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Biomedical subjects

Y Sakai

Publications and source records attributed to Y Sakai.

At least 505 records · Page 28Linked to original sources
PubMed1994

Immunohistochemical analysis of retinoblastoma gene product (pRB) expression in malignant and non-malignant liver diseases.

The retinoblastoma gene product is a nuclear phosphoprotein that undergoes cell cycle-dependent changes in its phosphorylation status. To analyze the expression of retinoblastoma gene product in the process of liver regeneration and the initiation of hepatocellular carcinoma, we studied immunohistochemically the expression of retinoblastoma gene product and DNA polymerase alpha (DPA) in 33 patients with various liver diseases. Only a few hepatocytes positive for retinoblastoma gene product were found in undamaged, nonregenerating liver tissues, whereas many hepatocytes positive for retinoblastoma gene product were detected in specimens of regenerating liver obtained from patients with acute or chronic liver diseases. Similarities were found between distribution patterns of hepatocytes positive for retinoblastoma gene product and those of hepatocytes positive for DPA, and a highly significant positive correlation was found between the number of hepatocyte nuclei stained for retinoblastoma gene product per 1000 nuclei examined (R-LI) and the number of hepatocyte nuclei stained for DPA per 1000 nuclei examined (D-LI) in tissues obtained from patients with nonmalignant liver disease. Hepatocellular carcinoma cells positive for DPA were detected in the 14 hepatocellular carcinoma specimens tested. In ten of these specimens, hepatocellular carcinoma cells positive for retinoblastoma gene product were found but not in the other four. For all hepatocellular carcinoma specimens, R-LI was proportional to D-LI. Thus in both nonmalignant and malignant liver, retinoblastoma gene product increased in proportion to proliferation of hepatocytes or hepatocellular carcinoma cells.

Adult↗
PubMed1994

Cloning and characterization of a Pseudomonas aeruginosa gene involved in the negative regulation of phosphate taxis.

Pseudomonas aeruginosa PAO1 exhibited a positive chemotactic response to P(i). The chemotactic response was induced by P(i) limitation. An alkaline phosphatase (AP) constitutive mutant showed a chemotactic response to P(i), regardless of whether the cells were starved for P(i). Sequence analysis and complementation studies showed that the P. aeruginosa phoU gene was involved both in the regulation of AP expression and in the induction of P(i) taxis. However, unlike AP expression, P(i) taxis was not regulated by the phoB gene product.

Alkaline Phosphatase↗
PubMed1994

Monitoring serum tryptic activity and effect of trypsin inhibitor on rat acute pancreatitis.

The effect of a novel synthetic trypsin inhibitor, 4-(2-succinimidoethylthio)-phenyl 4-guanidinobenzoate methanesulfonate (E3123), on severe acute pancreatitis was studied in trypsin-taurocholate-induced acute experimental pancreatitis in rats. Rats were divided into four groups according to difference of subdivided doses of E3123 with fixing the total dose at 3 mg/kg body weight. Group A: 1.5 mg/kg of E3123 subcutaneously (SC) each at 1 h before and after induction of pancreatitis. Group B: 1 mg/kg SC each at 1 h before, 1 and 3 h after induction. Group C: 1.5 mg/kg SC each at 1 and 3 h after induction. Group D: 1.5 mg/kg SC each at 3 and 5 h after induction of pancreatitis. The survival rate at 24 h was significantly improved in group B (77% in group B, vs. 36% in paired control; p < 0.01) and in group C (70 vs. 38%; p < 0.05), but not in group A or D. Residual tryptic activity of serum alpha 2-macroglobulin trypsin complex (alpha 2M-TRY) was reduced after the injection of E3123 though immunoreactive trypsin remained unchanged in the early phase of pancreatitis. The reduction of alpha 2M-TRY reflected the inhibitory capacity of E3123 in plasma. E3123 showed favorable effects on the initial stage of severe acute pancreatitis and the effects were probably based on the inhibition of alpha 2M-TRY activity in serum.

Acute Disease↗
PubMed1994

Localization of Alzheimer amyloid beta protein precursor and its relation to senile plaque amyloid.

The authors examined the ultrastructural localization of amyloid beta protein precursor (APP) in normal human brains immunohistochemically using 3 kinds of APP antisera. The patterns of immunoreaction differed between the antisera used. Antiserum 770, against APP1-770, predominantly labeled the cytoplasm of neurons, whereas antiserum Z31, against the pre-beta region of the APP, labeled astroglial processes intensely and neurons to a lesser extent. Antiserum 1736, against the N terminal of beta protein, labeled both neurons and astrocytes. Vascular smooth muscle cells and some of the endothelial cells in the cerebral arterioles and capillaries were labeled with Z31 and 1736. The APP exists in every cells, while various patterns of immunoreactivity may reflect the difference in the metabolic pathway of APP between cell types.

Aged↗
PubMed1994

Stromal keratitis induced by a unique clinical isolate of herpes simplex virus type 1.

Glycoprotein C (gC)-negative clinical isolates of herpes simplex virus type 1 (HSV-1) are very rare. An HSV-1 strain (TN-1), isolated from a patient with herpetic keratitis, exhibited a gC-negative phenotype. While a gC-negative mutant showed reduced pathogenicity and failed to induce herpetic stromal keratitis (HSK) in a previously reported mouse model, TN-1 induced HSK in mice comparable to RTN-1-20-3, a gC-positive recombinant virus derived from TN-1. Virus growth in eyes and brains and the mortality of TN-1-inoculated mice were equal to or higher than those of RTN-1-20-3-inoculated mice.

Animals↗
PubMed1994

Heart disease deaths in a Japanese urban area evaluated by clinical and police records.

BACKGROUND: By national statistics, Japanese ischemic heart disease (IHD) mortality is one of the lowest of all industrialized countries, and the proportion of deaths due to heart failure in heart disease is the highest. There may be a difference in diagnostic preference between Japan and other industrialized countries. METHODS AND RESULTS: IHD deaths according to the death certificates were reevaluated with World Health Organization MONICA criteria for those 25 to 74 years old by use of clinical and police records in a Japanese city with a population of 347,000. Their cause of death was given on the death certificates as IHD (International Classification of Diseases [ICD], ninth revision, codes 410-414), heart failure (428), or other heart diseases (393-405, 415-427, 429) in 1984 through 1986. Some deaths in 1985 through 1986 from stroke (430-438) or other diseases (250, 272, 278, 440-448, 797-799) were added. Of 409 subjects, 397 (97%) could be examined. Reevaluation of the 106 deaths originally diagnosed as IHD yielded 73 IHDs and 11 sudden deaths of unknown origin (SD), and reevaluation of 160 deaths originally called heart failure yielded 26 IHDs and 50 SDs. In total, reevaluation of all 397 deaths yielded 101 IHDs and 69 SDs. Some 88% of SD cases were originally certified as heart failure (72%) or IHD (16%). Only two SDs were originally certified as stroke. CONCLUSIONS: Assuming that 30% of SDs were due to IHD, the number of IHD deaths would be 122, which is 11% larger than the number of IHD deaths according to the death certificates. After reevaluation, the IHD mortality in this study area still was the lowest in the industrialized countries.

Adult↗
PubMed1994

Microinjection of norepinephrine into the paraventricular nucleus of the hypothalamus stimulates corticotropin-releasing factor gene expression in conscious rats.

To examine the physiological effects of norepinephrine (NE) in the paraventricular nucleus of the hypothalamus (PVH) on CRF gene expression and CRF release, NE was microinjected bilaterally into the PVH of conscious rats, and kinetic studies were performed on the levels of POMC messenger RNA (mRNA) in the anterior pituitary (AP), CRF mRNA in the PVH-containing hypothalamic fragment, and plasma ACTH. Plasma ACTH levels were increased dose dependently by NE (5-50 nmol/side) injection into the PVH. They reached their peaks after 30 min and returned to the basal values after 90 min. The POMC mRNA level in the AP and hypothalamic CRF mRNA level increased significantly 90 min after NE injection and increased further after 120 min. The POMC mRNA level in the AP and hypothalamic CRF mRNA level were increased dose dependently by NE (5-50 nmol/side) after 120 min. Intracerebroventricular pretreatment with prazosin abolished completely the increase in plasma ACTH levels after intrahypothalamic NE injection, whereas pretreatment with propranolol was without significant effect. These results suggest that NE stimulates CRF gene expression in the PVH and CRF secretion into the portal circulation, thus regulating positively the hypothalamic-pituitary-adrenal axis. alpha 1-Adrenergic receptors may mediate the action of NE on CRF neurons.

Adrenocorticotropic Hormone↗
PubMed1994

Mechanism of abnormal production of adrenal androgens in patients with adrenocortical adenomas and carcinomas.

The production of adrenal androgens can be modulated by the activities of steroidogenic enzymes and by the electron transfer system, NADPH-cytochrome P450 reductase (Red) and cytochrome b5 (b5), both of which have been shown to increase 17,20-lyase activity in vitro. To clarify the mechanism of diminished secretion of adrenal androgens in patients with adrenocortical adenoma and Cushing's syndrome and of excess secretion in patients with adrenocortical carcinoma, we investigated the enzymatic activities of cytochrome P45017 alpha, 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD), and Red as well as the content of b5 in five adenomas, three carcinomas, and two normal adrenal glands. An in vitro enzyme assay using a microsomal fraction of the tissues indicated that all the tumors had almost the same degree of 17 alpha-hydroxylase activities as the normal adrenals. However, the relative activity ratio of 17,20-lyase to 17 alpha-hydroxylase of the three adenomas was markedly diminished, and 3 beta-HSD activity was apparently lower in the three carcinomas. The messenger RNA concentrations of P45017 alpha were similar in all tumors, whereas those of 3 beta-HSD were markedly lower in the carcinomas than in other tissues. Both the content of b5 and the activity of Red were significantly lower in the adenomas. These results suggest that low concentrations of adrenal androgens in patients with adrenocortical adenomas are mainly due to low 17,20-lyase activity, which may be explained in part by a lower content of b5 and Red. In addition, high concentrations of adrenal androgens in patients with adrenocortical carcinoma are mainly due to the diminished activity of 3 beta-HSD.

3-Hydroxysteroid Dehydrogenases↗
PubMed1994

No mutation in cytochrome P450 side chain cleavage in a patient with congenital lipoid adrenal hyperplasia.

Molecular basis of lipoid adrenal hyperplasia (lipoid CAH) in a Japanese patient was investigated. A 46XY Japanese female patient was clinically diagnosed as having lipoid CAH based on her clinical history of adrenal crisis at birth and the low basal concentrations of cortisol, aldosterone, adrenal androgens and testosterone in serum. In vitro studies of testicular mitochondrial enzymes confirmed a specific impairment of cholesterol side chain cleavage (SCC) activity. However, in spite of the virtual reduction of SCC activity, the amounts of immunodetectable P450scc, adrenodoxin reductase, and adrenodoxin in testicular mitochondria were almost same as those of normal testis. Furthermore, the size of each protein was similar to that of normal testis. Enzymatic amplification of the complementary DNA encoding P450scc from the patient's testis RNA and its nucleotide analysis by direct sequencing revealed no mutation. These results indicate that defective P450scc is not the lesion in this patient, confirming a previous report showing no P450scc mutations in patients with lipoid CAH. The exact lesion causing lipoid CAH in this patient is currently unknown.

Adolescent↗
PubMed1994

[Stromal changes in cancer. Studies on changes of stroma promoted by gastric cancerous cells using alginate microcapsules].

Xenografting can be accomplished by using encapsulated cells in the alginate microcapsule. Using this technique, the experiment was made to investigate the stroma-promoting factors that were produced by the encapsulated differentiated (MKN-28) and undifferentiated (KATO-III) gastric cancerous cell lines. Fibronectin (FN) in the medium was quantified by single culture with the human fibroblast cell line (CCD-32Lu) and coculture with CCD-32Lu and the encapsulated MKN-28 ro KATO-III. Then following this procedure, each capsule including the gastric cancerous cells was subcutaneously transplanted into Wistar Rats. After 14 days, the surrounding tissues of the microcapsules were stained, and the localization of type III collagen, 4 and 6 chondroitin sulfate, and FN were observed by immunohistochemical stainings. The concentration of FN in both single culture and coculture medium gradually increased, especially in the medium complemented with KATO-III and CCD-32Lu. The measured point after 48 hours demonstrated the obvious increase compared to the single culture and coculture medium. Upon the histological comparison, it was found that the stromal proliferation around the tissue transplanted the microcapsules including MKN-28 or KATO-III were distributed more abundantly than the transplantation of microcapsules only. However, no difference was noted between the stroma of MNK-28 and KATO-III. In conclusion, this study suggests that any stroma-promoting factor is produced by the gastric cancerous cells.

Adenocarcinoma↗
PubMed1994

Single amino acid substitution (840Arg-->His) in the hormone-binding domain of the androgen receptor leads to incomplete androgen insensitivity syndrome associated with a thermolabile androgen receptor.

We have characterized the androgen receptor in a Japanese girl and her maternal cousin in a family with incomplete androgen insensitivity syndrome, and have investigated the molecular basis. Whole-cell androgen binding assay in cultured genital skin fibroblasts from both patients showed a normal maximum binding capacity and a normal apparent dissociation constant. However, androgen binding in fibroblasts from both patients decreased to 30% when the assay temperature was raised from 30 degrees C to 41 degrees C, indicating the presence of the thermolability of ligand binding to the androgen receptor. Sequence analysis of the coding exons of the androgen receptor gene from the patients revealed a single nucleotide substitution at position 2881 in exon G, resulting in the conversion of arginine (CGT) to histidine (CAT) at amino acid position 840 in the hormone-binding domain of the androgen receptor. The family study showed that the mothers and the maternal grandmother of the patients are heterozygous carriers for this mutation, whereas the father does not carry it, supporting the view that androgen insensitivity syndrome is an X chromosome-linked disorder. The single amino acid substitution may explain the qualitative abnormality of the androgen receptor displaying thermolability, which is thought to be the pathogenesis of incomplete androgen insensitivity syndrome in the patients.

Androgen-Insensitivity Syndrome↗
PubMed1994

Days required for 75% suppression of ventricular premature contractions by antiarrhythmic agents obtained from continuous in-hospital ECG monitoring.

To determine the number of days required to obtain 75% suppression of ventricular premature contractions (VPCs) by antiarrhythmic agents, which was expressed as t1/4, we performed 32 in-hospital continuous all day ECG monitoring trials in four groups of 28 symptomatic patients (ages; 54 +/- 20 years-old) with frequent VPCs. Nine patients had no organic heart disease (group 1, 11 trials), nine had valvular heart disease (group 2, 10 trials), three had dilated cardiomyopathy (group 3, 3 trials) and seven had myocardial infarction within two to four weeks onset (group 4, 8 trials). All patients were monitored by ECG telemetry with an arrhythmia analyzer, which could count hourly and daily VPCs. Class I antiarrhythmic agents were given in 18 trials, class II in two trials and class I+ class II in 12 trials. Plasma concentrations of the antiarrhythmic agents were monitored in 11 trials. In 21 trials, t1/4 could be obtained; ten (91%), six (60%), three (100%) and two trials (25%) in the four groups, respectively (p < 0.05). The value of t1/4 in the four groups was 6 +/- 6, 7 +/- 6, 14 +/- 11 and 13 +/- 2 days, respectively (mean 8 +/- 7 days; N.S.). Immediate response to the initial antiarrhythmic agent administration, expressed as percent VPC count after three hours, correlated significantly with t1/4 (r = 0.696, p = 0.0006), but ejection fraction, patient's age, control VPC counts or plasma antiarrhythmic agent level did not correlate with t1/4. In conclusion, t1/4 is a useful index for the evaluation of VPC suppression, revealing wide inter-individual variations and can be roughly estimated from the immediate response to the initial antiarrhythmic agent administration.

Adolescent↗
PubMed1994

Torsades de pointes in paced patients with sick sinus syndrome after disopyramide administration.

Three ventricular inhibited mode (VVI) pacemaker implanted patients, all above 65 years, female and having sick sinus syndrome suffered from torsades de pointes; one patient after 2.5 years and the other two patients within a day of disopyramide therapy. All had hypopotassemia and plasma disopyramide was below the therapeutic range in two patients. Torsades de pointes was induced following ventricular paced beats and suppressed by cessation of disopyramide in all or by setting a higher pacing rate in one. In our department, permanent VVI pacemakers were implanted in 43 patients with sick sinus syndrome including 26 with bradycardia-tachycardia syndrome, nine of whom were treated by disopyramide. Torsades de pointes was observed only in those disopyramide treated bradycardia-tachycardia patients. Our report stresses the proarrhythmic nature of combined VVI pacing and antiarrhythmic agents in the presence of hypopotassemia.

Aged↗
PubMed1994

Immunohistochemical studies on sympathetic and non-sympathetic nerve fibers and neuronal cell bodies in the pineal gland of cotton rats, Sigmodon hispidus.

Immunohistochemistry revealed the presence of tyrosine hydroxylase (TH)-, neuropeptide Y (NPY)-, calcitonin gene-related peptide (CGRP)- and substance P (SP)-immunoreactive nerve fibers and SP-immunoreactive neuronal cell bodies in the pineal gland of the cotton rat (Sigmodon hispidus). Abundant TH- and NPY-immunoreactive fibers were distributed evenly throughout the gland; less numerous CGRP- and SP-immunoreactive fibers were distributed in the superficial pineal and the stalk, but were scarce in the deep pineal. All the immunoreactive fibers were usually found around blood vessels. Since TH- and NPY-immunoreactive fibers in various pineal regions disappeared completely with superior cervical ganglionectomy, these fibers are all considered postganglionic sympathetic fibers. Intrapineal CGRP- or SP-immunoreactive fibers decreased considerably in number following superior cervical ganglionectomy, suggesting that some sympathetic fibers contain CGRP or SP. Bilateral bundles of nerve fibers under the transverse sinuses, corresponding to the nervi conarii, contained TH-, NPY-, CGRP- and SP-immunoreactive fibers, which continued into those distributed in the pineal capsule. In the nervi conarii, fibers immunoreactive for TH and NPY disappeared after superior cervical ganglionectomy, but those immunoreactive for CGRP and SP persisted. Thus, non-sympathetic, CGRP- and SP-immunoreactive fibers, together with sympathetic fibers, are presumed to enter the gland by way of the nervi conarii. Neuronal cell bodies, containing SP-like immunoreactivity and being possibly parasympathetic in nature, occurred occasionally in the superficial pineal.

Animals↗
PubMed1994

[The effect of stellate ganglion block on the local and global cardiac uptake of 123I-metaiodobenzylguanidine].

To investigate the effect of stellate ganglion block (SGB) on the cardiac uptake of 123I-metaiodobenzylguanidine (MIBG), four patients without heart disease underwent SGB. Studies were done twice: once with SGB and once without SGB. Anterior planar images and myocardial SPECT images were taken at 10 minutes and 60 minutes after MIBG injection both with and without SGB. Cardiac uptake of MIBG on planar images estimated by heart/liver ratio was significantly higher with SGB at both imaging times (p < 0.01, p < 0.05) than without SGB. SGB had no effect on the local uptake of MIBG on SPECT images. In conclusion, SGB did not change the local cardiac uptake of MIBG, but it appeared to increase the global myocardial uptake of MIBG.

3-Iodobenzylguanidine↗