Search PubMed⌕ Search

Biomedical subjects

M Numata

Publications and source records attributed to M Numata.

At least 55 records · Page 3Linked to original sources

Expression of 16 kDa proteolipid of vacuolar-type H(+)-ATPase in human pancreatic cancer.

Recent studies have shown that bafilomycin A1-sensitive vacuolar-type H(+)-ATPase (V-ATPase) plays important roles in cell growth and differentiation. However, there is no published study that has focused on the expression of V-ATPase in human tumour tissues. This study was designed to examine the mRNA and protein levels for the 16 kilodalton (kDa) proteolipid of V-ATPase in human pancreatic carcinoma tissues. We first investigated the mRNA level for V-ATPase in six cases of invasive pancreatic cancers and two normal pancreases, using reverse transcription-polymerase chain reaction technique. Then, we examined immunohistochemically the level of V-ATPase protein in 49 pancreatic cancers and ten benign cystic neoplasms of the pancreas, using antisera raised against the 16 kDa proteolipid. There was a notable difference in the level of V-ATPase mRNA between normal and pancreatic carcinoma tissues, with no evident difference in the expression of the beta-actin gene. Immunohistochemically, 42 out of 46 invasive ductal cancers (92%) displayed a mild to marked immunoreactivity for V-ATPase in the cytoplasm, whereas neither non-invasive ductal cancers nor benign cystic neoplasms expressed detectable immunoreactive proteins. These findings suggest that the overexpression of V-ATPase protein is characteristic of invasive pancreatic tumours. V-ATPase may play some crucial roles in tumour progression.

Adenocarcinoma↗

Expression of apolipoprotein A-1 mRNA in normal intrahepatic biliary tree.

Our previous study demonstrated that apolipoprotein A-1 (apo A-1) immunoreactive peptides were located diffusely in the cytoplasm, not only of human normal hepatocytes, but also of intrahepatic bile ducts and peribiliary glands. It is important to determine whether the presence of these immunoreactive peptides in intrahepatic biliary tree is caused by pinocytosis from the bile, or by intracellular protein synthesis. Thus, we investigated whether apo A-1 is synthesized by cells that line the biliary tree. Normal human liver samples obtained at surgery were used; and the expression and distribution of apo A-1 mRNA in normal human liver tissues were examined, using in situ hybridization histochemistry with a 35S-labeled oligonucleotide probe specific for apo A-1. On the autoradiogram, many silver grains were found to be distributed uniformly in hepatocytes. In addition, an appreciable apo A-1 mRNA signal was also observed in both the surface epithelial lining of the bile ducts and the epithelial cells of the peribiliary glands. In conclusion, these findings suggest that the apo A-1 found in bile is secreted both by hepatocytes and by intrahepatic bile duct cells and peribiliary glands.

Aged↗

Alveolar surface area-to-lung volume ratio in oleic acid-induced pulmonary edema.

It is unknown how the in vivo alveolar surface area-to-volume ratio (S/V) changes in low-pressure pulmonary edema. Here, the S/V is the area of the air-tissue interface per unit total volume (air plus tissue). We hypothesized that in oleic acid (OA)-induced edema inactivation of the pulmonary surfactant may increase surface tension and decrease the S/V at any given lung volume. OA (0.04 mg/kg) was intravenously injected into dogs. We measured the in vivo S/V (equivalent to the inverse of optical mean free path by light-scattering stereology and the pressure-volume (PV) curve 60-90 min after OA administration. OA administration decreased the lung volume at each transpulmonary pressure and increased the wet-to-dry weight ratio. The S/V decreased after OA administration (optical mean free path increased). The air-filled PV curves shifted downward after OA, but the saline-filled PV curves after OA administration did not differ significantly from control saline-filled curves. The difference in transpulmonary pressure between air- and saline-filled PV curves (an index of the magnitude of surface tension) was increased in OA-induced pulmonary edema. This study suggests that in OA-induced pulmonary edema the alveolar surface tension increases and the S/V decreases, presumably due to inactivation of surfactant by serum leakage to alveoli.

Animals↗

[Gallstone ileus].

Explore the source record for details and available documents.

Cholelithiasis↗

[A new strategy for the therapy of pancreatic cancer by proton pump inhibitor].

Bafilomycin A1 is a specific inhibitor of vacuolar type proton pump (V-ATPase). This study was designed to examine the effect of bafilomycin A1 on the growth of Capan-1 human pancreatic cells which overexpress V-ATPase. Nude mice bearing a xenografted tumor of Capan-1 cell line were treated for 4 weeks with bafilomycin A1 (1.0 mg/kg/day). This treatment inhibited tumor growth, which was significantly reduced as compared with controls after 21 days (p < 0.05). However, there were no significant differences in body weights between groups. Microscopically, a large number of tumor cells in the treated group showed signs of apoptosis. These findings suggest that apoptosis induced by bafilomycin A1 was the event involved in suppression of tumor growth in vivo.

Animals↗

The role of vacuolar H(+)-ATPase in the control of intragranular pH and exocytosis in eosinophils.

The presence of vacuolar H(+)-ATPase (V-ATPase) on exocytotic granules in eosinophils and the role of this enzyme in exocytosis were explored in this study. Antibody against 116-kd subunit of V-ATPase positively stained eosinophil granules in immunofluorescence analysis. When eosinophil lysate was extracted immunomagnetically with the same antibody, the extracted fraction contained a considerable amount of eosinophil peroxidase, a marker of eosinophil-specific granules, which indicates that V-ATPase was present on the membranes of eosinophil exsosomal granules. The pH of the eosinophil granules, measured fluorometrically with acridine orange as a delta pH-sensitive dye, was estimated to be 5.1. The acidity of the eosinophil granules was perturbed by bafilomycin A1, a potent selective inhibitor of V-ATPase, which indicates that the low pH of these granules is maintained by V-ATPase activity. BafilomycinA1 and NH4Cl, both of which raise the intragranular pH to neutral, inhibited the eosinophil peroxidase exocytosis induced by platelet-activating factor. These agents did not, however, affect the changes in cytosolic free calcium concentration [Ca2+]i induced by platelet-activating factor. These observations suggest that bafilomycin A1 inhibited a delta pH-requiring step in eosinophil exocytosis that was preceded by the [Ca2+]i transient in the signal transduction pathway, and, hence, the findings suggest the pivotal role of V-ATPase in maintaining intragranular pH and its function of eosinophil exosomal granules.

Ammonium Chloride↗

Expression and localization of mRNA encoding 16 kD subunit of vacuolar H(+)-ATPase in rat brain.

The 16 kD subunit of vacuolar H(+)-ATPase (V-ATPase) is essential for pumping protons into intracellular organella. Northern blot analysis revealed that the 16 kD subunit of V-ATPase is abundantly expressed in rat brain, and that the amount of transcripts is higher in the postnatal 15 days than in the adult age. On in situ hybridization, the mRNA signal for 16 kD subunit of V-ATPase was detected widely over the brain tissues of both adult and postnatal rats, with higher intensity in most of the gray matters located in the cerebellar cortex, hippocampus, thalamic nuclei, pontin nuclei, and olfactory bulb. In contrast, the signal in the cerebral cortex was preferentially enriched in the surface layers in the postnatal 10 days but was distributed diffusely and weakly over the entire layers thereafter. In all regions of brain, the mRNA signal was located predominantly in the neurons rather than in the glial components.

Animals↗

Fluctuation of blood pressure and pulse rate during colostomy irrigation.

PURPOSE: The aim of this study was to determine the effects of colostomy irrigation on the vital signs of patients with left colostomy. METHODS: Twenty-two consecutive patients who underwent abdominoperineal resection for cancer of the lower rectum and had left lower quadrant end colostomy were included in this study. Subjective symptoms, blood pressure, and pulse rate during the first irrigation were investigated. RESULTS: Fluctuation of blood pressure during instillation was 8.0/8.5 mmHg (average) and 25.0/17.9 mmHg during evacuation. Fluctuation of pulse rate was 5.5 per minute (average) during instillation and 11.5 per minute during evacuation. The number of subjects who showed more than 20% fluctuation of systolic pressure was 12 (54.5 percent) and that of diastolic pressure was 14 (63.6 percent). One of 22 patients complained of illness during irrigation. CONCLUSION: Although colostomy irrigation showed no significant effects on vital signs in the majority of patients, it caused a significant reduction in both blood pressure and pulse rate in a small number of patients. Careful attention should be paid to vital signs considering the possibility of such effects, especially on the initial irrigation.

Aged↗

Expression of basic fibroblast growth factor and its receptor in human pancreatic carcinomas.

We examined the expression of basic fibroblast growth factor (FGF) and FGF receptor by immunohistochemistry in 32 human pancreatic ductal adenocarcinomas. Mild to marked basic FGF immunoreactivity was noted in 19 (59.4%) of the 32 tumours examined, and 30 (93.3%) of the tumours exhibited a cytoplasmic staining pattern against FGF receptor. The tumours were divided into two groups according to the proportion of positively stained tumour cells: a low expression group (positive cells < 25%) and a high expression group (positive cells > or = 25%). No statistically significant difference in tumour size, differentiation, metastases or stage was found between the low and high basic FGF expression groups. However, a significant correlation was found between FGF receptor expression level and the presence of retroperitoneal invasion, lymph node metastasis, and tumour stage. In addition, low FGF receptor expression was significantly associated with a longer post-operative survival as compared with high FGF receptor expression, whereas there was no significant difference in post-operative survival between the low and high basic FGF expression groups. Increased expression of FGF receptor is correlated with the extent of malignancy and post-operative survival in human pancreatic ductal adenocarcinomas. Thus, overexpression of FGF receptor may prove to be a more useful prognostic marker than basic FGF expression level in pancreatic cancer patients.

Adult↗

Expression and localization of mRNA for the 16 KD subunit of V-ATPase in the rat embryo.

Vacuolar H(+)-ATPase (V-ATPase), an enzyme composed of multisubunits, is located in the membrane of intracellular organelles (e.g., lysosomes, and endosomes) and maintains the intraorganellar acidic pH by pumping protons across the membrane. Although there is growing evidence for some important role of V-ATPase in cell proliferation and differentiation, the functional significance of V-ATPase in vivo during mammalian development remains obscure. In the present study we investigated the expression and localization of mRNA for the 16 KD subunit of V-ATPase, an essential sector for enzymatic activity, in prenatal rat by Northern blot analysis and in situ hybridization with a specific oligonucleotide probe. With Northern blot analysis, consistent expression of the mRNA was observed in the embryos throughout the period examined (E14-E20). On in situ hybridization, mRNA signal was distributed with various intensities in both the epithelial and mesenchymal tissues at embryonic day 14 (E14). In E17 and E20 embryos, localization of strong signal became more restricted to distinct mesenchymal cells such as fibroblasts adjacent to the epithelia of skin, lung, and intestine, the cells of perichondrium, and myoblasts in the process of fusion. These results suggest that V-ATPase performs specific functions during the later stages of embryogenesis, especially at sites of mesenchymal differentiation and epithelium-mesenchyme interaction.

Adenosine Triphosphatases↗

Isolation of an antioxidant from Penicillium roquefortii IFO 5956.

In the search for antioxidants from microbial organisms, we found that Penicillium roquefortii IFO 5956 produced an antioxidant. This antioxidant was isolated from a culture broth of the strain, and its structure was identified to be 2,3-dihydroxy benzoic acid (1). The antioxidative activity of 1 was nearly equal to that of tert-butyl-4-hydroxyanisol (BHA).

Antioxidants↗

[Antitumor effects of alpha-linolenic acid on the human tumor transplanted in nude mice and on the metastasis of Vx-7 tumor in rabbit].

Many epidemiological studies and laboratory experimentations have shown that dietary omega-6 fatty acids stimulate and omega-3 fatty acids suppress tumorigenesis. On the other hand, some reports presented that parenteral administrations of unsaturated free fatty acids such as oleic, linoleic and linolenic acids inhibited the growth of a transplantable syngeneic tumor in mice. In this report, I examined the effect of alpha-linolenic acid on the growth of 17 lines of human tumor transplanted in nude mice and on the metastasis of Vx-7 tumor transplanted in rabbits. When alpha-linolenic acid was emulsified with HCO-60 and subcutaneously injected in the peripheral region of the transplanted tumor, complete cure rates for MKN-1, MKN-28, NOC-S and PL-14 human tumors were 100, 57, 25 and 75% respectively at a dose of 250 mg/kg/day for four days once a day, although it was not effective on GCH-nu and SKG-III. Using other tumor lines, T/C ratios of the transplanted tumor weight on day 31 were 4% for Taneda, 34% for Lx-1, 47% for Li-7, 31% for Sk-14, 49% for Kuronuma and 16% for Sawayama. When alpha-linolenic acid was intermittently injected in the same manner on day 3, 13, 17 and 24, T/C ratios of tumor weight were 24% for ALL, 34% for Taneda, 23% for Lx-1, 50% for Li-7, 47% for Sk-14 and 54% for Kuronuma. Mammary tumor line (Mx-1) did not respond to administrations of alpha-linolenic acid. Rabbit Vx-7 tumor cells transplanted via lympho-duct were trapped in lymphonodi to metastasize to other organs. When alpha-linolenic acid mixed with Lipiodol was injected once via lympho-duct on day 8 after tumor transplantation at a dose of 250 mg/kg, the tumor growth was reduced in lymphonodi poplitei to 14%, and thus highly inhibited the metastasis of tumor cells to lung.

Animals↗

[Pulmonary tuberculosis with systemic lymph node swelling].

A 31-year-old woman was admitted to our hospital because of cervical and axillar lymph node swelling. A chest X-ray film showed many nodular shadows and a cavity in the left upper lung field. The tuberculin test was positive. Transbronchial lung biopsy and cervical lymph node biopsy were done. Examination of the biopsy specimens revealed epithelial granulomas with caseous necrosis. Thus, pulmonary tuberculosis with systemic lymph node swelling was diagnosed. Examinations during the patient's hospital stay showed that she was not an immunocompromised host. Pulmonary tuberculosis with systemic lymph node swelling occurs only rarely in a non-immunocompromised host.

Adult↗

Total synthesis of a modified ganglioside, de-N-acetyl GM2.

Regio- and stereo-selective glycosylation of a sialyl donor 6 that carries a N-phthaloyl protecting group at C-5 with a lactosyl acceptor 7 armed with a pivaloyl group at O-2a was performed to give the expected glycotrioside 5. Subsequent glycosylation of 5 with 2-azido galactosyl donor 4 gave glycotetraosyl derivatives 18 and 19. After conversion of 18 into imidates 25 and 26, coupling with (2S,3R,4E)-3-O-benzoyl-2-N-tetracosanoylsphingenine (2) was executed to afford completely protected ganglioside analogues 27 and 28. Selective cleavage of the methyl ester and N,O-deprotection gave the target de-N-acetyl GM2 (1).

Carbohydrate Conformation↗