Biomedical subjects
Publications and source records attributed to Y Otani.
A 46-year-old female with mitral insufficiency complicated by hereditary hemorrhagic telangiectasia (Osler's disease) underwent successfully mitral valve replacement. The patient had a history of repeated large-volume nasal bleeding. Mitral valve replacement using a xenograft was safely performed with various attempts for preventing abnormal postoperative hemorrhage.
By the advent of extracorporeal shock wave lithotripsy (ESWL), the plan to manage choledocholithiasis has changed greatly. As a non-operative treatment, endoscopic sphincterotomy (EST) is intensively performed, but ESWL is much safer than EST in invasiveness and complications. Without EST, 5 Fr endoscopic naso-biliary drainage (ENBD) and percutaneous transhepatic biliary drainage (PTBD) aiming at preservation of the function of the papilla Vater were inserted to make drainage first for the patients with choledocholithiasis with obstructive jaundice who visited our hospital. After the cholangitis subsided, ESWL was performed under the direct cholangiography through ENBD and PTBD and excellent results were obtained which are herein reported. ENBD has been performed on 98 cases of choledocholithiasis over the past 4 years. ESWL has been performed on 42 cases (ENBD 36 cases and PTBD 6 cases). Choledocholithiasis completely disappeared in 31 cases (73.8%). For unsuccessful cases, EST, percutaneous transhepatic cholangioscopy (PTCS), or laparotomy was performed.
Two operative cases of emphysematous giant bullae of the lung accompanied with bronchial asthma were reported. Case 1: A 41-year-old man suffering from dyspnea and fever-up was diagnosed as emphysematous giant bullae of the right lung accompanied with severe bronchial asthma. Preoperative examination revealed severe hypoxemia (PO2 46 mmHg) and mixed type ventilatory disorder; VC 1.68 t (41%), FEV1.0 0.59 l (35%). On the first anesthesia, operation was postponed by the severe asthmatic attack and circulatory collapse. After the complete prevention of the attack by giving corticosteroid (25 mg/day) for two weeks, resection of giant bullae could be performed safely. Case 2: A 31-year-old man complaining wheeze was diagnosed as emphysematous giant bullae of bilateral upper lobes of lung accompanied with bronchial asthma. Preoperative and intraoperative states were uneventful, though, on the day after the operation, asthmatic attack occurred due to the difficulty in expectation of sputa. It took 12 hours and many kinds of drugs to improve the respiratory state. In the patients of bronchial asthma, preoperative sufficient suppression of hyperreactivity of airway tracts and postoperative careful treatment to avoid asthmatic attack seem to be indispensable.
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Stromelysin is a metalloproteinase that degrades extracellular matrix macromolecules including fibronectin, laminin, collagen IV and proteoglycans. We now report that cycloheximide, an inhibitor of protein synthesis, induces human stromelysin mRNA in fibroblast cultures in a time- and dose-dependent fashion. As determined by Northern hybridization, a 24-h treatment with cycloheximide increased stromelysin mRNA about 20-fold over the control level. In vitro translation or translation in cells after removal of cycloheximide resulted in increased levels of immunoprecipitable stromelysin suggesting that the cycloheximide-induced stromelysin mRNA was functional. Analysis of mRNA stability suggested that the cycloheximide effect is in part due to the increased activation of the stromelysin gene. In contrast to these results, cycloheximide did not induce collagenase mRNA but, rather, prevented its induction by interleukin-1 beta. These data provide evidence for discoordinate regulation of collagenase and stromelysin genes and suggest that a short-lived repressor protein may play a role in the stromelysin gene expression.
In order to investigate the role of collagenase in cancer invasion and metastasis, two collagenase activities of interstitial collagenase and type IV collagen degrading enzyme (type IV collagenase) were determined in 40 cases of human stomach cancer tissue. Elevated cancers which are known to have a propensity to cause blood-borne metastases showed higher activities of both interstitial collagenase and type IV collagenase than flat or ulcerous type of cancer. Using the parameters of lymph node metastasis vs tumor size or vs depth of cancerous invasion into the stomach wall, classification of the cases was attempted according to the degree of malignancy. In the cases with marked lymph node metastases in spite of small tumor size and/or shallow cancerous invasion into the stomach wall, type IV collagenase activity was higher than that in the cases with lower malignancy (p less than 0.025, p less than 0.05, respectively). These results suggest that collagenase in stomach cancer tissue play an important role in the invasion and metastasis of cancer cells. Type IV collagenase activity in stomach cancer tissue could be one of the useful biological markers for the degree of malignancy.
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We studied CT findings and Interventional Radiology including therapeutic procedures in 43 cases with abdominal blunt trauma, retrospectively. All of parenchymal organ's injuries, and injuries of duodenum & retroperitoneum were correctly diagnosed by CT. In 14 cases with only hemoperitoneum or no positive findings on CT, 4 cases were jejunal perforations, and remaining 10 cases were conservatively treated and relieved. We have to take care that the similar CT findings include the opposite results to need surgery and not.
We have determined that human stromelysin mRNA can be induced by interleukin-1 beta (IL-1 beta) and that the induced mRNA levels can be suppressed by retinoic acid and dexamethasone (Saus, J., Quinones, S., Otani, Y., Nagase, H., Harris, E.D., Jr., and Kurkinen, M. (1988) J. Biol. Chem. 263, 6742-6745). Here we show, by nuclear run-on and transient gene expression analyses, that IL-1 beta induction is a promoter function and that dexamethasone suppresses IL-1 beta-induced gene activity. For transient gene expression assays, 1.3 kilobase pairs of the stromelysin promoter region (-1303 to -11 relative to the transcription start site) and shorter fragments thereof were cloned into a human growth hormone reporter vector. In transfected human fibroblast cultures all the constructs, with the exception of the one containing the shortest promoter fragment (-53 to -11), responded to IL-1 beta induction. Interestingly, the ability of IL-1 beta to induce human growth hormone expression decreased as the length of the promoter fragment was reduced. Dexamethasone treatment suppressed the induced human growth hormone levels by approximately 50% irrespective of the promoter length. These results suggest that the 1.3-kilobase pairs stromelysin promoter fragment contains DNA elements required for IL-1 beta induction and dexamethasone suppression.
We have determined the complete primary structure for human matrix metalloproteinase-3 (MMP-3), which has 477 residues including a 17-residue signal peptide. The result indicates that MMP-3 is identical with stromelysin (Whitham, S. E., Murphy, G., Angel, P., Rahmsdorf, H.-J., Smith, B. J., Lyons, A., Harris, T. J. R., Reynolds, J. J., Herrlich, P., and Docherty, A. J. P. (1986) Biochem. J. 240, 913-916). A striking result is that MMP-3 and collagenase are 54% identical in sequence, suggesting a common origin for the evolution of the two proteinases. We also show that in human synovial fibroblast cultures human recombinant interleukin-1 beta rapidly induces high levels of MMP-3 mRNA and, conversely, that retinoic acid or dexamethasone can suppress the MMP-3 mRNA levels. Similar results were obtained for human synovial collagenase mRNA. The data suggest that MMP-3 and collagenase expression are coordinately modulated in synovial fibroblast cultures.
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LEW with BDE-heart graft received 0 (control), 15, or 40 mg cyclosporine (CsA)/kg b. wt. per day. On postoperative days 3, 5, 7, 10, and 14 in four animals each weight and cell count of thymus and spleen were determined, and thymus and spleen cell subpopulations were examined with monoclonal antibodies. The same tests were performed in FiS heart graft recipients without immunosuppression and ungrafted LEW which received 15 or 40 mg CsA. We expressed alterations in thymocyte subpopulations by using the differentiation ratio (DR), i.e., differentiated in % of all T-cells and by the ratio of helper to suppressor/cytotoxic T-cells (Th-Ts/c). In graft rejection the thymus showed no significant change in DR or Th-Ts/c. However, in the CsA-induced graft tolerance DR was elevated and at the same time Th-Ts/c declined, both showing maximum values on days 5 and 7 and a return to normal thereafter. FiS graft recipients exhibited similar thymus alterations as tolerant recipients, but less marked. In CsA-treated ungrafted LEW, elevation of DR was slight after 15 mg but very strong after 40 mg CsA (93% on day 7), and it did not return to normal in the latter group. Th-Ts/c was decreased in these ungrafted animals, but not as strongly as in tolerant graft recipients. Such thymus alterations were not observed in graft rejection. Spleen weights were strongly increased in graft rejection and unchanged in graft tolerance. Splenic Ts/c and Th-Ts/s were increased in CsA-treated tolerant recipients but not in graft rejection. We conclude that elevation of DR and decline of thymic Th-Ts/c in the initial postoperative phase are indicators of graft tolerance in organ recipients.
We studied in this paper the behavior of immunosuppressive and fibroblast proliferation inhibitory factors in the acute, chronic damage and cirrhotic alteration of the liver. We induced in LEW-rats acute hepatic necrosis by i.v. application of dimethylnitrosamine (DMNA: 35 mg/kg b.wt.) and by i.m. injection of CCl4 (1 ml/kg b.wt., twice a week). After 2-4 weeks we found chronic hepatic damage and after 8-10 weeks liver cirrhosis. As a control, untreated animals were used. Sera and liver factors were prepared from the animals and used for inhibition tests of fibroblast proliferation and MLC reaction. Furthermore, cell count and cell subpopulation of the thymus were determined by monoclonal antibodies (W3/25, OX-8). LF of untreated and DMNA-treated animals exhibited very strong unspecific inhibition effects of fibroblast proliferation and allogenic stimulation. However, with progression of hepatic damage (chronic hepatitis and cirrhosis) both suppressive abilities were gradually reduced. Normal sera showed very slight inhibition of allogenic stimulation but sera of animals with acute hepatic damage showed very strong inhibition. In the 2 weeks of CCl4 treatment, their inhibitory abilities were more than 40%, and with progression of hepatic damage they were gradually reduced. Normal sera or sera of animals with chronic hepatic damage could not suppress the fibroblast proliferation; however, sera of acute hepatic damage inhibited it very strongly. With chronic hepatic damage, the thymus gradually atrophied and, after 10 weeks of CCl4 treatment, it had atrophied completely. Thymocyte differentiation was found only in animals with acute hepatic damage. This suggests that factors which were liberated from the damaged hepatocytes caused differentiation of the thymocytes.
We performed 70% hepatectomy in LEW rats and examined immunologic alterations during hepatic regeneration; especially, thymus weight and cell count, T-cell subpopulations, differentiation ratio of thymocytes (DR) and ratio of T-helper to T-suppressor/cytotoxic cells (Th-Tsc). Strongest liver regeneration was observed on postoperative days 2-5 and it was completed on day 7. During hepatic regeneration a significant thymus atrophy in weight and cell count was found on day 3 and 5, it normalized from the 7th day on. T-cells were highly differentiated during liver regeneration with a DR of 35.7 +/- 2.5%, 64.0 +/- 4.4% and 38.8 +/- 3.0% on postoperative days 3, 5, and 7, respectively, and at the same time Th-Tsc ratio was reduced to 0.57 +/- 0.11, 0.38 +/- 0.04 and 0.57 +/- 0.05, respectively. DR and Th-Tsc ratio showed a trend to normalization from the 7th day on. No changes of thymus and T-cell subpopulations occurred in a sham-operated control group. Since we found such thymus alterations also in spontaneous or drug induced tolerant graft recipients, we conclude that the hepatic regenerative potential possesses a suppressive effect on immune responses.
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To obtain a sufficient operative field at the operation for cardiac cancer, especially with esophageal infiltration, thoracotomy or sternotomy has been added to laparotomy. These procedures are not easy and cause great stress in patients. Through our new technique, left sided thoracotomy and sternotomy can be eliminated in favor of transabdominal phrenotomy, which is able to be performed much easier to obtain a good operative field. In order to perform the phrenotomy, the diaphragm has to be stretched using our modified hook suspender, by which the costal arch is lifted strongly upward and cranially. With these procedures, about a 5cm long esophagus is able to be resected with lymph node dissection in the lower mediastinum without difficulty. No marked influence of the hook suspender as well as the phrenotomy has been recognized on respiratory and circulatory systems. The anastomosis between the esophagus and jejunum or residual stomach seems to be very difficult, because the site of the anastomosis is located quite deep in the mediastinum. This problem, however, can be completely resolved by means of a surgical stapling autosuture instrument.
The gene coding for the lipase of Pseudomonas fragi was cloned into Escherichia coli JM83 by inserting Sau3A-generated DNA fragments into the BamH I site of pUC9. The plasmid isolated, pKKO, was restriction mapped and the position of the lipase gene on the 2.0 kb insert was pinpointed by subcloning. DNA sequencing revealed that the open reading frame comprises 405 nucleotides and gives a preprotein of 135 amino acids with a predicted Mr of 14643. By comparing the putative lipase amino acid sequence with porcine pancreatic, rat lingual and Staphylococcus hyicus lipases the amino acid sequence around the reactive serine was found to be common among the types of lipase which have been reported.