Search PubMed⌕ Search

Biomedical subjects

K Sugino

Publications and source records attributed to K Sugino.

At least 73 records · Page 4Linked to original sources

Evidence for the participation of endogenous activin A/erythroid differentiation factor in the regulation of erythropoiesis.

Activin A/erythroid differentiation factor (EDF) is a human protein that induces differentiation of a murine erythroleukemia cell (the Friend cell). In this study, we demonstrate that endogenous activin A/EDF activity is present in murine bone marrow and spleen. In addition, this activity is secreted by bone marrow and spleen cells in primary culture. Administration of follistatin (a specific binding protein for activin A/EDF) to mice results in a decrease of erythroid progenitors in the bone marrow and spleen. These findings support the concept that activin A/EDF and follistatin have opposing actions in the regulation of erythropoiesis.

Activins↗

Purification and characterization of high molecular weight forms of inhibin from bovine follicular fluid.

High molecular mass forms [95 kilodaltons (kDa)] of bovine inhibin-A as well as the known forms of intermediate (55 kDa) and low (32 kDa) mass were purified from bovine follicular fluid by ion exchange chromatography on DEAE-Sepharose, immunoaffinity chromatography using a monoclonal antibody directed against bovine 32-kDa inhibin-A, gel permeation HPLC on TSK-gel, and reverse phase HPLC. The 95-kDa inhibin-A had similar suppressive activity on FSH secretion from cultured rat anterior pituitary cells as the 55- and 32-kDa inhibins. There is, however, a possibility that the inhibin activity detected with larger forms may be due to that of the 32-kDa form that results from proteolytic processing during incubation with rat pituitary cells. Both sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting analysis using monoclonal antibodies specific for 32-kDa inhibin alpha- or beta A-subunits revealed that the 95-kDa inhibin preparation contained two forms of inhibin (105 and 95 kDa), which were composed of either a 50- or a 40-kDa alpha-subunit linked by a disulfide bond(s) to a 55-kDa beta A-subunit. Amino-terminal sequence analysis showed that the 50-kDa alpha-subunit and the 55-kDa beta A-subunit were generated by removal of a signal peptide from each corresponding primary translation product [the first NH2-terminal 17 residues of the inhibin alpha-subunit (residues 1-360) and the first 20 residues of the inhibin beta A-subunit (residues 1-425)] and suggested that the 40-kDa alpha-subunit was formed by proteolytic processing of the 50-kDa alpha-subunit. On the basis of our findings, we propose that in bovine follicular fluid, the larger 105-kDa form of inhibin is processed successively to form the lowest molecular mass form, 32 kDa inhibin, through the smaller 95- and 55-kDa forms.

Amino Acid Sequence↗

[Prognostic factors in patients with invasive differentiated thyroid carcinoma who underwent palliative resection].

In order to determine surgical strategy for locally advanced thyroid carcinoma, a multivariate analysis of prognostic factors was carried out with 70 patients of locally advanced thyroid carcinoma who underwent palliative surgery. Multivariate analysis was conducted by Cox's proportional hazard model. The patients have been followed up from 5 to 26 years. We have demonstrated the influence of age, sex, distant metastasis, pathological findings, numbers of adjacent organs, infiltrated, extent of resection, external irradiation and 131I therapy on survival. The result of this study showed that age had an impact on survival. The survival rate of the patients under 40 years was much better than that of the patients 40 years and over. The result implies that aggressive surgery and postoperative adjuvant therapy should be considered in the old patients, but not always be indication in the young patients.

Adenocarcinoma↗

[Does L-thyroxine administration in a dose to suppress TSH secretion induce metabolic bone disturbance in patients with thyroid carcinoma?].

We investigated whether L-thyroxine for TSH suppression may induce metabolic bone disturbance, especially in trabecular bone. Subjects were 75 premenopausal women (mean age: 37.7) who underwent surgery at Ito Hospital or Yokohama City University Hospital from 1972 to 1988 for differentiated thyroid carcinoma. All of them received L-thyroxine for the purpose of TSH suppression. According to the duration of the drug therapy after surgery, they were divided into 3 groups: Group I patients were treated for more than 10 years after surgery (17 cases), Group II from 5 to 10 years (28 cases), and Group III less than 5 years (30 cases). The control group was consisted of 15 premenopausal women (mean age: 37.0). There was no significant difference in age among these 4 groups. Quantitative CT was used for evaluation of trabecular bone mineral content. Mean bone mineral contents determined in Group I, Group III, Group II and control group patients were 204.7, 213.1, 207.6, 222.6 mg/cm3, respectively. There was no significant difference among them. It is concluded that L-thyroxine can be administered safely without metabolic disturbance in trabecular bone.

Adenocarcinoma↗

[The "addiction trends" seen among the wives of alcoholics].

It has been noticed that wives of alcoholics tend to show an unhealthy relation to their husbands characterized by "addiction," which might hamper the recovery of their husbands from alcohol dependence. Generally speaking, the addiction differs from person to person in its strength and its behavioral expression. The present authors thought that it might be helpful for both wives and therapists if the approximate picture of addiction could be grasped by means of a standardized form of questionnaire. The questionnaire, ASTWA, which consists of 24 questions, was designed to make clear the wives' character trends and their addictions. As for the character traits, the obsessive-compulsive tendency and the tendency to low self-esteem were estimated by four questions each. The two types of addiction, "control" patterns and "caring" trends, were tested. The former was checked in two directions, namely "dominating" tendency and "involved" tendency, with four questions each. The caring trends were estimated by eight questions. A total of 162 wives were asked to rate their answers to the 24 questions as 1, 2, or 3, which stand for none, occasionally, or frequently. The test was carried out at various stages of sobriety. A total of 78 married employees of the Mie prefectural government were tested as control. Those whose added score exceeded 39 points were rated to have a tendency to "addiction." More detailed assessments were done in terms of the character traits and the addictions. The wives who scored more than 14 points in the character traits category were considered to have an affinity toward "addiction." The two types of addiction, i.e., "relation addiction," and "care addiction," were clearly demonstrated in this test. It was noticed that in many cases the scores decreased favorably in parallel with the prolonged term of abstinence of their husbands.

Alcoholism↗

Follistatin, an activin-binding protein, associates with heparan sulfate chains of proteoglycans on follicular granulosa cells.

Follistatin, an activin-binding protein secreted by cultured rat granulosa cells, was shown to associate with the cell surface by affinity labeling with 125I-activin. Addition of follistatin to the cultured cells demonstrated a typical ligand-binding saturation curve, suggesting that granulosa cells have a specific binding site for follistatin. This binding was markedly inhibited by heparin and heparan sulfate, but not by chondroitin sulfates A and C, keratan sulfate, and dermatan sulfate. When granulosa cells were treated with glycosaminoglycan-degrading enzymes before or after addition of follistatin to the cultures, heparinase and heparitinase treatments resulted in significant suppression of the binding, whereas treatment with chondroitinase ABC had no effect. A competition study of the binding using heparin derivatives demonstrated that follistatin seemed to recognize O-sulfate groups in the heparin molecule. Heparitinase-treated granulosa cells exhibited almost full responsiveness to activin, indicating that the enzyme treatment had no effect on activin and receptor interaction. These results suggest that follistatin/activin-binding protein binds to heparan sulfate side chains of proteoglycans on the granulosa cell surface to regulate the various actions of activin.

Activins↗

Solid cell nests of the thyroid gland.

The histogenesis and clinical significance of solid cell nests (SCN) of the thyroid are not fully understood. From August 1987 to December 1989 a total of 2544 patients with thyroid and parathyroid diseases underwent surgery at Ito Hospital, and SCN were revealed within the thyroid parenchyma in 21 (0.8%). Distribution of SCN was not limited to the upper one-third of the lateral lobe, and SCN were found even in the isthmus lobe. In 5 cases microcysts were also noted within SCN, and their content was thought to be acidic proteoglycan. Immunohistochemical study revealed that SCN were negative for thyroglobulin and calcitonin but positive for carcinoembryonic antigen. Thirteen of 21 cases showed positive immunostaining with cytokeratin. Scattered calcitonin-positive cells were noted around the SCN. It is suggested from these findings that SCN of the thyroid are closely related to certain cells of ultimobranchial body vestiges which may be not of neuroectodermal origin but of endodermal origin.

Adult↗

Activin-binding protein is present in pituitary.

A binding protein for activin was purified from bovine pituitary by affinity chromatography on dextran sulfate-Sepharose CL-4B and activin-Affi-Gel 10. A 52,700-fold purification over the starting crude homogenate was achieved. The purified preparation showed two bands of 36 and 33 kilodalton in sodium dodecyl sulfate-polyacrylamide gel electrophoresis under nonreducing conditions. The ability of each form of the protein to specifically bind activin was determined by ligand blot analysis and binding competition study. Each protein was found to have the same NH2-terminus and its sequence was identical to that of follistatin, which is a specific inhibitor of identical to that of follistatin, which is a specific inhibitor of FSH release. Moreover, the binding protein was shown to inhibit the spontaneous FSH release from cultured pituitary cells as does follistatin. These properties are the same as activin-binding protein that we have obtained from rat ovary. These results support a conclusion that activin-binding protein/follistatin exists also in the pituitary. Activin-binding protein has an ability to inhibit the activin-induced augmentation of FSH release from cultured pituitary cells as does inhibin. However, the inhibitory pattern by the binding protein was quite distinct from that of inhibin, suggesting that there may be different mechanism(s) for their antagonistic actions. Stoichiometric inhibition as shown by gel filtration analysis indicates that activin-binding protein binds activin to form an inactive equimolar complex having neither stimulatory nor inhibitory activity for FSH secretion by the pituitary. These findings suggest that activin is actually involved in FSH secretion in the pituitary and that the activin action in the pituitary is regulated by activin-binding protein/follistatin.

Activins↗

Characterization of antisera directed against follistatin/activin-binding protein peptides.

An attempt was made to develop immunologic probes directed against follistatin/activin-binding protein (ABP), for use in investigating the distribution of ABP in various tissues. Five oligopeptides corresponding to different regions of the predicted ABP amino acid sequence (peptides 1-12, 28-43, 123-134, 270-281 and 300-315) were synthesized chemically, and coupled to Limulus polyphemus hemolymph hemocyanin. The peptide-hemocyanin conjugates were then used to immunize rabbits, and the immunoresponses were monitored by enzyme-linked immunosorbent assay. Reactivity of the antipeptide antisera with ABP was determined by SDS-polyacrylamide gel electrophoresis and immunoblotting analysis. All of the peptides produced immune responses. The antiserum to peptide 123-134 recognized all forms of ABP, whereas the antiserum to peptide 300-315 reacted specifically and sensitively with the long forms of ABP. These two antisera exhibited only a limited cross-reaction with other proteins or none at all. Therefore, they will be useful for studying the distribution of ABP in various tissues.

Amino Acid Sequence↗

[The excisional range of tracheal infiltration of the thyroid cancer].

We studied histopathologically the infiltrative modes in 17 cases with tracheal infiltration of the thyroid cancer, and studied its excisional range. 1) Macroscopically, morphologies in the regions of the trachea were divided into 3 types. Types I and II were noted in 4 cases for each and Type III was noted in 9 cases. 2) When the infiltrative modes in the trachea were divided into localized and infiltrative types, localized type was noted in all cases of type I, and infiltrative type was noted in all cases of Type II. The both types were noted in 2 cases and 7 cases of Type III, respectively. 3) Infiltrative region of the tracheal mucous membrane in all cases of Types I and III was localized in the range of the infiltrative region of the extratracheal mucous membrane. The infiltrative region of the tracheal mucous membrane was wider in 2 cases of Type II comparing with that of the extratracheal mucous membrane. It is considered that radical treatment of types I and III can be obtained by the excisional range of the infiltration of the extratracheal mucous membrane. Operative diagnosis is necessary because wider range infiltration of the cancer is observed in the tracheal mucous membrane of Type II.

Adenocarcinoma↗

[Meaning in measurement of bone mineral content as preoperative evaluation of aged patients].

Recently, mean span of life has been prolonged, and extensive operations are performed on aged patients. However, there are cases which have a difference between their chronological and actual ages. Bone mineral content (BMC) decreases with age and the decrease in BMC might suggest deterioration of immunological competence as observed in osteoporosis. Whether BMC can be an index for evaluation of geriatric patients' actual age from the aspect of immunological competence was investigated. Subjects were 54 cases aged more than 60. Twenty-one healthy young males and females were enrolled as the control group. Quantitative CT is used for assessment of BMC. The value obtained by dividing BMC by the standard BMC of the same age and sex, was defined as BMC index. BMC indices of normal BMC group were more than 0.8 and those of decreased BMC group were less than 0.8. Some immunological markers were investigated. Lymphocyte subset OKT3+ was reduced and juvenile lymphocytes expressed by OKT6+ and OKT3+-(OKT4+ + OKT8+) increased (corrected). Increased in juvenile lymphocyte and decrease in lymphocyte blast transformation and competence of generating interleukin 2 were observed in decreased BMC group. BMC is useful as preoperative evaluation for geriatric operative cases and patients of BMC index below 0.8 need to be paid attention to postoperative infection.

Aged↗

[Bone metabolism in thyroidectomized patients--evaluation of bone mineral content by quantitative CT].

The bone mineral content in the patients who had undergone operation for thyroid carcinoma was measured by quantitative CT. Thirty-eight cases were enrolled as the subjects. All cases were papillary adenocarcinoma of the thyroid. The totally thyroidectomized group consisted of 3 males and 14 females, and the non-totally thyroidectomized group (post-lobectomy) 3 males and 18 females. Thirty-eight healthy males and females were assigned to the control group. For evaluation of bone mineral content, quantitative CT was used and bone mineral content in the patient's lumbar vertebrae was measured. Concurrently, bone metabolic parameter in serum was determined. No significant difference was observed in the mean bone mineral content among the above three groups. To make correction by sex and age, BMC-index was defined as the value that the bone mineral content in each case was divided by the standard mean by the same age and sex. No significant difference was observed in BMC-index among the above three groups. No significant correlation was observed in serum calcitonin level with the bone mineral content and BMC-index. It suggests that no influence is exerted on bone metabolism if serum calcitonin is maintained in the physiological level.

Adenocarcinoma, Papillary↗

Inhibin alpha-subunit monomer is present in bovine follicular fluid.

The 26 kDa form of the inhibin alpha-subunit monomer was isolated from bovine follicular fluid. Both sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting analysis revealed that the 26 kDa form of the alpha-subunit monomer is composed of 6 kDa and 20 kDa fragments linked together by a disulfide bond(s). The NH2-terminal sequence and amino acid analyses of each fragment showed that those fragments are derived from residues 18 to 60 and 227 to 360, respectively, of the inhibin alpha-subunit precursor (residues 1 to 360) as deduced from the cDNA sequence. Thus, it is concluded that removal of the putative signal peptide (residues 1 to 17) and the middle portion (residues 61 to 226) from the alpha-subunit precursor generates the 26 kDa form of the alpha-subunit. In the in vitro rat pituitary assay, the 26 kDa alpha-subunit exhibited neither inhibin-like nor FSH-release stimulating activity.

Amino Acid Sequence↗

A case of hepatoblastoma occurring in an adult.

We present herein a rare case of hepatoblastoma occurring in an adult male. The patient was 22 years old and his laboratory investigations on admission showed a marked elevation of alpha-fetoprotein in the serum. CT scan and other examinations revealed a primary tumor, 6.5 cm in size, in the left hepatic lobe with metastasis in the head of the pancreas. Thus left hepatic lobectomy and pancreaticoduodenectomy were performed, but metastasis to the right hepatic lobe, left lung and abdominal skin were found 2 months later. Despite repeated courses of chemotherapy with adriamycin and cisplatin, the patient died 9 months after his operation. Pathological findings revealed poorly differentiated type hepatoblastoma. A review of the literature revealed only twelve other such cases.

Adult↗

[A statistical comparison study of glaucoma in the Third Affiliated Hospital of China Medical College and Kyushu University].

We classified 331 glaucoma patients who visited the eye clinic of the Third Affiliated Hospital of China Medical College during the 2 year period from January 1985 to December 1986 according to the type of glaucoma. The results were compared with those obtained from 275 glaucoma patients who visited the eye clinic of Kyushu University during an overlapping period of 2 years, from January 1986 to December 1987. Patients with glaucoma were found to comprise 1.5% of the 22,869 outpatients in the Third Affiliated Hospital of China Medical College, and 1.8% of the 15,585 outpatients in Kyushu University. The distribution of various types was as follows: primary angle closure glaucoma (76.4%), primary open angle glaucoma (4.8%), secondary glaucoma (11.8%), exfoliation glaucoma (0) and congenital glaucoma (5.7%) in the Third Affiliated Hospital of China Medical College, and primary angle closure glaucoma (34.5%), primary open angle glaucoma (12.7%), secondary glaucoma (22.2%), exfoliation glaucoma (14.9%) and congenital glaucoma (10.9%) in Kyushu University. The present results suggest that the incidence of primary angle closure glaucoma in China is higher than in Japan, and that the incidence of primary angle closure glaucoma is higher than that of primary open angle glaucoma in these two countries. It is of interest that the high incidence of primary angle closure glaucoma in China and Japan coincides with the study in Canadian Eskimos. The incidences of secondary glaucoma and exfoliation glaucoma in Japan are higher than in China. This might be due to differences in diagnostic facilities in the two countries.

Adult↗

Changes in the levels of endogenous antioxidants in the liver of mice with experimental endotoxemia and the protective effects of the antioxidants.

Gram-negative bacterial endotoxin (lipopolysaccharide) induces hepatic damage in mice caused by lipid peroxidation, and administration of antioxidants (coenzyme Q10 and alpha-tocopherol) suppresses this lipid peroxidation, preserves energy metabolism, and enhances the survival of endotoxin-administered mice. Therefore experiments were done to determine whether experimental endotoxemia in mice affected the levels of endogenous antioxidants and whether treatment with antioxidants altered these levels. Endotoxin produced decreases in hepatic endogenous antioxidants with time: reduced coenzyme Q9, alpha-tocopherol, and reduced glutathione were lowered to 29.9%, 27.1%, and 45.4% of the control levels, respectively, 24 hours after administration. Exogenously administered coenzyme Q10 (oxidized) accumulated in the liver and showed a maximal plateau between 8 and 16 hours after injection when 82% of coenzyme Q10 was converted to the reduced form. Coenzyme Q10 administered with endotoxin totally or partially prevented the decreases in these endogenous antioxidants, and furthermore, total coenzyme Q10 and the reduced form, both at levels of approximately 30 mg protein, were consumed during the period of elevated lipid peroxidation, 16 hours after endotoxin injection. These results indicate that coenzyme Q10 acts in vivo as an antioxidant after it has been converted to the reduced form. alpha-Tocopherol administered also showed an 84-fold accumulation in the liver 8 hours after injection, completely preventing any decrease in endogenous reduced coenzyme Q9 and partially preventing reduction of glutathione, which indicated an in vivo antioxidant action of alpha-tocopherol. These results support the assumption that administered coenzyme Q10 or alpha-tocopherol functions cooperatively with endogenous antioxidants to prevent tissue damage caused by lipid peroxidation in endotoxemia.

Animals↗