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Biomedical subjects

A Kubota

Publications and source records attributed to A Kubota.

At least 91 records · Page 5Linked to original sources
PubMed1998

Adrenal hemorrhage associated with Klebsiella oxytoca bacteremia.

Septic adrenal hemorrhage is classically caused by meningococcemia. An autopsied case is presented of a 45-year-old man with adrenal hemorrhage due to Klebsiella oxytoca bacteremia following placement of a central venous catheter. He died 5 hours after developing disseminated intravascular coagulation (DIC). The bacterial entry site may have been the catheter. The cause of death was considered to be pulmonary edema due to bacteremia rather than adrenal insufficiency due to hemorrhage. Septic adrenal hemorrhage should be recognized as a subtype of sepsis rather than adrenal insufficiency, and may be caused in conditions of severe sepsis with DIC, independent of the microorganic variety.

Adrenal Gland Diseases↗
PubMed1998

[Telomerase activity of tumors in the head and neck].

Telomerase is a maintaining enzyme of telomere repeats. Telemorase is expressed in immortal and cancer cells, but not in the normal tissues. We investigated telomerase activity of tumors in the head and neck. Telomerase activity was found in all of the cell lines derived from squamous cell carcinomas of the head and neck. Six of 9 (67%) primary fresh tissues from squamous cell carcinomas of the head and neck contained detectable telomerase activity. There were no apparent relationship between telomerase activity and clinical stage. Telomerase activity differed, depend on the responses to chemotherapy and radiotherapy: complete response, 0 of 3(0%); partial response; 0 of 1(0%); no change; 7 of 7 (100%). Therapy-resistant tumor seemed to have much telomerase activity and much malignant potential. In benign tumors, neither of 2 benign parotid tumors expressed telomerase activity, but one of 2(50%)papillomas had the telomerase activity. Telomerase is considered useful tumor marker for the diagnosis and prognosis.

Biomarkers, Tumor↗
PubMed1998

Vitamin E prevents apoptosis in cortical neurons during hypoxia and oxygen reperfusion.

Cerebral ischemia followed by oxygen reperfusion induces apoptosis in hippocampal neurons in stroke-prone spontaneously hypertensive rats (SHRSP) but not in Wistar Kyoto rats (WKY). The overproduction of oxygen-free radicals that occurs in the tissues of SHRSP is implicated in reoxygenation injury after hypoxia. Antioxidants inhibit reoxygenation injury in hippocampal slices, and temporal cortices in Alzheimer's disease increase sensitivity to oxygen-free radicals. Because this sensitivity may contribute to the development of the disease, we have studied hypoxia and oxygen reperfusion using cortical neurons isolated from WKY and SHRSP (at 15 days of gestation). We have tried to determine whether cortical neurons are damaged under these conditions, and whether neurons from SHRSP are more vulnerable than those from WKY. We have tried also to verify whether neuronal damage is minimized by vitamin E using the following techniques: (a) Trypan blue staining, (b) in situ staining of apoptosis, (c) ultrastructural examination, and (d) measurement of lactic dehydrogenase (LDH) activity in the bathing medium. Furthermore, we have examined the mechanisms involved in the development of neuronal damage and have studied ways of minimizing it. We demonstrated that 36 hours of hypoxia significantly increased the rate of cell death in SHRSP (p < 0.01), although 12 to 24 hours of hypoxia did not increase cell death in either WKY or SHRSP. In addition, 6 to 36 hours of hypoxia and 1.5 to 5 hours of oxygen reperfusion heavily damaged cells of both WKY and SHRSP, and most became apoptotic or necrotic. In contrast, cells incubated with 50 to 300 microg/ml of vitamin E remained intact, although 10 to 20 microg/ml of vitamin E did not totally preserve the cells. Moreover, vitamin E protected the neurons from high concentrations of sodium nitroprusside (nitric oxide donor) in a dose-dependent manner. Vitamin E, when added to the cells, increased in concentration in a time-dependent manner over a 24-hour period and in a dose-dependent manner below 200 microg/ml, and it was detected mostly in the mitochondria. We also demonstrated that serial treatments with allopurinol (a xanthine oxidase inhibitor) or superoxide dismutase preserved neurons during hypoxia and oxygen reperfusion. These data indicate that SHRSP neurons are weaker than WKY neurons in long-term hypoxia; oxygen radical generation occurs in the early minutes after reperfusion, and then the oxygen-free radicals cause heavy damage to the cells; and antioxidants including vitamin E react with the radicals, thereby preventing apoptosis and necrosis. Therefore, antioxidants appear to be the most important agents in lowering oxygen-free radical damage in cortical neurons.

Animals↗
PubMed1997

Gastric inhibitory polypeptide activates MAP kinase through the wortmannin-sensitive and -insensitive pathways.

The signal transduction pathways of a cloned human gastric inhibitory polypeptide (GIP) receptor have been investigated in CHO cells stably expressing this receptor. Exposure of GIP receptor expressing cells to GIP significantly increased MAP kinase activity. Time course analysis showed that a rapid and marked increase in MAP kinase activation was detected and that this activation reached maximal levels 10 min after the addition of GIP. Dose-response analysis showed that GIP activated MAP kinase activity in a dose-dependent manner with an ED50 value of 5.9 x 10(-10) M of GIP. Wortmannin, a potent inhibitor of phosphatidylinositol 3-kinase (PI3-kinase), partially inhibited GIP-induced MAP kinase activation, suggesting that GIP activates MAP kinase through two different, wortmannin-sensitive and -insensitive pathways. It has been demonstrated that in CHO cells cAMP attenuates MAP kinase activity by inhibiting Raf-1. Since GIP elevates intracellular cAMP, we examined the effects of cAMP on MAP kinase activation. Interestingly, forskolin, which increased intracellular cAMP levels, significantly inhibited MAP kinase activation by GIP, but did not affect MAP kinase activation by GIP in the presence of wortmannin, suggesting that the wortmannin-sensitive pathway activates an MAP kinase cascade at or above the level of Raf-1 and that the wortmannin-insensitive pathway activates an MAP kinase cascade below the level of Raf-1. These findings demonstrate that the GIP receptor is linked to the MAP kinase cascade via at least two different pathways.

Androstadienes↗
PubMed1997

GSTM1 gene polymorphism as a possible marker for susceptibility to head and neck cancers among Japanese smokers.

Increased risk of lung cancer has been reported in individuals with glutathione S-transferase M1 (GSTM1) gene deletion, with limited evidence for head and neck (HN) cancer. Here, we report the results of a case-control study in Japanese HN cancer patients (n = 158) and community controls (n = 174). GSTM1 null genotype (GSTM1(-)) was distributed more in smoker patients than in control subjects (56.7% vs. 48.5%) but not in non-smoker patients (48.3%). In smokers, GSTM1(-) was detected at increased frequency in non-larynx cancer (62.7%, odds ratio 1.77, 95% CI 1.04-3.01) but not in larynx cancer (48.1%). In larynx cancer GSTM1(-) was presented at higher frequency in patients < 60 years old than in those > or = 60 years old (78.6% vs. 36.8%). These findings suggest that the GSTM1 gene polymorphism potentially modifies the risk for HN cancer depending on smoking history, the region of cancer and age.

DNA, Neoplasm↗
PubMed1997

Angiotensin II inhibits protein kinase A-dependent chloride conductance in heart via pertussis toxin-sensitive G proteins.

BACKGROUND: Angiotensin II receptors are reported to be abundant in the guinea pig ventricle; their coupling to adenylate cyclase in the heart, however, remains controversial. Therefore, we investigated the effect of angiotensin II on Cl- conductance activated by cAMP-dependent protein kinase. METHODS AND RESULTS: After minimizing the contribution of other ionic currents, exposure of single guinea pig ventricular cells to isoproterenol (40 to 50 nmol/L; 36 degrees C) elicited a typical protein kinase A-dependent Cl- conductance. Subsequent application of angiotensin II reduced the isoproterenol-induced conductance with an IC50 of 0.24 +/- 0.08 nmol/L. Angiotensin II also inhibited the Cl- currents, which were activated through stimulation of adenylate cyclase by forskolin and histamine receptors. CV-11974 (1 mumol/L), an antagonist selective for the angiotensin type 1 receptor, prevented the effect of angiotensin II. Angiotensin II did not inhibit the current that had been persistently activated by intracellular GTP gamma S (100 mumol/L), a nonhydrolyzable guanine nucleotide, plus isoproterenol. In addition, prior incubation of myocytes with pertussis toxin prevented the angiotensin II inhibitory action. Cl- conductance, when activated directly by intracellular dialysis with cAMP (1 mmol/L), was not affected by angiotensin II. Radioimmunologic measurement of cellular cAMP in the dissociated myocytes showed that angiotensin II inhibited the isoproterenol-induced increase of cAMP. CONCLUSIONS: Angiotensin II receptors negatively couple to adenylate cyclase via pertussis toxin-sensitive G proteins, thereby inhibiting cardiac protein kinase A-dependent Cl- conductance.

Adenylate Cyclase Toxin↗
PubMed1997

Esophageal atresia in Osaka: a review of 39 years' experience.

BACKGROUND: One hundred fifty-nine patients who had esophageal atresia with or without tracheoesophageal fistula have been treated at Osaka University Medical School and its affiliated hospitals since the initial (Japanese) experience of Dr T. Ueda in 1957. METHODS: These cases were divided chronologically into three groups. With earlier recognition of surgical neonates and the development of perinatal care, the long-term survival of these patients has steadily improved over 39 years from 28% in the first period (1957 to 1967) to 80% in the third period (1980 to 1995). Of 141 patients treated in the second and third periods (1968 to 1995), 92 (65.2%) had associated anomalies. Cardiovascular and gastrointestinal malformations were the most frequently seen major anomalies. VATER or VACTER association was seen in 12.8% (18 of 141) of these patients. Survival of these cases according to Waterston risk factors was 100% for group A, 100% for group B, and 50% for group C, whereas the new classification proposed by Spitz showed survival of 92% for group 1, 50% for group 2, and 0% for group 3, showing better differentiation among the three groups. RESULTS: There was a long gap between the proximal and distal esophageal ends in seven patients (type A), in all of whom primary anastomosis was possible after 28 to 128 days of elongation by bouginage. Although the survival of esophageal atresia patients dramatically improved in recent years, there is still a high incidence of early and long-term postoperative complications, ie, anastomotic leakage (26.5%), recurrent fistula (7.2%), anastomotic stricture (49.1%), postoperative pneumonia or atelectasis (57.0%), tracheomalacia (25.8%), and gastroesophageal reflux (52.0%). CONCLUSIONS: Recently, there have been changing patterns in the occurrence of complications, which are mainly attributed to technical improvement, better perinatal care and early recognition of pathophysiologic conditions such as tracheomalacia and gastroesophageal reflux.

Abnormalities, Multiple↗
PubMed1997

Analysis of DNA ploidy using fresh frozen tissues of head and neck squamous cell carcinomas.

The DNA ploidy of fresh frozen tissues of head and neck squamous cell carcinomas was determined by flow cytometry to investigate whether DNA ploidy is correlated with various clinical and pathological parameters. The subjects were 51 patients who had been treated radically by our department. The DNA ploidy pattern was classified into three types, diploid, single aneuploid and multiploid, according to the DNA index and the DNA histogram. This is our original classification. No particular correlation could be detected between the DNA ploidy pattern and sex, age, primary tumour site or disease stage. The degree of tissue differentiation tended to be poorer in aneuploid tissues than in diploid tissues. The efficacy of chemotherapy was higher in aneuploid cases than in diploid cases. The recurrence rate was significantly lower in diploid cases than in multiploid cases. When disease stage, degree of histological differentiation, efficacy of the chemotherapy and the DNA ploidy pattern were subjected to multivariate analysis for correlation with the prognosis, the DNA ploidy pattern showed the highest correlation. The results suggest that the DNA ploidy as analyzed by flow cytometry can be used as an important prognostic factor.

Aged↗
PubMed1997

Myasthenia gravis and alopecia areata.

Of 202 patients with myasthenia gravis (MG), 6 (3%) developed alopecia areata. All six patients had a thymoma verified by pathology; the frequency of alopecia areata rose to 17% of 35 MG patients with a thymoma. In one patient who had no recognizable tumor in the mediastinum, an ectopic thymoma was present in the anterior neck.

Adolescent↗
PubMed1997

Long-term follow-up of a girl with the neonatal form of Bartter's syndrome.

We followed up a girl with the neonatal form of Bartter's syndrome for sixteen years and determined the sensitivity to angiotensin II before and during the indomethacin treatment. A 4-month-old girl was admitted to our hospital, because of severe hypokalemia and growth retardation. Initially we treated her with spironolactone and potassium supplements. This treatment increased plasma potassium levels and her growth. At the age of one year she was diagnosed as having Bartter's syndrome. Since then she has been treated with indomethacin at an initial dose of 3 mg/kg/day combined with spironolactone and potassium. After the start of the indomethacin treatment, her growth increased dramatically, and her final height was normal adult height. Her puberty developed normally and menarche occurred at the age of 12 years. Levels of serum sodium, chloride, plasma aldosterone and urinary prostaglandin E2 were also normalized. Levels of angiotensin I and II were improved but not within the normal range, but plasma potassium levels slightly decreased after plasma aldosterone levels were normalized and did not change during the treatment period. Plasma renin activity remained high until about the age of 8 years, after which it decreased to almost within the normal range. At 5 months after the start of indomethacin (3 mg/kg/day), her vascular sensitivity to angiotensin II had been improved, and after 2 years and 5 months, her vascular sensitivity was further improved. At this time renin activity had decreased after angiotensin II infusion, but plasma aldosterone did not change. At the age of 16 years (dose of indomethacin: 0.5 mg/kg/day), plasma aldosterone increased after angiotensin II infusion. These data suggest that indomethacin and spironolactone are effective treatments for the neonatal form of Bartter's syndrome, especially during childhood.

Angiotensin I↗
PubMed1997

Elevated L-kynurenine level and its normalization by prednisolone in a patient with eosinophilia-myalgia syndrome.

We report a L-tryptophan-induced case of eosinophilia-myalgia syndrome in a Japanese woman and describe the time course of changes in tryptophan metabolism observed during steroid therapy. She had taken 1.0 g of the implicated L-tryptophan daily. When admitted due to painful swelling of her extremities, eosinophil count was 22.3 x 10(9)/L. Before prednisolone treatment, her serum L-kynurenine level was 10.2 mumol/L, a level about three-fold higher than the normal value, while serum tryptophan level was abnormally low (23.1 mumol/L). On the 14th day of prednisolone treatment (40 mg daily), L-kynurenine was declined to 8.1 mumol/L and, concomitantly, L-tryptophan level increased to the normal range (51.0 mumol/L). Subsequently, on the 42nd day of therapy, serum L-kynurenine was normalized. In contrast, serum serotonin level was unchanged throughout the course of this therapy. Prednisolone dramatically reduced the elevated serum L-kynurenine with a reciprocal increase in serum L-tryptophan indicates that abnormal tryptophan metabolism, may play a role in the pathogenesis of eosinophilia myalgia syndrome, and that the observed effect of steroid treatment was due to suppression of elevated activity of indoleamine 2, 3-dioxygenase, a first rate-limiting enzyme of the kynurenine pathway.

Anti-Inflammatory Agents↗
PubMed1997

Insulin-like growth factors prevent apoptosis in cortical neurons isolated from stroke-prone spontaneously hypertensive rats.

Cerebral ischemia induces a massive efflux of glutamate causing delayed neuronal death in stroke-prone spontaneously hypertensive rats (SHRSP) but not in Wistar Kyoto rats (WKY). It is obvious that L-N-nitroarginine (L-NNA; NO synthase (NOS) inhibitor), benzamide (poly(ADP-ribose) synthetase inhibitor), and growth factors are involved in reducing neuronal cell death due to toxic conditions, especially phosphatidylinositol 3 (PI3)-kinase activity; however, no studies have clarified whether genetic vulnerability to neurotoxic states is present in cortical neurons isolated from SHRSP. For this purpose, we prepared cortical neurons from WKY and SHRSP (15 weeks of gestation) to test the genetic vulnerability involved in the pathogenesis of stroke as well as apoptosis of cortical neurons isolated from SHRSP. We also examined the mechanisms necessary to reduce apoptosis under neurotoxic states using ultrastructural and biochemical techniques. Cortical neurons from SHRSP were in fact found to be more vulnerable than neurons from WKY and resulted in apoptosis when treated with nitric oxide (NO)- and N-methyl-D-aspartate (NMDA)-mediated neurotoxic agents. Growth factors, especially insulin-like growth factor (IGF), rescued neurons from NO- and NMDA-mediated neurotoxicity, particularly those from SHRSP. Conversely, benzamide and L-NNA reduced NMDA-mediated neurotoxicity but not NO-mediated toxicity. The ability to protect neurons from neurotoxicity was as follows: IGF-->nerve growth factor epidermal growth factor-->L-NNA-->benzamide. In addition, it was demonstrated that wortmannin, a PI3-kinase inhibitor, lessened the protective effects of these growth factors against NO-mediated toxicity. The data thus indicate that genetic factors related to neuronal vulnerability to apoptosis are involved in the pathogenesis of stroke lesions in SHRSP. PI3-kinase activity, which is stimulated by growth factors, is closely related to protective effects against NO- and NMDA-mediated toxicity in cortical neurons, especially those isolated from SHRSP. Moreover, the genetic vulnerability observed in SHRSP neurons is possibly linked to the inadequate activation of signaling pathways in the downstream of protein tyrosine kinases.

Animals↗
PubMed1997

Insulin-like growth factor-1 attenuates apoptosis in hippocampal neurons caused by cerebral ischemia and reperfusion in stroke-prone spontaneously hypertensive rats.

Cerebral ischemia followed by reperfusion induced apoptosis in stroke-prone spontaneously hypertensive rats (SHRSP) but not in Wistar Kyoto rats (WKY). Our in vitro studies revealed that IGF-1 prevented apoptosis caused by nitric oxide- and N-methyl-D-aspartate-mediated toxic agents in cortical neurons isolated from SHRSP. In addition, it was reported that IGF-1 given 1 hour before ischemia significantly attenuated the incidence of myocyte apoptosis after myocardial ischemia and reperfusion. IGF-1 (20 micrograms/rat) was administered ip 1 hour before the clipping of both common carotid arteries in WKY and SHRSP. Rats underwent cerebral ischemia for 20 minutes and reperfusion for 6 days before they were killed. We cut the brain coronally, removed sections from the hippocampal CA1 region, and examined the neurons in these samples using an electron microscope. We tried to clarify whether pretreatment using IGF-1 decreases the number of apoptotic neurons in SHRSP with cerebral ischemia followed by reperfusion. SHRSP with normal cerebral circulation had 30.4 +/- 8.0 apoptotic neurons per 1000 neurons. Cerebral ischemia followed by reperfusion significantly (p < 0.01) increased the number of apoptotic neurons (235.2 +/- 25.2/1000 neurons) in SHRSP. In contrast, pretreatment with IGF-1 reduced the number of apoptotic neurons in SHRSP (82.8 +/- 11.2/1000 neurons; p < 0.01) under otherwise identical conditions. We concluded that the genetic vulnerability to apoptosis in SHRSP neurons was involved in the pathogenesis of stroke lesions and that this vulnerability was attenuated by the IGF-1 pretreatment.

Animals↗
PubMed1997

[Hexokinase gene].

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Diabetes Mellitus, Type 2↗
PubMed1996

Evaluation of cholecystokinin, gastrin, CCK-A receptor, and CCK-B/gastrin receptor gene expressions in gastric cancer.

The brain-gut hormones, cholecystokinin (CCK) and gastrin, regulate the growth of gastrointestinal mucosa and tumor cells. In this study, reverse transcription-polymerase chain reaction (RT-PCR) was used to evaluate messenger RNA expression for CCK, gastrin, CCK-A receptor, and CCK-B/gastrin receptor in surgical specimens of gastric cancers and in normal antrum and body mucosa of the stomach. The CCK mRNA expression was detectable in 4/14 (29%) samples of gastric cancer and in 3/12 (25%) samples of antral mucosa. However, the gastrin mRNA expression was not detectable in any gastric cancer samples, although it was detectable in all the samples of antral mucosa. The CCK-A receptor mRNA expression was detectable in 5/14 (36%) samples of gastric cancer and in 7/12 (58%) body mucosa. Three cases out of 14 (21%) of gastric cancer expressed both CCK gene and CCK-A receptor gene. The CCK-B receptor mRNA expression was detectable in only 1/14 (7%) samples of gastric cancer, although it was detectable in 10/12 (83%) body mucosa of the stomach. These findings may suggest a greater role for CCK and CCK-A receptor than for gastrin and CCK-B receptor in gastric cancers.

Cholecystokinin↗
PubMed1996

Glucocorticoid-mediated gene suppression of rat cytokine-induced neutrophil chemoattractant CINC/gro, a member of the interleukin-8 family, through impairment of NF-kappa B activation.

The glucocorticoid dexamethasone inhibited the production of the rat cytokine-induced neutrophil chemoattractant CINC/gro, a counterpart of human melanoma growth-stimulating activity that belongs to the interleukin-8 (IL-8) family, in the normal rat kidney epithelial cell line NRK-52E stimulated with interleukin-1 beta (IL-1 beta), lipopolysaccharide, or tumor necrosis factor alpha. The accumulation of CINC/gro mRNA induced by these activators was also decreased comparably by dexamethasone. A nuclear run-on assay revealed that dexamethasone decreased the IL-1 beta-induced transcription of the CINC/gro gene. The half-life of CINC/gro mRNA transcripts did not change significantly after exposure to dexamethasone, suggesting that this glucocorticoid acts mainly at the transcriptional level. Transfection with luciferase expression vectors containing 5'-deleted and mutated CINC/gro gene sequences demonstrated that the 5'-flanking region containing the NF-kappa B binding site is involved in the IL-1 beta- and dexamethasone-induced activation and repression of the CINC/gro gene expression, respectively. Furthermore, a tandem repeat of the NF-kappa B sequence in the CINC/gro gene conferred the inducibility by IL-1 beta and suppression of luciferase activity by dexamethasone. In an electrophoretic mobility shift assay, dexamethasone diminished the IL-1 beta-induced formation of NF-kappa B complexes, which consisted of p65 and p50. Western blotting revealed that dexamethasone inhibited the IL-1 beta-induced translocation of p65 from the cytoplasm into the nucleus, while the nuclear level of NF-kappa B p50 remained almost unchanged. In addition, the degradation of I kappa B-alpha induced by IL-1 beta was not inhibited by dexamethasone. These results indicated that the suppression of the CINC/gro gene transcription by glucocorticoid occurs through the impairment of NF-kappa B activation, possibly by interference with the translocation of NF-kappa B p65 from the cytoplasm into the nucleus, thereby suppressing transactivation of the CINC/gro gene.

Animals↗