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Biomedical subjects

S Kawamura

Publications and source records attributed to S Kawamura.

At least 271 records · Page 15Linked to original sources

[Small cell carcinoma of the bladder. Small cell lung cancer-associated ganglioside (Fuc GM1) expression].

A 61-year-old male visited us with chief complaints of macroscopic hematuria and bladder irritation symptoms. Cystoscope, U/S, MRI, and CT showed an extensive non-papillary, wide-based tumor centering around the anterior wall of the bladder. Transabdominal U/S-guided full-thickness biopsy indicated a pT3a (Biopsy) primary small cell carcinoma of the bladder containing neuroendocrine granules. Immunohistochemical studies revealed Fuc GM1, an antigen related to small cell carcinoma of the lung. Neoadjuvant therapy consisted of preoperative irradiation at 50 Gy and intra-arterial infusion chemotherapy with CDDP and THP. Since a follow-up full thickness biopsy indicated pT0 (Biopsy), total cystectomy was performed. Examination of the resected specimen also indicated pathological CR.

Carcinoma, Small Cell↗

[The phase IV studies with Estracyt in prostatic cancer--supplementary report: results of long-term therapy].

Two hundred patients with prostatic cancer were enrolled in our previous study between 1984 and 1987. In this study, 96 patients of them were observed for 1 year or more after oral administration of Estracyt (estramustine sodium phosphate). Of these 96 cases, 33 patients were treated with Estracyt as primary treatment and 63 patient had been treated with other treatments before Estracyt treatment. Twelve patients were treated only with Estracyt and 84 patients also received other treatments. Thirty-eight patients were on primary therapy, 37 patients were on maintenance therapy, and 11 patients were on primary therapy, 37 patients were on maintenance therapy, and 11 patients were on the re-activated stage therapy and 10 patients were others. In conclusion, among the 67 cases in which the due judgement of the effect was possible, Estracyt was markedly effective in 10 cases (14.9%), effective in 16 cases (23.9%), slightly effective in 15 cases (22.4%) and ineffective in 26 cases (38.8%). The survival rate was 92.6% at the first year, 66.0% at the third year and 46.3% at the fifth year in the follow-up study. Adverse reactions were observed in 22 cases (22.9%), among which the administration was discontinued in 3 cases.

Aged↗

[Favorable prognoses in 24 adult patients with acute leukemia, surviving over five years since 1985].

Since 1985 we have experienced 24 leukemia cases with long-term survival, who were treated with one of three types of postremission therapy. Of them, 20 patients were physically fit for ordinary work and returned to their work as workers or housewives during long-term follow-up period. Two housewives gave birth. We have devised three types of postremission therapy; 1) multidrug combination therapy with gradually longer intermissions (January 1980-March 1983); 2) controlled randomized clinical trial by the Japanese Foundation for the Multidisciplinary Treatment of Cancer, April 1983-March 1985-March 1988). In a group who underwent multidrug combination therapy without prednisolone, 12 of 20 patients who achieved complete remission have shown continued complete remission, as of November 1991, including seven 5-year survivors. These results indicate that improvement of postremission therapy makes it possible for adult patients with acute leukemia to survive 5 years or longer.

Adolescent↗

[Renal cell carcinoma metastasizing to choroid plexus of lateral ventricle; a case report].

A rare case of renal cell carcinoma metastasizing to the choroid plexus of the lateral ventricle is reported. A 59-year-old woman was admitted to our institution on November 26, 1987 complaining of left-half headache for one month. She had a past history of right nephrectomy due to renal cell carcinoma 4 years before admission, and of right radical mastectomy due to breast cancer 10 years before admission. She had no abnormal neurological findings and laboratory results were normal. CT scan revealed a well-circumscribed, apparently homogeneously enhancing mass in the left lateral ventricle with mild ventricular dilatation. Left vertebral angiogram showed a tumor stain fed by the left posterior choroidal artery. The most likely diagnosis was thought to be metastasis of renal cell carcinoma. The patient underwent the operation for tumor removal via the posterior interhemispheric transcallosal approach 14 days after admission. A histological examination of the tumor determined the diagnosis of clear-cell type renal cell carcinoma. The operation was uneventful and the patient was discharged 20 days after operation without neurological deficit. But she had recent-memory disturbance, low activity, and gait disturbance in May 1989. CT scan revealed ventricular dilatation and tumor recurrence at the same site. She also suffered from diabetes due to the regrowth and invasion of primary tumor to the pancreas. She was discharged free of neurological defects after ventriculo-peritoneal shunt. In December 1989, she gradually deteriorated due to the regrowth of the intraventricular metastatic lesion, and now she is bedridden. Choroid plexus metastasis is quite rare, and, to our knowledge, only three cases have been described.

Carcinoma, Renal Cell↗

Enhancement of the actions of smg p21 GDP/GTP exchange protein by the protein kinase A-catalyzed phosphorylation of smg p21.

We have previously shown that cyclic AMP-dependent protein kinase (protein kinase A) phosphorylates smg p21A and -B, ras p21-like small GTP-binding proteins. In the present study, we investigated the function(s) of this phosphorylation by use of the smg p21B purified from human platelets. smg p21B bound to plasma membranes and the protein kinase A-catalyzed phosphorylation of smg p21B reduced this binding. Moreover, the phosphorylation of smg p21B enhanced the two actions of its specific GDP/GTP exchange protein, named GDP dissociation stimulator, when tested in a cell-free system: one is the action to stimulate the GDP/GTP exchange reaction of smg p21B, and the other is the action to inhibit the binding of smg p21B to membranes. Consistently, smg p21B was translocated from the membranes to the cytoplasm when it was phosphorylated by protein kinase A in intact platelets in response to prostaglandin E1 or dibutyryl cyclic AMP. The protein kinase A-catalyzed phosphorylation of smg p21B affected neither its basal GDP/GTP exchange reaction, basal GTPase activity, nor the GTPase activity stimulated by its specific GTPase activating protein. On the other hand, we have recently clarified that the structure of the C-terminal region of the post-translationally processed human platelet smg p21B is Lys-Lys-Ser-Ser-all-trans-geranylgeranyl Cys181 methyl ester, and that this modification of the C-terminal region is essential for smg p21B to bind to membranes. We furthermore determined here that protein kinase A phosphorylated Ser179 in this C-terminal region of smg p21B. These results indicate that protein kinase A-catalyzed phosphorylation of smg p21B makes smg p21B sensitive to the actions of smg p21 GDP dissociation stimulator.

Blood Platelets↗

Role of the C-terminal region of smg p21, a ras p21-like small GTP-binding protein, in membrane and smg p21 GDP/GTP exchange protein interactions.

Limited proteolysis with trypsin of smg p21B, a ras p21-like small GTP-binding protein having the same putative effector domain as ras p21s, produced the N-terminal fragment and the C-terminal tail of Lys-Lys-Ser-Ser-geranylgeranyl-Cys methyl ester. The Mr values of the intact smg p21B, the N-terminal fragment, and the C-terminal tail were estimated to be about 22,000, 20,500, and less than 1,000, respectively, by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Both the GDP- and GTP-bound forms of the intact smg p21B bound to various membranes and phosphatidylserine-linked Affi-Gel. However, both the GDP- and GTP-bound forms of the N-terminal fragment failed to bind to membranes and phosphatidylserine-linked Affi-Gel. In contrast, the C-terminal tail bound to membranes and phosphatidylserine-linked Affi-Gel. The N-terminal fragment contained a GDP/GTP-binding and GTPase domain and exhibited these two activities, but the C-terminal tail did not show any such activity. A GTPase-activating protein for smg p21 stimulated the GTPase activity of both the intact smg p21B and the N-terminal fragment. In contrast, a GDP/GTP exchange protein for smg p21, named GDP dissociation stimulator, stimulated the GDP/GTP exchange reaction of the intact smg p21B but not that of the N-terminal fragment. These results indicate 1) that smg p21B is composed of at least two functionally different domains, the N-terminal GDP/GTP-binding and GTPase domain and the C-terminal membrane-binding domain, 2) that smg p21B binds to membranes through its C-terminal hydrophobic and basic domain, and 3) that this C-terminal domain is also essential for the smg p21 GDP dissociation stimulator action but not for the smg p21 GTPase-activating protein action.

Amino Acid Sequence↗

Stoichiometric interaction of smg p21 with its GDP/GTP exchange protein and its novel action to regulate the translocation of smg p21 between membrane and cytoplasm.

We have previously purified a GDP/GTP exchange protein for smg p21A and -B, members of a ras p21/ras p21-like small GTP-binding protein superfamily. This regulatory protein, named smg p21 GDP dissociation stimulator (GDS), stimulates the dissociation of both GDP and GTP from and the subsequent binding of both GDP and GTP to smg p21s. We show here that smg p21 GDS forms a complex with both the GDP- and GTP-bound forms of smg p21B at a molar ratio of about 1:1. Both the GDP- and GTP-bound forms of smg p21B bound to membranes. smg p21 GDS inhibited this binding and moreover induced the dissociation of the prebound smg p21B from the membranes. These results indicate that smg p21 GDS stoichiometrically interacts with smg p21B and thereby regulates its GDP/GTP exchange reaction and its translocation between membranes and cytoplasm.

Animals↗

Calcium-dependent regulation of cyclic GMP phosphodiesterase by a protein from frog retinal rods.

In vertebrate photoreceptors, light reduces cyclic GMP concentration and closes cGMP-activated channels to induce a hyperpolarizing response. As Ca2+ can permeate the channels and the Na(+)-Ca2+ exchanger continuously extrudes Ca2+, closure of the channel results in a reduction of the inter-rod Ca2+ concentration. This is believed to be one of the mechanisms of light-adaptation produced by activation of guanylate cyclase. Effects of Ca2+ on the cGMP phosphodiesterase (PDE) have been reported, but their physiological significance has remained unclear. We have perfused the inside-out preparation of a frog rod outer segment (I/O ROS, originally termed truncated ROS, and find that Ca2+ in a physiological range regulates the light-activation of PDE. Therefore, PDE regulation by Ca2+ must be involved in light-adaptation in rods. The effect is mediated by a newly found protein which binds to disk membranes at high Ca2+ concentrations and prolongs PDE activation.

3',5'-Cyclic-GMP Phosphodiesterases↗

Effects of a Ca2+ entry blocker (nilvadipine) on acute focal cerebral ischemia in rats.

The effects of nilvadipine, a Ca2+ entry blocker, on focal cerebral ischemia were investigated in rats having unilateral middle cerebral artery occlusion. All rats had 24 h ischemia, and were divided into three groups (ten rats per group). Groups 1 and 2 received 1.0 and 3.2 mg/kg nilvadipine s.c. respectively, just after the occlusion. Control rats received an equal volume of the vehicle. Control animals had a % infarct volume of 28.2 +/- 11.4%, and a left/right hemispheric volume ratio of 112 +/- 12%. Group-1 and -2 rats had % infarct volumes of 25.5 +/- 11.6% and 13.9 +/- 9.2% (p less than 0.01) respectively, and left/right hemispheric volume ratios of 111 +/- 9% and 103 +/- 7% (p less than 0.05), respectively. Thus, the drug reduced the infarct size and the brain edema in a dose-dependent manner. The significant decrease in the infarct volume was observed in the periphery of the frontoparietal cortex. This study supports the hypothesis that nilvadipine may be a potential therapeutic agent for cerebral ischemia. Neuropathological findings suggest the possible therapeutic effects of the drug in the ischemic penumbra.

Acute Disease↗

Rat middle cerebral artery occlusion using an intraluminal thread technique.

A modification of the previous methods of producing cerebral ischaemia in rats (Koizumi et al., Longa et al.), using an intraluminal thread technique, is described. The middle cerebral artery is occluded by introducing a simple 3-0 nylon thread (0.20-0.249 mm in diameter) through the internal carotid artery in the neck. It has been proven that with this method reproducible focal cerebral ischaemia can be achieved which resembles human stroke. Therefore this simple and relatively non-invasive model is suitable for the pathophysiological investigation of ischaemic stroke and the testing of potential therapies.

Animals↗

The usefulness of cyclophosphamide pretreatment for subrenal capsule assay against human esophageal cancer.

In order to suppress the host immune reaction in subrenal capsule assay (SRCA) using normal immunocompetent mice, the effects of cyclophosphamide (CPM) pretreatment were compared to those obtained after cyclosporine A (CSA) treatment. CPM and CSA suppressed the host reaction until day 6 and day 12, respectively, however, the histological evaluation of the tumors on day 6 revealed no differences between the two groups. The cytotoxicity of CPM in mouse serum against P388 cells was measured to evaluate the residual activity of CPM against the implanted tumor. No cytotoxicity was observed in the serum 36 hours after the CPM injection. In the histological analysis of clinical samples, inflammatory infiltration was observed in only 4 of 25 samples and tumor cell preservation recognized in 27 of 28 samples. A persistence of tumor cells was recognized in the samples rich in tumor cells. Adequate growth of the tumor in the control groups was obtained from 30 of 33 tumors (91 per cent), and the response rates of this assay were comparable to those of prior clinical experiences on each of these drugs. These results indicated the feasibility of SRCA with CPM pretreatment as a predictive test of chemotherapeutic agents for esophageal cancer.

Animals↗

Failure of blood pressure control by a new combined alpha- and beta-blocking agent (amosulalol) in a patient with pheochromocytoma.

A 42-year-old woman with pheochromocytoma received preoperatively a combined alpha- and beta-adrenoceptor blocking agent, amosulalol, exerting some inhibitory action on both receptors. Severe hypertension and remarkable fluctuation of heart rate occurred following this medication. Although it is claimed currently that a combined blocking agent is useful for the management of this disease, it should be administered with caution.

Adrenal Gland Neoplasms↗

Histological analysis of high-grade superficial bladder tumour.

Segmental cystectomy or total cystectomy was performed in 26 patients with newly diagnosed stage T1, grade 3 transitional cell carcinoma of the bladder. Their histological specimens were assessed with regard to types of tumour cell spread, small vessel involvement and coexistent carcinoma in situ. Patients were followed for 12 to 141 months. Broad front type and tentacular type spread were seen in 57.7% and 38.5%, respectively. Small vessel involvement was seen in 38.5% of patients. Coexistent carcinoma in situ was found in as many as 65.4%. Urethral recurrence was found in 4 patients out of 26. These data suggest that the high incidence of coexistent carcinoma in situ may be the most important cause of the unsatisfactory prognosis for stage T1, grade 3 bladder cancer.

Aged↗