Effect of leukotriene B(4) receptor antagonist (ONO4057) on hepatic allografting in rats.
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Biomedical subjects
Publications and source records attributed to Y Uchida.
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A 49-kDa chitinase (pI7.3) was purified to homogeneity from the culture supernatant of Streptomyces griseus HUT 6037 by ultrafiltration, DEAE-Sephadex A-50 and Sephadex G-100 column chromatographies, and chromatofocusing. The purified enzyme was stable up to 40 degrees C. The N-terminal amino acid sequence of the enzyme was highly homologous to the N-terminal region of the fibronectin type III-like domain of S. olivaceoviridis chitinase 01 belonging to family 18 glycosyl hydrolases. The 49-kDa chitinase hydrolyzed partially N-acetylated chitosan more easily than colloidal chitin. The hydrolyzate of 54% deacetylated chitosan by the enzyme was separated by CM-Sephadex C-25 column chromatography. The structures of the oligosaccharides obtained were determined by MALDI-TOF MS analysis combined with exo-glycosidase digestion. In addition to GlcNAc, (GlcNAc)2, and (GlcNAc)3, hetero-chitooligosaccharides with GlcNAc at the reducing end were detected. Thus, the specificity of the enzyme for the hydrolysis of the beta-1,4-glycosidic linkages in partially N-acetylated chitosan was similar to that of the family 18 chitinases.
We have performed a retrospective study to evaluate whether surgical treatment is beneficial in patients with hepatic metastases from breast cancer. Between September 1985 and September 1998, 25 patients with hepatic metastases (14 solitary and 11 multiple), eight of whom had extrahepatic metastases, underwent hepatectomy. All of the detectable liver metastasis were resected in all of the cases. There were no severe postoperative complications. All but one of the patients received adjunctive polychemotherapy after the hepatectomy. After the hepatectomy, recurrent tumors were detected in 18 of the patients, being located in the liver in 12 (67%) of them. Overall, however, hepatectomy ensured that the liver was clinically recurrence-free for a median of 24 months (range 2-132 months). Eleven patients died of recurrent tumors, two died of other causes and the remaining 12 are currently alive. The 2- and 5-year cumulative survival rates after hepatectomy were 71% and 27%, respectively, and the median survival duration was 34.3 +/- 3.2 months, much better than the period of 8.5 months for another series of patients treated with standard or non-surgical therapies at our institution. The number and the size of hepatic metastases, the interval between treatment of the primary lesion and hepatectomy, and the existence of extrahepatic metastasis were not adverse prognostic factors. In conclusion, our data, although limited and highly selective, suggest that surgical treatment of hepatic metastases from breast cancer may prolong survival in certain subgroups of patients to a greater extent than standard or non-surgical therapies.
BACKGROUND: Nocturnal gastric acid breakthrough is defined as night-time periods when gastrin pH falls below 4.0 for greater than 1h during administration of a proton pump inhibitor. This phenomenon is a serious problem for patients who require strict control of their gastric acid secretions. AIM: To investigate the prevalence of nocturnal gastric acid breakthrough in Japanese subjects during administration of rabeprazole, and to clarify the relationship between Helicobacter pylori infection and nocturnal gastric acid breakthrough. METHODS: Thirty-one normal male volunteers were examined by ambulatory 24 h gastric pH monitoring four times: without medication, after a morning or an evening dose of 20 mg rabeprazole, and after administration of an H2-receptor antagonist at bedtime, in addition to the morning dose of rabeprazole. H. pylori infection was determined by the 13C-urea breath test and an assay for serum anti-H. pylori antibody. RESULT: Nocturnal gastric acid breakthrough was observed in 12 patients (39%) after the morning dose of 20 mg rabeprazole. In all cases, nocturnal gastric acid breakthrough was inhibited completely by administration of the H2-receptor antagonist at bedtime. Only one patient with nocturnal gastric acid breakthrough had H. pylori infection. CONCLUSION: The absence of H. pylori infection appears to be closely related to the occurrence of nocturnal gastric acid breakthrough during dosing with a proton pump inhibitor.
In order to locate the genetic regions in the swine genome that are responsible for economically important traits, a resource population has been constructed by mating two female Meishan pigs with a male Göttingen miniature pig. In subsequent generations, 265 F2 offspring were produced from two F1 males and 19 F1 females. The F2 offspring were scored for eight traits including growth rate, teat number, vertebra number and backfat thickness, and genotyped for 318 genetic markers spanning the swine genome. Least-square analysis revealed quantitative trait loci (QTL) effects for vertebra number on chromosomes 1 and 2; for teat number on chromosomes 1 and 7; for birth weight on chromosome 1; for average daily gain between 4 and 13 weeks of age on chromosomes 9 and 10; for backfat thickness on chromosome 7; and for backskin thickness on chromosome 3.
Mechanisms of initiation of phase III contractions in the jejunum during the digestive state are not well understood. To test whether phase III can be induced by a local injection of various agents in a jejunal segment, a polyethylene tube was chronically placed in a branch of the jejunal artery, and force transducers were chronically placed in the upper jejunum. Local injection of atropine, hexamethonium and xylocaine induced caudal-migrating phase III in the injected segment only in the digestive state, and simultaneous intra-arterial infusions of L-arginine, an NK-1 antagonist, or 5-hydroxytryptamine (5-HT) 1P and 3 antagonists inhibited the induced phase III. Intravenous atropine and hexamethonium also inhibited xylocaine-induced phase III contractions. Atropine and hexamethonium-induced phase III were brought about by inhibition of neural transmission at nicotinic receptors in the inhibitory pathway to NO neurones. NK-1, 5-HT1P and 5-HT3 receptors are present in the excitatory but not the inhibitory pathway to NO neurones. Xylocaine appears to stop neuronal transmission from mechanoreceptors to NO neurones. Thus, the initiation of spontaneous occurrence of phase III in the digestive jejunum is likely to be brought about by transient cessation of postprandial contractions in a segment of the jejunum.
BACKGROUND: In various drug-induced gastric mucosal injuries, it has been speculated that changes in gastric mucosal energy metabolism differ according to the cause of injury. This study was conducted to investigate the role of energy metabolism in two drug-induced gastric mucosal injuries in humans. METHODS: The subjects were patients with acute gastric mucosal injury due to non-steroidal anti-inflammatory drugs (NSAID) or steroids, and normal controls. Two sets of tissue specimens from the antrum and corpus of the stomach were obtained. One specimen from each area was used for histological analysis and the other was stored in liquid nitrogen. The stored tissues were homogenized. Adenosine triphosphate (ATP), adenosine diphosphate (ADP) and adenosine monophosphate (AMP) were measured by the luciferin-luciferase method. RESULTS AND CONCLUSIONS: In the NSAID group, the ATP levels and the total adenine nucleotide (TAN) levels in both the antrum and corpus were significantly lower than in the control group. In the steroid group, no significant differences were observed in either the ATP or TAN levels. The NSAID decreased energy metabolism in the entire stomach while the steroid had a negligible effect on energy metabolism.
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Omega-hydroxyceramides (omega-OHCer) are the predominant lipid species of the corneocyte lipid envelope in the epidermis. Moreover, their omega-esterified-derivatives (acylCer) are major components of the stratum corneum extracellular lamellae, which regulate cutaneous permeability barrier function. Because epidermal omega-OHCer appear to be generated by a cytochrome P450-dependent process, we determined the effects of a mechanism-based inhibitor of omega-hydroxylation, aminobenzotriazole (ABT), on epidermal omega-OH Cer formation and barrier function. We first ascertained that ABT, but not hydroxybenzotriazole (OHBT), a chemical relative with no P450 inhibitory activity, inhibited the incorporation of [14C]-acetate into the omega-OH-containing Cer species in cultured human keratinocytes (68.1% +/- 6.9% inhibition versus vehicle-treated controls; p < 0.001), without altering the synthesis of other Cer and fatty acid species. In addition, ABT significantly inhibited the omega-hydroxylation of very long-chain fatty acids in cultured human keratinocytes. Topical application of ABT, but not OHBT, when applied to the skin of hairless mice following acute barrier disruption by tape-stripping, resulted in a significant delay in barrier recovery (e.g., 38.3% delay at 6 h versus vehicle-treated animals), assessed as increased transepidermal water loss. The ABT-induced barrier abnormality was associated with: (i) a significant decrease in the quantities of omega-OHCer in both the unbound and the covalently bound Cer pools; (ii) marked alterations of lamellar body structure and contents; and (iii) abnormal stratum corneum extracellular lamellar membrane structures, with no signs of cellular toxicity. Furthermore, pyridine-extraction of ABT- versus vehicle-treated skin, which removes all of the extracellular lamellae, leaving the covalently attached lipids, showed numerous foci with absent corneocyte lipid envelope in ABT- versus vehicle-treated stratum corneum. These results provide the first direct evidence for the importance of omega-OHCer for epidermal permeability function, and suggest further that acylCer and/or corneocyte lipid envelope are required elements in permeability barrier homeostasis.
Ex-chromate workers are frequently afflicted with lung cancers, especially central-type squamous cell carcinomas (SCCs) of the lung. However, little is known about the molecular and cellular biologic characteristics of chromate-induced lung cancers. We investigated expression of cyclin D1, bcl-2, and p53 proteins in chromate-induced lung cancers by immunohistochemistry, compared with those in lung cancers from nonexposed individuals and those in individuals with pneumoconiosis. Of 19 chromate-induced lung cancers, 16 tumors were SCCs, including 11 central and 5 peripheral types. Eleven (69%) of 16 chromate SCCs showed cyclin D1 expression. In contrast, cyclin D1 expression was observed in only 3 (12%) of 26 SCCs from nonexposed individuals and 6 (16%) of 37 SCCs that developed in patients with pneumoconiosis, respectively. The frequency of cyclin D1 expression proved to be significantly higher in chromate-induced SCCs than in SCCs from nonexposed individuals and from those with pneumoconiosis (P < .001). When comparisons were extended to all histologic types of lung cancer, cyclin D1 expression was observed significantly more often in chromate-induced lung cancers than in lung cancers from nonexposed subjects and those from patients with pneumoconiosis (11 [58%] of 19 v 5 [10%] of 52, P < .001, and 7 [11%] of 63, P < .001, respectively). Frequencies of bcl-2 and p53 expression were not significantly different among lung cancers from ex-chromate workers, nonexposed individuals and those with pneumoconiosis. The current study suggests that cyclin D1 expression may be involved in the development of chromate-induced lung cancers, although its underlying mechanism remains to be determined.
To improve patients' quality of life and decrease pollution risks to medical personnel, we tested the usefulness of a nitric oxide (NO) inhalation system consisting of a nasal cannula and a demand valve in an open circuit system. To estimate the content of NO entering the lung with the open system, concentrations of NO and nitrogen dioxide (NO2) were measured in a mechanical lung model, and then nitrocylhaemoglobin (NO-Hb), methaemoglobin (Met-Hb), and nitrite (NO2-) + nitrate (NO3-) concentrations in venous blood were measured in eight healthy subjects. Exhaust NO and NO2 in the open system were also observed in 14 healthy subjects. In the lung model, NO concentration delivered with the open system was approximately 1/11 of that in the gas tank. Increases in Met-Hb and NO2- + NO3- with the open system showed that the concentration of delivered NO was approximately 1/9 of that in the gas tank. The open system reduced exhaust NO to 1/10 in human subjects. These data suggest that this NO inhalation system delivers sufficient NO to spontaneously breathing patients. In addition, these findings indicate that there is little environmental toxicity associated with the open circuit system.
We investigated whether the expression of membrane-type-1 matrix metalloproteinase (MT1-MMP), matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-2 (TIMP-2) was consistent with the proposed roles of these proteins in promoting metastasis in colorectal cancer. The expression of MT1-MMP was significantly more frequent in deeply invasive carcinomas (P = 0.007) and in cases of vascular invasion (P = 0.02). The frequency of detection of MMP-2 in the stroma was much greater in vascular invasion-positive cases (42%) than in negative cases (20%; P = 0.02). The rate of detection of TIMP-2 in tumour cell cytoplasm increased with the depth of invasion (P = 0.03). TIMP-2 in the stroma was found more frequently in tumours with lymphatic invasion and lymph node metastasis (P < 0.05). Significant correlations were found between detection of MT1-MMP and MMP-2 in tumour cell cytoplasm (P < 0.05), of MT1-MMP and TIMP-2 in tumour cell cytoplasm (P < 0.01), and of MMP-2 and TIMP-2 in tumour cell cytoplasm (P < 0.01). Immunohistochemical detection of MT1-MMP and TIMP-2 might be useful for monitoring infiltration in colorectal carcinoma but is not correlated with distant metastases.
OBJECTIVES: The aim of this study was to clarify the dynamics of lymphatic drainage of the pleural cavity to understand the mechanism of malignant pleural effusion. METHODS: We injected carbon particles into the pleural cavity of monkeys subjected to general anesthesia. We then observed the parietal pleura with a video-assisted thoracoscope and scanning and transmission electron microscopes to examine the regions of the parietal pleura where the carbon particles had been absorbed. RESULTS: The video-assisted thoracoscope showed that the carbon particles had gone directly to the costal, mediastinal, and diaphragmatic pleura by 10 to 15 minutes after injection. From the scanning and transmission electron microscopes, we found that the parietal pleura in the costal and mediastinal regions consisted of 3 elements: a layer of small mesothelial cells, the macula cribriformis, and lymphatic lacunae. Stomata (3-5 microm in diameter) were found between the small mesothelial cells. The macula cribriformis was composed of densely packed collagen fibrils and had many foramina (3-10 microm in diameter). Intrapleurally injected carbon particles were carried into the lymphatic lacunae via the stomata and vesicles of the mesothelial cells and the foramina of the macula cribriformis. The lymphatic lacunae filled with carbon particles were richly distributed in both the anterior costal pleura and the mediastinal pleura. CONCLUSION: We suggest that the mesothelial stomata and the macula cribriformis are structures essential to the absorption of macromolecules and cellular elements from the pleural cavity into the lymphatic system.
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In this study, we examined the use of 111In-labelled platelet imaging to predict the outcome of partial splenic embolization (PSE) in patients with idiopathic thrombocytopenic purpura (ITP). Thirty-eight patients with a clinical diagnosis of ITP underwent 111In-labelled platelet scintigraphy. Twenty-four patients with intractable ITP underwent PSE after 111In-labelled platelet scintigraphy. The conventional spleen/liver ratio at 1 h and 192 h and the normalized spleen/liver ratio [(spleen uptake at 192 h/liver uptake at 192 h)/(spleen uptake at 1 h/liver uptake at 1 h)] were compared between responders and non-responders to PSE. Patients with ITP showed a significant reduction in platelet counts, increased platelet associated IgG, decreased platelet survival, and an increased conventional spleen/liver ratio at 192 h. No significant difference was found between patients who had and who had not undergone previous medical treatment. A significant difference was observed in the mean conventional spleen/liver ratio at 192 h between responders and non-responders, but there was substantial overlap among individuals. The mean normalized spleen/liver ratio was significantly higher in responders than non-responders; there was less overlap between the two groups with the normalized spleen/liver ratio than the conventional spleen/liver ratio. The therapeutic outcome of PSE is predicted more accurately using a normalized spleen/liver uptake ratio of 111In-labelled platelets in patients with idiopathic thrombocytopenic purpura than a conventional splenic/hepatic uptake ratio on delayed images.
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The expression of thrombomodulin and neural cell adhesion molecule (NCAM) was studied immunocytochemically in biopsied muscle specimens from 10 patients with rhabdomyolysis with different etiologic factors, including 5 with malignant hyperthermia. We have already reported that thrombomodulin was expressed on regenerating muscle cell membranes as well as on vessel walls in patients with various neuromuscular diseases, including Duchenne muscular dystrophy, Becker muscular dystrophy and inflammatory myopathy. We found increased expression of thrombomodulin not only on the sarcolemma, but also in the sarcoplasm of a fair number of muscle fibers in the acute phase of rhabdomyolysis. The granular pattern of thrombomodulin expression in the sarcoplasm seems to be a characteristic finding in the acute phase of rhabdomyolysis. Most muscle fibers which expressed NCAM on the sarcolemma also expressed thrombomodulin. However, the muscle fibers which expressed thrombomodulin in the sarcoplasm did not express NCAM, and showed a degenerative appearance on electron microscopic examination. These results suggest that thrombomodulin is expressed in the sarcoplasm during the acute degeneration phase of rhabdomyolysis in addition to the expression on the sarcolemma during the muscle fiber regeneration as shown in our previous study, and the former process, which is characterized by the granular expression of thrombomodulin in the sarcoplasm, may be a characteristic finding in rhabdomyolysis.