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Biomedical subjects

Y Komatsu

Publications and source records attributed to Y Komatsu.

At least 253 records · Page 14Linked to original sources

Extremely high levels of CA19-9 and CA125 antigen in benign mucinous ovarian cystadenoma.

A Japanese woman had a mucinous cystadenoma of the left ovary associated with very high serum levels of CA19-9 (3170 u/ml) and CA125 (1705 u/ml). Such high levels of both antigens have not been reported previously in patients with benign ovarian mucinous cystadenoma. Immunostaining demonstrated CA19-9 and CA125 in the tumor, and different patterns of expression were noted depending on the differentiation of the epithelium. The postoperative tumor marker profile suggested that no residual tumor was left after the operation.

Aged↗

Effect of anti-allergic agents on chemotaxis of neutrophils by stimulation of chemotactic factor released from hepatocytes exposed to ethanol.

In an attempt to clarify a mechanism of neutrophil infiltration in the liver of alcoholics and possible therapeutic effect of antiallergic agents on accumulation of these cells in the liver, we investigated chemotaxis of neutrophils by stimulation of a chemotactic factor released from rat hepatocytes exposed to ethanol. When hepatocytes were incubated with more than 30 mM ethanol for 24 hr, chemotactic activity for both rat and human neutrophils was demonstrated in the conditioned medium. An enhanced chemotactic activity of the conditioned medium was reduced in the presence of antibody against KC/gro protein, one of the interleukin-8-related cytokines in rodents. Antiallergic agents such as azelastine or ketotifen at a concentration of > 0.01 microM markedly reduced chemotaxis of neutrophils. Prednisolone at a concentration of > 10 microM also reduced chemotaxis of neutrophils. These results suggest that neutrophil accumulation in the liver of human alcoholics could be induced by a chemotactic factor produced by the ethanol-treated hepatocytes and that antiallergic agents could be effective against the extent of alcoholic hepatitis by reducing chemotaxis of neutrophils.

Adult↗

A case of primary gastric choriocarcinoma and a review of the Japanese literature.

A 63-year old woman who had experienced melena for 2 weeks was admitted to Tokyo University Hospital. Gastric adenocarcinoma was diagnosed endoscopically and histologically, and a total gastrectomy was performed soon thereafter. Pathological examination of the resected stomach revealed choriocarcinoma of the stomach. Although chemotherapy was administered after surgery, she died 3 months after admission. Autopsy confirmed the diagnosis of primary gastric choriocarcinoma, a rare, but highly malignant tumor. It is characteristic; macroscopically it forms a necrotic mass with bleeding, and microscopically it often consists of adenocarcinoma and choriocarcinoma. Since its prognosis is extremely poor, we must take into account the possibility of primary gastric choriocarcinoma when a hemorrhagic gastric tumor with necrosis is found.

Aged↗

Plasticity of excitatory synaptic transmission in kitten visual cortex depends on voltage-dependent Ca2+ channels but not on NMDA receptors.

Long-term potentiation (LTP) of excitatory synaptic transmission occurs in in vitro slices of cat and rat visual cortex. Earlier studies suggested that activation of N-methyl-D-aspartate (NMDA)-selective glutamate receptors is essential for the induction of LTP. However, our studies on kitten visual cortex demonstrate that LTP induction requires the activation of low-threshold Ca2+ channels in postsynaptic cells but not of NMDA receptors.

Animals↗

A novel type of B-cell mitogen isolated from juzen-taiho-to (TJ-48), a Japanese traditional medicine.

Juzen-taiho-to (TJ-48), a Japanese traditional medicine, is known to have various immunological activities including the induction of B-cell proliferation. We investigated the properties of the pectic polysaccharide fraction of TJ-48 (F-5-2) which is most active in the proliferation of spleen cells. To an extent equal to that of TJ-48, F-5-2 induced the proliferation of B-cells, particularly those holding both sIgM and sIgD. The proliferation induced by F-5-2 was T-cell independent and macrophage dependent. The macrophages could be substituted for a soluble factor(s) secreted from the macrophages but not for IL-1. Generally, B-cell mitogens are known to induce the proliferation of B-cells and subsequently differentiation into plasma cells. However, although F-5-2 induced the B-cell differentiation, it arrested their development in the intermediate stage of the B-cell differentiation. The B-cells induced by F-5-2 produced IgM antibody in response to IL-6 and an antigen (SRBC) but not IgG antibody. F-5-2 induced the expression of IL-6R not only on IgM+ and IgG+ B-cells but also on IgD+ B-cells. These results suggest that F-5-2 is a new type of B-cell mitogen.

Animals↗

Expression of Na(+)-K(+)-ATPase alpha- and beta-subunits along rat nephron: isoform specificity and response to hypokalemia.

The activity of Na(+)-K(+)-adenosinetriphosphatase (Na(+)-K(+)-ATPase), the sodium pump, which drives active Na+ reabsorption along the nephron, varies over an order of magnitude, depending on the nephron segment, and activity is increased in the outer medullary collecting tubule (MCT) during hypokalemia. The aims of the present study were to assess abundance of sodium pump alpha 1- and beta 1-subunits in dissected nephron segments of the rat by immunoblotting, to determine if alpha 2- or alpha 3-protein could be detected in the collecting tubules, as suggested by Barlet-Bas et al. (C. Barlet-Bas, E. Arystarkhova, L. Cheval, S. Marsy, K. Sweadner, N. Modyanov, and A. Doucet. J. Biol. Chem. 268: 11512-11515, 1993) for rabbit, and to determine if alpha 1 and beta 1 were increased in MCT by hypokalemia. Tubules from the rat were resolved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (12-100 mm/lane), blotted, and probed with subunit-specific antisera. alpha 1 and beta 1, detected in all tubule segments assayed, were highest in cortical and medullary thick ascending limbs and proximal convoluted tubule (PCT), lower in the MCT and barely detectable in proximal straight tubule. In the cortical collecting tubule (CCT), alpha 1 abundance was equivalent to that in PCT, whereas beta 1 and enzymatic activity were both less than one-half of that in PCT. After 2 wk of a K(+)-deficient diet, alpha 1- and beta 1-subunit levels in MCT increased 3.4 +/- 0.6- and 11.7 +/- 4.0-fold, respectively, associated with a 5-fold increase in activity. alpha 2 and alpha 3 were not detected in the CCT or MCT.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Molecular cloning of hamster brain and atrial natriuretic peptide cDNAs. Cardiomyopathic hamsters are useful models for brain and atrial natriuretic peptides.

Brain and atrial natriuretic peptides (BNP and ANP) are cardiac hormones with diuretic, natriuretic, and vasodilatory activities. Cardiomyopathic hamsters are widely used animal models of heart failure. Due to the structural divergence of BNP among species, examination on pathophysiological roles of BNP using cardiomyopathic hamsters is so far impossible. We therefore isolated hamster BNP and ANP cDNAs, and investigated synthesis and secretion of these peptides in normal and cardiomyopathic hamsters. The COOH-terminal 32-residue peptide of cloned hamster preproBNP with 122 amino acids, preceded by a single arginine residue, supposedly represents hamster BNP showing < 50% homology to rat BNP. Alpha-hamster ANP, 28-residue peptide, is identical to alpha-rat ANP. In hamsters, BNP and ANP occur mainly in the ventricle and the atrium, respectively. The 32-wk-old hypertrophic cardiomyopathic BIO14.6 strain exhibited ventricular hypertrophy. The 32-wk-old dilated cardiomyopathic BIO53.58 strain remained at the stage without apparent heart failure. In BIO14.6 and BIO53.58 strains at this age, ventricular BNP and ANP gene expressions are augmented, and the plasma BNP concentration is elevated to 136 and 108 fmol/ml, respectively, three times greater than the elevated plasma ANP concentration, which well mimics changes of the plasma BNP and ANP concentrations in human heart failure. Cardiomyopathic hamsters, therefore, are useful models to investigate the implication of BNP in human cardiovascular diseases.

Amino Acid Sequence↗

A monoclonal antibody to C-type natriuretic peptide--preparation and application to radioimmunoassay and neutralization experiment.

C-type natriuretic peptide (CNP), the third member of natriuretic peptides, has recently been discovered from the porcine brain. Using a polyclonal antiserum to CNP, we demonstrated that CNP-like immunoreactivity (CNP-LI) is present mainly in the central nervous system. Recently, however, we have discovered the production and secretion of CNP in vascular endothelial cells. These observations suggested that CNP may act not only as a neuropeptide but also as a local regulator of vascular tone or growth. In order to further clarify the pathophysiological significance of CNP, we aimed at the preparation of a monoclonal antibody to CNP. A monoclonal antibody to CNP, KY-CNP-I, has been produced. This monoclonal antibody belongs to the immunoglobulin G1 subclass and has high affinity for CNP. Using this monoclonal antibody, we established a specific radioimmunoassay (RIA) for CNP. The RIA detected CNP-LI in rat brain extracts and culture media conditioned with bovine endothelial cells. In addition, the pretreatment of cultured aortic smooth muscle cells with KY-CNP-I attenuated cyclic GMP production induced by CNP in vitro. The preadministration of KY-CNP-I to rats also attenuated plasma cyclic GMP increase after intravenous injection of CNP in vivo. These results indicate that this monoclonal antibody is a useful tool to clarify the pathophysiological role of CNP as a neuropeptide and as a local vascular regulator.

Animals↗

[Validity of the values of maximal oxygen intake for women recommended in the 'Quantity of exercise for developing health' by Ministry of Health and Welfare].

The purpose of this study was to examine the value of maximal oxygen intake per kilogram body weight (VO2max/wt) recommended for women between 20 and 29 years of age by the Ministry of Public Welfare. The subjects were 199 female college students, who were not in the habit of drinking and smoking. Results obtained were as follows: After controlling the effects of age and percent body fat (%fat), VO2max/wt showed a significant correlations with %fat, high-density lipoprotein cholesterol and systolic blood pressure. The values of VO2max/wt corresponding to borderline values of these CHD risk factors ranged from 27.6 to 29.5ml/kg.min. The highest value of VO2max/wt was very close to the value recommended for women older than 60 years of age by the Ministry of Public Welfare. The subjects were then divided into 4 groups; at above and below the value of VO2max/wt (35ml/kg.min) recommended for women between 20 and 29 years of age, and at above and below the value of VO2max/wt (31ml/kg.min) recommended for women older than 60 years of age by the Ministry of Public Welfare. There were no significant differences among 4 groups in occurrence of abnormal values in CHD risk factors. The results of this study support the validity of the value of VO2max/wt (31ml/kg.min) recommended for women older than 60 years of age by the Ministry of Public Welfare. However, it seems that it is not necessary to recommend the value of VO2max/wt (35ml/kg.min) for women between 20 and 29 years of age, who were not in the habit of drinking and smoking.

Adult↗

Studies on orally active cephalosporins. I. Synthesis and structure-activity relationships of new 3-substituted carbamoyloxymethyl cephalosporins.

The synthesis and antibacterial activities of 7 beta-[2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamido]-3-N,N - dimethylcarbamoyloxymethyl-3-cephem-4-carboxylic acid (E1100) and its analogs are described, as well as oral absorbability and in vivo activities of the 1-(isopropoxycarbonyloxy)ethyl ester (E1101) and its analogous esters. The introduction of acyclic and cyclic lower alkyl groups at the N-position of 3-carbamoyloxymethyl cephems influences antibacterial activities, especially against H. influenzae, and oral absorbability of their prodrug esters. The structure-activity relationships are also discussed.

Administration, Oral↗

Studies on orally active cephalosporins. II. Synthesis and structure-activity relations of new [(E) or (Z) 3-substituted carbamoyloxy]-1-propenyl cephalosporins.

In an effort to find a new oral cephalosporin with well-balanced antibacterial spectrum, good oral absorbability and long plasma half-life, a series of oxyimino aminothiazolyl 3-[(E)- or (Z)-N-substituted carbamoyloxy]propenyl cephems was synthesized and evaluated for antibacterial activity and oral absorbability. The substituents of the carbamoyloxy group affected their in vitro activity and bioavailability after oral administration of their pivaloyloxymethyl esters at the C-4 position. The compound possessing an N,N-dimethylcarbamoyloxy moiety at the C-3 position showed good oral absorption and well-balanced antibacterial activity. In this report, the structure-activity relationships and the structure-oral absorbability relationships of 3-(N-substituted carbamoyloxy)-propenyl cephems are described.

Administration, Oral↗

[Study of clinical usefulness of an antiandrogen, TZP-4238, as a drug for treatment of benign prostatic hypertrophy--its influence on sexual function].

Using chlormadinone acetate (CMA) as the control drug, a double-blind study was carried out to examine not only the effects of 17 alpha-acetoxy-6-chloro-2-oxa-4,6-pregnadiene-3,20-dione (TZP-4238;) on subjective urinary symptoms but also, especially, that on the sexual function in patients with benign prostatic hypertrophy (BPH). The clinical efficacy rate in relation to the subjective urinary symptoms was about the same in the two treatment groups; 45.9% in the TZP-4238 group and 50.0% in the CMA group. However, the incidence of adverse effects on the sexual function showed a marked difference between the two groups. The TZP-4238 group revealed a lower suppressive effect on the function than the CMA group (45.1% vs. 71.4%). In relation to their causation of other adverse effects, there were no differences between the two drugs. Accordingly, in consideration of the facts that TZP-4238 with less influence on the sexual function affords a superior quality of life to elderly patients, while achieving effective treatment by means of a convenient single daily administration, TZP-4238 was surmised to be a more useful drug than CMA as an antiandrogen for the treatment of BPH.

Aged↗

Age-dependent long-term potentiation of inhibitory synaptic transmission in rat visual cortex.

Long-term potentiation (LTP) of inhibitory synaptic transmission in rat visual cortex was investigated using intracellular recording in slice preparations. The inhibitory postsynaptic potential (IPSP) of layer V cells evoked monosynaptically by layer IV stimulation was recorded while excitatory postsynaptic potentials (EPSPs) were blocked by adding NMDA and non-NMDA receptor antagonists to the perfusate. Separate presynaptic fiber groups were activated by two stimulating electrodes placed in layer IV. One electrode was used to test the effect of conditioning stimulation; the other served as a control. Trains of high-frequency stimulation (50 Hz, 1 sec) were applied at an interval of 10 sec as a conditioning stimulation. The LTP of IPSP induced by the conditioning stimulation had properties similar to those known for LTP of EPSP in hippocampal CA1: (1) it was specific to the conditioned pathway; (2) repetitive application of the conditioning stimulation saturated the LTP; (3) LTP was induced by conditioning stimulation at intensities higher than a threshold; (4) weak conditioning stimulation to one pathway, which alone failed to induce LTP, induced associative LTP when strong conditioning stimulation was simultaneously applied to the other pathway; (5) weak conditioning stimulation sometimes induced short-term potentiation. In contrast to these similarities, LTP of IPSP was induced by a wider range of stimulus frequencies than that capable of generating LTP of EPSPs in CA1. It was induced not only by a brief high-frequency stimulation but also by an intermediate-frequency (2 Hz) stimulation continued for 5 min. In addition, the LTP induction was not dependent on postsynaptic membrane potential. Finally, the LTP of IPSP was more easily induced in developing than in mature rats. This age dependence suggests that LTP of IPSPs may contribute to the improvement of response selectivity of visual cortical cells through visual experience during postnatal development.

Aging↗

Effects of choreito consumption on struvite crystal growth in urine of cats.

The effect of a dietary supplement, choreito, on in vitro struvite crystal growth in feline urine was evaluated. Adult specific-pathogen-free cats (4 females, 4 males) considered to be clinically normal on the basis of physical examination findings and normal results of CBC, serum biochemical analyses, and urinalyses obtained before the beginning of the study were used. Before 24-hour urine sample collections were made, cats were fed a commercial canned diet with 0 or 500 mg of choreito supplement/kg of body weight for at least 2 weeks in a cross-over design with 4 cats/treatment. Filtered urine samples were analyzed for urine pH, specific gravity, osmolality, and urine electrolytes. The struvite activity product was calculated, using a statistical software program that calculates urine saturation. Urine samples were placed in wells of cell culture plates, increasing concentrations of ammonium hydroxide were added to adjacent wells to stimulate struvite crystal growth, and the plates were incubated at 37 C. Crystal growth was assessed by determination of number of crystals and supersaturation index by direct visualization, using an inverted microscope. Supplementation of the diet with choreito (at this concentration) did not change urine pH, specific gravity, osmolality, urine electrolyte composition, or calculated struvite activity product. However, supplementation significantly (P < 0.05) reduced crystal number and supersaturation index. These results indicate that direct observation of struvite crystal formation in whole urine may more accurately predict the effects of treatments to prevent or treat struvite urolithiasis than do calculations based on electrolyte concentration that do not account for the effect of urine macromolecules.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Randomized controlled study of sequential methotrexate and 5-fluorouracil therapy with or without 5'-deoxy-5-fluorouridine against advanced gastrointestinal cancer. Hirosaki Cooperative Study Group for Cancer Chemotherapy].

Seventy-five patients with gastrointestinal cancer were entered in this study. The number of eligible cases were 38 in the group treated with sequential methotrexate (MTX)/5-fluorouracil (5-FU) with 5'-deoxy-5-fluorouridine (5'-DFUR) (group A) and 34 in the group without 5'-DFUR (group B). The treatment schedules were as follows: MTX/100 mg/m2 was given intravenously (i.v.) followed by 5-FU 600 mg/m2 i.v. 2 hours later and leucovorin 15 mg/body i.v. 8 and 20 hours later. This cycle was repeated once a week. In group A, 5'-DFUR 1,200 mg/body/day was given orally 5 consecutive days per week. Three of 35 cases in group A showed PR, while no case showed PR in group B. Median survival time was 5.0 months in group A and 5.3 months in group B, respectively. Gastrointestinal toxicity was commonly observed, and diarrhea was more frequent in group A (p < 0.05).

Adult↗

[Surgical indication for unruptured cerebral aneurysm in patients with ischemic cerebrovascular disease].

A series of 44 cases is presented of patients who received surgical treatment for unruptured aneurysms in the anterior circulation, and which were associated with ischemic cerebrovascular disease (CVD). The age of patients varied from 34 to 76 (mean 62.8) years old. The associated ischemic CVD was transient ischemic attack (TIA) in ten, minor completed stroke in 23, and major completed stroke in 11 cases. Thirty five patients recovered fully. However, there were three deaths due to new cerebral infarction or delayed intracranial hemorrhage within 30 days after surgery (mortality 6.8%). Transient morbidity occurred in four patients (9.1%), and permanent morbidity in two patients (4.5%). In six cases, new ischemic events occurred after the surgery. In contrast, all 40 patients whose unruptured aneurysms were not associated with CVD fully recovered from the surgery they underwent. The authors indicate three risk factors which might lead to complication; diabetes mellitus, aneurysms located in the middle cerebral artery, and those larger than 6mm in diameter. Another three life-threatening factors are; elderly patients (> 65 year-old), male, aneurysms larger than 7mm in diameter. Direct surgery for unruptured aneurysms in ischemic CVD patients should be considered in cases free of risk factors indicated above. Eight cases in this series had extracranial carotid artery stenosis on the same side as the aneurysm. Carotid endoarterectomy (CEA) was performed prior to aneurysmal clipping in six patients, and their postoperative courses were excellent. In two patients, clipping was performed prior to CEA, and transient morbidity occurred in one of them.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗