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Biomedical subjects

Y Kinoshita

Publications and source records attributed to Y Kinoshita.

At least 19 recordsLinked to original sources

Cloning and characterization of gastrin receptor from ECL carcinoid tumor of Mastomys natalensis.

We report here the cDNA cloning of a putative gastrin receptor from enterochromaffin-like (ECL) carcinoid tumor of Mastomys natalensis. For this study, we used the polymerase chain reaction technique to amplify transmembrane domain sequences related to rat pancreatic cholecystokinin (CCK)-A receptor from the ECL tumor cDNA library. The amino acid sequence deduced from the cloned cDNA showed 85.7% and 49.0% identity to canine parietal cell gastrin receptor and rat pancreatic CCK-A receptor, respectively. Ligand binding studies using COS-7 cells transfected with the cDNA showed the same binding specificity for gastrin and CCK-8 as the gastrin receptor on the Mastomys carcinoid tumor membrane. Both gastrin and CCK-8 elevated free cytosolic calcium concentration in COS-7 cells expressing the cloned receptor. RNA blot analysis revealed the expression of the gastrin receptor in both Mastomys stomach and brain.

Amino Acid Sequence

Activation of Src-like protein-tyrosine kinase Lyn and its association with phosphatidylinositol 3-kinase upon B-cell antigen receptor-mediated signaling.

Crosslinking of membrane-bound immunoglobulins, which are B-cell antigen receptors, causes proliferation and differentiation of B cells or the inhibition of their growth. The receptor-mediated signaling involves tyrosine phosphorylation of cellular proteins. The Src-like protein-tyrosine kinase Lyn is expressed preferentially in B cells and is an intracytoplasmic constituent of the B-cell antigen receptor complex. Crosslinking of membrane-bound immunoglobulin M with antibody induced rapid increases in the kinase activities of Lyn and Lyn-associated phosphatidylinositol 3-kinase. Crosslinking of B-cell antigen receptor also induced association of Lyn with an 85-kDa noncatalytic subunit of phosphatidylinositol 3-kinase. Thus, Lyn is functionally associated with membrane-bound immunoglobulin M and seems likely to participate in B-cell antigen receptor-mediated signaling.

B-Lymphocytes

Morphological and functional alterations of the hypothalamic-pituitary system in brain death with long-term bodily living.

Hypothalamic hormones as well as anterior pituitary hormones were detected in the peripheral plasma after the diagnosis of brain death. It is possible that residual hypothalamic tissue was functioning after satisfying the usual criteria of total brain death. To examine this possibility, endocrinological and morphological alterations of the hypothalamic-pituitary system was evaluated in 28 brain dead patients. Intrinsic ADH was depleted in the plasma shortly after the diagnosis of brain death. Anterior pituitary hormones were initially detected in all patients, but gradually disappeared. The direct TRH (thyrotropin releasing hormone) stimulation to the anterior lobe was responded to well. Morphological studies showed a partial necrosis of the anterior lobe and the preservation of the posterior lobe for as long as a week. These data prove that the pituitary is partially preserved after brain death. LH-RH (luteinizing hormone releasing hormone) was detected in the peripheral plasma of all patients and GRF (growth hormone releasing factor) was detected in half of the patients for as long as 15 days, but autopsy revealed the fact that the brain tissue including the hypothalamus became extensively necrotic after the sixth day of brain death. In order to solve this controversy it is proposed that these hormones originate from extracranial tissues such as pancreas. The detection of hypothalamic hormones after the diagnosis of brain death therefore is not contradictory to the concept of total brain death.

Adolescent

Acinar cell carcinoma of the pancreas with elevated serum alpha-fetoprotein levels: a case report and a review of 28 cases reported in Japan.

A 60-year-old male with elevated serum AFP levels is reported. Other tumor markers apart from AFP were normal. Serum AFP did not bind to Con A or Lentil-lectin by affinity chromatography. Abdominal ultrasonography, computed tomography and endoscopic retrograded cholangiopancreatography demonstrated a tumor extending from the body to the tail of the pancreas. The tumor was strongly suggested to be an acinar cell carcinoma of the pancreas, based on the histological findings of the resected specimen. The peroxidase-antiperoxidase method showed cancer cells to be positive for AFP. In Japan, only 27 cases of pancreatic cancer with elevated serum AFP level have been reported. This is the first Japanese case of pancreatic cancer in which the binding of serum AFP to lectins was investigated.

Carcinoma

Diagnostic significance of nuclear DNA content and nuclear area in oral hyperplasia, dysplasia, and carcinoma.

The nuclear DNA content and the nuclear area in hyperplasia, dysplasia, and carcinoma of the oral cavity were quantitatively analyzed by microspectrophotometry. In carcinoma, marked variability of the nuclear DNA content and the nuclear area was found. The mean nuclear DNA content, the variance of the nuclear DNA content, the frequency of cells above tetraploid (4 C), the mean nuclear area, and the variance of nuclear area in hyperplasia and dysplasia were significantly different from these values with carcinoma. In some cases of leukoplakia and verrucous hyperplasia with subsequent malignant formation, the values were beyond the lower limit of carcinoma. The results suggest that the nuclear DNA and the nuclear area are important objective indices for predicting malignant potential of precancerous lesions.

Carcinoma, Squamous Cell

A case of deletion of the short arm of chromosome 10 with severe hearing loss and brainstem dysfunction.

A male newborn infant with a deletion of the short arm of chromosome 10p 14 was described. In addition to the typical clinical features, electrophysiologic studies showed brainstem dysfunction and severe hearing loss when examined with auditory brainstem response and photopalpebral reflex. These electrophysiologic studies may be of benefit for early evaluation of brainstem functions and hearing ability of the patients of such chromosomal aberration and may also be useful predictors of psychomotor development.

Abnormalities, Multiple

Establishment of an enzyme immunoassay using monoclonal antibody (HG1-219) and its application for the diagnosis of hepatocellular carcinoma.

A monoclonal antibody (MoAb HG1-219) against a human gastric cancer cell line (HuG-1) and its shedding antigen (HG1-219 Ag) was generated and a solid-phase sandwich enzyme immunoassay (EIA-219) was developed. The mean serum HG1-219 Ag concentration in normal individuals was 30.5 +/- 14.5 U/ml measured by EIA-219. When the mean +3 SD of the antigen concentration in normal individuals was used as a cut-off level, 4.3% (2/47) of patients with chronic hepatitis, 9.1% (4/44) of cirrhotic patients and 37.5% (18/48) of patients with hepatocellular carcinoma (HCC) had HG1-219 Ag above the cut-off value. The positive rates of a-fetoprotein (AFP) (> 400 ng/ml) and protein induced by vitamin K absence or antagonist-II (PIVKA-II) for HCC were 26.7% (12/45) and 33.3% (12/36), respectively. There was no significant correlation between HG1-219 Ag and AFP or PIVKA-II in patients with HCC. The combination assay of EIA-219, AFP and PIVKA-II for HCC gave the positive rate of 75% (27/36). The effect of periodic acid on the HG1-219 Ag and the inhibition of EIA-219 by CA 19-9 suggest that the epitope of HG1-219 Ag is a suger chain similar to CA 19-9.

Animals

Characterization of multiple forms of carbonyl reductase from chicken liver.

Three enzyme forms (CR1, CR2 and CR3) of carbonyl reductase were purified from chicken liver with using 4-benzoylpyridine as a substrate. CR1 was a dimeric enzyme composed of two identical 25-kD subunits. CR2 and CR3 were monomeric enzymes whose molecular weights were both 32 kD. CR1 exhibited 17 beta-hydroxysteroid dehydrogenase activity as well as carbonyl reductase activity in the presence of both NADP(H) and NAD(H). CR2 and CR3 had similar properties with regard to substrate specificity and inhibitor sensitivity. They could exhibit the activity only with NADPH and had no hydroxysteroid dehydrogenase activity. CR2 and CR3 cross-reacted with anti-chicken kidney carbonyl reductase antibody, though CR1 did not. The results suggest that CR1 is a hydroxysteroid dehydrogenase, and CR2 and CR3 are similar to each other and to the kidney enzymes.

17-Hydroxysteroid Dehydrogenases

Absence of response to hypothalamic stimulation test in brain death.

Immunoreactive corticotropin-releasing hormone (CRH) and growth hormone-releasing hormone (GHRH) are present in the plasma of the brain dead patients. These hypothalamic hormones may reflect some residual brain function after brain death. To examine the hypothalamic function, insulin-induced hypoglycemia and arginine infusion were performed in brain dead patients. Plasma CRH and GHRH were present initially, but levels did not increase significantly for 120 minutes after insulin injection. GH, adrenocorticotropic hormone, and cortisol levels did not increase either. Arginine load did not induce GH. These results suggest that hypothalamic hormones in the plasma after whole brain death do not reflect hypothalamic functions. The hormones may originate from extrahypothalamic sources such as the pancreas or adrenal gland.

Adolescent

[Age-related effects of gastroduodenoscopy on arterial oxygen saturation].

Although endoscopy is widely used for safe and accurate examinations of gastroduodenal disease cases, several investigators reported arterial oxygen desaturation occurring during endoscopy. Endoscopy-induced oxygen desaturation is hazardous because it increases the risk of cardiac arrhythmia. This study is designed to investigate whether gastroduodenal endoscopy causes remarkable oxygen desaturation in elderly patients in comparison with younger ones and to study whether nasal oxygen administration can prevent it. Forty-four patients over 61 years old and 37 patients younger than 60 were divided into two groups, to one of which 100% oxygen (2 l/min) was administered through nasal prongs. During endoscopy, blood pressure, pulse rate, and arterial oxygen saturation (SaO2) were recorded at one-minute intervals by a pulse oximeter. Intubation of the endoscope caused a transient drop in oxygen saturation both younger and older patients with greater drops in older subjects (1.7 +/- 0.4% in the young and 3.3 +/- 0.8% in the old groups). In the older groups, two out of 20 patients who had no oxygen administration showed a saturation decrease of over 7%. On the other hand, no younger subject showed such a large degree of oxygen desaturation. Oxygen administration effectively prevented the endoscopy-induced desaturation both in younger and in older patients. In summary, the results of this study suggested that older subjects had a greater decrease of oxygen saturation during gastroduodenofiberscopy and that oxygen administration is useful to prevent the endoscopy-induced desaturation.

Aging

[A pathological study of incidental carcinoma of the prostate. Pathological study of age-groups].

We reviewed 66 patients with stage A adenocarcinoma of the prostate who were treated at our 7 affiliated hospitals in Yokohama between 1984 and 1988. Of 1377 patients who underwent subcapsular prostatectomy (SCP) or transurethral resection of the prostate (TUR-P) for benign prostatic hyperplasia, 66 patients (4.8%) were diagnosed as an incidental carcinoma of the prostate. Of these patients, 36 and 30 were in stage A1 and A2, respectively. In the 66 patients, 59 (4.5%) were detected in 1315 TUR-P and 7 (11.3%) in 62 SCP. Elderly patients over 80 years of age had a higher risk of stage A2 disease. In histological grade, well, moderately and poorly differentiated adenocarcinoma were found in 48 patients (72.7%), 13 (19.7%) and 5 (7.6%), respectively. Among the patients with stage A prostate carcinoma the majority of the age-group less than 79 years old had well differentiated adenocarcinoma. In the age-group more than 80 years old, there were 6 (37.5%) moderately and 2 (12.5%) poorly differentiated tumors. In other words, the age-group more than 80 years old tended to have the moderately or poorly differentiated adenocarcinoma more frequently than those other decades. We expect an increase in the number of patients with stage A2 disease in the future with the expansion of the operative indication, especially in elderly patients.

Adenocarcinoma

[Pedunculated hepatocellular carcinoma suspected of right adrenal tumor: a case report].

We report a rare case of extrahepatic growing hepatocellular carcinoma which was clinically diagnosed as right adrenal tumor. A 61-year-old woman was admitted for further examination of right flank pain and hypertension. Abdominal computed tomographic scan and echogram revealed a suprarenal mass. Hypercatecholaminemia was suspected from urinary analysis. Preoperative diagnosis was right adrenal tumor; suspected pheochromocytoma. On operation, we found the tumor was pedunculated from right lobe of liver and compressing normal right adrenal gland. Its clinical diagnosis was hepatocellular carcinoma. Ten months after operation she is still alive. We discuss the difficulty of differential diagnosis between extrahepatic growing hepatocellular carcinoma and adrenal tumor.

Adrenal Gland Neoplasms

Enhancement of DNA synthesis in rat thymocytes by stimulating their muscarinic acetylcholine receptors.

The binding of 3H-acetylcholine (ACh) to acetylcholine receptors (AChRs) on rat thymocytes was examined and found to be inhibited by the treatment with several antagonists against nicotinic and muscarinic AChRs. This result suggested that thymocytes have AChRs with different affinity, and bear both nicotinic and muscarinic AChRs on their surfaces. To make clear the functional significance of the AChRs, DNA synthesis of the thymocytes stimulated with ACh was examined. 3H-thymidine uptake of thymocytes was significantly increased when the cells were stimulated with ACh or another cholinergic agonist. The increment of DNA synthesis caused by ACh in thymocytes was not reduced by treatment with nicotinic antagonists, but was decreased by treatment with any of the muscarinic antagonists. Concentration of the intracellular second messengers, inositol 1,4,5-triphosphate (IP3) and guanosine 3',5'-cyclic monophosphate (cGMP) was also made higher by ACh stimulation. It is discussed that the enhancement of intracellular IP3 and cGMP concentrations after stimulation of muscarinic AChRs appears to be related with the increment of thymocyte DNA synthesis.

Acetylcholine

Inhibitory effect by 1,25-dihydroxyvitamin D3 on concanavalin A-stimulated proliferation of rat thymic lymphocytes.

It has been reported that vitamin D3 derivatives promote the differentiation of monocytes into macrophages, while the derivatives suppress mitogen-stimulated proliferation of human peripheral blood-mononuclear cells (PBMC). However, their effect on thymic lymphocytes which are in the course of differentiation and maturation into T cells has not been thoroughly examined. The authors studied the inhibitory effect by 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] on concanavalin A (Con A)-stimulated proliferation of rat thymic lymphocytes and explored its mechanism. The proliferation of rat thymic lymphocytes stimulated with Con A was suppressed by 1,25-(OH)2D3 in a dose-dependent manner between a range of 10(-10) M to 10(-8) M. Because this suppressive action of 1,25-(OH)2D3 was markedly reduced by removal of coexisting adherent cells or by treatment with indomethacin which suppresses the prostaglandin E2 (PGE2) synthesis, it seems likely that PGE2, released from macrophages with the stimulation of 1,25-(OH)2D3, is involved in the suppressive action. Further studies on the inhibitory mechanism clarified that PGE2 from the contaminated macrophages suppressed the formation and release of interleukin-2 (IL-2), whereas the expression of IL-2 receptors on thymic lymphocyte with Con A stimulation was not affected. These results suggest that vitamin D3 derivatives might possibly contribute to regulation of in vitro proliferation of thymic lymphocytes.

Animals

[Clinical analysis of 46 cases of radiation cystitis].

We experienced 46 cases of radiation cystitis between 1973 and 1990, 10 of which showed intractable bleeding and 17 recurrent bleeding. We clinically analyzed these cases to determine the factors responsible for intractable and recurrent bleeding. Intractable bleeding was suggested to related to the aggravation of the local condition of the urinary tract and recurrent bleeding with an increase of complications, especially diabetes mellitus and hypertension. In conclusion, long-term follow up of local conditions and complications is important in the prevention of intractable and recurrent bleeding of radiation cystitis.

Adult

[Clinical studies on tosufloxacin (TFLX) in urology].

We clinically evaluated the usefulness of a new oral antimicrobial agent, TFLX, in the field of urology. The dose administered was 150 mg t.i.d and the duration of administration was 3 days. The clinical effect was evaluated according to the criteria of the Japanese UTI committee. The clinical response obtained on 164 female patients with acute simple cystitis was excellent in 118, moderate in 44 and poor in 2 patients. The efficacy rate was 98.78%. The clinical response obtained on 4 male patients with acute simple cystitis was excellent in 2 and moderate in 2 patients. The efficacy rate was 100%. The clinical response obtained on 3 female patients with simple pyelonephritis was excellent in 2 and moderate in 1 patient. The efficacy rate was 100%. The clinical response obtained on one patient with non-gonococcal urethritis was excellent by doctor's evaluation. The clinical response obtained on 7 patients with complicated UTI was excellent in 3 and moderate in 4 patients. The efficacy rate was 100%. Three patients complained of stomach distress or malaise and 2 patients developed rash. No abnormal laboratory data were observed. Thus, TFLX appears to be safe and suitable for use in the field of urology.

4-Quinolones

Gastroesophageal reflux after endoscopic injection sclerotherapy.

The effect of sclerotherapy of esophageal varices on the gastroesophageal reflux was studied. Gastroesophageal reflux was monitored by a 24-h pH-monitoring catheter introduced into the distal esophagus. The results of pH monitoring of 16 patients who underwent sclerotherapy were compared with those of 21 patients with untreated varices. Seven of the 16 treated patients showed high occurrence rates of gastroesophageal reflux comparable to those observed in cases with severe reflux esophagitis. In the untreated group, only one patient showed pathological reflux (there was a significant difference between treated and untreated groups; p less than 0.01). When the level of reflux was compared with factors that might influence sclerotherapy-induced gastroesophageal reflux, there was a positive correlation between the magnitude of reflux and amount of sclerosant injected paravariceally in the submucosal tissue (p less than 0.05). The results indicate that the paravariceal injection of sclerosant for the treatment of esophageal varix may cause pathological gastroesophageal reflux after sclerotherapy is completed.

Analysis of Variance