) leads to functional changes that might influence their transit in the pulmonary capillaries. Human leukocytes were passed through 5- or 3-micron-pore polycarbonate filters under controlled conditions. Morphometric analysis showed that the majority of PMN were deformed and that this deformation persisted longer after filtration through 3-micron filters than through 5-micron filters (P < 0.05) but did not result in the cytoskeletal polarization characteristic of migrating cells. Flow cytometric studies of the filtered PMN showed that there was a transient increase in the cytosolic free Ca2+ concentration after both 3- and 5-micron filtration (P < 0.01) with an increase in F-actin content after 3-micron filtration (P < 0.05). Although L-selectin expression on PMN was not changed by either 5- or 3-micron filtration, CD18 and CD11b were increased by 3-micron filtration (P < 0.05). Priming of the PMN with N-formyl-methionyl-leucyl-phenylalanine (0.5 nM) before filtration resulted in an increase of CD11b by both 5 (P < 0.05)- and 3-micron (P < 0.01) filtration. Neither 5- nor 3-micron filtration induced hydrogen peroxide production. We conclude that mechanical deformation of PMN, similar to what occurs in the pulmonary microvessels, induces both structural and functional changes in the cells, which might influence their passage through the pulmonary capillary bed.

Actins↗

PubMed1997

[A case of myeloradiculoneuropathy associated with persistent high titers of anti-GM1 and anti-GD1b antibodies].

A 60-year-old woman was admitted to our hospital with bilateral weakness of the lower limbs. She had been suffering from spastic paraparesis of unknown origin for 12 years since she was 48. Myelopathy with the Th6 level appeared when she was 52 and underwent gradual deterioration. On admission, she showed spastic paraparesis and myelopathy with the Th6 level. A thoracic spinal MRI examination revealed a wholly thin spinal cord. EMG demonstrated that the conduction velocity of the peroneal nerve was 37.8m/sec, and F waves were not evoked on stimulation of the peroneal nerve. Although the anti-GM1 and anti-GD1b antibody titers in the serum were increased on admission, their values decreased transiently after whole plasmapheresis. There was accompanying impairment of the radiculoneuropathy and myelopathy. It is important to measure the titers of anti-ganglioside antibodies in patients with myeloradiculoneuropathy of unknown origin, and whole plasmapheresis is considered to represent a useful treatment for this type of illness.

Autoantibodies↗

PubMed1997

[A case of inoperable advanced gastric cancer remarkably responding to combined chemotherapy with UFT-E, MMC and PSK].

A 55-year-old male consulted a local doctor with the complaint of epigastralgia. Examination of the upper gastrointestinal tract revealed gastric cancer (Borrmann Type II) and he was referred to our hospital for operation. A few lymph nodes were palpable in the left supraclavicular fossa, and the biopsy of those lymph nodes revealed metastatic adenocarcinoma. The CT scan of the abdomen showed enlargement of paraaortic lymph nodes. Then, the patient was determined inoperable (T3, N4, H02 P01, M1 stage IVb). He was treated as an outpatient with UFT-E (300 mg/day, orally), Krestin (PSK 3.0 g/day, orally) and Mitomycin C (MMC 6 or 8 mg once a week, intravenously repeated interval of 4 weeks). The total dose of UFT-E, PSK and MMC was 219 g, 1,095 g and 136 mg, respectively. One month later, lymph nodes in the supraclavicular fossa disappeared, and the lesion in the stomach completely responded. We have followed the patient for more than one year. He visits our the outpatient department and has kept working until now.

Adenocarcinoma↗

PubMed1996

Formation of crossline as a fluorescent advanced glycation end product in vitro and in vivo.

Crossline is one of the major advanced glycation end products resulting the reaction mixture of free amino group(s) such as epsilon-one in lysine with D-glucose in vitro. To study crossline formation on proteins in vitro and in vivo, polyclonal antiserum to the crossline hapten was prepared. This antiserum reacted with bovine and human serum albumin that had been modified by prolonged incubation with glucose as well as with crossline itself. Antisera did not react with unmodified serum albumin or the other Maillard-related compounds. Crossline was formed in a time-dependent manner when a mixture of six different proteins was incubated with glucose at pH 7.2 or 9.0. Crossline levels could be measured in rat lens proteins and the levels increased with age. The crossline content of lens proteins in diabetic rats was more than two-fold higher than that of age-matched controls. Results of this study suggest that most proteins containing advanced glycation end products have crossline-like structures. Measurement of crossline-like structures in biological specimens may provide an index of aging and of the development of diabetic complications.

Animals↗

PubMed1996

A family of novel DNA-binding nuclear proteins having polypyrimidine tract-binding motif and arginine/serine-rich motif.

NP220 is a DNA-binding nuclear protein originally cloned from human cell lines. Human NP220 (hNP220) has an arginine/serine-rich motif found in non-small nuclear RNP splicing factors (SR proteins) and shares three domains (MH1, MH2 and MH3) with an acidic nuclear matrix protein, matrin 3. The MH2 domain repeats three times and has homology to the polypyrimidine tract-binding motif of heterogeneous nuclear RNP I/L. NP220 also has a DNA-binding domain and nine repeats of the sequence LVTVDEVIEEEDL (acidic repeat). We have now isolated mouse equivalents of NP220 (mNP220s) and found that NP220s form a family of proteins with four members produced by alternative splicing of a common pre-mRNA. Two longer forms (NP220alpha and NP220beta) have all functional domains mentioned above while two shorter forms (NP220gamma and NP220delta) lack the DNA-binding domain and the acidic repeat. The structural aspects of NP220s are distinct from that of the SR proteins but rather resemble U2AF and Tra2 which activate a specific 3'-splicing site of specific genes in response to differentiation-dependent signals.

Amino Acid Sequence↗

PubMed1996

A large DNA-binding nuclear protein with RNA recognition motif and serine/arginine-rich domain.

cDNA species encoding a large DNA-binding protein (NP220) of 1978 amino acids was isolated from human cDNA libraries. Human NP220 binds to double-stranded DNA fragments by recognizing clusters of cytidines. Immunofluorescent microscopy with antiserum directed against NP220 revealed a punctate or "speckled" pattern and coiled body-like structures in the nucleoplasm of various human cell lines. These structures diffused in the cytoplasm during mitosis. Western blot analysis showed that NP220 is enriched in the lithium 3,5-diiodosalicylate-insoluble fraction of nuclei. The domain essential for DNA binding is localized in C-terminal half of NP220. Human NP220 shares three types of domains (MH1, MH2, and MH3) with the acidic nuclear protein, matrin 3 (Belgrader, P., Dey, R., and Berezney, R. (1991) J. Biol. Chem. 266, 9893-9899). MH1 is a 48-amino acid sequence near the N terminus of both human NP220 and rat matrin 3. MH2 is a 75-amino acid sequence homologous to the RNA recognition motifs of heterogeneous nuclear RNP I and L. It is repeated three times in NP220 and twice in matrin 3. MH3 is a 60-amino acid sequence at the C terminus of both NP220 and matrin 3. NP220 has an arginine/serine-rich domain commonly found in pre-mRNA splicing factors. Close to the domain essential for DNA binding, there are nine repeats of the sequence LVTVDEVIEEEDL. Thus, NP220 is a novel type of nucleoplasmic protein with multiple domains.

Amino Acid Sequence↗

PubMed1996

Intravenous catecholamines alter hepatic blood flow in conscious dogs with experimental hepatic denervation.

Hepatic blood flow is regulated by the autonomic nervous system; however, blood flow through the denervated liver has been controversial. The purpose of this study is to evaluate the changes in hepatic blood flow caused by experimental hepatic denervation during the intravenous infusions of catecholamines (dopamine or dobutamine) with or without prior administration of alpha-adrenoceptor antagonist (phenoxybenzamine) or beta-adrenoceptor antagonist (propranolol). The liver blood flow was measured using transit time ultrasonic flow meter probes at the portal vein and hepatic artery in conscious dogs which (a) underwent hepatic denervation (denervation group, n = 9) and (b) were intact (control group, n = 10). Norepinephrine concentrations in the liver were determined to evaluate the effects of hepatic denervation and were decreased at 1 week and 4 weeks after hepatic denervation. In the control group, dopamine and dobutamine produced an increase of portal venous blood flow (PVF). Conversely, hepatic denervation reduced the increase in PVF by dopamine and dobutamine. Dopamine with prior administration of phenoxybenzamine produced a much larger increase in PVF in both groups. Pretreatment of propranolol in both groups abolished the increasing effects of dopamine and dobutamine in PVF. Dopamine reduced the hepatic arterial blood flow (HAF) regardless of hepatic denervation. During dobutamine infusion, HAF was decreased by hepatic denervation and prior administration of propranolol. These results suggest that hepatic denervation reduces the increasing effects of catecholamines on the hepatic blood flow through greater enhancement of alpha-adrenergic effects than of beta-adrenergic effects in the hepatic vascular autonomic nerve response.

Animals↗

PubMed1996

The effects of intravenously infused catecholamines on hepatic blood flow in conscious dogs with experimental obstructive jaundice.

This study was conducted to examine how the effects of dopamine and dobutamine on hepatic blood flow were influenced by obstructive jaundice in a conscious canine model. Prior to biliary obstruction, portal venous blood flow (PVF) increased in response to the infusion of either dopamine or dobutamine: dopamine infused at 8 micrograms/kg per min produced an increase of 19 +/- 0% in PVF, while dobutamine infused at 16 micrograms/kg per min produced an increase of 30 +/- 2%. Although hepatic arterial blood flow (HAF) decreased dose-dependently in response to the infusion of dopamine, no significant change was observed in HAF in response to any dose of dobutamine. Obstructive jaundice attenuated or completely abolished the PVF-increasing effect of dopamine, whereas it did not significantly alter the effect of dobutamine on hepatic blood flow. In dogs with obstructive jaundice, dopamine at 16 micrograms/kg per min produced a decrease of 17 +/- 3% in PVF. These findings suggest that dobutamine is more effective than dopamine for increasing hepatic blood flow in patients with obstructive jaundice.

Animals↗

PubMed1996

Morphological and anthropological aspects of human triangular deciduous lower first molar teeth.

The crown and root morphology, and bilateral occurrence of human deciduous lower first molars that exhibited a triangular occlusal outline, taken from excavated samples of Japanese, Jomonese and Iraqi origin, were investigated. The crowns of triangular teeth had smaller mesiodistal and larger buccolingual diameters than normally shaped deciduous lower first molars. An elongated buccolingual diameter was derived from the buccal projection of the distobuccal cusp and lingual projection of the portion between the metaconid and distolingual cusp. In this analysis, all triangular deciduous lower first molars in which root morphology could be observed were accompanied by additional distolingual roots. Correlation between the right- and left-hand sides of this trait was high.

History, 15th Century↗

PubMed1996

Meanings of c-erbB and int-2 amplification in superficial esophageal squamous cell carcinomas.

BACKGROUND: Accumulation of genetic abnormalities is linked to the development and progression of cancer. We therefore analyzed the correlation between the clinical characteristics of superficial esophageal squamous cell carcinoma patients and oncogene amplifications. METHODS: Between 1980 and 1991, there were 63 cases of superficial esophageal carcinoma (Tis and T1 cancer) at Keio University Hospital. The T1 cases were divided into two groups: T1a cases, in which the tumor had invaded the lamina propria, and T1b cases, in which the tumor had invaded the submucosa. DNA was isolated from paraffin-embedded blocks. Oncogene amplification was determined by slot-blot hybridization. RESULTS: Amplification of int-2 and c-erbB was detected in 14 and 5, respectively, of the 54 cases. Three of 12 T1b patients with int-2 amplification died of distant organ metastasis. The survival rate for the group with int-2 amplification was significantly lower than that without int-2 amplification. All 4 T1b patients with c-erbB amplification had lymph node metastasis at operation. CONCLUSIONS: These findings mean that genetic abnormalities are a useful marker for treating patients with superficial esophageal squamous cell carcinomas.

Carcinoma, Squamous Cell↗

PubMed1996

Usefulness of fat-suppression magnetic resonance imaging for oral and maxillofacial lesions.

In magnetic resonance imaging (MRI) of the oral and maxillofacial region, where large amounts of fat are normally present, the high signal intensity of fat on T1-weighted images (T1WI) and the chemical-shift artifact have limited the utility of paramagnetic contrast agents. Eliminating fat signal by fat-suppression techniques can increase the value of contrast-enhanced MRI. The present study was designed to evaluate the utility and role of chemical-shift imaging for fat suppression in the detection of oral and maxillofacial lesions in 22 patients (17 with malignant tumors, two with benign tumors, and three with inflammation). The depiction of lesions on the postcontrast fat-suppression T1WI was compared with that of conventional pre- and postcontrast T1 and T2WI on a four-grade scale (grades 0-3). The postcontrast fat-suppression T1WI (average grade, 2.86) were significantly superior to the precontrast T1WI (0.82) and postcontrast T1WI (1.86) and T2WI (1.68). Postcontrast fat-suppression T1WI were particularly beneficial in the detection of central necrosis or extracapsular invasion of metastatic neck lymph nodes as well as in defining the lesion extent at fat-containing areas such as the bone marrow or cheek. These findings demonstrated that the fat-suppression technique is extremely useful in the delineation of oral and maxillofacial lesions without increase of the scan time or image postprocessing procedures.

Actinomycosis↗

PubMed1996

Evaluation of the genotoxicity of stevioside and steviol using six in vitro and one in vivo mutagenicity assays.

Stevioside, a constituent of Stevia rebaudiana, is commonly used as a non-caloric sugar substitute in Japan. The genetic toxicities of stevioside and its aglycone, steviol, were examined with seven mutagenicity tests using bacteria (reverse mutation assay, forward mutation assay, umu test and rec assay), cultured mammalian cells (chromosomal aberration test and gene mutation assay) and mice (micronucleus test). Stevioside was not mutagenic in any of the assays examined. The aglycone, steviol, however, produced dose-related positive responses in some mutagenicity tests, i.e. the forward mutation assay using Salmonella typhimurium TM677, the chromosomal aberration test using Chinese hamster lung fibroblast cell line (CHL) and the gene mutation assay using CHL. Metabolic activation systems containing 9000 g supernatant fraction (S9) of liver homogenates prepared from polychlorinated biphenyl or phenobarbital plus 5,6-benzoflavone-pretreated rats were required for mutagenesis and clastogenesis. Steviol was weakly positive in the umu test using S.typhimurium TA1535/pSK1002 either with or without the metabolic activation system. Steviol, even in the presence of the S9 activation system, was negative in other assays, i.e. the reverse mutation assays using S.typhimurium TA97, TA98, TA100, TA102, TA104, TA1535, TA1537 and Escherichia coli WP2 uvrA/pKM101 and the rec-assay using Bacillus subtilis. Steviol was negative in the mouse micronucleus test. The genotoxic risk of steviol to humans is discussed.

Animals↗

PubMed1996

Rapid diagnosis of methicillin-resistant Staphylococcus aureus bacteremia by nested polymerase chain reaction.

OBJECTIVE: The purpose of this study was to establish a rapid and sensitive diagnostic method for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia in postoperative patients. SUMMARY BACKGROUND DATA: As a result of diffusion and abuse of third-generation cephalosporin antibiotics in the 1980s in Japan, an outbreak of MRSA infection has been posed. In the field of surgery, severe postoperative infections with MRSA such as MRSA bacteremia, which may lead to multiple organ failure, have emerged with a high mortality. METHODS: Thirty-five patients with high fever (above 38.5 C) or watery diarrhea or both within 2 weeks after gastrointestinal major surgery and 6 healthy volunteers were examined. Nested polymerase chain reaction was used to detect mecA and toxic shock syndrome toxin-1 (TSST-1) genes in blood specimens. RESULTS: The mecA and TSST-1 genes were not detected in the blood samples of any of the six healthy volunteers. In all 12 samples from which MRSA colonies were isolated by blood culture, mecA and TSST-1 genes were detected. Although it took at least 48 hours to identify MRSA by the blood culture method, the presence of mecA and TSST-1 genes was determined by nested polymerase chain reaction method within only 3 to 4 hours after blood sampling. CONCLUSIONS: This method, as a sensitive and rapid monitoring system for MRS bacteremia, would be clinically beneficial for prevention of cross infection and for early determination of appropriate treatment for infected patients.

Bacteremia↗

PubMed1996

Synthesis of secretory protein in regenerating liver of rat after partial hepatectomy.

Albumin immunoreactivity in the liver was examined on days 2, 5 and 10 after two-thirds partial hepatectomy by light and ultrastructural immunoperoxidase methods and the ultrastructural area of the rough endoplasmic reticulum (ER) in hepatocytes was measured. Albumin immunoreactivity was seen in the rough ER and Golgi apparatus of all hepatocytes in the hepatectomized liver and ultrastructural analysis showed a significantly greater area of rough ER on day 5 than on days 2 or 10. Albumin mRNA was studied by the in situ hybridization technique using radioisotopes and their numbers were determined visually. Albumin mRNA was present as grains in all hepatocytes and the grains varied in number during regeneration of the liver, being more abundant on day 5 than on days 2 or 10. The activity of [3H]-leucine incorporated into albumin synthesis, an indicator of translational activity, was higher on days 5 and 10 than on day 2 and was highest on day 5. In conclusion, albumin synthesis varied during liver regeneration after partial hepatectomy, being reduced at the peak of cell proliferation on day 2 and being most active on day 5.

Albumins↗

PubMed1996

Overexpression of Bcl-2 and mutations in p53 and K-ras in resected human non-small cell lung cancers.

We investigated expression of Bcl-2, mutations in p53, and K-ras oncogene in 51 resected human non-small cell lung cancers. The studies were designed to test for the possibility of cooperativity between these oncogenes and p53 in the pathogenesis of lung cancer. An inverse relationship was found between expression of Bcl-2 and mutant p53 by immunohistochemistry (P < 0.01; Fisher exact test), suggesting that either Bcl-2 overexpression or mutations in p53 may fulfill a critical function in the pathogenesis of human non-small cell lung cancers. Tumors that harbored K-ras codon 12 mutations seldom had p53 mutations or overexpressed Bcl-2. Statistical analysis of these data showed that mutations in p53 and K-ras or overexpression of Bcl-2 and mutations in K-ras occurred at a frequency that could be explained only by chance [P > 0.1 in each case (Fisher exact tests)]. This suggests that cooperativity between mutant K-ras and mutant p53 or mutant K-ras and overexpressed Bcl-2 is not a common mechanism in the pathogenesis of human non-small cell lung cancers.

Adenocarcinoma↗