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Biomedical subjects

T Shinagawa

Publications and source records attributed to T Shinagawa.

At least 91 records · Page 5Linked to original sources

[A resected case of hepatocellular carcinoma effectively treated by hepatic artery embolization and systemic chemotherapy].

A 64-year-old male complaining of abdominal fullness was admitted to hospital for close examination. Hepatocellular carcinoma was diagnosed by various imaging techniques and the patient was treated by 3 transarterial embolizations and 2 courses of systemic chemotherapy with CDDP. The tumor was reduced and the effect was judged to be a partial response to these therapies. By resection, a residual mass had histologically no live cancer cells. This case was considered to have had a complete response with multidisciplinary treatment.

Antineoplastic Combined Chemotherapy Protocols↗

[Primary carcinoma of the female urethra].

An 80-year-old female patient with urethral carcinoma is reported. A red, easily bleeding mass at the urethral meatus was diagnosed as transitional cell carcinoma by biopsy. Complete resection of the urethra and tubeless cystostomy were performed. Postoperative M-VAC therapy a combination of methotrexate, vinblastine, adriamycin and cisplatin was employed.

Aged↗

Human ovarian theca cells are a source of renin.

Human ovarian follicular fluid contains renin-like activity. In normal women, circulating levels of prorenin, the biosynthetic precursor of renin (EC 3.4.23.15), change in parallel with changes in progesterone during the menstrual cycle. Therefore, the ovary has been implicated as a source of plasma prorenin. In the present studies, we report the finding of high concentrations of prorenin in human ovarian follicular fluid (3000 ng.ml-1.hr-1 vs. 10-40 ng.ml-1.hr-1 in normal human plasma) obtained from follicles of women prepared for in vitro fertilization. The inactive renin-like enzyme was identified as prorenin by its activation characteristics, its molecular weight of 47,000, which is the same as that for recombinant prorenin, and its cross-reactivity with human renal renin antibodies. Culture of isolated human theca cells and isolated granulosa cells indicated that prorenin is secreted by theca cells but not by granulosa cells. Prorenin production by theca cells peaked during the first 10 days of culture and gradually decreased by 17 days. Active renin levels were 10% or less of the prorenin levels. Prorenin was barely detectable in medium from granulosa cells cultured for 24 days. Immunohistochemical staining of human ovaries (n = 5) with anti-human renin antibody demonstrated the presence of renin primarily in theca cells. These studies suggest that the theca cell is the source of the large quantities of prorenin in human ovarian follicular fluid.

Enzyme Precursors↗

Characterization of pure human renal renin. Evidence for a subunit structure.

Renin was completely purified from human kidney cortex employing a rapid three-step procedure which included homogenization and ammonium sulfate precipitation, aminohexyl-pepstatin affinity chromatography, and affinity chromatography using a synthetic octapeptide renin inhibitor (H-77) with a reduced peptide bond (-CH2-NH- instead of -CO-NH-) between Leu5-Leu6, Three kg of cortex dissected from 10 kg of human cadaver kidney yielded 1.7 +/- 0.5 mg of protein (mean +/- S.E. for five procedures) with a specific activity of 1094 +/- 166 Goldblatt units/mg of protein and an overall recovery of 52 +/- 2%. Both gel filtration high performance liquid chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) revealed a molecular weight of 44,000, although Mr = 22,000 and 18,000 bands were also identified by SDS-PAGE. The pH optima with sheep angiotensinogen were 5.5 and 7.8 and the Km was 0.31 microM. With pure human substrate the pH optimum was 6.0 and the Km was 1.15 microM. Enzyme activity was inhibited by two different anti-human renal renin antibodies. Amino-terminal sequencing demonstrated a leucine residue at the 1-position. Sequencing of 15 additional amino acids agreed with that predicted from the gene sequence and indicated that prorenin is converted to renin following cleavage at the carboxyl end of two basic residues, Lys-2 Arg-1. As with SDS-PAGE analysis, high performance liquid chromatography in the presence of 6 M urea demonstrated Mr = 44,000, 22,000, and 18,000 bands. Immunoblot studies revealed that all of these bands cross-reacted with antihuman renin antibody. Amino-terminal sequencing indicated the Mm = 22,000 band is the amino terminus and the Mr = 18,000 band the carboxyl terminus of Mr = 44,000 renin. In the aqueous phase, these subunits bound to H-77 suggesting that they represent components of the active enzyme complex. Unlike mouse renin, there was no evidence of disulfide bonds. These results raise the question of whether human renin circulates as a subunit aggregation as well as a single chain protein. This may serve as a possible mechanism to regulate renin activity in plasma and tissues.

Amino Acid Sequence↗

Complete purification of human renal renin and sequence of the amino terminus.

Renin was completely purified from human kidney cortex using a rapid 3-step procedure which included homogenization and ammonium sulfate precipitation, aminohexyl pepstatin affinity chromatography, and affinity chromatography using a synthetic octapeptide renin inhibitor (H-77) with a reduced peptide bond between Leu5 - Leu6. Three kg of cortex dissected from 10 kg of human cadaver kidney yielded 0.7 mg protein with a specific activity of 1123 GU/mg protein and an overall recovery of 52%. Both gel filtration high pressure liquid chromatography and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS PAGE) revealed a molecular weight of 44,000, although 22,000 and 18,000 molecular weight bands were also identified by SDS PAGE. Amino terminal sequencing demonstrated a leucine residue at the 1 position indicating that prorenin is converted to renin following cleavage at the carboxyl end of two dibasic residues, Lys-2-Arg-1. Sequencing of the first 19 amino acids was in agreement with the sequence deduced from human renin cDNA sequence.

Amino Acid Sequence↗

Natural history of minute hepatocellular carcinoma smaller than three centimeters complicating cirrhosis. A study in 22 patients.

Twenty-two patients with cirrhosis and minute hepatocellular carcinoma less than 3 cm in diameter were followed for periods of 6-37 mo without specific treatment. The survival curve drawn by the Kaplan-Meier method showed a 1-yr survival of 90.7%, a 2-yr survival of 55.0%, and a 3-yr survival of 12.8%. The ultrasonic patterns of these masses in the liver were correlated with the size and showed a tendency to change from a low echo pattern to a low periphery and, finally, to a massive pattern. The growth speed calculated from the doubling time for tumor volume varied considerably from case to case with an average of 6.5 +/- 5.7 mo; it also changed in some cases during the observation period. Serum alpha-fetoprotein levels were generally low, rarely assisted in diagnosis, but tended to increase when the mass attained a diameter of greater than 3 cm; sudden acceleration in the rate of increase in alpha-fetoprotein level often coincided with a change of ultrasonic pattern to the massive one.

Aged↗

Perineurial cell tumor and the significance of the perineurial cells in neurofibroma.

The authors attempted to clarify the exact cell components of neurofibroma by immunohistochemical and ultrastructural studies. Materials were randomly selected, 40 cases of neurilemoma and neurofibroma (-tosis) in addition to 2 cases of tumors composed exclusively of perineurial cells and three cases of normal peripheral nerve. The applied markers included antisera of S-100 protein for Schwann cells, blood coagulation factor XIIIa for endoneurial fibroblasts or perineurial cells, and laminin and collagen type IV for the basement membrane. S-100 protein was demonstrated only in normal or neoplastic Schwann cells, but not in perineurial cells. On the other hand, factor XIIIa was often recognized in endoneurial fibroblasts and perineurial cells, but not in Schwann cells. Neurofibroma was basically composed of a mixture of Schwann cells, perineurial cells, and endoneurial fibroblasts, the population of each type of cell differing according to the case and area within a given tumor. Perineurial cell tumor exclusively composed of perineurial cells, though rare, appears to be a definite entity, and its characteristic histological and ultrastructural features were described.

Adult↗

Biochemical similarity of expressed human prorenin and native inactive renin.

Prorenin is secreted by mammalian cells transfected with a human preprorenin expression construct. The purpose of this investigation was to compare the physicochemical properties of expressed prorenin in culture medium with the known characteristics of human inactive renin, which accounts for nearly half the renin in plasma and kidney. We found that expressed human prorenin strongly resembles human renal and plasma inactive renin. The expressed prorenin was inactive and could be equally activated by acid (dialysis to pH 3.3) or trypsin. Acid activation was completely reversible; reexposure to acid could reactivate the expressed inactive renin. Exposure to cold (-5 degrees C for 3 days) could also activate expressed renin. The Michaelis-Menten constant of acid-activated expressed renin with sheep substrate was 0.29 microM, and the pH optimum was 7.8. Expressed inactive renin bound to a cibacron-blue affinity column and could be eluted with 0.5M NaCl. All the above characteristics resemble those of human renal and plasma inactive renin. In addition, the molecular weight of expressed prorenin and human chorionic renin was 47,000, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and 46,000, as measured by high-performance liquid chromatography. These data, taken together with the published observation that native human inactive renin cross-reacts with antibodies generated against amino acid sequences in the prosegment of renin, provide strong support for the hypothesis that human inactive renin is prorenin.

Cold Temperature↗

Abnormality of circulatory reflex and aldosterone response during head-up tilting in patients with primary aldosteronism.

Abnormality of the circulatory reflexes has been reported in patients with primary aldosteronism. However, changes in blood pressure, heart rate, plasma renin activity (PRA), and plasma aldosterone concentration (PAC) after head-up tilting in primary aldosteronism have not yet been reported. Seven patients with primary aldosteronism were tilted to a 65 degree head-up position which was maintained for 30 min. Systolic blood pressure decreased significantly 5 min after tilting and remained at this level during the period of tilting. Diastolic blood pressure did not change during the tilting. Heart rate increased after 5 min of tilting and this level of heart rate was maintained for 30 min. Plasma renin activity was low and did not change during tilting. However, plasma aldosterone concentration increased significantly 20 min after tilting. Plasma cortisol concentration and plasma ACTH concentration also increased significantly. These results suggest that primary aldosteronism causes abnormalities of the circulatory reflexes. The increase of endogenous ACTH may increase plasma aldosterone concentration in patients with primary aldosteronism.

Adrenocorticotropic Hormone↗

Incidence of portal vein thrombosis in liver cirrhosis. An angiographic study in 708 patients.

Portal vein thrombosis was thought to be a common complication of liver cirrhosis in the past. The incidence of angiographically demonstrable portal vein thrombosis was studied in 708 consecutive patients with unequivocal cirrhosis seen in the past 10 yr in whom either transhepatic portography or superior mesenteric arterial portography clearly delineated the major portal vein system. Excluding 2 cases that were thought to be associated with past splenectomy, there were 4 cases of portal vein thrombosis related to cirrhosis, all in a decompensated stage. The calculated incidence of portal vein thrombosis was 0.573% of all cirrhotic patients without splenectomy in the past. They constituted 23.5% of the 17 cases of extrahepatic portal vein obstruction encountered during the same period. There were 78 cases of idiopathic portal hypertension similarly studied angiographically, and the incidence of portal vein thrombosis unrelated to splenectomy was 2.86%. A statistical survey based on 247,728 necropsies recorded in the Japan Autopsy Registries of 1975-1982 showed a 0.05489% incidence of portal vein thrombosis and a 6.58857% incidence of cirrhosis of all types among them, suggesting that portal vein thrombosis is not a common complication of cirrhosis in Japan in recent years.

Adult↗

Ultrastructure of cartilaginous tumors and S-100 protein in the tumors. With reference to the histogenesis of chondroblastoma, chondromyxoid fibroma and mesenchymal chondrosarcoma.

Twelve cartilaginous tumors were studied by electron microscopy and the presence of S-100 protein was studied immunohistochemically in order to clarify the cell origin of chondroblastoma, chondromyxoid fibroma, and mesenchymal chondrosarcoma. Three chondroblastomas were characterized by round or ovoid tumor cells with some cytoplasmic processes, well-developed organelles and thick fibrous laminae in the nuclear membrane, occasional multinucleated giant cells and scanty chondroid matrix. S-100 protein was demonstrated in the tumor cells and some multinucleated giant cells Two chondromyxoid fibromas revealed tumor cells of varied shapes with characteristic cartilaginous differentiation and abundant chondroid matrix. Spindle tumor cells showed the ultrastructural features of cartilage cells rather than of fibroblasts and S-100 protein was also demonstrated in their cytoplasm. Chondroblastoma and chondromyxoid fibroma were considered to arise from chondrocytes. Mesenchymal chondrosarcoma ultrastructurally exhibited round tumor cells with cartilaginous nature in cartilage islands. Poorly-differentiated portions were composed of primitive round or elongated cells with occasionally admixed round cells with ultrastructural features of cartilaginous differentiation. S-100 protein was demonstrated in the cells in cartilage islands and in single cells admixed in poorly-differentiated portions. These results support the hypothesis of primitive mesenchymal origin with a tendency to differentiate toward cartilage cells.

Cartilage↗