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Biomedical subjects

M Abe

Publications and source records attributed to M Abe.

At least 973 records · Page 54Linked to original sources

Effect of recombinant human granulocyte colony-stimulating factor on granulocytopenia in mice induced by irradiation.

We report the effect of human granulocyte colony-stimulating factor (hG-CSF) on the recovery from granulocytopenia induced by irradiation. Female 9-week old C3H/He mice were used. The irradiation schedule was as follows: Group 1 and 2 received whole-body irradiation of 1 Gy and 5 Gy, respectively, on day 0; Group 3 and 4 received whole-body irradiation of 0.5 and 1.0 Gy, respectively, for 5 consecutive days; Group 5 received upper hemibody irradiation of 3 Gy for 5 consecutive days. Daily subcutaneous injections of G-CSF (3 x 10(5) Unit/mouse) or 0.3 ml of saline to each group were started from the day after the first irradiation and continued for 18 days. Mice were sampled randomly from each group, and the total number of leukocytes, erythrocytes of peripheral blood, nucleated cells in femur, and spleen weight were counted and measured, respectively, on day 0, 3, 5, 7, 9, 12, and 18. The leukocyte counts decreased with an increase in radiation doses. In Group 1 and 2 mice, G-CSF enhanced the leukocyte count more than saline. In Group 3 mice, the recovery of leukocytopenia was facilitated by G-CSF, but in Group 4 mice, G-CSF had no effect on the leukocyte count decrease or on leukocytopenia recovery. In Group 5 mice, G-CSF greatly affected leukocytopenia recovery. Increase in spleen weight paralleled the peripheral leukocyte count. Daily administration of recombinant hG-CSF accelerated the granulocytopenia recovery which was induced by irradiation, and it may be a useful therapeutic agent for treating myelosuppressive cases.

Agranulocytosis↗

High dose, external beam and intraoperative radiotherapy in the treatment of resectable and unresectable pancreatic cancer.

Ninety patients with pancreatic cancer were treated by external beam radiotherapy (EBRT) and/or intraoperative radiotherapy (IORT) with or without surgical resection of the tumor, and the results were compared with those of a historical control comprising 112 patients treated by surgery alone. At an early stage of this study, postoperative EBRT (50-60 Gy) or IORT (25-33 Gy) was given alone, but recently the two modalities have been combined. The combination of high doses of EBRT and IORT was well tolerated provided that the gastrointestinal tract was not irradiated during IORT. Although EBRT plus IORT appeared to yield better results than either EBRT or IORT alone, the difference was not significant on multivariate analysis, and patients receiving EBRT, IORT, or EBRT + IORT were grouped together. Patients receiving radiotherapy in addition to macroscopically curative surgery had a slightly longer median survival time (14 months) than those receiving curative surgery alone (10 months), but the 3-year survival rate was similar (21% vs. 19%). In patients who underwent noncurative resection, the median survival time was significantly longer for the irradiated group (12 months) than for the control group (6.5 months). Also, in patients with unresectable lesions but no distant metastases, irradiation prolonged the median survival time significantly (8 vs. 3.5 months). In this group, there was one 5-year survivor, who received EBRT of 55 Gy plus IORT of 30 Gy to his unresectable pancreatic body lesion. Patients with metastases were also treated for palliation of symptoms, but it was found that irradiation prolonged the median survival time even in such cases (4.5 vs. 2.5 months). Based on these results, we plan to use EBRT plus IORT in all pancreatic cancer patients with no metastases.

Adult↗

Neuropeptide Y in the specific hypothalamic nuclei of rats treated neonatally with monosodium glutamate.

Neuropeptide Y (NPY) concentration was determined by radioimmunoassay in selected hypothalamic regions microdissected from fresh brain slices of rats treated neonatally with monosodium glutamate (MSG). Fourteen weeks after MSG treatment, significant decreases in NPY concentration were found in the paraventricular nucleus (PVN) and arcuate nucleus (ARH), while there was no appreciable change in the ventromedial nucleus (VMH) and lateral area (LH). The decrease in NPY in the ARH-PVN system may contribute to the endocrine and metabolic disturbances seen in MSG-treated animals.

Animals↗

Enhanced superoxide anion generation but reduced leukotriene B4 productivity in thioglycollate-elicited peritoneal macrophages.

Lipoxygenase metabolism of arachidonic acid was compared between peritoneal macrophages from untreated rats and those from rats on day 7 after intraperitoneal injection of thioglycollate broth (TG). Resident macrophages (M phi) from untreated rats produced mainly LTB4 (303 +/- 25 pmol/5 x 10(6) cells) and 5-HETE (431 +/- 56 pmol/5 x 10(6) cells) when stimulated with 5 micrograms/ml calcium ionophore A23187 for 20 min at 37 degrees C. On the other hand, TG-elicited M phi generated less amounts of lipoxygenase metabolites (157 +/- 10 pmol LTB4 and 319 +/- 19 pmol 5-HETE/5 x 10(6) cells) with the same stimulus. Then, leukotriene productivity was examined by using subcellular fractions of each M phi lysate and an unstable epoxide intermediate, leukotriene A4. LTA4 hydrolase activity was mainly contained in soluble fractions from the both groups of M phi. The cytosol fraction from the resident M phi exhibited the following specific and total activity; 2.2 +/- 0.1 nmol LTB4/mg protein/5 min and 12.2 +/- 0.5 nmol LTB4/5 min per 10(8) cells. On the contrary, the cytosol fraction from the TG-elicited M phi showed 1.9 +/- 0.1 nmol LTB4/mg protein/5 min and 9.6 +/- 0.3 nmol LTB4/5 min per 10(8) cells. The resident M phi, however, generated 0.14 +/- 0.04 nmol O2-/min/4 x 10(5) cells whereas the TG-elicited M phi did 0.49 +/- 0.13 nmol O2-/min/4 x 10(5) cells when stimulated with wheat germ lectin. These results suggest that the TG-elicited macrophages show enhanced superoxide production but generate less lipoxygenase metabolites.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Pharmacokinetics of 2-nitroimidazole hypoxic cell radiosensitizers in rodent peripheral nervous tissue.

The concentrations of seven 2-nitroimidazoles--including misonidazole, etanidazole (SR-2508), pimonidazole (Ro 03-8799), desmethylmisonidazole (Ro 05-9963), RK28, RP170, and KU2285--were measured in the sciatic nerves of C3H/He mice using reverse-phase high-performance liquid chromatography. Drug exposure to the peripheral nervous system was highest for misonidazole, followed by desmethylmisonidazole, etanidazole, pimonidazole and RK28. The lower drug exposure of pimonidazole and RK28 seemed to be related to their lower hydrophilicity. The apparent biological half-lives of the compounds in the peripheral nerves were correlated to their hydrophilicity: the more hydrophilic the compound, the longer the apparent biological half-life in the peripheral nervous tissue of the mice. Measurement of drug exposure in the rodent peripheral nervous system, rather than in the brain, was a better indicator for estimating the occurrence of clinical peripheral neuropathy by 2-nitroimidazoles.

Animals↗

Use of the micronucleus assay for the selective detection of radiosensitivity in BUdR-unincorporated cells after pulse-labelling of exponentially growing tumour cells.

To determine the radiosensitivity of non-S-phase tumour cells in vitro, survival curves of SCC VII tumour cells were obtained after a short block with hydroxyurea. Dose-response curves of micronucleus (MN) frequency appearing in non-S-phase cells were also determined by excluding S-phase cells with immunofluorescence staining to 5-bromo-2'-deoxyuridine (BUdR). Both the dose-response curves of MN frequency and survival curves were analysed by a linear-quadratic model (surviving fraction = exp (-alpha D-beta D2), MN frequency = aD+bD2+c). A good correlation between the alpha/beta and alpha/beta ratios was observed. In both BUdR-unincorporated and asynchronous cell cultures, the regression lines between the surviving fraction and micronucleus frequency were statistically identical. Therefore, it was shown that cell survival curves, which cannot be obtained directly by the routine colony-formation technique, can be calculated using the micronucleus frequency and the regression line in asynchronous cell cultures. Therefore, it should be possible to detect the response to irradiation of quiescent cells in tumours using the immunofluorescence staining to BUdR and the MN frequency assay.

Bromodeoxyuridine↗

A single human keratin 18 gene is expressed in diverse epithelial cells of transgenic mice.

The expression of keratin 18 (K18) is restricted in humans primarily to a variety of single layered or simple epithelia. However, direct introduction of a cloned K18 gene into cultured, somatic cells by DNA transfection has been shown to result in the promiscuous expression of K18 even while the endogenous mouse form of K18 (Endo B) remains silent. To determine if the cloned K18 genomic DNA fragment contains sufficient information to be regulated appropriately when subjected to a normal developmental environment, and to determine if the cloned gene is expressed in diverse epithelia, the K18 gene, including 2.5 kb of 5' flanking sequence and 3.5 kb of 3' flanking sequence, has been introduced into the germ line of mice. Mice from all three resulting K18 transgenic lines express the gene in an appropriate tissue-specific pattern that includes hepatocytes, simple epithelia of the intestinal tract, ductal cells of several glands and epithelial cells of the thymus. No expression of K18 was found in muscle, heart, or in most of the brain even in mice carrying 18 copies of the K18 gene. In most tissues, the level of K18 RNA was directly proportional to copy number and was as efficiently expressed as the endogenous Endo B gene. The K18 protein was identified by both protein blotting methods and indirect immunofluorescence staining. No pathological consequences of overexpression of the K18 gene were observed. The cloned K18 gene appears to contain all cis-acting DNA sequences necessary for appropriate expression. In addition, diverse epithelial cell types are able to express this single human gene.

Animals↗

Simplified co-purification of vascular smooth muscle calponin and caldesmon.

A method for the co-purification of calponin and caldesmon from bovine aorta smooth muscle was established involving heat treatment, ammonium sulfate fractionation (0-30 and 30-50%), CM52 column chromatography, and Ultrogel AcA44 gel filtration. The yields of calponin and caldesmon from 200 g of smooth muscle were 17 and 32 mg, respectively. This simplified, fast, and efficient method for the purification of calponin and caldesmon constitutes a useful tool for studying thin filament-linked regulation of smooth muscle contraction.

Animals↗

Effect of calponin on actin-activated myosin ATPase activity.

Calponin inhibited the actin-activated myosin MgATPase activity in a dose-dependent manner without affecting the phosphorylation level of myosin light chain. This inhibition was Ca2(+)-independent. The decrease in enzymatic activity of myosin was correlated with binding of calponin to actin-tropomyosin filaments. Caldesmon showed a further inhibition of the calponin-induced inhibition of MgATPase activity of the thiophosphorylated myosin. Calponin-induced inhibition of the myosin MgATPase activity was reversed by the addition of calmodulin only in the presence of Ca2+. These results suggest that calponin acts as an inhibitory component of smooth muscle thin filaments.

Actins↗

Point mutations of c-ras genes in human bladder cancer and kidney cancer.

Point mutations of c-ras genes at codons 12, 13 and 61 were analyzed in 26 cases of bladder cancer and 16 cases of kidney cancer. DNA prepared from either frozen tissues or 10% formalin-fixed, paraffin-embedded tissues were amplified by means of polymerase chain reaction methods, and mutations were analyzed by dot blot hybridization assays with oligonucleotide probes. In three cases of bladder cancer c-ras mutations were found, at codons 13 and 61 of c-Ha-ras and at codon 61 of c-Ki-ras, while no mutation was found in kidney cancer. No mutation was found in normal bladder epithelial tissues from the same patients. Our findings, taken together, may indicate relative scarcity of c-ras mutations in these types of human cancer. The results of dot blot hybridization assays and DNA sequencing showed a G-to-C transition of the first nucleotide at codon 13 c-Ha-ras. This is the first time that such a point mutation has been detected in human cancer tissues.

Aged↗

Frequent glycine-to-aspartic acid mutations at codon 12 of c-Ki-ras gene in human pancreatic cancer in Japanese.

Point mutations at codons 12 and 13 of c-Ki-ras gene were analyzed in human pancreatic cancer. DNAs obtained from sample tissues were amplified by means of polymerase chain reaction and were analyzed by dot blot hybridization assays with oligonucleotide probes appropriate for detecting mutations at these codons. Out of 38 evaluated cases, point mutations at codon 12 were found in 35 cases; these mutations resulted in changes of the coded amino acid to aspartic acid in 24 cases, to valine in 9 cases, to arginine in 2 cases and to cysteine in one case. In one case, a glycine-to-aspartic acid mutation was found at codon 13. In two cases, two distinct mutations were simultaneously present. The frequency pattern of mutations at codon 12 was somewhat different from those given in two previous reports on the similar analysis of pancreatic cancers in European countries. This may indicate the presence of possible genetic or non-genetic factors in determining preferential mutational patterns at these particular codons.

Adult↗

A case of pancreatic oncocytic tumor.

An uncommon case of potentially malignant oncocytoma arising in the pancreatic tail of 54-year-old woman is reported. The tumor was encapsulated and measured 11 x 7 x 6 cm. The tumor cells were uniform in appearance, plump and polyhedral, with distinct finely granular eosinophilic cytoplasm, and were arranged in solid acinar groups. Electron microscopy revealed that the tumor cells contained numerous mitochondria in the cytoplasm. In the present case, the tumor cells showed perineural and small venous invasion in the pancreas and potentially malignant characteristics. However, neither recurrence nor metastasis has been detected 3 years after resection. These findings indicate that the present tumor had apparent low-grade malignancy.

Adenoma↗

Influence of temperature on the inheritance of adult life span in Drosophila melanogaster.

Mating experiments were performed at 27 degrees C, 22 degrees C, and 17 degrees C, to investigate the inheritance of adult life span of highly inbred strains of Drosophila melanogaster. Effects of temperature difference were quantitatively analyzed at the genotypic level. In the temperature range of 17-27 degrees C the autosomal longevity alleles, A1 and A2, exerted major effects. Their effects produced longer life spans as the temperature decreased. The sex-linked longevity alleles, X1 and X2, played a secondary role in influencing life span, and they displayed different effects at different temperatures. Each genotype showed correspondence to the life span expected from the combinations of these longevity genes at the respective temperatures. The genetic loci controlling life span in these inbred strains were named JmA and JmX from "Ju-myo" which means life span or longevity in Japanese.

Animals↗

[A successfully treated case of infective endocarditis due to Candida tropicalis].

A 34-year-old man, a heavy drinker, was admitted with a high fever and hematuria two months previously. Surgery was performed for acute sever pancreatitis and postoperatively antibiotics were administered with intravenous hyperalimentation. After discharge he was readmitted and infective endocarditis was strongly suspected because of high fever, hematuria, Osler's nodes, Janeway's lesions, splinter hemorrhages and mitral regurgitation. Penicillin G in combination with Gentamycine therapy was started on the first hospital day. On the second hospital day, blood culture revealed Candida tropicalis so Miconazole therapy was commenced. On the forth hospital day, he underwent surgery for replacement of a mitral prosthesis with a prosthetic valve because he had embolus in the radial artery. Despite intensive antifungal therapy, he showed no improvement in clinical symptoms. Then we changed the antifungal drug from Miconazole to Amphotericin B and 5-fluorocytosine. On the 109th hospital day, his clinical symptoms improved. Antifungal therapy was halted and at present 10 months later, he is healthy.

Adult↗

[Influence of the changes in food intake patterns and smoking and drinking habits on stroke--20-year follow-up survey in the Oki-Islands, Shimane Prefecture, Japan].

In 1968 (the first survey), the food intake patterns and smoking and drinking habits of the 3,546 male and 4,350 female inhabitants aged 40-74, of the Oki-Islands, Shimane, Japan were investigated. The response rates were 64% for males and 65% for females. A second survey according the same protocol was carried out from 1987 to 1988. A total of 1,140 males and 1,694 females were randomly selected from the cohort members who were completely followed up from 1968 to 1987. The overall response rates at the second survey were 91.2% for male and 88.9% for female. The results are summarized as follows: 1. 'Saltless' dietary habits significantly advanced in both sexes of all age groups (40-49, 50-59, and 60-74 years old in 1968) and in both hypertensives and normotensives; the frequency of pickle intake significantly decreased, while that of miso soup intake did not change. Nutritional improvement was remarkable in that the frequency of fish, meat, eggs, milk, green vegetable and fruit intakes increased in both sexes of all age groups and in both hypertensives and normotensives. 2. The frequency of smoking significantly decreased in all age groups and in both male hypertensives and normotensives, in contrast with that of drinking. The frequencies of smoking and drinking showed the same tendencies in females. 3. The frequencies of smoking, drinking, and miso soup intake were higher in males who died from strokes than in those who died from other causes from 1968 to 1987, in contrast with the intakes of eggs and milk.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

A test of K(+)-sensitive electrode responses to changes in K+ concentration.

Tests of K(+)-sensitive microelectrodes were made using a plastic chamber, which consisted of upper and lower compartments separated by a partition with a small opening in the center. After the upper and lower compartments were filled with 25 and 100 mM KCl respectively, the tip of a K(+)-sensitive electrode was moved up and down through the partition opening, while recording potential changes. Some hydrodynamic events associated with electrode movement and effects of gravity upon spherical diffusion are discussed.

Diffusion↗

Combined effect of radiation and YM-881 (SMANCS) on murine tumors and bone marrow.

The combined effect of radiation and YM-881 (SMANCS) was studied in vitro and in vivo. When 0.25 microgram/ml of YM-881 was simultaneously combined with radiation, during and after irradiation for 30 min in total, Dq decreased from 3.3 Gy to 1.4 Gy without changing D0 in the dose-survival curve of exponentially growing SCC VII tumor cells. Five or ten times administrations of 0.1 mg/kg YM-881 at an interval of 24 h did not inhibit tumor growth. However, administration of 0.1 mg/kg YM-881 just before every irradiation which was repeated five times at an interval of 24 h yielded dose modifying factors (DMFs) of 1.8-1.2 when the tumor response to treatment was evaluated by the time for the tumors to regrow to three times the original volume. Administration of YM-881 ten times just before every irradiation yielded DMFs of 1.3-1.2. Adverse effects of the combination on bone marrow were examined by spleen colony assay. After five injections of 0.1 mg/kg YM-881, the mean number of CFU-S per femur decreased to 77% of the pretreatment level, but this was not significant statistically (0.1 greater than p greater than 0.05). The slope of radiation response curve for CFU-S per femur was not affected by the combination.

Animals↗