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Biomedical subjects

M Koga

Publications and source records attributed to M Koga.

At least 289 records · Page 16Linked to original sources
PubMed1994

Expression patterns of messenger ribonucleic acids encoding prohormone convertases (PC2 and PC3) in human pituitary adenomas.

OBJECTIVE: Prohormone convertases (PC2 and PC3) have been reported to play an important role for prohormone processing in rodent pituitaries. However, expression of mRNAs encoding these enzymes has not been characterized in human pituitaries. In addition, altered or insufficient prohormone processing has been reported in some human pituitary adenomas. Thus, the expression patterns of these mRNAs in non-tumorous and tumorous human pituitaries should be examined. DESIGN: Total RNAs were extracted from non-tumorous or tumorous human pituitaries to analyse PC2 and PC3 mRNA expression. SAMPLES: Five ACTH producing adenomas, 11 GH producing adenomas, one PRL producing adenoma and five non-functioning adenomas were obtained at surgery. Two non-tumorous pituitaries were also included in this study. MEASUREMENTS: The contents were quantitatively measured by Northern blot analysis using rat PC3 cDNA or human PC2 cDNA as a probe. The method was also developed for the detection of PC2 mRNA by Southern blot analysis of reverse transcriptase-polymerase chain reaction (RT-PCR) products. RESULTS: PC2 and PC3 mRNAs in non-tumorous samples were detected by Northern blot analysis whereas their contents in tumorous samples varied from high levels to undetectable. Marked variation of PC3 mRNA levels was observed among GH producing adenomas. ACTH producing adenomas were observed to express PC3 mRNA. Northern blot analysis also revealed that PC2 mRNA levels in ACTH producing adenomas were low except for one sample. PC2 mRNA expression in GH producing adenomas was confirmed by Southern blot analysis of RT-PCR products. This procedure also confirmed the various levels of PC2 mRNA expression among ACTH producing adenomas. CONCLUSION: The expression of PC2 and PC3 mRNA in human pituitaries has been confirmed. However, their expression has been observed to vary quantitatively and not to be restricted to certain types of pituitary cells.

Adenoma↗
PubMed1994

Histochemical and ultrastructural studies of inclusion bodies found in tissues from three siblings with I-cell disease.

Tissues from three siblings with inclusion-cell (I-cell) disease (a 16 month old boy and two fetuses aborted at 20 and 18 weeks) were investigated histologically, histochemically and ultrastructurally. The lymphocytes, fibroblasts, endothelial cells, epithelial cells and histiocytes of various organs were affected. The cells had many intracytoplasmic vacuoles, which showed positive staining with colloidal iron, periodic acid-Schiff (PAS), alcian blue, and Sudan III and IV. Ultrastructurally, the cells contained various inclusion bodies, showing vesicles, granules, flocculent material, amorphous electron-dense globules and myelin structures. The amounts and ultrastructural features of the inclusion bodies differed among the various kinds of cells.

Abortion, Induced↗
PubMed1994

Distribution of urinary hippuric acid concentrations by ALDH2 genotype.

OBJECTIVES: To clarify the relation between the genetic polymorphism of ALDH2 (low Km aldehyde dehydrogenase) and toluene metabolism. METHODS: The study subjects were 253 toluene workers (192 men and 61 women with an age range of 18-66). The genotypes of ALDH2 were classified by artificial restriction fragment length polymorphism into the homozygous genotype of normal ALDH2 (NN), the homozygous genotype of an inactive ALDH2 (DD), and the heterozygous genotype of normal and inactive ALDH2 (ND). The concentrations of hippuric acid (HA), the main metabolite of toluene, was determined in urine specimens of 253 toluene workers. The HA measurements in previous occupational health examinations were also referenced. The HA concentrations corrected for creatinine (HA/C) were compared with the biological exposure index (BEI) for toluene, which is 2.5 g/g creatinine. To estimate the toluene exposures, urinary o-cresol concentrations were also determined and compared with another BEI for toluene--that is, 1.0 mg urinary o-cresol/g creatinine. RESULTS: Incidence of each genotype in the toluene workers was almost the same as that in non-exposed controls who lived in the same area as the toluene workers. The incidence of each of the three genotypes also did not differ by smoking habit. Mean urinary HA concentrations were not significantly different in the groups with the different genotypes of ALDH2. The HA concentrations of > 70% of the 890 total samples were < 1.0 g/l. The number of urine samples > 3.0 g/l was 28 (5.4%) in the NN group and 19 (6.4%) in the ND group. No urine samples in the DD group were > 3.0 g/l HA. The distribution of urinary HA in the DD group was significantly different from those in both the NN and ND groups (P < 0.05). Seven (4.9%) of the 136 total specimens in the NN group and four (4.7%) of the 82 total specimens in the ND group exceeded the BEI. There were, however, no urine specimens that exceeded the BEI in the DD group. The maximum HA concentration after correction for creatinine in the DD group was 1.86 g/g creatinine. The percentages of urine specimens in which o-cresol concentrations exceeded this BEI were 14.3% in the NN group, 9.1% in the ND group, and 15.4% in the DD group. Therefore, the exposure rate for all three genotypic groups of workers was almost the same. CONCLUSIONS: The HA concentrations of toluene workers with ALDH2 DD genotype were lower than those of the NN and ND genotypes when they were exposed to relatively high concentrations of toluene. The exposures of the DD group were suspected to be underestimates because they were based on the BEI for the NN genotype.

Adolescent↗
PubMed1994

Effects of therapy on anterior pituitary functions in patients with primary intracranial germ cell tumor.

Intracranial germ cell tumors are known to be frequently associated with anterior pituitary hypofunction and diabetes insipidus. In general, these manifestations are not ameliorated even after successful radiotherapy. Since platinum based chemotherapy is introduced as a therapeutic approach to these tumors, its effectiveness is compared with the outcome obtained by radiotherapy in terms of tumor regression and endocrine functions. In this study, six patients received conventional radiotherapy and one received chemotherapy as an initial treatment. In all patients, complete remission was achieved irrespective of the therapeutic method. Their diabetes insipidus was not improved. Many patients treated with radiotherapy did not show the complete improvement of pre-existing hypofunction of the anterior pituitaries. In contrast, chemotherapy achieved almost complete hormonal remission. These clinical observations suggest that chemotherapy is quite effective in oncological as well as endocrinological aspects in treating intracranial germ cell tumors.

Adolescent↗
PubMed1994

Inhibitory effect of FK506 on intercellular adhesion molecule-1 (ICAM-1) expression on cultured thyroid cells.

The effect of FK506, an immunosuppressive agent, on phytohemagglutinin (PHA) or interferon gamma (IFN gamma)-induced intercellular adhesion molecule-1 (ICAM-1) expression on cultured human thyroid cells from patients with Graves' disease was investigated. Primary cultured thyroid cells were incubated for three days with IFN gamma (10 to 800 U/ml) or PHA (1 to 50 micrograms/ml) in the presence of FK506. The surface expression of ICAM-1 was measured by flow cytometry. In some experiments, polyclonal anti-IFN gamma antibody was added to the culture to determine whether ICAM-1 expression was blocked. FK506 inhibited the PHA-induced ICAM-1 expression in thyroid cells, but not the induction by IFN gamma. PHA-induced ICAM-1 expression was not inhibited by the polyclonal anti-IFN gamma antibody. FK506 did not affect the proliferation of thyroid cells. This data indicates that the inhibitory effect of FK506 on ICAM-1 expression in primary cultured thyroid cells may be due to actions on infiltrating lymphocytes in the thyroid gland. Further studies are necessary to elucidate whether the inhibition of ICAM-1 by FK506 results in the suppression of autoimmune reactions in the thyroid gland.

Cells, Cultured↗
PubMed1994

[A successful case of two-staged operation for Stanford type B acute dissecting aneurysm complicated with total occlusion of the distal abdominal aorta].

A successful case of two-staged operation for Stanford type B acute dissecting aneurysm complicated with total occlusion of the distal abdominal aorta was reported. A 62-year-old male patient with a long history of systemic hypertension developed acute severe chest, back and bilateral legs pain. An enhanced CT demonstrated Stanford type B dissecting aneurysm with occlusion of the left renal artery and bilateral common iliac arteries. On the day of admission, an emergent right axillo-femoral bypass operation using 8 mm ringed EPTFE graft was undertaken to rescue the ischemic legs. The patient's postoperative course was complicated with acute renal failure and paralytic ileus, which were treated with medical treatment. Four months later, the second operation was done for the localized residual dissecting aneurysm in the proximal descending thoracic aorta. The aneurysm was excised, and the entry was closed with Dacron patch using the previously placed axillo-femoral bypass as a technique for preventing distal ischemia. He was recovered uneventfully and was discharged in a good condition.

Acute Disease↗
PubMed1994

Urinary kallikrein activity is increased during the first few weeks of exercise training in essential hypertension.

OBJECTIVE: To determine whether the renal kallikrein-kinin and dopamine systems participate in lowering blood pressure during mild exercise in hypertensives. DESIGN: After a general clinical observation period of 4 weeks, 27 essential hypertensives were divided into two groups. The exercise group underwent blood lactate threshold exercise, using a cycle ergometer for 60 min three times a week for 10 weeks. The non-exercise group was observed at the outpatient clinic. Blood pressure and humoral parameters were measured at weeks 0, 1, 2, 4 and 10 in both groups. METHODS: Blood pressure was measured indirectly with an automatic blood pressure recorder. Twenty-four-hour urinary kallikrein activity (by kininogenase assay), total or free dopamine and total noradrenaline (by high-performance liquid chromatography) were also measured. RESULTS: In the non-exercise group blood pressure and humoral parameters did not change. In the exercise group the change in resting blood pressure between weeks 0 and 10 was statistically significant. The change in 24-h urinary kallikrein activity of the exercise group was significantly greater than that of the non-exercise group between weeks 0 and 1 and weeks 0 and 2. Moreover, the change in systolic blood pressure (SBP) between weeks 0 and 2 was negatively correlated with the change in urinary kallikrein activity between weeks 0 and 2, the change in total dopamine between weeks 0 and 2 was negatively correlated with the change in diastolic blood pressure in the same period, and the change in SBP between weeks 0 and 10 was positively correlated with the change in total noradrenaline in the same period in the exercise group. Subjects with a relatively high baseline urinary kallikrein activity had a significantly greater change in SBP between weeks 0 and 10 than subjects with a relatively low baseline activity. CONCLUSIONS: The renal kallikrein-kinin and dopamine systems may participate in lowering blood pressure during the first few weeks of exercise training. The subsequent reduction of sympathetic activity may be involved in maintaining the lowered blood pressure. Mild exercise is more effective in reducing blood pressure in hypertensives who have a relatively high basal renal kallikrein-kinin system activity.

Adult↗
PubMed1994

[Surgical treatment of infective endocarditis--an analysis of the risk factors for operative mortality and long-term follow-up].

From September, 1978, through January, 1993, 67 patients (mean age: 44 years) underwent surgical treatment for infective endocarditis (IE) at Kagoshima University. Of 67 patients, 36 showed active endocarditis and 31 healed endocarditis at the time of operation. The over-all hospital mortality was 22.4% (15/67). Risk factors associated with operative mortality by univariate analysis included increased blood urea concentration (BUN), increased cardiothoratic ratio, higher New York Heart Association functional class, infection status (active/healed), aortic valve infection, prolonged aortic cross-clamp time, annular abscess, and calendar year. The patients were operated earlier in the latter part of this series (1988-1993. Multiple logistic regression analysis demonstrated three factors to be statistically significant: BUN, operative year, and aortic valve infection. Complete survival information was obtained in all 52 discharged patients with a mean follow-up time of 4.8 years. There were 5 late deaths including 3 patients with valve related complication. The actuarial survival rate at 10 years after operation excluding hospital mortality was 89%, 92% for active infection 88% for healed infection. The actuarial freedom from valve related complication was 86% at 10 years. The degree of activity of the infection is not a risk factor for operative mortality by multiple logistic regression analysis. We conclude that surgical intervention should be undertaken without delay in the patients with IE before development of hemodynamic deterioration causing renal dysfunction and hypercatabolism.

Adolescent↗
PubMed1994

Transforming activity of a newly cloned androgen-induced growth factor.

Our previous study demonstrated that androgen-dependent growth of mouse mammary carcinoma cells (SC-3) was mediated through an induction of heparin-binding growth factor, termed as androgen-induced growth factor (AIGF). Here, we report that NIH3T3 cells stably transfected with AIGF expression vector exhibit the abilities of tumor formation in nude mice, focus formation in monolayer culture and colony formation in soft agar. Thus, this newly cloned growth factor can be categorized as an oncogene. In addition, androgen-induced enhancement of DNA synthesis in SC-3 cells can be blocked by simultaneous incubation with AIGF antisense oligonucleotides. The possibility is also addressed that AIGF exerts its biological activity through an interaction with fibroblast growth factor (FGF) receptor. Transfection of expression vector encoding a variant form of FGF receptor-1 cloned from SC-3 cells into FGF receptor-negative L6 cells results in AIGF-dependent inhibition of differentiation. These results demonstrate that the ability of androgen to elicit transformed phenotype of SC-3 cells is mediated through AIGF induction and its interaction with FGF receptor-1.

Animals↗
PubMed1994

[Clinical experience with the CHAUX multi-purpose retractor].

We have performed dissection of the ITA using the CHAUX retractor in many patients. This retractor is a two-point sternal/IMA and valve retractor, with four sternal blades with individual and independent dual movement. The sliding sternal blade assemblies permit movement along the horizontal plane of the side arm. This retractor can be used for other types of cardiac surgery, as well. We obtained good results with its use for repair of distal aortic arch aneurysm. We conclude that this retractor is safe and useful for cardiac surgery.

Humans↗
PubMed1993

Intrahepatic splenosis mimicking a liver tumor.

A rare case of ectopic splenic tissue in the liver is presented which mimicked a liver tumor. It is considered that some splenic tissue was seeded in the liver during the splenectomy that the patient underwent 23 years ago. Computed tomography (CT), magnetic resonance imaging (MRI), and angiographic features of this lesion were almost indistinguishable from those of other liver tumors.

Choristoma↗
PubMed1993

The clinical significance of reactivity to individual epitopes of the hepatitis C viral genome.

In order to analyze the clinical significance of the various HCV epitopes, we compared the results of different HCV specific assays with HCV-RNA, determined in serum by RT-PCR method using primers to the 5' untranslated region of HCV-RNA. Among 73 patients with chronic NANB liver disease, 93% were positive for C22-3, 96% for C33C, 81% for C100-3 and 91% for RT-PCR. Positivity rates for 537 healthy subjects were 1.7% for C100-3 and 2.9% for second generation anti-HCV. A total of 6 persons were positive for C22-3 but not C100-3; all were negative for HCV-RNA. In 11 of 30 patients treated with interferon and HCV-RNA became negative and remained so for more than 24 months. In these 11 sustained responders, C100-3 and C33C antibody declined progressively, but C22-3 antibody showed a little change after treatment by quantitative analysis. The discrepancy of changes to NS region and core region after interferon treatment is consistent with a different clinical significance of reactivities to these HCV epitopes. Thus negative reactivity to NS region but positive for core region among healthy subjects may indicate past infection with HCV. Presence of antibodies to NS epitopes is implicated in HCV replication, while core epitopes indicate both present and past HCV infection.

Antigens, Viral↗
PubMed1993

Androgen-induced growth factor and its receptor: demonstration of the androgen-induced autocrine loop in mouse mammary carcinoma cells.

SC-3 cells derived from mouse mammary carcinoma (Shionogi carcinoma 115) exhibit remarkable growth enhancement and cell morphology change in response to androgen stimuli. These events are mediated through an androgen-induced growth factor (AIGF). Amino acid sequence deduced from cDNA reveals that AIGF has 215 amino acids with a signal peptide and scattered regions homologous to fibroblast growth factor (FGF) family proteins. The biological ability of AIGF to stimulate SC-3 cell growth is inhibited by heparin or suramin. More importantly, antisense oligodeoxynucleotide of AIGF can block androgen-induced growth of SC-3 cells. Upon synthesis under the control of androgen, AIGF is immediately secreted into the extracellular space without intracellular accumulation. At the early phase (18-24 h) of androgen stimulation, however, AIGF is mainly associated with the glycosaminoglycan on the cell surface or extracellular matrix. In addition, treatment of SC-3 cells with sulfation blocker (chlorate) or heparitinase results in the abolishment of their ability to respond to androgen or AIGF, indicating that heparan sulfate has important roles for condensing AIGF on or near the cell surface as well as potentiating the biological activity of AIGF. Then, AIGF can bind to the FGF receptor. Northern blot analysis and cDNA cloning indicate that SC-3 cells predominantly express the FGF receptor 1 with some altered amino acid sequences. Transfection of expression vectors of AIGF and this variant form of FGF receptor 1 into FGF receptor-negative myoblast cells (L 6 cells) confirms that a variant form of FGF receptor 1 is a receptor of AIGF. These results clearly demonstrate that an autocrine mechanism is operating in androgen-induced growth of SC-3 cells.

Amino Acid Sequence↗
PubMed1993

Effects of retinoic acid on steroid and vitamin D3 receptors in cultured mouse osteosarcoma cells.

The effect of retinoic acid (RA) on the expression of osteoblast-related genes as well as on steroid/vitamin D3 receptor contents was examined using cultured osteosarcoma cell line (BFO cells). Northern blot analysis revealed that mRNAs encoding osteocalcin, pro-alpha 1 (I) collagen and bone morphogenetic protein 4 (BMP-4) are expressed in BFO cells. Stimulation with RA, however, failed to alter their mRNA content, although the transcripts for retinoic acid receptor (RAR)-alpha and -gamma were present in BFO cells. In addition, alkaline phosphatase activity (AP) was significantly but modestly increased by RA treatment. These results suggest BFO cells have well differentiated osteoblastic properties. In contrast to the effects of RA on osteoblast-related gene regulation, RA was found to increase the quantity of estrogen receptor as well as of 1,25-dihydroxy vitamin D3 receptor (VDR) in BFO cells. The quantities, assessed by ligand binding assays, were approximately 200% more than those of the controls after 24 h stimulation with 10(-9)-10(-8) M RA. These RA effects on ER and VDR seem to be specific, since glucocorticoid receptor quantities were not affected by RA treatment. These results suggest that RA regulates ER and VDR quantities in BFO cells.

Alkaline Phosphatase↗
PubMed1993

Crossover comparison between the depressor effects of low and high work-rate exercise in mild hypertension.

1. The relationship between work-rate and the antihypertensive effect of exercise in hypertensives, and the mechanism of that effect, were investigated by a crossover clinical trial. 2. Ten mild hypertensives were randomly divided into two groups. One group performed low work-rate exercise (LWE) on a cycle ergometer for 10 weeks (blood lactate threshold; approximately 50% of maximum oxygen consumption [Vo2max]). After a 10 week interval without exercise training, these subjects were then switched to a high work-rate exercise (HWE) regimen (4 mmol/L of blood lactate; approximately 75% of Vo2max) for another 10 weeks. In the other group, the order of exercise training was reversed. Since two patients withdrew from the protocol during HWE periods, statistical analysis was performed on the data from the remaining eight patients. There were no order effects observed in any of the data from the two groups. 3. During both LWE and HWE, resting blood pressure (BP) fell significantly after the initiation of exercise therapy (P < 0.05). Furthermore, the overall effects of 10 weeks of LWE and HWE on BP were not significantly different. 4. The work-rate at the lactate threshold, which reflects physical fitness, had increased significantly by 16 W (P < 0.01) after the LWE period and by 11 W (P < 0.01) after the HWE. 5. During the LWE period, changes in haemodynamic and humoral variables were not significant, except for a reduction in plasma norepinephrine at week 10 (P < 0.05). In the HWE period, changes in haemodynamic and humoral variables were not significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Splicing in Caenorhabditis elegans does not require an AG at the 3' splice acceptor site.

The dinucleotide AG, found at the 3' end of virtually all eukaryotic pre-mRNA introns, is thought to be essential for splicing. Reduction-of-function mutations in two Caenorhabditis elegans genes, the receptor tyrosine kinase gene let-23 and the collagen gene dpy-10, both alter the AG at the end of a short (ca. 50-nucleotide) intron to AA. The in vivo effects of these mutations were studied by sequencing polymerase chain reaction-amplified reverse-transcribed RNA isolated from the two mutants. As expected, we find transcripts that splice to a cryptic AG, skip an exon, and retain an unspliced intron. However, we also find significant levels of splicing at the mutated 3' splice site (AA) and at nearby non-AG dinucleotides. Our results indicate that for short C. elegans introns an AG is not required for splicing at either the correct 3' splice site or incorrect sites. Analysis of a splice site mutant involving a longer, 316-nucleotide C. elegans intron indicates that an AG is also not required there for splicing. We hypothesize that elements besides the invariant AG, e.g., an A-U-rich region, a UUUC motif, and/or a potential branch point sequence, are directing the selection of the 3' splice site and that in wild-type genes these elements cooperate so that proper splicing occurs.

Animals↗
PubMed1993

Epidemiology and long term prognosis of hepatitis C virus infection in Japan.

In Japanese blood donors, positivity for antibodies to hepatitis C virus (HCV) ranges from 0.2% in subjects under 20 to 3.9% in those over 50 years. It is estimated that at least 2.3 million Japanese have contracted HCV infection through contaminated blood. HCV carrier state was confirmed by polymerase chain reaction for HCV-RNA in subjects positive for antibodies to more than one viral protein (70% of cases). Subjects positive for core antibody alone, however, were found to be HCV-RNA negative with normal liver function, and are considered to have only a past history of HCV infection (30% of cases). Acute hepatitis C progresses to chronic infection in about 90% of cases. In comparison with hepatitis B, chronic hepatitis C leads more frequently to cirrhosis and liver cancer, and rarely remits spontaneously. In typical HCV infection, aminotransferase activities fluctuate markedly in the early stages, then become relatively stable for 10 years or more, with chronic persistent hepatitis shown by histological examination. Thereafter, aminotransferase activities may change dramatically, with progression to chronic active hepatitis and rapid development of cirrhosis and hepatocellular carcinoma. On average, it takes about 30 years for chronic hepatitis C to progress from initial infection to cirrhosis and cancer, but the disease progresses much more rapidly in elderly patients.

Adult↗