Biomedical subjects

M Sakamoto

Publications and source records attributed to M Sakamoto.

At least 397 records · Page 22Linked to original sources

PubMed1994

Increased formation of oxidative DNA damage, 8-hydroxydeoxyguanosine, in human livers with chronic hepatitis.

8-Hydroxydeoxyguanosine (oh8dG) is a promutagenic DNA lesion produced by oxygen radicals. We examined alterations in the oh8dG level in human livers which have chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. The oh8dG content in livers with chronic hepatitis was significantly higher than the oh8dG content in normal livers (P < 0.05). There was also a significant correlation between the oh8dG content in noncancerous liver tissues with individual serum alanine aminotransferase concentration (r = 0.515; P < 0.001). Thus, chronic inflammation in the liver produces oxidative DNA damage, which may increase the risk for genomic alterations causing hepatocarcinogenesis.

Alanine Transaminase↗

PubMed1994

Hepatitis C virus infection in spouses of patients with type C chronic liver disease.

OBJECTIVE: Survey for markers of hepatitis C virus (HCV) infection in spouses of patients with HCV-related chronic liver disease. DESIGN: Cross-sectional clinical, serologic, and molecular biological study of spouses of patients with HCV viremia and chronic liver disease. SETTING: University and city hospitals. PARTICIPANTS: Spouses (52 men and 102 women; mean age, 56 +/- 11 years) of 154 patients with HCV viremia (102 men and 52 women; mean age, 58 +/- 10 years), of whom 66 had chronic hepatitis, 49 had liver cirrhosis, and 39 had primary hepatocellular carcinoma. METHODS: Tests for HCV-associated antibodies were done using a second-generation enzyme immunoassay and immunoassays with synthetic oligopeptides deduced from the HCV core gene. Hepatitis C virus RNA was detected by polymerase chain reaction with primers deduced from the 5'-noncoding region and HCV genotypes by reaction with type-specific primers deduced from the HCV core gene. RESULTS: Hepatitis C virus-associated antibodies were detected in 42 (27%) spouses, of whom 25 were also positive for HCV RNA. Of 112 (73%) spouses without detectable antibodies, 2 had chronic liver disease. The development of markers of HCV infection in spouses increased with the duration of marriage, ranging from 1 to 60 years (30 +/- 11 years). CONCLUSIONS: Spouses of patients with HCV viremia and chronic liver disease have an increased risk for acquiring HCV, which is proportional to the duration of marriage. They should be followed routinely for markers of HCV infection and liver disease.

Aged↗

PubMed1994

Plasmin-induced reduction of heparan sulfate in cultured vascular endothelial cell layer.

Plasmin-induced alteration of glycosaminoglycans (GAGs) was investigated using a cell culture system of vascular endothelial cells derived from bovine aorta. In the cell layer, the incorporation of [3H]glucosamine into GAGs, a marker of the sugar chain formation, was slightly decreased by plasmin. On the other hand, the incorporation of [35S]sulfate, a marker of the sulfation, was markedly decreased by the protease. Plasminogen also induced a weak but similar change. Characterization of the cellular GAGs showed that plasmin inhibited the incorporation of both [3H]glucosamine and [35S]sulfate into the major component heparan sulfate at a similar degree. In the other GAGs, the [35S]sulfate incorporation was significantly decreased by plasmin without a change of the [3H]glucosamine incorporation. The leakage of lactate dehydrogenase from the endothelial cells was significantly increased by plasmin, suggesting that the protease exhibited cytotoxicity. The present data suggest that the anticoagulant activity on the surface of vascular endothelium mediated by the anticoagulant heparan sulfate may be reduced by plasmin which will be generated from plasminogen by plasminogen activators derived from endothelial cells.

Animals↗

PubMed1994

Calcium regulation of tissue plasminogen activator and plasminogen activator inhibitor-1 release from cultured human vascular endothelial cells.

Tissue plasminogen activator (t-PA) produced by vascular endothelial cells converts plasminogen to plasmin which degrades fibrin. Since t-PA activity is greatly potentiated in the presence of fibrin (1,2), the activator is implicated in intravascular fibrinolysis. On the other hand, endothelial cells also produce plasminogen activator inhibitor-1 (PAI-1) (3). The inhibitor associated with vascular endothelium rapidly inhibits t-PA, while that released into the liquid phase has a little anti-activator activity (4). However, clinical studies have shown that elevation of plasma PAI-1 level is a risk factor of thrombosis (5,6). It is thus suggested that the balance between t-PA and PAI-1 is important for the regulation of fibrinolysis. The release of t-PA and PAI-1 from vascular endothelial cells is regulated by physiological factors including thrombin (3,7), histamine (8), vasoconstrictor peptide endothelins (9,10) and cytokines (11). In addition, the regulation of the t-PA release and that of the PAI-1 release are not necessarily coupled. It has been shown that activated protein kinase C and cyclic AMP are involved in the stimulation and suppression, respectively, of the endothelial t-PA and PAI-1 production (12,13). However, the role of intracellular calcium in the regulation of endothelial t-PA and PAI-1 release has remained to be elucidated. In the present study, we investigated the effect of calcium ionophore A23187 on the release of t-PA antigen (t-PA:Ag) and PAI-1 antigen (PAI-1:Ag) from cultured vascular endothelial cells derived from human umbilical vein.

Antigens↗

PubMed1994

Transforming growth factor beta-induced tolerance to cadmium cytotoxicity in cultured vascular endothelial cells.

We investigated whether or not transforming growth factor beta (TGF beta 1) affects the sensitivity to cadmium of bovine aortic endothelial cell in a culture system. Cadmium cytotoxicity was evaluated by [3H]adenine release assay. It was found that pretreatment with recombinant human TGF beta 1 (rhTGF beta 1) of the confluent cultures resulted in a reduction of cadmium cytotoxicity, suggesting that the cytokine induced a tolerance to cadmium in the cells. Such a tolerance was induced slightly by either recombinant human tumor necrosis factor alpha or recombinant human basic fibroblast growth factor but not by recombinant human interleukin-1 beta and -6; rhTGF beta 1 was the most potent inducer. rhTGF beta 1 failed to induce the tolerance in the presence of anti-rhTGF beta 1 antibody. Pretreatment with the antibody alone caused a significantly sensitive response to cadmium, suggesting that endogenous TGF beta 1 can physiologically contribute to protection against cadmium cytotoxicity in endothelial cells. The accumulation of cadmium was increased in the extracellular fraction but significantly decreased in the intracellular fraction of the cells by pretreatment with rhTGF beta 1. The cadmium content was significantly decreased in the particulate fraction but not in the cytosol fraction. Gel filtration chromatography of the cytosol fraction revealed that cadmium was bound to high-molecular-weight protein and metallothionein; both peaks were slightly increased by pretreatment with rhTGF beta 1. It was concluded that rhTGF beta 1 induces a tolerance to cadmium in cultured endothelial cells, caused by a decrease in the cadmium accumulation in the particulate fraction of the cells. TGF beta 1 may serve as a protective factor against cadmium cytotoxicity in vascular endothelial cells.

Animals↗

PubMed1994

Basic fibroblast growth factor suppresses tissue plasminogen activator release from cultured human umbilical vein endothelial cells but enhances that from cultured human aortic endothelial cells.

Since basic fibroblast growth factor (bFGF) modulates the functions of vascular endothelial cells, we hypothesized that this factor may be involved in the regulation of the blood coagulation-fibrinolytic system mediated by the cells. Confluent cultures of vascular endothelial cells from human umbilical vein were treated with recombinant human bFGF (bFGF) in a serum-free medium and the content of tissue plasminogen activator antigen (t-PA:Ag) in the medium was determined by EIA. Treatment with bFGF resulted in a significant decrease in the release of t-PA:Ag from the cells accompanied with a less t-PA activity in the medium. In contrast, the t-PA:Ag release from human aortic endothelial cells was significantly increased by bFGF. The bFGF-induced decrease in the t-PA:Ag release from the venous endothelial cells was completely blocked by anti-bFGF antibody. The incorporation of [3H]leucine into the acid-insoluble fraction of the cells was significantly increased by bFGF; however, the activity of lactate dehydrogenase leaked into the medium was significantly decreased, suggesting that the suppression of the t-PA:Ag release caused by bFGF in the venous endothelial cells was not due to either a nonspecific inhibition of protein synthesis or a nonspecific cell damage. Since bFGF is postulated to be released from damaged endothelial cells, the present data suggest the regulation by bFGF of hemostasis mediated by endothelial cells when the vascular endothelium was damaged.

Aorta↗

PubMed1994

Nucleolar organizer regions in small nodular lesions representing early stages of human hepatocarcinogenesis.

BACKGROUND: It is believed that in the early stages of hepatocarcinogenesis, some adenomatous hyperplasias (AH) progress to early hepatocellular carcinoma (eHCC), and that many eHCC develop into overt hepatocellular carcinoma (HCC) through nodule-in-nodule formation. However, the proliferative activity of these small nodular lesions has not been fully investigated. METHODS: Cell proliferative activity was assessed by counting nucleolar organizer region-associated proteins (Ag-NOR) in paraffin sections of 12 AH nodules, 25 eHCC nodules, and 8 nodule-in-nodule lesions. In nodule-in-nodule lesions, an area of well-differentiated HCC corresponding to eHCC and a discrete inner nodule area composed of obvious HCC were examined. RESULTS: Mean Ag-NOR numbers of extranodular parenchyma, AH, and eHCC were 1.35, 1.35, and 1.75 (P < 0.01), respectively. With regard to the relative Ag-NOR number compared with that of parenchyma, there was no overlap between AH and eHCC with a border of 1.1-fold except in one specimen. In nodule-in-nodule lesions, the mean Ag-NOR number (2.53) in the inner nodular area was much higher (P < 0.01) than that of the area of eHCC (mean, 1.88). CONCLUSIONS: A stepwise increment of Ag-NOR number was demonstrated in accordance with the multistep of the AH to eHCC to nodule-in-nodule lesion sequence of hepatocarcinogenesis. Thus, it was proposed that the Ag-NOR count may be a practical and objective parameter for assessing the malignant potential of hepatocellular neoplasms histopathologically.

Aged↗

PubMed1994

Six-year longitudinal analysis of adenovirus type 3 genome types isolated in Yamagata, Japan.

Five hundred eighty-seven adenovirus type 3 (Ad3) isolates were established from children with acute respiratory infections (ARI) from 1986 to 1991, in Yamagata, Japan. Ad3 could be found in almost all the months during the 6 years when two epidemics occurred, in 1987 and 1989. A molecular epidemiological study was done on 346 of the 587 isolates, using restriction endonucleases; BamHI, HindIII, SmaI, and BgIII were used. The Ad3 isolates were classified into seven genome types. The genetic differences among the seven genome types were < 0.9%, and their phylogenetic tree, estimated by the neighbor-joining method, correlated highly with their monthly distribution. One genome type predominated for 56 months, while the other six related genome types cocirculated for a short period. These results suggested that the predominant genome type of Ad3 might have been endemically perpetuated in the Yamagata area with minor genomic variations. Furthermore, the outbreaks of Ad3 may have been due not to the appearance of a new genome type but rather to the endemic genome type.

Adenovirus Infections, Human↗

PubMed1994

A unique sequence located downstream from the rice mitochondrial atp6 may cause male sterility.

Asymmetric cell-fusion of the japonica cultivar of Oryza sativa (rice) with cytoplasmic-male-sterile (CMS) plants bearing cytoplasm derived from Chinsurah Boro II, resulted in two classes of cytoplasmic hybrids (cybrids), fertile and CMS. Southern-blot analysis of the mitochondrial DNA (mtDNA) indicates recombination events around a number of genes; however, the appearance of the CMS character is tightly correlated to reorganization around the atp6 gene, suggesting recombination downstream from the atp6 gene is involved in CMS. The nucleotide sequence downstream from atp6 contains a pseudogene which was probably created by recombination of the mitochondrial genome. Sense and antisense transcripts of the downstream region of atp6 were found in CMS- and restored CMS (fertile)-lines, but not in the normal (fertile) line. In the CMS line, several antisense transcripts of the atp6 gene were also found. However, in the restored line which contains a nuclear-encoded gene, Rf-1, the levels of these transcripts were lower than in the CMS line. These results suggest abnormal transcripts of the atp6 gene produced in the antisense direction may be involved in CMS, and that products of the nuclear-encoded restorer gene may reduce abnormal transcription in this region of the mitochondrial genome.

Base Sequence↗

PubMed1994

Microsoft Excel Program for creating attractive survival curves.

This paper describes the design of a Microsoft Excel Program which interactively creates attractive and outstanding survival curves. This program enables medical researchers to easily create quality presentation graphs of survival curves and obtain high quality slides and prints, which can be inserted in papers or used directly at medical meetings. Through the use of vertical bars, this program can display the exact points where censored cases occur on survival curves, making it possible to monitor censoring patterns between groups. Furthermore, this program can also create survival curves based on the proportional hazards model for specific patterns of covariate values, given estimated regression coefficients and baseline survival function. This program may be a most useful and effective tool in creating medical research papers containing survival analysis.

Age Factors↗

PubMed1994

The organization of statistical activities at medical research institutions.

In this paper, we discuss the organizational structure for the conduct of statistical activities at medical Colleges and Universities. Here, we have particularly focused on two significant statistical activities, i.e., statistical consultation and research. The consulting service for medical researchers consists of practical statistical analysis, instruction on computer manipulation and software, response to reviewer's comments and statistical design of prospective studies. From our various experiences, we describe the actual implementation of statistical consultations for medical researchers. It has played an important role in supporting medical research. In addition, we also outline some research, with respect to new ways of applying statistics in medical science. This paper concludes that it may be practical for the existing computer center or department of medical informatics, in charge of the computing service, to conduct statistical activities until formal organizations are established at the academic institution. To realize the conduct of statistical activities by Department of Medical Informatics, it needs a team of biostatisticians, data analysts and computer personnel.

Computer Systems↗

PubMed1994

Sclerotherapy of hydroceles with polidocanol.

Fifteen patients with hydroceles of the testis or spermatic cord were treated by aspiration and injection of the sclerosant solution polidocanol. The cure rate of hydroceles after one sclerotherapy session was 73%, and the overall cure rate using the procedure was 87%. No patient experienced pain during or after the procedure, which was conducted without anaesthesia. No complications were observed. It is concluded that sclerotherapy of hydroceles with polidocanol may be a useful alternative to open operation, due to its ease of administration, low frequency of complications, and high rate of effectiveness, and that this agent is preferable to certain other drugs in that it causes no pain during or after the injection.

Adult↗

PubMed1994

Alteration of glycosaminoglycans induced by cadmium in cultured vascular smooth muscle cells.

Alteration of glycosaminoglycans (GAGs) in cultured bovine aortic smooth muscle cells after exposure to cadmium was investigated. It was revealed that cadmium increased the accumulation of GAGs metabolically labeled with [3H]glucosamine but decreased that with [35S]sulfate in the cell fraction, the cell surface fraction and the medium fraction. This suggested that cadmium stimulated the biosynthesis of GAGs but inhibited their sulfation in the cells. A similar alteration was observed in cadmium-treated human aortic smooth muscle cell layer. Of tested cations including cadmium, bismuth, cobalt, copper, lead, manganese, nickel and zinc, only cadmium stimulated [3H]glucosamine incorporation, with a strong inhibition of the [35S]sulfate incorporation in the bovine cells. Characterization of bovine smooth muscle GAGs showed that the cadmium-induced increase in the [3H]glucosamine incorporation was mainly observed in heparan sulfate; the inhibition of the [35S]sulfate incorporation occurred non-selectively. Cadmium accumulated in bovine vascular smooth muscle cells in a dose-dependent manner with an increase in the leakage of lactate dehydrogenase into the medium. The present data suggest that vascular smooth muscle cells respond to the cytotoxicity of cadmium and promote the GAG synthesis with a reduction of their sulfation. It is postulated that this response may be a defensive one to the damage of the vascular tissue caused by cadmium but would be a component of the metal-induced atherosclerosis.

Animals↗

PubMed1994

The hr locus and the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in newborn mice.

In mice, the recessive mutation hairless (hr) controls the cutaneous response to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) but its influence on TCDD's systemic toxicity is unclear. To clarify this, we compared the effects of lactational TCDD exposure on standardized litters of newborn HRS/J mice homozygous for either hr or + that were fostered by haired dams exposed to 0, 6, 8 or 12 micrograms TCDD/kg body weight on postnatal day 0. At 12 micrograms/kg, TCDD was lethal to both haired and hairless pups. At the lower doses (6 and 8 micrograms/kg) the survival of hr/hr pups was significantly lower than +/+ pups. Affected pups succumbed following a 1 to 2-day period of cachexia and wasting. As has been reported for other mouse strains, TCDD exposure impacted on their neonatal development and lessened the time to eye opening for both haired and hairless pups. However, the hairless animals were affected at lower doses than were the haired. The results of this study document that the hr/hr genotype does influence the systemic toxicity of TCDD in mice.

Animals↗

PubMed1994

Predictive factors for postoperative recurrence of hepatocellular carcinoma.

BACKGROUND/AIMS: The survival rate for hepatocellular carcinoma after hepatectomy remains unsatisfactorily low because of the high recurrence rate. The purpose of this study was to elucidate predictive factors for postoperative recurrence of hepatocellular carcinoma. METHODS: Univariate analysis and a multiple regression model were used to retrospectively determine the factors potentially related to recurrence in 98 patients with hepatocellular carcinoma who had undergone curative hepatic resection. RESULTS: DNA diploidy, absence of alcohol abuse, and absence of vascular invasion were determined to be independent favorable predictive factors using a multivariate analysis with Cox's proportional hazards model. A predictive index was developed using these three factors according to the following equation: 1.486 x (O = DNA diploidy or 1 = DNA aneuploidy) + 1.138 x (O = absence or 1 = presence of alcohol abuse) + 0.946 x (O = absence or 1 = presence of vascular invasion). This index was used to classify the patients into two groups with good or poor prognosis. The median time for disease recurrence for the two groups was 24.1 and 9.2 months, respectively (P < 0.001). CONCLUSIONS: The results may be useful in the determination of treatment strategies and postoperative follow-up schedules and in the design and analysis of future clinical trials of therapy for hepatocellular carcinoma.

Aged↗

PubMed1994

Suppression of plasminogen activator inhibitor type 1 release from cultured human umbilical vein endothelial cells by basic fibroblast growth factor.

We investigated the release of plasminogen activator inhibitor type 1 (PAI-1) from cultured vascular endothelial cells after exposure to basic fibroblast growth factor (bFGF). Treatment with human recombinant bFGF of confluent cultures of endothelial cells derived from human umbilical vein resulted in a reduction of the accumulation of PAI-1 antigen (PAI-1:Ag) in the conditioned medium. The suppressive effect of bFGF completely disappeared in the presence of anti-bFGF antibody. The reduction of endothelial PAI-1:Ag release induced by bFGF was suggested to be independent of intracellular accumulation of cyclic AMP. On the other hand, nordihydroguaiaretic acid (NDGA), an inhibitor of the lipoxygenase pathway of arachidonic acid metabolism, suppressed the spontaneous release of PAI-1:Ag by itself; in the presence of NDGA, bFGF failed to further suppress the PAI-1:Ag release. The effect of bFGF and indomethacin, an inhibitor of the cyclooxygenase pathway, was additive on the PAI-1:Ag release. The present data suggest that bFGF reduces the endothelial PAI-1:Ag release via suppression of the putative lipoxygenase pathway which up-regulates a part of the spontaneous PAI-1:Ag release.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1994

Stimulation by zinc of cultured vascular endothelial cell proliferation: possible involvement of endogenous basic fibroblast growth factor.

Vascular endothelial cells from bovine aorta were cultured with zinc sulfate (20 microM or less) for 24 h and labeled with [3H]thymidine or [14C]leucine during the last 3 h of the culture. It was found that the cell number was significantly increased by zinc alone; the incorporation of both [3H]thymidine and [14C]leucine was also stimulated by the metal. The stimulation by zinc occurred in the presence or absence of exogenous basic fibroblast growth factor (bFGF). However, other heavy metals including copper, manganese and nickel did not exhibit such a stimulatory effect, suggesting that zinc plays a particular role in endothelial cell proliferation. Stimulation of the [3H]thymidine incorporation by zinc disappeared in the presence of either cycloheximide or anti-bFGF IgG; in addition, a lipoxygenase inhibitor nordihydroguaiaretic acid diminished the zinc stimulation but a cyclooxygenase inhibitor indomethacin did not exhibit such an inhibitory effect. These results indicated that zinc stimulated the proliferation of endothelial cells through the lipoxygenase pathway which mediates the stimulation by endogenous bFGF. In other words, the metal may amplify the endogenous bFGF-dependent proliferation of the cells.

Animals↗

PubMed1994

Adrenergic cell group in rostral ventrolateral medulla of cat: its correlation with central chemoreceptors.

We have proposed a hypothesis that secondary neurons mediating central respiratory chemoreception are not restricted to the medullary superficial layer. This idea was further examined in the present physiological and morphological studies. We identified the 'S' area, i.e. the medullary surface area where cold blockade produced apnea, in anesthetized, spontaneously breathing cat. We then evaluated how the apnea was modified by injection of CO2-saturated saline into the vertebral-basilar artery. The CO2 injection caused immediate reappearance of respiratory rhythm, although intensity of inspiratory activity was smaller than in the control. This incomplete recovery suggests that the responsive structure extends deeply below the surface. The extent of the cell group underlying the 'S' area was evaluated by morphological study. Medullary transverse sections including the 'S' area were treated with three distinct antisera against phenylethanolamine N-methyltransferase (PNMT), dopamine-beta-hydroxylase (DBH), and 5-hydroxytryptamine (5-HT). The PNMT-labelled cell group was found to exactly underlie the 'S' area, although the DBH- and the 5-HT-labelled cell groups did not show close topographic correlation with the 'S' area. PNMT cells were located in the region ventral to retrofacial nucleus within 0.5-1.5 mm depth beneath the surface. These results suggest that adrenergic cells in the rostral ventrolateral medulla are important candidates for secondary neurons mediating central respiratory chemoreception.

Animals↗