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Biomedical subjects

T Segawa

Publications and source records attributed to T Segawa.

At least 19 recordsLinked to original sources

Stimulation of calcium sequestration by mezerein, a protein kinase C activator, in saponized rabbit platelets.

1. The saponin-permeabilized platelet was used to examine the effect of mezerein, a moderate activator of protein kinase C (C-kinase), on the sequestration of Ca2+ to its intracellular storage sites. 2. We found that the activation of C-kinase by mezerein causes the potentiation of the Ca2+ sequestration. 3. It was suggested that C-kinase in platelets might function as a negative feedback regulator for the agonist-induced Ca2+ mobilization and might be involved in its oscillation.

Animals

A new antibiotic, cypemycin. Taxonomy, fermentation, isolation and biological characteristics.

A new peptide antibiotic, cypemycin, with a molecular weight of 2,097 (M+H), was isolated from the culture broth of Streptomyces sp. OH-4156. The antibiotic possesses cytocidal activity against P388 leukemia cells in vitro at a concentration of 1.3 microgram/ml (IC50 values), and the antibiotic showed antimicrobial activities against Micrococcus luteus (MIC, 0.2 microgram/ml).

Amino Acid Sequence

Ultrastructural substrates for increased lung water content in experimental pulmonary edema.

We examined the relationship between the incidence of ultrastructural changes in the alveolar septum and the extravascular lung water content. Pulmonary edema was induced in 18 mongrel dogs by either dextran (n = 12) or alloxan (n = 6) administration. Six other dogs served as controls. Extravascular lung water content was measured by the thermal-dye double indicator dilution method. Specimens of lung tissue were examined with an electron microscope, and the incidence of 13 types of pathological changes in the alveolar septum was studied. For each type of pathological change, the incidence was correlated with the magnitude of lung water content. The following results were obtained. The incidence of edematous changes in the alveolar interstitium (widening of the interstitial space, and dispersion and disarray of collagen fibres in the interstitial space) was well correlated with lung water content (r = 0.78, p < 0.01, and r = 0.84, p < 0.01, respectively). The correlation was not significant in the remaining types of changes. We conclude that the incidence of the pathological changes in the alveolar septum is increased along with the increase in the content of lung water in both dextran- and alloxan-induced experimental pulmonary edema in dogs.

Alloxan

Primary signet ring cell adenocarcinoma of the prostate: a case report and literature review.

We report a rare case of primary signet ring cell adenocarcinoma of the prostate in a 61-year-old male, who died of systemic lymphatic spread. Autopsy ruled out another primary signet ring cell adenocarcinoma outside the prostate. However, immunohistochemically, the tumor stained negatively for prostate-specific antigen. A review of the literature revealed only 15 case reports, including our case.

Adenocarcinoma, Mucinous

Fluorescence digital image analysis of thrombin and ADP induced rise in intracellular Ca2+ concentration of single blood platelets.

Cytoplasmic free Ca2+ concentration, [Ca2+]i, was estimated in single rabbit blood platelets by digital imaging microscopy with the use of the specific Ca(2+)-indicator dye Fura-2. Uneven distribution and low level of [Ca2+]i was found in the resting platelet even in the presence of extracellular 1 mM Ca2+. Thrombin at 1 unit/ml immediately caused a transient increase in [Ca2+]i, which was followed by a secondary and sustained increase in [Ca2+]i. The distribution of increased levels of [Ca2+]i was also shown to be uneven within the cell. The presence of 1 mM EGTA in the medium only slightly decreased the initial rise in [Ca2+]i, but completely inhibited the latter phase, a sustained rise in [Ca2+]i. This result shows that the initial rise of [Ca2+]i might not be caused by Ca2+ influx, but might be induced by mobilization of Ca2+ from intracellular Ca2+ storage sites. This speculation is further supported by the fact that the elevated [Ca2+]i induced by thrombin immediately decreased to the base line value when 3 mM EGTA was applied. Thus, thrombin induced elevation of [Ca2+]i is suggested to consist of two different processes, namely the mobilization of Ca2+ from the intracellular storage sites and the successive Ca2+ influx through the receptor activated Ca2+ channels. Stimulation with ADP also caused a rapid elevation of platelet [Ca2+]i, but this effect of ADP was different form that of thrombin. Thus, the ADP induced rise in [Ca2+]i was accompanied by oscillation and was inhibited by extracellular EGTA. Our present experiment is the first report that clearly and directly reveals the differences between the effects of thrombin and ADP on [Ca2+]i of platelets.

Adenosine Diphosphate

Pretreatment with catalase or dimethyl sulfoxide protects alloxan-induced acute lung edema in dogs.

We tested the preventive effects of catalase, an enzymatic scavenger of hydrogen peroxide, or dimethyl sulfoxide (DMSO), a hydroxyl radical scavenger, on intravenous alloxan-induced lung edema in four groups of pentobarbital sodium-anesthetized, ventilated dogs for 3 h: saline (20 ml.kg-1.h-1) infusion alone (n = 5), alloxan (75 mg/kg) + saline infusion (n = 5), catalase (150,000 U/kg) + alloxan + saline infusion (n = 5), or DMSO (4 mg/kg) + alloxan + saline infusion (n = 5). Catalase or DMSO significantly prevented the increase in plasma thromboxane B2 and 6-keto-prostaglandin F1 alpha over 3 h after alloxan and the accumulation of extravascular lung water after 3 h [3.95 +/- 0.52 (SE) g/g with catalase, 3.06 +/- 0.42 g/g with DMSO] but not early pulmonary arterial pressor response. An electron microscopic study indicated that catalase or DMSO significantly reduced the endothelial cellular damages after alloxan. These findings strongly suggest that hydrogen peroxide and hydroxyl radical are major mediators responsible for intravenous alloxan-induced edematous lung injury in anesthetized ventilated dogs.

6-Ketoprostaglandin F1 alpha

Differing actions of endothelin-1 on canine systemic resistance and capacitance vessels.

In anesthetized open-chest dogs, an intravenous bolus injection of endothelin-1 (ET-1, 400 pmol/kg) caused transient hypotension (initial hypotensive phase; phase 1), followed by a continuous elevation of blood pressure (late hypertensive phase; phase 2). The constriction and dilation of the systemic capacitance and resistance vessels were evaluated from the change in mean circulatory pressure (MCP) and in total peripheral resistance (TPR) in phases 1 and 2. To examine the modification of the action of ET-1 on the blood vessels by the baroceptor reflex or by the endothelium-derived relaxing factor (EDRF) released by ET-1 in phase 1, we performed experiments in dogs under total spinal anesthesia (TSA group), methylene blue-treated dogs (MB group) as well as in the untreated dogs (control group). ET-1 decreased the TPR significantly, and increased the MCP significantly in phase 1 in the control (n = 8) and TSA (n = 8) groups; there was no difference between the groups. ET-1 had no significant effect on TPR but increased the MCP significantly in MB group (n = 8) during phase 1. The percentage increase of MCP in the MB group significantly exceeded that of the control group. ET-1 increased both the TPR and MCP significantly in phase 2 in the control group (n = 8). This study indicated that the vasoconstrictor action of ET-1 on the systemic capacitance vessels in phase 1 did not result from a baroceptor reflex, and that the vasodilator action of ET-1 on the systemic resistance vessels may be at least in part mediated via EDRF released by ET-1. We suggest that the vasoconstrictor action of ET-1 on the systemic capacitance vessels is strong, but the vasodilator action of EDRF on the systemic capacitance vessels is weak.

Animals

Isolation of substance P binding protein from rat brain.

Substance P (SP) binding protein of rat brain was solubilized by digitonin. The solubilized proteins were then purified by sequential gel filtration, concanavalin A lectin Sepharose, and SP-affinity chromatography. The calculated molecular weight of this purified SP binding protein was 76-74 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The rabbits were immunized with the purified protein and resulting polyclonal anti-sera were tested. The immune serum significantly inhibited [3H]SP binding to the 3-[(3-cholamidopropyl)dimethylammonio]-1-propane sulfonate solubilized membrane fractions from rat brain, whereas pre-bleed antiserum failed to inhibit the binding. This polyclonal antibody also inhibited the activity of 45Ca influx into astroglioma cells stimulated by SP, but does not inhibit that stimulated by histamine. Furthermore, this polyclonal antibody recognized the 76-74 kDa band as assessed by Western blotting. These data strongly suggest that this polyclonal antibody could recognize a part of the natural SP receptor site.

Animals

[Recurrent hepatocellular carcinoma after hepatic resection].

A total of 125 patients with hepatocellular carcinoma (HCC) treated by hepatic resection in our department from 1970 to 1989 were reviewed to determine recurrent factors, recurrent modes of HCC and to assess the treatment for recurrent HCC. Seventy-five of 125 patients had recurrent tumors after the first hepatic resection. The 1-, 2-, and 3-year cumulative recurrent rates after hepatic resection were 25%, 52% and 67% respectively. The size of the tumor, intrahepatic metastasis, portal vein involvement, clinical stage and DNA ploidy pattern were judged as useful predictive factors for recurrence of HCC after hepatic resection. In the patients with intrahepatic metastases, the bilateral lobes of the remnant liver were the most frequent recurrent sites. The treatment for recurrent HCC was divided into 3 groups such as re-resection, transcatheter arterial embolization (TAE) and palliative treatment. The survival curves of patients receiving re-resection and TAE were significant better than those of patients receiving palliative treatment. Patients treated by re-resection for recurrent HCC had the longest survival. The 1-, 3- and 5-year cumulative survival rates after re-resection were 84%, 60% and 48% respectively. It is concluded that the early detection of recurrent HCC is important and re-resection or TAE is effective treatment for recurrent HCC.

Adult

[Evaluation of hepatectomy in small hepatocellular carcinoma--comparison with transcatheter arterial embolization therapy].

Therapeutic effect on 81 hepatectomized patients with hepatocellular carcinoma (HCC) less than 5cm in diameter was compared to that achieved by transcatheter arterial embolization therapy (TAE) in 61. The 5-year cumulative survival rate after hepatectomy was 38%, which was better than that of TAE (8%). Outcome after hepatectomy was better than that after TAE, according to tumor size in less than 2cm in diameter and single nodule. The 3-, and 5-year survival rates for curative hepatectomy were significantly better than those for TAE. But there was no significant difference in survival curves between relative noncurative hepatectomy and TAE. In terms of hepatic reserve with reference to Child's classification, the survival curve for TAE was better than that for relative noncurative hepatectomy in patients with Child-A, but there was no significantly difference between these two methods. Survivors more than 3 years after hepatectomy and TAE were 24 (48.0%) and 11 (23.4%) patients, respectively. Nineteen of 24 patients with hepatectomy had recurrent HCCs, of which reresection was done in 6, TAE in 11 and other treatments in 2. The advantage of hepatectomy in comparison with TAE is a possibility of long-term survival, if curative hepatectomy is performed.

Adolescent

[Circumvention of the intrinsic multidrug-resistance in renal cell carcinoma].

Most of renal cell carcinomas (RCCs) are refractory at the start of chemotherapy. We have demonstrated that the frequently elevated expression of the multidrug resistance gene (MDR) in RCCs is associated with the intrinsic vinca alkaloids and anthracyclines resistance. The preliminary clinical trials using verapamil or amiodarone in combination with vinblastine or doxorubicin to overcome multidrug-resistant (MDR) tumors could not achieve satisfactory results owing to severe cardiovascular toxicities of such reversing agents. In the present study, we studied the sensitizing ability of bis-benzyl-isoquinoline (cepharanthine) and SDB-ethylenediamine (N-1379) in natural MDR kidney cancer cells. Cepharanthine remarkably sensitized vinblastine and doxorubicin sensitivities in those cells with high MDR RNA levels. From a clinical point of view, cepharanthine seems to be a potent and less toxic agent to treat natural MDR kidney cancers.

Alkaloids

Histamine H2-receptor in atrium: signal transduction and response.

We have examined the signal transduction for H2-receptor mediated positive chronotropic response of guinea-pig right atrium. Our results indicate that phospholipid methylation is rapidly induced by histamine acting on H2-receptor in guinea-pig right atrium and therefore plays a predominant role in the signal transfer of H2-receptor-mediated cyclic AMP generation to exert positive chronotropic effect of atrium, as well as GTP-binding protein activation.

Adenylyl Cyclases

Caroli's disease associated with hepatolithiasis: a case report and review of the Japanese literature.

A 27-year-old woman was admitted to Nagasaki University Hospital complaining of abdominal pain and fever. Percutaneous transhepatic cholangiography showed multiple cystic dilatations of the intrahepatic bile ducts without stone formation. The illness was diagnosed as a pure type of Caroli's disease. No surgical intervention was made. Subsequently, the patient suffered repeated attacks of cholangitis, and six years later, computed tomography demonstrated cystic lesions of both lobes of the liver and stones within the cystic lesions of the right lobe. We collected 62 cases of Caroli's disease reported in the Japanese literature, including our own case. Among them, cholangitis was found in 43.5%, hepatolithiasis in 30.6%, esophageal varices in 17.7% and cholangiocarcinoma in 8.1%. It is difficult to successfully treat Caroli's disease involving both lobes of the liver. Long-term repeated cholangitis could lead to fibrosis of the liver, hepatolithiasis, portal hypertension and cholangiocarcinoma. Considering the above-mentioned aspects of the disease, careful follow-up studies are required in each case.

Adult

Subchronic oral toxicity of glyoxal via drinking water in rats.

The subchronic oral toxicity of glyoxal via drinking water and the effect on in vivo protein synthesis in tissues following a single treatment with this substance were assessed in Sprague-Dawley male rats. Animals received drinking water containing glyoxal levels of 2000, 4000, and 6000 mg/liter ad libitum for 30, 60, and 90 days in Phase I. In Phase II, the high-dose and control-1 groups fed the diet ad libitum, and a diet-limited control-2 group given the same amount of diet as consumed by the high-dose group were maintained for 90 and 180 days. The study designs included observations of clinical signs, body weights, major organ weights, gross and histopathological examinations, serum clinical chemistry, and biochemical examinations such as glyoxalase activity and glutathione content in selected tissues. Body weight gain and organ weights significantly decreased with dosage. Although consumption of food and water was also depressed in the exposed group, the reduction of body weight gain was greater in the high-dose group than in the diet-limited control 2 group. Histopathological examinations revealed only a slight papillary change in the kidneys from the high-dose group at both 90 and 180 days terminations in Phase II. The induction of both glyoxalase I and II was observed in liver and erythrocytes at 30-day termination of the exposed groups. Serum enzyme and protein levels were significantly reduced by the mid- and/or high-dose exposures. With a single oral high-dose treatment of glyoxal, a great decline in the incorporation of L-[3H]leucine was shown particularly in the liver, and this probably led in part to a reduction in the serum protein levels in rats following subchronic exposure to glyoxal. These data indicated an overall low degree of systemic toxicity to rats exposed subchronically to glyoxal via drinking water.

Animals

Solid and cystic tumor of the pancreas in an adult male.

A solid and cystic tumor (SCT) was located at the head of the pancreas in a 43-year-old Japanese male, and pancreatoduodenectomy was performed on the suspicion of papillary carcinoma or cystadenocarcinoma of the pancreas. The lesion, which measured 4.5 x 4.5 x 4.0 cm, was clearly demarcated by connective tissue. The cut surface showed solid grayish-white areas with central cystic degenerative changes. The solid areas consisted of small round cells proliferating in a small solid or a pseudopapillary pattern. The tumor cells partially invaded the surrounding normal pancreatic parenchyma. Immunohistochemical studies revealed positive staining for alpha-1-antitrypsin and neuron-specific enolase, but no staining for known pancreatic hormones. Moreover, ultrastructural studies showed the absence of zymogen granules and the presence of anullate lamellae and neurosecretory granules. On the basis of these findings, a diagnosis of SCT of the pancreas was established. In order to clarify the histogenesis and biological behavior of the tumor, it is necessary to accumulate and analyze similar cases, an endeavor which in turn will contribute to the successful management of this disease.

Adult

Characterization of the carbohydrate chain on the substance P receptor in the rat brain cortex: effect of lectins on [3H]substance P binding.

The characteristics of the carbohydrate chain on the rat cerebral cortical substance P (SP) receptor were studied. We examined the effects of pretreatment with three lectins (concanavalin A, wheat germ agglutinin, lens culinaris agglutinin) on the [3H]SP binding activities. Each lectin can bind to the specific carbohydrate chain. Among these lectins, only concanavalin A inhibited specific [3H]SP binding by reducing the affinity of the binding sites. The inhibitory action of concanavalin A was dose-dependent and diminished by the addition of alpha-methyl-D-mannoside. The present results suggest that the rat cortical SP receptor has either a biantennary complex-type or a high mannose-type of carbohydrate chain, and that the carbohydrate chain is implicated in the SP binding activity of the SP receptor system.

Animals