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Biomedical subjects

M Sugimoto

Publications and source records attributed to M Sugimoto.

At least 289 records · Page 16Linked to original sources

Immunogenetic study of thyroid hormone autoantibodies in a family.

Haplotypes of the human major histocompatibility complex (HLA) and immunoglobulin G heavy chain allotype (Gm) were determined in nine members of a family in which three sisters had thyroid hormone autoantibodies (THAA) in serum. Among three sisters with THAA, two of them were hypothyroid and treated with synthetic thyroid hormones (patients nos. 1 and 2). The other remaining sister (patient no. 3) was euthyroid. Light chain allotype (Km) in them was also examined. Three patients had the same two Gm haplotypes. Km (1) allotype was negative in these three patients. HLA haplotypes of patient no. 1 were the same as those of patient no. 2. However, HLA haplotypes of patient no. 3 were completely different from those of patients nos. 1 and 2. The same combination of Gm haplotypes and the absence of Km (1) allotype were not observed in the remaining members without THAA. These results suggest that genes linked to Gm and Km allotypes are associated with the production of THAA at least in our patients.

Autoantibodies↗

Regulation of plaque size and host range by a vaccinia virus gene related to complement system proteins.

A vaccinia virus variant, LC16m8, and its parental Lister (Elstree) strain (LO) were employed to identify the viral gene(s) responsible for plaque size and host range: the large-plaque-forming LO strain but not the small-plaque-forming LC16m8 strain can actively proliferate in Vero (YTV) cells. Previously, we suggested that some particular gene(s) present in the HindIII D fragment of LO DNA was responsible for these biological activities. In the present experiment, the mapping of the putative gene was done by introducing various subfragments of the HindIII D fragment of LO DNA into the gene of LC16m8 strain and screening of the resultant virus variants for the capability of forming large plaques or of proliferating well in Vero cells. The results indicated that an open reading frame (called ps/hr gene) in LO HindIII D fragment was responsible for either plaque size or host range. This gene encoded a polypeptide of 317 amino acids related to the regulators of complement activation (RCA) gene family of mammals. Thus, the present genetic analysis provided direct evidence for a previously unrecognized function of RCA-related proteins encoded by the virus.

Amino Acid Sequence↗

Comparative analysis of nucleotide sequences of the partial envelope gene (5' domain) among human T lymphotropic virus type I (HTLV-I) isolates.

Human T-cell lymphotropic virus type I (HTLV-I) is associated with adult T-cell leukemia/lymphoma (ATL) and HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The nucleotide sequences of 640 bp of the proviral genome (positions 5158-5797) derived from 11 HTLV-I-infected persons were analyzed using the polymerase chain reaction and M13-based sequencing techniques. Patterns of single nucleotide substitutions were characterized from the extracellular domain of the envelope gene (gp46). Compared with other retroviruses, the nucleotide sequences of the HTLV-I external envelope gene are highly conserved among the genotypes studied. We found no evidence of dual infections with HTLV-II among the seropositive asymptomatic persons or in patients with either ATL or HAM/TSP. No unique sequence differences were observed in the envelope gene of the HTLV-I isolates derived from patients coinfected with human immunodeficiency virus type 1 (HIV-1). However, comparative analysis of these data and other published HTLV-I envelope sequences indicated the presence of four subtypes of HTLV-I in relation to their geographic origin.

Base Sequence↗

Incorporation of cortical bone autografts following intraoperative extracorporeal irradiation in rabbits.

In an experimental study using 60 rabbits, a cortical bone segment of the unilateral tibial diaphysis was resected, irradiated extracorporeally, and reimplanted immediately as an autograft. The subsequent process of graft incorporation was examined over a 26-week period by roentgenography, histology, and histomorphometry. The irradiation doses were 0 (control), 50, 100, and 200 Gy. Roentgenographic and histologic examinations revealed that cortical bone autografts irradiated at 50 to 200 Gy were incorporated in the same manner as non-irradiated controls. By histomorphometry, the mean unresorbed fraction of the grafts at 6 weeks post-implantation was estimated to be 88.4% for the control group and 89.4% for the 200 Gy group. That of 26 weeks postimplantation was 17.5% for the control and 28.5%, 26.1%, and 27.8% for the 50, 100, and 200 Gy groups, respectively. Cumulative new bone formation showed a similar but inverse pattern of difference between the control and irradiated groups at 26 weeks. However, these differences were not statistically significant and were considered to be slight when compared with the overall similarity of the process. The total cross-sectional area of cortical bone at 26 weeks was similar to that of the contralateral side in all groups. In none of the adopted evaluation methods was any difference detected among the three irradiated groups with different doses. The results of this study suggest that extracorporeal irradiation of autografts at the specified doses impairs possible cellular contribution of the grafted marrow to the incorporation process, but does not interfere with the contribution of the matrices. The results provide useful information concerning the method of limb salvage surgery using intraoperatively-irradiated autografts.

Animals↗

Predominant recognition of human T cell leukemia virus type I (HTLV-I) pX gene products by human CD8+ cytotoxic T cells directed against HTLV-I-infected cells.

We established long-term cell lines of cytotoxic T lymphocytes (CTL) specific for human T cell leukemia virus type I (HTLV-I) from peripheral blood lymphocytes (PBL) of a patient with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), an HTLV-I-carrier with Sjögren syndrome, and an asymptomatic HTLV-I-carrier, by repeated stimulation with autologous HTLV-I-infected T cells in vitro. CTL derived from the patient with HAM/TSP expressed CD8 antigen, and their function was restricted by HLA-A2. They showed cytotoxic effects predominantly against the target cells expressing HTLV-I p40tax among the autologous B cell lines infected with vaccinia recombinants containing various HTLV-I genes which served as targets. These data are consistent with the previously reported findings that fresh PBL of HAM/TSP patients contain p40tax-specific CTL activity. Furthermore, CTL derived from the patient with Sjögren syndrome without neurological involvement also demonstrated cytotoxicity predominantly to p40tax. The cytotoxicity to the target cells experimentally expressing p40tax was blocked by unlabeled HTLV-I-infected cells possessing HLA-A2. HTLV-I-specific cytotoxicity was also inhibited by unlabeled B cells bearing p40tax. Thus, HTLV-I p40tax-specific cytotoxicity is mediated by the major CTL population activated by native HTLV-I antigens in patients with HAM/TSP or Sjögren syndrome. In contrast to the CTL of these patients, CTL similarly induced from the asymptomatic HTLV-I-carrier, which were highly cytotoxic to autologous HTLV-I-infected T cells, did not show significant levels of cytotoxicity to autologous B cells expressing p40tax.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Human papillomavirus type 6 and 11 E4 gene products in condyloma acuminata.

The human papillomavirus type 6 (HPV-6) E4 gene was expressed in Escherichia coli as a fusion protein with E. coli beta-galactosidase (E4-beta-Gal), and rabbit antibody against the E4-beta-Gal was prepared. By Western blotting with this antibody, we detected E4 gene products in six out of 18 condyloma acuminata specimens. In four specimens (C-1, C-13, C-14 and C-19), the E4 protein was found as a 10K/11K doublet, but in other specimens (C-8 and C-23), only the 11K protein was detected. By Southern blot analysis, it was found that C-13 harboured HPV-6 DNA but that C-1 and C-8 harboured HPV-11 DNA, indicating that the E4 proteins of HPV-6 and -11 have cross-reactive antigenicity. After incubation at 37 degrees C of the C-23 tissue specimen, the 10K protein was clearly detected. These results suggest that the 10K protein may be derived from the 11K protein by a modification such as proteolytic cleavage before and/or after specimens were taken.

Base Sequence↗

Protective immunity against bovine leukaemia virus (BLV) induced in carrier sheep by inoculation with a vaccinia virus-BLV env recombinant: association with cell-mediated immunity.

The effects of vaccination of sheep with a recombinant vaccinia virus (rVV) expressing the bovine leukaemia virus (BLV) envelope glycoprotein (gp60) were studied by determining BLV titres in peripheral blood leukocytes after vaccination and challenge. The proliferation of BLV was suppressed markedly, not only when rVV was inoculated prior to challenge with BLV, but also when it was inoculated after challenge. These results indicate that vaccination with rVV induces protective immunity that can suppress the growth of BLV in carrier animals. Since rVV induced a strong anti-BLV delayed-type hypersensitivity response without producing detectable levels of binding or neutralizing antibodies, and there was no apparent correlation between the humoral immune response and BLV proliferation, a cell-mediated immune response was assumed to play a major role in protective immunity.

Animals↗

Increased expression in vivo and in vitro of foreign genes directed by A-type inclusion body hybrid promoters in recombinant vaccinia viruses.

We constructed A-type inclusion body (ATI) hybrid promoters, that is, late ATI promoters followed by tandemly repeated early regions of the promoter for the 7.5-kDa protein (the 7.5-kDa promoter). The repetition of the whole early promoter sequence of the 7.5-kDa gene, including the upstream consensus sequence and initiation region, efficiently increased the early expression of the bacterial chloramphenicol acetyltransferase gene in recombinant vaccinia virus. Recombinant vaccinia virus could express influenza virus hemagglutinin via the hybrid promoter more efficiently, induced higher levels of neutralizing antibody and cytotoxic T lymphocytes, and consequently protected mice more efficiently against challenge with influenza virus than did recombinant vaccinia virus containing the widely used 7.5-kDa promoter.

Base Sequence↗

Changes in bone after high-dose irradiation. Biomechanics and histomorphology.

We studied the effects of high-dose irradiation on the mechanical properties and morphology of cortical bone in rabbits for 52 weeks after a single dose of 50 Gy of electron-beam to the tibia. After four weeks, the bending strength of the irradiated bone was unchanged, but at 12 weeks, the strength had decreased significantly. At 24 weeks after irradiation mean strength was less than half of controls but by 52 weeks there was a tendency toward recovery. Similar, synchronous changes of damage and recovery were seen in cortical porosity, haematopoietic cells in the bone marrow and endosteal new bone formation.

Animals↗

A case of extraadrenal pheochromocytoma with papillary thyroid carcinoma.

A 63-year-old housewife with a history of partial thyroidectomy was referred to our hospital because of a neck mass and abdominal tumor. Aspiration biopsy of the neck tumor revealed the recurrence of papillary thyroid carcinoma. Magnetic resonance imaging (MRI) of the abdomen and urinary and plasma catecholamine levels indicated that the tumor beside the abdominal aorta was an extraadrenal pheochromocytoma. Two tumors were excised and histologic studies confirmed the diagnosis. So far two cases of extraadrenal pheochromocytoma with papillary thyroid carcinoma have been reported. The present case indicates that the presence of papillary thyroid carcinoma should be considered in patients with extraadrenal pheochromocytoma.

Abdominal Neoplasms↗

[A case of adult Wilms' tumor--review of the literature on histopathological features and prognosis].

A case of Wilms' tumor in a 57-year-old woman is reported. She was with a complaint of a palpable mass on the right upper abdomen. CT scan showed a non-hemogenous mass arising from the lower pole of the right kidney. After transarterial embolization, right transabdominal radical nephrectomy was performed under the diagnosis of renal cancer. Histopathological study revealed Wilms' tumor stage 2. Over the two years after surgery the patient is disease-free. Wilms' tumor is rare in adults. The prognosis of adult Wilms' tumor is recognized to be poorer than that of children. Recently, Wilms' tumors in children are classified into two histopathological groups, that is "favorable histology" and "unfavorable histology" according to the cell differentiation. Based on a collection of the previous Japanese and English reports, we analyzed the relationship between the histopathological features and the prognosis in adult Wilms' tumor. Ten cases of unfavorable histology have very poor prognosis, with the two year survival rate of 22%. In contrast, that of 24 cases of favorable histology was 71%. In particular, all cases of the epithelial predominant type presenting favorable histology, including stag 4 cases, survived over two years. Our case was the epithelial predominent type presenting favorable histology. That is probably one of the chief reasons of the good prognosis. In conclusion, the above-mentioned results show that in adult Wilms' tumor, the prognosis of unfavorable histology is very poor, but that of a low stage or the epithelial type presenting favorable histology is, as in children, relatively good.

Aged↗

[Positive rate of serum anti-HCV in various liver diseases and the clinico-pathological study of chronic liver disease in alcoholics].

The aim of this study was to elucidate the positive rate of serum anti-HCV in alcoholic (with negative HBsAg and without blood transfusion history) and non-alcoholic (type-B and type-NANB) patients with chronic liver diseases. The clinico-pathological difference between anti-HCV positive and negative alcoholic patients was also investigated. Anti-HCV (Chiron C-100-3) was assayed with Ortho EIA kit in 196 patients. Liver function tests and the histological findings were evaluated in 111 cases of chronic hepatitis (CH) and 39 of liver cirrhosis (LC). Following results were obtained. [1] Positive rate of serum anti-HCV in alcoholic patients was 40% in CH, 36% in LC and 100% in hepatocellular carcinoma. In non-alcoholic type-NANB group, it was 75%, 68% and 69%, respectively. [2] Serum GGT/ALT ratio was higher in anti-HCV negative patients than positive patients both in CH and LC alcoholics. In non-alcoholic group, it was higher in type-NANB patients than type-B patients. [3] Among the histological findings in CH alcoholics, lymph follicles in the portal area were characteristic in anti-HCV positive patients, while these were not seen in negative patients. [4] In LC alcoholics, regenerative nodules were irregular in size in anti-HCV positive patients, while these were even and small in negative patients. [5] Serum HCV-RNA was detected in two out of 14 anti-HCV negative patients. [6] A female alcoholic patient who showed positive serum anti-HCV and negative HCV-RNA was presented. [7] For the evaluation of the influence of HCV in alcoholics, further studies have to be continued with more sensitive HCV markers.

Adult↗

[Influence of hepatitis C virus on the alcoholic liver diseases].

In order to know the influence of hepatitis C virus (HCV) on the alcoholic liver diseases (ALD), 124 patients with ALD were divided into two groups by positive or negative anti-HCV, and differences of histological findings, laboratory data, evolution of histopathology and liver disease of those who developed hepatocellular carcinoma (HCC) between both groups were investigated. There were 31 patients (25%) in the anti-HCV positive group and 93 patients (75%) in the negative group. Histologically, viral changes were seen in most patients (55%) of the positive group, whereas those were seen in a few patients (15%) of the negative group. The patients of the positive group showed higher serum adenosine deaminase levels compared with those of the negative group. However, as regards the evolution of histopathology, amount of alcohol consumed seemed to be more responsible than positive anti-HCV. Three out of 6 patients with HCC were anti-HCV positive cirrhotics, although there were three anti-HCV negative HCC patients: one with cirrhosis and two with hepatic fibrosis.

Adenosine Deaminase↗

Glutathione S-transferase in alcoholic fatty liver.

Hepatic glutathione (GSH) S-transferase (GST) activity and the tissue distribution of a cationic GST were investigated in biopsy liver samples obtained from patients with alcoholic liver diseases. GST activities in alcoholic fatty liver were significantly high, whereas those in cirrhosis were significantly low compared with normal liver. In fatty liver, immunohistochemically, the staining of the enzyme was strongly positive in hepatocytes around intensive fatty metamorphosis. Then, using experimental chronic alcohol-fed rats, the changes in hepatic GST and GSH peroxidase (GPx) activities and lipid peroxide (LPO) and GSH contents in alcoholic fatty liver were evaluated. Hepatic GST isoenzymes were analyzed and tissue distribution of cationic and neutral GSTs was also investigated. Liver GSH content decreased at two weeks and increased at six weeks. Liver LPO content was elevated at four and six weeks and cytosolic GPx activity was enhanced at four weeks. Cytosolic GST activity was enhanced at six weeks. The cationic and neutral GST isoenzyme pattern was unchanged compared with normal liver. Immunohistochemically, the distribution and intensity of the staining of GSTs were essentially unchanged. There was no evidence of an increase in the GST isoenzyme with selen-independent GPx activity. However, GSTs were strongly stained in the hepatocytes with fatty droplets. Thus, in alcoholic fatty liver, hepatic GST and GPx activities are thought to be enhanced by different mechanisms. The elevated GPx activity may relate to the production of LPO. However, the enhancement of GST activity may result from some other causes which include the enzyme induction.

Alanine Transaminase↗

[Studies on the mode of progression of alcoholic liver disease].

In order to elucidate the mode of progression of alcoholic liver disease, relationships among the drinking style, laboratory data, anti-HCV antibody and histological changes were investigated on 36 patients in whom the liver biopsy was repeatedly done. Following results were obtained (1) In the group of continuous drinking over 100g ethanol per day, histological progression was found in 11 of 13 patients (85%) regardless of positive anti-HCV. On the other hand, in the group of abstinence or temperance less than 60g daily alcohol intake, histological improvement was found in 6 of 11 patients (55%). (2) Histological improvement was predominantly seen by abstinence or temperance in the cases with lower levels of serum IgA and adenosine deaminase (ADA) on hospitalization and those with rapid decrease in serum gamma-GTP after hospitalization. In conclusion, the amount of ethanol was considered to be the most important factor to affect on a progression of alcoholic liver diseases. Assessment of laboratory data such as IgA and ADA on hospitalization and change in gamma-GTP after hospitalization were also thought to be useful in foreseeing the prognosis of alcoholic liver disease.

Alcohol Drinking↗

[Distribution of glutathione S-transferase isozymes in rat small intestinal mucosa].

We have investigated the longitudinal distribution of glutathione S-transferase (GST) isozymes in the trisected small intestine mucosa of rats. Only GST subunits 1 and 7 were detected by Western blot analysis of the intestinal cytosol using antiserum for GST1-1, 1-2, 3-4 and 7-7. Cytosolic GST1-1, 3-4 and 7-7 were assayed by the quantitative ELISA. There was a marked decline of the concentration of GST1-1 from proximal (35.17 nmol/g tissue) to distal intestine (1.67 nmol/g tissue). GST3-4 was hardly detected in the intestinal mucosa. Among the GSTs, GST7-7 existed in the highest concentration in any segment of intestine, i.e. 58.76 nmol/g tissue (61% of GSTs) in the proximal intestine and 32.38 nmol/g tissue (93% of GSTs) in the distal intestine.

Animals↗

[Influence of estradiol and testosterone on carbon tetrachloride-induced liver damage in the rat].

The aim of the study was to know influences of estrogen and testosterone on carbon tetrachloride-induced liver damage in male Wistar rats. One hundred and two rats were divided into following six groups on the basis of the treatment: olive oil as control (O), carbon tetrachloride (0.1 ml/100 g, C), estradiol benzoate (0.1 mg/100 g, E), testosterone propionate (5 mg/100 g, T), C + E and C + T, in which each drug was intraperitoneally injected twice per week for consecutive 12 weeks. In the C + E group, decreases in serum albumin level at the 4th week and total cholesterol level at the 8th week seemed to be suppressed. And fibrotic change and fatty change were weak on the histological observation. However, hepatocellular hyperplasia was observed in 40% cases after the 8th week. On the flow cytometry analysis of the liver at the 4th week, an enhancement of hepatocellular proliferation was shown. Survival rate of the C + E group rats was lower than C group rats. On the other hand, in the C + T group, liver injury occurred in the same grade as C group, and the survival rate was worst among all six groups. These results suggest that simultaneous administration of estrogen with carbon tetrachloride could reduce hepatic injury, though it might cause hepatocellular hyperplasia.

Animals↗