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Biomedical subjects

M Sunagawa

Publications and source records attributed to M Sunagawa.

At least 55 records · Page 3Linked to original sources
PubMed1997

Complications after cyst excision with hepaticoenterostomy for choledochal cysts and their surgical management in children versus adults.

The aim of this study was to review the cases 200 children and 40 adults who had cyst excision combined with hepaticoenterostomy (CEHE) for choledochal cyst, with particular emphasis on post-CEHE complications and their surgical management. Patients who had CEHE at the age of 15 years or less were defined as children, and those aged 16 years or older were defined as adults. The mean age when patients became initially symptomatic was 3 years in children and 26 years in adults. Eleven adults became symptomatic as children (< or = 15 years of age). The mean age of CEHE in children and adults was 4.2 years and 35 years, respectively. The time interval between the onset of initial symptoms and CEHE was significantly less in children than in adults (P < .0001). Of the 200 children, 176 had primary CEHE, and 24 had secondary CEHE converted from cystoenterostomy or other biliary surgery. Seventy children had intraoperative cyst endoscopy, which enabled us to examine the proximal intrahepatic bile ducts for stenosis and debris, and to wash out debris, protein plugs, and stones from the intrapancreatic ducts. Of the 40 adults, 22 had primary CEHE, 18 had secondary CEHE. The mean follow-up period was 10.9 years in children and 10.7 years in adults. The number of patients with post-CEHE complications in children and adults was 18 (9.0%) and 17 (42.5%), respectively. The post-CEHE complication rate in children was significantly lower than in adults (P < .0001). The 18 children had 25 post-CEHE complications such as cholangitis, intrahepatic bile duct stones, pancreatitis, stone formation in the intrapancreatic terminal choledochus or pancreatic duct, and bowel obstruction. Twenty-seven post-CEHE complications developed in the 17 adults including 2 cases of cholangiocarcinoma. There were no post-CEHE complications in the 70 children who had intraoperative cyst endoscopy. No stone formation was seen in the 145 children who had CEHE at the age of 5 years or less. Eight stone formations were seen in seven (12.7%) of the remaining 55 children aged over 5 years. Stones developed in seven (17.5%) adults. The incidence of post-CEHE stone formation in children aged 5 years or less was significantly lower than in other children and adults (P < .0001). Reoperation was required in 15 children: revision of hepaticoenterostomy in 4, percutaneous transhepatic cholangioscopic lithotomy (PTCSL) in 1, excision of intrapancreatic terminal choledochus in 2, endoscopic sphincterotomy of the papilla of Vater in 1, pancreaticojejunostomy in 1, and laparotomy for bowel obstruction in 6. Ten adults required reoperations: revision of hepaticoenterostomy in 2, PTCSL in 2, left hepatic lobectomy in 1, endoscopic sphincterotomy in 2, exploratory laparotomy in 2, and adhesiolysis in 1. The authors conclude that early diagnosis followed by CEHE is the treatment of choice for choledochal cyst, and intraoperative cyst endoscopy is recommended as a valuable adjunct to CEHE.

Adolescent↗
PubMed1997

Synthesis and biological properties of a new series of anti-MRSA beta-lactams; 2-(thiazol-2-ylthio)carbapenems.

A series of 1 beta-methylcarbapenems containing variously C-2 substituted thiazol-2-ylthio groups were synthesized, and their in vitro anti-MRSA activity was examined. Among them, 1 beta-methyl-2-(4-arylthiazol-2-ylthio)carbapenems exhibited superior anti-MRSA activity. Introduction of a cationic moiety in the C-2 side chain not only reduced the binding to HSA but also increased the stability against DHP-I, without affecting the anti-MRSA activity. It was also found that the distance between the cationic moiety and the carbapenem skeleton was related to the strength of HSA binding and the stability against DHP-I.

Anti-Bacterial Agents↗
PubMed1997

Differences in the rate of donor leucocyte migration between natural and drug-assisted tolerance following rat liver transplantation.

The number involved in and the rate of migration of donor leucocytes into the following recipient organs (spleen, thymus, bone marrow, lung and mesenteric lymph nodes) were measured in two rat models of orthotopic liver transplantation (OLT) using donor-specific MHC class I antibodies. The first OLT model is one that does not require immunosuppression in order to achieve tolerance and involved the transplantation of DA (MHC haplotype, RT1a) livers into PVG (RT1c) recipients. The second model was one that required a 7-day (10 mg/kg) treatment with cyclosporin A (CsA) to achieve tolerance and used DA donors into Lewis (RT1(1)) recipients. Recipient organs were biopsied on days 3, 20 and 87 following OLT and donor leucocyte migration was quantified by immunohistochemistry and computer densitometry of immunoblots of detergent-solublized tissues in order to resolve both membrane-bound and soluble donor MHC class I antigen. In a separate experiment, spleen biopsies were taken following OLT on days 3 and 15 from the naturally tolerizing OLT model (DA into PVG), treated with and without CsA for 7 days and compared with the (DA into Lewis) model. The initial rate of leucocyte migration between days 3 and 21 following OLT was found to be the most rapid into the spleen, followed by the bone marrow and mesenteric lymph nodes in the naturally tolerant (DA into PVG) model when compared with the (DA into Lewis) model. The number of donor leucocytes in the spleen and mesenteric lymph nodes in both models was, however, approximately the same by 87 days. No real difference in the rate of leucocyte migration was seen in the thymus or the lung for both transplant models over the time course assayed. CsA was found to lower the rate of donor leucocyte migration only over the period it was administered. The rate of donor leucocyte migration into the spleen was still much lower 15 days after OLT in the (DA into Lewis) model compared with the (DA into PVG) model treated with and without CsA. Thus the differences in the rate of donor leucocyte migration into the spleen, bone marrow and mesenteric lymph nodes immediately following OLT may offer an explanation as to why the (DA into PVG) combination is able to accept a transplanted liver without immunosuppressive therapy.

Animals↗
PubMed1997

Structure-activity relationships of carbapenem compounds to anti-Haemophilus influenzae activity and affinity for penicillin-binding proteins. Effect of 1 beta-methyl group and C-2 side chain.

The anti-H. influenzae activity of meropenem (1a) was much higher than those of imipenem (4). panipenem (2b) and biapenem (7). To clarify the major structural features responsible for the anti-H. influenzae activity of carbapenem compounds, the structure-activity relationship to the anti-H. influenzae activity was investigated. The anti-H. influenzae activities of meropenem (1a) and 1 beta-methyl-panipenem (2a) were much higher than those of desmethyl-meropenem (1b) and panipenem (2b). respectively. Two carbapenems (5, 6) and imipenem (4), that have a strong basic C-2 side chain, showed lower anti-H. influenzae activity than meropenem (1a) having a weakly basic C-2 side chain and N-acetyl thienamycin (3) having a neutral C-2 side chain, respectively. As a result, we found that the introduction of the 1 beta-methyl group or the reduction of the basicity (cationic character) of the C-2 side chain increased the antimicrobial activity and bactericidal activity of carbapenems against H. influenzae due to their increased affinity for PBP-4 and PBP-5.

Anti-Bacterial Agents↗
PubMed1997

Habutobin splits the Arg16-Gly17 bond in the A alpha chain of rabbit fibrinogen.

We reported previously that habutobin, a thrombin-like enzyme from Trimeresurus flavoviridis venom, clotted only rabbit fibrinogen, whereas human, monkey, bovine, dog, rat and guinea-pig fibrinogens were unaffected. In the present study, we investigated the cleavage site of the rabbit A alpha chain by habutobin. The fibrinopeptide released by habutobin was identical to the fibrinopeptide A released by thrombin, and its amino acid sequence corresponded to A alpha 1-16 of rabbit fibrinogen. It was clarified therefore that habutobin cleaves the Arg16-Gly17 bond in the A alpha chain of rabbit fibrinogen.

Amino Acid Sequence↗
PubMed1997

The novel calcium sensitizer levosimendan activates the ATP-sensitive K+ channel in rat ventricular cells.

Levosimendan, a new Ca++-sensitizing and positive inotropic agent, was reported to act as a coronary vasodilator and protect ischemic myocardium. To elucidate the mechanisms of these actions, the possible electrophysiological effects of levosimendan on isolated rat ventricular cells were examined by the patch-clamp technique with whole-cell and single-channel recordings. Levosimendan (3 and 10 microM) markedly shortened action potential duration and activated an outward current at potentials positive to -70 mV. The increased current was abolished by glibenclamide, a blocker of the ATP-sensitive K+ (K[ATP]) current. Stimulation of K[ATP] current was dose dependent, with an EC50 value of 4.7 microM; a maximal effect occurred at 30 microM. The L-type Ca++ current was not affected by levosimendan (0.2-10 microM). In single-channel current recording in open cell-attached patches, K[ATP] channels, which had been inhibited by 0.3 mM ATP, were activated by levosimendan. However, levosimendan did not stimulate the K[ATP] channels that exhibited high spontaneous activity in ATP-free solution. Levosimendan also could not stimulate K[ATP] channels that had rundown in ATP-free solution. However, levosimendan could stimulate rundown K[ATP] channels that were reactivated by nucleotide diphosphates. K[ATP] channels inhibited by 0.5 mM AMP-PNP, a nonhydrolyzable ATP analog, were not stimulated by levosimendan; however, the channels were stimulated by levosimendan in the presence of 30 to 50 microM ADP. Levosimendan stimulates cardiac K[ATP] channels that are suppressed by intracellular ATP. It appears that levosimendan acts synergistically with nucleotide diphosphates. These properties of levosimendan may help protect ischemic myocardium because activation of K[ATP] channels by levosimendan would likely occur in ischemic regions in which intracellular ADP concentration is increased and intracellular ATP concentration is decreased.

Action Potentials↗
PubMed1996

Habutobin releases plasminogen activator (U-PA) from bovine pulmonary artery endothelial cells.

Habutobin is a thrombin-like enzyme, contained in the venom of Trimeresurus flavoviridis, which has the strongest toxic effect in cases of habu bite. The present study was undertaken to examine the effect of habutobin on the release of plasminogen activators using cultured endothelial cells of the bovine pulmonary artery. The chemical characteristics of the plasminogen activators released into the conditioned medium were determined by fibrin autography and immunological analysis. A chromogenic substrate (S-2251) microassay was employed for quantitative estimation of the plasminogen activator activity in the conditioned medium and euglobulin fraction derived from the conditioned medium. The levels of plasminogen activator inhibitor released into the conditioned medium were determined by reverse fibrin autography. Fibrin autography revealed that cultured bovine pulmonary artery endothelial cells spontaneously released tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA) into the conditioned medium with no stimulus. Exposure of confluent cultures to 50 nM habutobin, however, induced a time-dependent increase in the level of plasminogen activator activity in both the conditioned medium and euglobulin fraction, and the plasminogen activator activity in the euglobulin fraction at 24 hr was significantly higher than that in the control (P < 0.05). Reverse fibrin autography demonstrated that the lysis-resistant zone of the supernatant of the euglobulin fraction (habutobin exposure) was wider than that in the case of no stimulus. These findings suggest that habutobin induced a time-dependent increase in the levels of plasminogen activator and plasminogen activator inhibitor concomitantly.

Animals↗
PubMed1996

Effect of Habu (Trimeresurus flavoviridis) antivenom on changes of hemostatic parameters following administration of crude venom from T. flavoviridis in rabbits.

We carried out experiments to examine the efficacy of Habu antivenom in relation to variations of hemostatic parameters induced by the administration of crude venom to rabbits. For neutralization of the crude venom by Habu antivenom, the correlation between the concentrations of Habu antivenom (Y) and crude venom (X) was expressed by the equation: Y = -0.473 + 0.539X. We examined the variations in hemostatic parameters in the state which crude venom was neutralized by Habu antivenom following the administration of crude venom (1 mg/kg) from Trimeresurus flavoviridis. Although the hemostatic parameters [level of fibrinogen, antithrombin III (AT-III) activity and alpha 2-plasmin inhibitor (alpha 2-PI) activity] underwent decreases after the administration of crude venom, they revealed fluctuations within the normal range after the Habu antivenom administration. The AT-III activity, however, decreased gradually until 90 min after the antivenom administration. These results suggested that Habu antivenom was effective in improving the abnormal coagulant activity induced by crude venom. However, the neutralization effect towards the coagulant activity of crude venom by the Habu antivenom did not continue for a long time and did not lead to recovery of the AT-III activity. Since excessive doses of antivenom can induce serious medical problems, we expect that simultaneous use of antivenom and AT-III preparation, instead of excessive and single use of Habu antivenom could provide a useful therapy for snake bites from the present study.

Animals↗
PubMed1996

Heterotopic splenic autotransplantation in a neonate with splenic rupture, leading to normal splenic function.

Loss of the spleen in infants and young children frequently results in overwhelming infection. To preserve splenic function, heterotopic splenic autotransplantation after splenectomy was performed on a newborn in whom the spleen was traumatized beyond repair because of birth trauma. Postoperatively, the percentage of pitted red blood cells that accurately reflects splenic reticuloendothelial function was normal. Splenic scintigrams obtained 3 weeks after the operation showed uptake by the reimplanted tissue. The otherwise mandatory long-term antibiotic prophylaxis could be reduced to 3 weeks in the newborn. At 7 years of age, the patient has not shown any increased susceptibility to infections.

Antibiotic Prophylaxis↗
PubMed1996

Lack of intestinal pacemaker (C-KIT-positive) cells in infantile hypertrophic pyloric stenosis.

The pathogenesis of infantile hypertrophic pyloric stenosis (IHPS) is not well understood. Recent studies have shown that the protonocogene c-kit is essential for the development or maintenance of autonomic gut motility, and also show that the c-kit gene protein product (C-KIT) positive cells in the mammalian gut are responsible for intestinal pacemaker activity. This study examines cells in the pyloric muscles of 23 patients (16 with IHPS, 7 controls) for the presence of the C-KIT (C-KIT+), using immunohistochemical techniques with antihuman C-KIT sera. In the controls, many C-KIT immunoreactive (IR+) cells were observed in the muscle layers. The myenteric plexuses were demarcated by a moderate number of C-KIT-IR+ cells. However, in the IHPS patients, C-KIT-IR were either absent or significantly reduced. No C-KIT-IR+ cells were found around the myenteric plexuses. These findings suggest that a lack of c-kit expression (as an indicator of intestinal pacemaker activity) in the hypertrophic pyloric smooth muscles may be an important factor in the pathogenesis of IHPS.

Biological Clocks↗
PubMed1996

Localization of intestinal pacemaker cells and synapses in the muscle layers of a patient with colonic hypoganglionosis.

Bowel dysmotility in association with hypoganglionosis remains unexplained. The proto-oncogene c-kit encodes a transmembrane tyrosine kinase receptor, and the c-kit protein-product (C-KIT) positive cells in the mammalian gut are responsible for intestinal pacemaker activity. The authors examined the localization of intestinal pacemaker cells in the muscle layers of a patient with colonic hypoganglionosis, using an antihuman C-KIT serum. In the normoganglionic ileum, many C-KIT immunoreactivity positive (C-KIT-IR+) cells were present in the muscle layers. In contrast, there were no C-KIT-IR+ cells in the muscle layers of the hypoganglionic colon. These findings suggest that a lack of c-kit expression may be responsible for the autonomic gut dysmotility in hypoganglionic bowels.

Colon↗
PubMed1996

[Neurotoxicity of carbapenem compounds and other beta-lactam antibiotics].

The neurotoxic potencies are considerably different among various beta-lactam antibiotics. Some carbapenem antibiotics, a new class beta-lactam antibiotic, also induce convulsion in human and laboratory animals. This article reviews the structure activity relationship for the neurotoxicity of beta-lactam antibiotics, especially carbapenems. As for the neurotoxicity of carbapenem antibiotics, the presence of amino group in the C-2 side chain is an important factor in inducing convulsion and the strength of basicity of the amino group is correlated with the convulsant activity. The beta-lactam ring of carbapenem is not necessary to evoke convulsions. The neurotoxicity of carbapenem antibiotics is related to only a part of the structure, including the C-2 side chain, but not to the carbapenem skeleton itself. In comparison with other beta-lactam antibiotics, it has been found that the structure responsible for the convulsive action of carbapenems is significantly different from penicillins and cephalosporins in which the beta-lactam ring is essential to evoke convulsion. The induction of convulsions by carbapenem antibiotics is predominantly caused through the inhibition of gamma aminobutyric acid receptor in a similar manner as with penicillins and cephalosporins. However, the detail mechanism may be different not only among carbapenems, cephalosporins, and penicillins but among carbapenem compounds themselves. It is important to know the neurotoxic potential of a compound by investigating the effect of direct administration into the central nervous system such as intraventricular administration, since the penetration through blood-brain barrier or the pharmacokinetic property is varied in seriously ill patients. Possible drug interactions regarding neurotoxicity are also discussed. We hope these findings described here will be helpful in developing more efficient and safer beta-lactam antibiotics of a new generation.

Animals↗