Bilateral centripetal lipid keratopathy with diffuse anterior scleritis.
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Biomedical subjects
Publications and source records attributed to M Ochiai.
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The thermal and photochemical solvolysis of the two stereoisomeric 2-phenyl-1-propenyl(phenyl)iodonium tetrafluoroborates has been investigated in alcoholic solvents of varying nucleophilicity. The product profiles and rates of product formation in the thermal reaction are all compatible with a mechanism involving cleavage of the vinylic C-I bond assisted by the group in the trans position (methyl or phenyl), always leading to rearranged products. Depending on the nucleophilicity of the solvent, the primarily formed cations may or may not further rearrange to more stable isomers. The less reactive Z compound also yields some unrearranged vinyl ether product in the more nucleophilic solvents via an in-plane S(N)2 mechanism. The mechanism of the photolysis involves direct, unassisted cleavage of the vinylic, and aromatic, C-I bond in an S(N)1 mechanism. This produces a primary vinyl cation, which is partially trapped prior to rearrangement in methanol. The unrearranged vinyl ethers are mainly formed with retention of configuration via a lambda3-iodonium/solvent complex in an S(N)i mechanism. Thermal and photochemical solvolyses of iodonium salts are complementary techniques for the generation of different cation intermediates from the same substrate.
[reaction: see text]. Exposure of (E)-beta-alkylvinyl(phenyl)-lambda3-iodanes to thioamides in dichloromethane at room temperature was found to result in a bimolecular nucleophilic substitution (S(N)2) at the vinylic carbon atom to give inverted (Z)-enethiols and/or (Z)-S-vinylthioimidonium salts. Vinylic S(N)2 reactions with thioureas are also discussed.
[reaction: see text] Exposure of cyclic acetals to 1-tert-butylperoxy-1,2-benziodoxol-3(1H)-one in the presence of tert-butyl hydroperoxide and potassium carbonate in benzene at room temperature results in oxidative ring cleavage to glycol monoesters via intermediate tert-butylperoxy ortho esters.
In the processes of carcinogenesis caused by genotoxic carcinogens, DNA-adduct formation and resultant genetic changes are crucially important. In this report, the relationship between DNA-adduct levels and mutant frequencies (MFs), DNA-adduct levels and cancer incidences, and MFs and cancer incidences induced by heterocyclic amines (HCAs), to which humans are exposed on daily basis were investigated. There was no direct correlation between adduct levels and MFs detected after feeding Big Blue mice with 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), in a comparison among various organs. Further, there was no direct correlation between DNA-adduct levels and cancer incidences, in a comparison among various organs of F344 rats. Since DNA-adducts are fixed as mutations after cell proliferation, and mutations in cancer-related genes result in cancer development, it is expected that MFs directly correlate with cancer incidences. However, there was no direct correlation between MFs and cancer incidences. Possible mechanisms involved in the discordance between DNA damage markers and cancer incidences are discussed.
The transradial approach (TRA) has been used for diagnostic and interventional cardiology. It has not previously been determined how many times the same radial artery can be cannulated without complications. A total of 812 patients (502 men and 310 women) underwent angiography or angioplasty via the TRA between 1997 and 1999 at our institution with a total of 1,438 procedures. Sheaths were 5 (55%) or 6 Fr (45%). Dropout rates of 3.5% and 7.9% were found at the second TRA attempt in the men and the women, respectively. Of the 62 TRA failures, 56 (90%) were due to narrowing or occlusion of the radial artery after the previous TRA procedure. A third TRA procedure was possible in 90% of the men and 80% of the women. A fifth TRA procedure was possible in 70% of the men and 50% of the women. The dropout rates for TRA increased as successive punctures were performed. This was primarily due to vessel narrowing and occlusion occurring as a function of multiple punctures.
We evaluated applicability of the endotoxin test to DTaP vaccines. Although no DTaP vaccine batches showed immediate interference with the activating activity of spiked endotoxin on the clotting of Limulus amaebocyte lysate (LAL), a gradually progressing interference depending on the time after spiking was seen for some of the batches. The interfering DTaP vaccine batches, however, showed no significant effect onin vitro TNF-alpha induction in RAW264.7 cells and pyrogenicity in rabbits of spiked endotoxin. Aluminium hydroxide gel in the vaccines was suggested to be one of the causes of the interference. Accordingly, a careful evaluation of the interfering effect was assumed crucial for the effective application of the endotoxin test to check residual biological activity of endotoxin in DTaP vaccines.
While gallbladder carcinoma is occasionally associated with pancreaticobiliary maljunction, spontaneous necrosis of carcinoma is extremely rare. We herein present a case of spontaneous necrosis of gallbladder carcinoma associated with direct invasion of viable cancer cell nests to the muscularis propria and subserosal layer located beneath the primary nodules. A 65-year-old Japanese man was admitted to a local hospital, complaining of repeated discomfort in the right hypochondrium. Ultrasonography and computed tomography scanning revealed cholecystitis associated with gallstones. Cholecystectomy was performed, and operative cholangiography demonstrated pancreaticobiliary maljunction. The resected gallbladder showed multiple mixed stones filled with necrotic debris and bile sludge. Scrutiny of the mucosal surface revealed multiple small necrotic nodules in the fundus, which were histologically confirmed to be necrotic remnants of a cancerous glandular structure. Small nests of papillary adenocarcinoma were found beneath the nodules in the muscularis propria and in the venous structure located in the connective tissues next to the divided margin of the gallbladder bed. Resection of S4a and S5 of the liver and resection of the extrahepatic bile duct was then performed to remove the remaining cancerous tissues and/or micrometastasis in the liver and bile duct. The biliary tree was reconstructed with a hepaticoduodenostomy. No cancer nests or any precancerous lesions were found in the additionally resected specimens. This case indicates a unique morphological feature of gallbladder carcinoma associated with pancreaticobiliary maljunction, which provides some insight into the pathogenesis of spontaneous necrosis of gallbladder carcinoma.
Although retroperitoneal or psoas abscess is an unusual clinical problem, the insidious and occult characteristics of this abscess sometimes cause diagnostic delays, resulting in considerably high morbidity and mortality. In particular, psoas abscess caused by perforated colon carcinoma is uncommon. We report a case of psoas abscess caused by a carcinoma of the cecum. A 72-year-old Japanese woman was admitted to our hospital, with pain in the right groin and buttock. The pain had appeared 6 months before admission, and the symptoms had then been relieved by oral antibiotics. On March 25, 1999, inflammatory signs in the right buttock indicated localized cellulitis, and incision and drainage was performed at a local hospital. The patient was referred to our hospital on the same day. On admission to our hospital, computed tomography (CT) scan revealed a thick right-sided colonic wall and enlargement of the right ileopsoas muscle. Barium enema and colonofiberscopy revealed an ulcerated tumor occupying the entire circumference of the cecum. A retroperitoneal abscess and fistula had been formed by the retroperitoneal perforation of cecum carcinoma: surgical resection was performed after remission of the local inflammatory signs. Operative findings indicated that the cancerous lesion and its surrounding tissues were firmly attached to the right iliopsoas and major psoas muscle, and en-bloc resection, including adjacent muscular tissue, was performed. The fact that carcinoma of the colon could be a cause of psoas abscess and cellulitis in the gluteal region should be considered when an unexplained psoas abscess is diagnosed.
Although polycystic liver disease (PLD) is known to be associated with autosomal dominant polycystic kidney disease, a finding of PLD with pancreatic ductal adenocarcinoma is extremely rare. We have experienced one such case of a ductal adenocarcinoma of the pancreas in a patient with Potter type III cystic disease of the liver and kidney. A 63-year-old man was admitted to our hospital because of obstructive jaundice. Six months previously, on admission to a local hospital for treatment of diabetes mellitus, he had been found to have polycystic disease of the liver and kidney. Ultrasound examination revealed dilatation of the intrahepatic bile duct and the common bile duct. Blood tests showed an elevated total bilirubin level. Abdominal computed tomography scans and magnetic resonance imaging demonstrated polycystic lesions in the liver and the bilateral kidneys. Percutaneous transhepatic cholangio-drainage was performed, and fluorography of the biliary tree revealed obstruction of the lower common bile duct, causing jaundice. This appears to be a case of independent association of pancreatic ductal adenocarcinoma with polycystic disease of the liver and kidney. The patient's sister, who also had polycystic disease of the liver and kidney, had died of squamous cell carcinoma of the tongue. Although familial associations of carcinomas with polycystic liver disease may be extremely rare, they provide a perspective for the etiology of polycystic liver disease.
Myocardial ischemia initiates an acute inflammatory response, in which polymorphonuclear leukocytes (PMNs) are major participants. We investigated whether increased PMN activity in the peripheral blood is a marker for high-grade coronary artery stenosis in patients with angina pectoris. PMN activity was examined in 45 patients by measuring the luminol-dependent chemiluminescence (CL) response of the peripheral blood upon addition of phorbol myristate acetate (PMA). The CL of patients with angiographic filling delay was 1.6-fold higher than in patients without delay (480+/-54 vs. 302+/-33 counts/PMN, P<0.01). The CL of patients with a filling delay of the left anterior descending artery (LAD) was 1.7-fold higher than in patients without an LAD filling delay (537+/-79 vs. 317+/-27 counts/PMN, P<0.01). With the CL cut-off at 400 counts/PMN, the sensitivity and specificity for detecting an angiographic filling delay of the LAD were 69 and 75%, respectively. These data indicate that PMN activity in the peripheral blood is increased with the presence of a flow-limiting coronary lesion showing an angiographic filling delay. Measuring PMN activity may be a useful approach to assess indications for and timing of angiography and/or adjunctive invasive therapies in patients with angina pectoris.
Severe combined immunodeficiency (Scid) mice have defects in V(D)J recombination and DNA double-strand breaks repair caused by an inherited genetic defect in the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs). Scid mice are highly susceptible to development of T-cell lymphomas, and because of the nature of its association with DNA repair and recombination, DNA-PKcs is considered to belong to the caretaker class of tumor suppressor genes. In the present study, the susceptibility of Scid mice to colon carcinogenesis due to administration of azoxymethane (AOM) was investigated. Significantly higher susceptibility in terms of induction of both aberrant crypt foci (ACFs), putative pre-cancerous lesions of the colon and colon cancers was observed as compared with the isogenic strain, C.B-17 mice. The incidences of colon tumors, either adenomas or adenocarcinomas, in Scid and C.B-17 mice after administration of AOM (10 mg/kg body weight/week) for 6 weeks were 87% (26 of 30) and 50% (15 of 30), respectively, by experimental week 22 (P < 0.01). The multiplicity of colon tumors in Scid mice was also significantly higher than in C.B-17 mice, being 2.2 +/- 1.5 and 0.9 +/- 1.2, respectively (P < 0.001). The present study clearly demonstrated high susceptibility of Scid mice to colon carcinogenesis, which might be attributable to disruption of the caretaker role of DNA-PK in colonic epithelial cells.
The study investigated whether patients hospitalized for unstable angina pectoris (UAP), who subsequently develop complete coronary thrombosis (acute transmural myocardial infarction (AMI)) despite medical treatment, exhibit platelet hyperaggregability in an assay system that does not employ agonist stimulation. The study comprised 89 patients with UAP (Braunwald type B). Unfractionated heparin and nitrate were administered to all patients via continuous intravenous drip together with aspirin taken orally. Citrated platelet-rich plasma (230-250x 10(3)/microl) was obtained on admission and again, in some patients, following the AMI. Platelet aggregability was measured in an optically modified cone-plate viscometer that enables the detection of platelet aggregation without agonist stimulation. A continuous shear rate of 1,200/s was employed. Of the 89 patients, 85 were finally stabilized, while 4 developed an AMI accompanied by persistent ST-segment elevation with increased levels of plasma creatine kinase within 3 h after starting the treatment. The extent of platelet aggregation on admission was significantly greater in these 4 patients compared with the 85 who were stabilized (87.8+/-6.8%, n=4 vs 26.8+/-9.1%, n=85; mean+/-SD). These data suggest that platelet hyperaggregability mediated mainly by fibrinogen binding to the activated glycoprotein IIb/IIIa complex occurs before a complete thrombotic occlusion and this evaluation may provide important information before the onset of myocardial infarction.
Routine chest radiography demonstrated abnormal opacities in the right lower lung field of a 54-year-old man with idiopathic interstitial pneumonia. A high-resolution chest CT scan showed diffuse air-space consolidation in the right lower lung with replacement of a honeycomb area. The diagnosis was adenocarcinoma, and a right lower lobectomy was performed. Histopathologic examination showed moderately differentiated adenocarcinoma and the pathological stage was T3 N0 M0 (Stage IIB). About 1 year later, the cancer recurred with diffuse air-space consolidation in the whole of the right lung and the left middle and lower lung, which resulted in the patient's death. It was difficult to discriminate between an acute change for the worse of idiopathic interstitial pneumonia and a recurrence of lung cancer on the basis of the CT findings in this patient. It is important to elucidate the CT features of lung cancer associated with idiopathic interstitial pneumonia.
The pyrogen test or the endotoxin test has been playing a crucial role in detecting endotoxin in parenteral drugs. The current test methods, however, have disadvantages such as requiring a relatively high number of animals or an inadequacy in direct evaluation of in vivo activity. We made an attempt to establish a new in vitro assay method that can overcome the shortcomings of the current assay methods. We standardized the system of tumor necrosis factor-alpha (TNF-alpha) induction from the peripheral blood of rabbits for assaying endotoxin activity. This in vitro assay showed a linear dose-response regression between 0.1 and 5.0 endotoxin units per milliliter of endotoxin and a definite homogeneity of variance by logarithmically transforming the endotoxin and TNF-alpha concentrations in the reaction mixtures at 5 h of incubation at 37 degrees C. The assay showed a definite correlation with the pyrogen test but not with the endotoxin test when endotoxins from various bacteria were tested.
Diphtheria tetanus acellular pertussis combined (DTaP) vaccines have been successfully used in Japan by controlling their potencies and toxicities with animal models. In accordance with the recent practical introduction of DTaP vaccines of various formulations, a question has been raised in other nations as to the efficacy of a quality control system based on animal tests and standard preparations. The World Health Organization issued its guidelines on the production and quality control of acellular pertussis vaccines in 1998 along with the concept of quality control by ensuring that production lots were consistent with clinical trial lots, rather than by comparing them with standard preparations in traditional laboratory tests. However, because it is not feasible to evaluate the combined use of vaccines from different manufacturers in a clinical study, the alternative trend of quality control may give rise to a difficulty in rationalizing the practical immunizations to use vaccines of different brands in a mixed consequence. A standardized national regulation system to ensure the equivalence of approved products would be essential for such an immunization practice. The success of the Japanese DTaP vaccination suggests the possibility of an effective quality control of DTaP vaccines by means of standardized test systems.
Tetra-n-butylammonium oxido-lambda(3)-iodane, prepared from 1-hydroxy-1,2-benziodoxol-3(1H)-one by reaction with tetra-n-butylammonium fluoride, directly undergoes oxygen atom transfer to alpha,beta-unsaturated carbonyl compounds, yielding epoxides.
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