Biomedical subjects
Publications and source records attributed to T Beppu.
We describe a case of intralober pulmonary sequestration in association with tuberculosis. Sequestrations of the lung are classically divided into two types of extralober and intralober. Intralober pulmonary sequestration in association with tuberculosis is rare. We diagnosed the present case to be Pryce type 1 with tuberculosis infection.
We performed a clinical evaluation on the antiemetic profile and the plasma concentration of Azasetron Hydrochloride (a new selective 5-HT3 receptor antagonist), in transcatheter arterial chemoembolization using CDDP for unresectable hepatocellular carcinoma. Antiemetic effects were examined in 32 patients in the serotone group (administration of serotone 10 mg + methylprednisolone 125 mg) and in 77 patients of the control group (administration of metoclopramide 20-30 mg + methylprednisolone 500 mg). The response rate and the CR ratio in serotone group was 97% and 66%, respectively. These results were statistically higher than in the control group. Although all patients had chronic liver diseases, no side effects and complications related to administration of serotone were observed. The average area under the concentration (AUC) curve of plasma serotone in five patients with liver cirrhosis was 531 ng.h/ml, which was greater than that of a healthy volunteer. In conclusion, serotone is a new, safe and useful antiemetic drug in TACE therapy for hepatocellular carcinoma.
In order to provide a high dose of cis-diammine dichloro platinum (CDDP) into the regional lymph nodes and surrounding organs during operation, "intraoperative local infusion chemotherapy (ILIC)" was devised and has been applied to advanced gastric cancer patients. The aims of this method are 1) to reduce the possibility of metastasis by affecting the cancer cells before flowing out; 2) to administer drugs to the cancer cells which evade surgical resection; 3) to administer drugs to the lymphatic flow; and 4) to reduce the systemic side effects. After the laparotomy, the part of the stomach for gastrectomy was isolated from the blood supply, applying clamps to the proximal and distal parts of the stomach and hemostats to feeding blood vessels. Through a feeding artery to the tumor, 50 mg of CDDP was injected. Twenty-four patients underwent ILIC from June 1986 to December 1993. The 5-year survival rate was significantly better in the ILIC group compared to the control group which was selected by the matched pair method. The newly devised ILIC chemotherapy is a promising way to improve the prognosis of advanced gastric cancer patients. A randomized prospective study should be undertaken.
We evaluated the efficacy of microwave coagulation therapy (MCT) in 84 patients with hepatocellular carcinomas (HCC) and 40 with metastatic liver tumors (MLT). The response rates calculated with diagnostic imaging were 92% in HCC and 80% in MLT. The regional recurrence rates were relatively higher in patients with MLT (33%) than in HCC (14%). The average surgical margin in operative MCT group was 11 mm. The cumulative survival rates at three and five years were 63% and 38% in HCC and 43% and 33% in MLT, respectively. The complications were similarly encountered in HCC and MLT (12% versus 13%). When these observations are taken together, MCT is a radical and safe locoregional therapy which can keep an adequate surgical margin and assure long survival.
Gastrointestinal bleeding in patients with portal hypertension is usually secondary to esophageal varices, but massive bleeding from gastric mucosal lesions and colonic mucosal lesions including colorectal varices, have been variably described. These lesions are called portal hypertensive gastropathy and colopathy. The incidence and profile of portal hypertensive gastropathy (PHG) has been frequently reported during the last decade, and many studies showed that development of PHG is influenced by coexisting esophageal varices, absence of major portal systemic shunts, severity of liver disease and sclerotherapy and is directly correlated with portal venous pressure. Although hyperdynamic congestion seems to be the underlying mechanisms for the development of PHG, results of gastric mucosal blood flow in patients with PHG is controversial. The treatment can be currently recommended to prevent bleeding, is oral administration of propranolol which decreased portal venous pressure. The clinical feature and profile of portal hypertensive colopathy is classified two groups, which are named colorectal varices and colonic mucosal lesions including vascular spider, dilated fine branching vessels. Although colorectal varices are usually seen at rectum and sigmoid colon, colonic mucosal lesions are seen all part of colon. Significant relationship between colorectal varices and liver disease has been reported and colorectal varices is highly appeared in patients with extrahepatic portal obstruction. Such patients are revealed arteriovenous communications at angiogram. In general, colonic resection or transanal ligation should be the first option for treatment of bleeding colonic varices and colonic mucosal lesions. Transendoscopic sclerotherapy may be an alternate choice.
Radicicol, an inhibitor of Src-family protein-tyrosine kinases, causes morphological reversion of v-src- and v-Ha-ras-transformed fibroblasts and arrest of the cell cycle at both the G1 and the G2 phases. Radicicol was found to inhibit the growth of several other oncogene-transformed cell lines and human carcinoma cell lines and to revert their cell morphology to be flat. In the radicicol-treated flat cells, actin stress fiber bundles were reorganized. Since this effect of radicicol on these cell lines was inhibited by cycloheximide, de novo protein synthesis is required for the morphological reversion. Screening of cellular proteins enhanced in response to radicicol by two-dimensional gel electrophoresis suggested that the amount of gelsolin, an actin regulatory protein, was distinctly increased upon radicicol treatment. Western blot and Northern blot analyses showed that radicicol enhanced transcription of the gelsolin gene in human carcinoma cell lines, as a result of which the amount of gelsolin was increased several folds. Injection with an anti-gelsolin antibody into cells and successive treatment with radicicol resulted in approximately 80% reduction of the number of flat cells with stress fibers in comparison with controls treated with an irrelevant antibody. These results show that elevated expression of gelsolin is associated, at least in part, with the suppression of transformation and the restoration of actin stress fibers in human carcinoma cells by radicicol.
Apoptosis is morphologically related to premature mitosis, an aberrant form of mitosis. Staurosporine, a potent protein kinase inhibitor, induces not only apoptotic cell death in a wide variety of mammalian cells but also premature initiation of mitosis in hamster cells that are arrested in S phase by DNA synthesis inhibitors. Here we report on the biochemical differences between the two phenomena commonly caused by staurosporine. Rat 3Y1 fibroblasts that had been arrested in S phase with hydroxyurea underwent apoptosis by treatment with staurosporine, whereas S-phase-arrested CHO cells initiated mitosis prematurely when similarly treated with a low concentration of staurosporine. Chromosome condensation occurred in both apoptosis (3Y1) and premature mitosis (CHO). However, neither formation of mitotic spindles nor mitosis-specific phosphorylation of MPM-2 antigens was observed in apoptosis of 3Y1 cells, unlike premature mitosis of CHO cells. The p34cdc2 kinase activated in normal and prematurely mitotic cells remained inactive in the apoptotic cells, probably because the active cyclin B/p34cdc2 complex was almost absent in the S-phase-arrested 3Y1 cells. The absence of intracellular activation of p34cdc2 in apoptosis was confirmed by immunohistochemical analyses using a specific antibody raised against Ser55-phosphorylated vimentin which is specifically phosphorylated by p34cdc2 during M phase. Furthermore, phosphorylation of histones H1 and H3, which is associated with mitotic chromosome condensation, did not occur in the apoptotic cells. These results indicate that the two phenomena, staurosporine-induced apoptosis and premature mitosis, are different in their requirement for p34cdc2 kinase activation and histone phosphorylation.
A new gene encoding a heat shock protein 70 family protein of Schizosaccharomyces pombe (Sp), named sks2+, was cloned as a weak suppressor for the K-252a-sensitive mutation, ucm1. The nucleotide sequence of sks2+ revealed an open reading frame of a 613-amino-acid (aa) protein. The deduced aa sequence of sks2+ showed significant homology with Saccharomyces cerevisiae (Sc) Ssb1p and Ssb2p responsible for protein synthesis by non-organelle-localized ribosomes, as well as with other proteins of the HSP70 family. The cells lacking the functional sks2+ gene were viable and showed no increased sensitivity to K-252a but grew slowly with an elongated morphology. These results suggest that the sks2+ gene product plays a role in the cell cycle progression and is able to confer drug resistance in a multicopy state.
We have recently constructed a physical map of the Streptomyces griseus 2247 genome using the restriction enzymes AseI and DraI, which revealed that this strain carries a 7.8 Mb linear chromosome. Based on this map, precise macrorestriction fragment and cosmid maps were constructed for both ends of the chromosome, which localized the afsA gene 150 Kb from the left end. Two afsA- mutants were found to have suffered chromosomal deletions that removed the afsA locus. The sizes of the deletions were 20 and 130 Kb at the right end and 180 and 350 kb at the left end, respectively. Hybridization experiments using cosmids carrying a deletion endpoint indicated that the ends of the chromosome in the mutants were fused to form a circular chromosome.
Replacement of Trp39 of Rhizomucor pusillus pepsin (RMPP) by Asn or Cys resulted in a marked decrease in the milk-clotting and proteolytic activities. Kinetic analysis with chromogenic synthetic oligopeptides as substrates revealed that the mutations caused marked changes in the kcat value, but only slight changes in the Km value. Similar enzymatic properties were observed in mutants of Tyr75, which was shown to have a role in enhancing the catalytic activity. Both Tyr75Asn and Trp39Asn mutants rapidly lost the activity at high temperatures due to autocatalytic digestion at two sites. The structures of several aspartic proteinases including RMPP, as revealed by X-ray crystallographic studies, showed that Trp39 occupies a position close to Tyr75 and the N delta atom of Trp39 within hydrogen-bonding distance of the hydroxyl side chain of Tyr75. These observations suggest that Trp39 plays a role in maintaining Tyr75 in the correct orientation in aspartic proteinases, including RMPP.
A serine protease (SSP) of Serratia marcescens is one of the extracellular enzymes secreted from this Gram-negative bacterium. SSP is produced as a large precursor and converted to a mature protein by cleavages removing an NH2-terminal signal sequence and a COOH-terminal pro-region. This COOH-terminal pro-region is integrated into the outer membrane and has a functional role for the export of the mature protein across the outer membrane. Southern hybridization analysis with a DNA fragment encoding the COOH-terminal pro-region as the probe showed a wide distribution of nucleotide sequences encoding SSP exporter-like proteins among Serratia species. Moreover, S. marcescens IFO 3046, from which the ssp gene had been cloned, was found to contain two ssp homologues (ssp-h1 and ssp-h2). They were cloned and their nucleotide sequences were determined. The two ssp homologues were found to exist in tandem on the genome and their amino acid sequences showed 81% identity to each other. Both of them showed 55% identity in amino acid sequence to preproSSP. In addition, both showed end-to-end similarity to the 100 kDa serotype-specific antigen (Ssa1) of Pasteurella haemolytica. Escherichia coli JM105 containing ssp-h1 gene produced a 53 kDa protein corresponding to the NH2-terminal portion and a 49 kDa protein corresponding to the COOH-terminal portion, both of which were rigidly integrated in the outer membrane. Consistent with the significant similarity of the COOH-terminal portions of the homologues to that of SSP, they showed the ability to translocate the mature SSP part across the outer membrane into the medium. Furthermore, the NH2-terminal portion of the homologue was not translocated into the outer membrane without its COOH-terminal part. All of these data show that the SSP homologues are outer membrane proteins that are translocated into the outer membrane with the aid of the translocator function of their COOH-terminal part.
OBJECTIVES: Progression from systemic inflammatory response syndrome (SIRS) to sepsis, severe sepsis, and septic shock has been demonstrated in a variety of patients. However, the presence of SIRS alone was not helpful in predicting the development of multiple organ dysfunction syndrome (MODS) since SIRS includes many nonprogressive conditions. This study was conducted to investigate the clinical significance of SIRS in postoperative patients. DESIGN: Retrospective study. SETTING: The surgical department of a university hospital. PATIENTS: Two hundred ninety-two consecutive patients who received elective common gastrointestinal surgery (esophagectomy, pancreatoduodenectomy, hepatectomy, gastrectomy, colorectal resection, and laparoscopic cholecystectomy) between 1992 and 1995. INTERVENTIONS: Patients were analyzed for preoperative physiologic status, surgical stress parameters, and postoperative status of SIRS, complications, and end-organ dysfunction. MEASUREMENTS AND MAIN RESULTS: Duration of SIRS or positive criteria's number of SIRS after surgery significantly correlated with surgical stress parameters (blood loss/body weight and operation time) and peak serum C-reactive protein concentrations. SIRS that continued or reappeared after postoperative day 3 was an early sign of postoperative complications. SIRS continuing consecutively for 2 days after postoperative day 3 had a 70.6% positive predictive value and a 92.5% negative predictive value for postoperative complications. Septic complications and prolongation of SIRS were associated with MODS. Five of six patients who met the SIRS criteria for >30 days developed severe MODS, and three of them died. CONCLUSIONS: SIRS is a useful criterion for the recognition of postoperative complications and end-organ dysfunctions. Early recovery from SIRS may arrest the progression of organ dysfunction.
To regulate the perfusion flow rate of a centrifugal blood pump, a microcomputer controller was developed. The computer monitored the flow rate of the pump with an electromagnetic flowmeter or an ultrasonic pulse Doppler flowmeter, rotational speed of the pump, aortic pressure, and the amount of blood in a reservoir. A discrete integral controller with a control interval of 1 s was adopted for the controller. For the safety of the control system, we added functions for detecting a clamp on the tubing, a dislocation of the flow sensor, or an inverse direction of the flow sensor. During a standby period, the computer calculated the rotational speed from aortic pressure to minimize the forward or the backward flow at the start of the pump perfusion. The automatic flow controller was used on 5 patients during cardiac operations and maintained the flow rate within +/-6% of the set point.
A 66-year-old male presented with cerebellovestibular symptoms and hypesthesia of the V2 area of his face. Neuroimaging only detected a cerebellopontine angle (CPA) meningioma. The CPA meningioma was removed using the lateral suboccipital approach, which exposed small neurinomas arising from the trochlear and abducens nerves. Both neurinomas were removed intracapsularly. Postoperatively hypesthesia resolved, but other symptoms were unchanged. A karyotypic analysis of chromosome 22 and estrogen receptor analysis suggested absence of neurofibromatosis II, but the cause(s) of the genesis of the multiple diverse tumors was not determined. This extremely rare combination of neurinomas and meningioma was probably incidental, as there are no reports of any case which a combination of the trochlear and the abducens nerve neurinomas, much less one accompanied by a meningioma.
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The afsA gene of Streptomyces griseus has been postulated to encode a key enzyme for A-factor biosynthesis from primary metabolites commonly present in Streptomyces strains. Escherichia coli cells harboring afsA under the control of the T7 promoter specified distinct A-factor activity in the culture broth, as determined by induction of streptomycin production and aerial mycelium and spore formation in an A-factor-deficient S. griseus mutant strain. Production of the substance(s) having A-factor activity was inhibited by cerulenin, an inhibitor of fatty acid biosynthesis. These observations suggest that afsA encodes a key enzyme in the A-factor biosynthetic pathway in which a beta-keto acid derived from fatty acid biosynthesis and a glycerol derivative serve as precursors.
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