Search PubMed⌕ Search

Biomedical subjects

T Hirata

Publications and source records attributed to T Hirata.

At least 307 records · Page 17Linked to original sources

Preservation of Mycobacterium leprae in vitro for four years by lyophilization.

Although the viability of Mycobacterium leprae suspended in distilled water with or without 10% fetal calf serum was reduced approximately 10(-2) to 10(-4) from that of the starting material during the process of lyophilization, bacilli capable of multiplication in nude mouse foot pads were found in the lyophilized samples stored for 4 years at 4 degrees C. The multiplication rate of the lyophilized bacilli which were suspended in 10% serum-water was much higher than that of the bacilli suspended in water only. On the other hand, no reduction of the viability of M. leprae suspended in 10% skim milk-water was demonstrated during the process of lyophilization as well as storage for 2 years at 4 degrees C. From the results obtained here, it could be suggested that M. leprae might be preserved in vitro by means of lyophilized M. leprae was extremely stable during cryopreservation when the bacilli were suspended in 10% skim milk-water. Therefore, the composition of the solution for suspending the bacilli is definitely critical for the maintenance of M. leprae viability by means of lyophilization.

Animals↗

[Studies on 13 cases of active tuberculosis diagnosed at autopsy for the first time].

It is reported not only that the incidence of active tuberculosis has not decreased but also that the cases of active tuberculosis who had been diagnosed at autopsy for the first time may have increased. The background factors and clinical courses of 13 cases of active tuberculosis whom we could not diagnose as tuberculosis until autopsy were investigated. According to the autopsy reports, the three fourths of the cases had active tuberculosis lesions in several organs as miliary tuberculosis. All of the cases were treated in serious condition of liver cirrhosis, leukemia, and other malignant diseases. Although fever of unknown origin was an important symptom, it was difficult to make a correct diagnosis because the fever was thought to be originated not from active tuberculosis but from the underlying diseases themselves. It was also difficult to diagnose from chest x-ray findings unless tuberculosis was suspected clinically. The education about tuberculosis should be held repeatedly. And we should try to think from different direction for the strange and unexpected clinical features of the patients with liver cirrhosis, leukemia, and other malignant diseases.

Aged↗

The development and practical use of information systems in the pharmaceutical industry.

To provide information on the efficacy, safety, and quality of medicine promptly and accurately, we have developed two databases: a literature database with numerical data, and a Drug Information database. By an easy-to-use, company-wide information network system, over 1,000 medical representatives in more than 80 offices throughout Japan can retrieve information. Information derived from the system is displayed on the terminal and the original documents are automatically output through a facsimile.

Databases, Bibliographic↗

[A case of food-dependent exercise-induced anaphylaxis associated with repeated episodes of syncope].

This report describes a patient with food-dependent exercise-induced anaphylaxis (FEA). A 25-year-old female has had three episodes of syncopal attack associated with urticaria in the past two years: the attacks have been developed by exercise after taking meals made of wheat flour. She has an allergic predisposition to metals. No abnormal findings were observed in the routine work up for syncope including, ECG, 24-hour Holter ECG, UCG, tilt table test, and EEG examinations. A provocative test for FEA was performed. It included food (sandwich) intake followed by exercise. The serum histamine concentration was elevated to a three times higher than the control value after the provocation. Accordingly, she was diagnosed as FEA and advised not to take wheat flour prior to physical exercise. No syncopal episode has been observed during the 16 months since the diagnosis.

Adult↗

[Antitumor activity of navelbine (vinorelbine ditartrate), a new vinca alkaloid analog].

The antitumor activity of navelbine (vinorelbine ditartrate, KW-2307) against murine and human transplantable tumors was compared with those of other vinca alkaloids, vindesine (VDS), vincristine (VCR) or vinblastine (VLB). KW-2307 and VDS increased the life span of mice bearing ascitic tumors (P 388 leukemia, L 1210 leukemia, EL-4 lymphoma, Colon 26, FM 3 A mammary carcinoma and M 5076 sarcoma) slightly more than VCR or VLB. A significant difference was not found in the antitumor activities against 6 murine solid tumors (B 16 melanoma, Colon 26, FM 3 A mammary carcinoma, Lewis lung carcinoma, M 5076 sarcoma and Sarcoma 180). However, a remarkable difference was observed in the antitumor activities against 11 human tumors inoculated into nude mice. The activity of KW-2307 was more than those of other 3 drugs against 4 human non-small cell lung carcinomas (Lu-65, Lu-99, LC-6 and L-27) and 2 stomach carcinomas (St-4 and St-40). KW-2307 and VDS were also effective in inhibiting the growth of 2 human breast carcinomas (MX-1 and Br-10).

Animals↗

Localization and developmental expression of a novel protein kinase C delta gene.

The expression and localization of a novel protein kinase C delta (nPKC delta) mRNA were investigated using Northern blotting and in situ hybridization in the developmental process of mouse brain. In adult mice, nPKC delta was abundantly expressed in the thalamus, moderately in the pons and the cerebellum, but faintly in the cerebral cortex and the spinal cord. By in situ hybridization, the signals were observed specifically at the sensory and motor relay nuclei of the thalamus, the dorsal cochlear nuclei of the pons, and the molecular layer of the cerebellum. When developmental changes in the expression of nPKC delta gene were analyzed by in situ hybridization, it was not detectable in embryonic and neonatal brains, very weakly expressed in the thalamus in the first week, and highly expressed at two weeks of age. These results suggest that the gene expression of nPKC delta is strictly controlled by both the cell type and the developmental process.

Animals↗

Activities of thymidylate synthetase and thymidine kinase in gastric cancer.

In a previous clinical study, sequential methotrexate and 5-fluorouracil has shown improved efficacy for treating advanced gastric cancer of the poorly differentiated type. In this study, we investigated whether difference in the levels of thymidylate synthetase (TS) and thymidine kinase (TK) activities in gastric cancer tissue account for selectivity of the treatment. Activity of TS was higher in 19 cases of the poorly differentiated type than in 16 cases of the well differentiated type (P < 0.02), whereas TK activity was lower in the poorly differentiated type than in the well differentiated type (P < 0.01). Thus, the TS/TK ratio was significantly higher in poorly differentiated gastric cancers than in well differentiated cancers (P < 0.001). These results suggest that a greater dependence upon the de novo pathway of pyrimidine synthesis in poorly differentiated gastric carcinomas may enhance the efficacy of sequential methotrexate and 5-fluorouracil treatment.

Adenocarcinoma↗

Omentopexy for revascularization of free tracheal grafts in rats.

In rats, we examined the effect of an omentum wrapping on the vascularization of the trachea and on regeneration of the mucosal epithelium in the very early stage after free tracheal grafting. Two pieces of trachea were obtained from each donor rat. One piece was transplanted into the peritoneal cavity of the recipient rat and wrapped with omentum. The other piece was transplanted subcutaneously into the abdominal wall, without omentopexy. Recipients were sacrificed at random on days 1, 2, 3, and 4 after operation (5 rats/day). The increase of blood vessels rose significantly earlier in the omentopexy tracheas than in those without omentopexy (p less than 0.01), with all the former showing a normal ciliated, columnar epithelium in the membranous region of the trachea on day 4, accompanied by excellent epithelial regeneration in the cartilaginous region. These results suggest that omentopexy causes revascularization to occur earlier and to be completed in a shorter time, and that it also promotes epithelial regeneration following free tracheal grafting.

Animals↗

Laser Doppler velocimetry measurement of canine mucosal circulation response to bronchial artery reperfusion after lung transplantation.

Left lung transplantation accompanied by reestablishment of the circulation of the bronchial arteries by simultaneous transplantation of part of the aorta was performed on seven dogs. Mucosal circulation of the bronchi at the anastomosis was evaluated using laser Doppler velocimetry (LDV). Since the donor lung must maintain blood supply through the bronchial arteries, the donor aorta from its ascending portion to the descending portion below the outlet for the last bronchial artery was retained with the lung graft. The distal end of the left brachiocephalic artery was sutured to the side of the recipient aorta when the blood supply to the bronchial arteries was to be restored. The LDV values before reperfusion of the bronchial arteries were 20 to 65% (mean: 42.8%) of the preoperative value. Since the LDV values increased to 36 to 125% (mean: 79.9%) of the control, blood flow to the bronchial mucosa increased evidently. Four out of seven dogs died one to two days after the operation due to bleeding and operative stress. One dog was sacrificed on the 4th postoperative day and another on the 16th. The last dog died 40 days after surgery. The unfavorable course of the LDV values in these three dogs suggest that the method used does not ensure an adequate blood supply to the bronchial arteries in the long term.

Animals↗

Neovascularization effect with He-Ne laser in the rat trachea.

The tracheal tissue of a rat was heterotopically transplanted beneath the abdominal skin of a syngenetic rat, and the transplanted graft was irradiated with a He-Ne laser (2.41 J/cm2). Four or seven days following transplantation, Chinese ink staining was used to ascertain the number of newly generated vessels. Rats sacrificed on day 4 were divided into 3 groups, according to the number of laser irradiation treatments: A0, A2, and A4. Similarly, rats sacrificed on day 7 were divided into groups B0, B2, and B4. Among the A groups, vascular counts were 49.5 +/- 31.1 in group A0 (n = 6), 108.9 +/- 34.7 in group A2 (n = 7), and 90.9 +/- 24.6 in group A4 (n = 4). Neovascularization was significantly more pronounced in the irradiated groups that in the non-irradiated group. In the B groups, vascular counts were 148 +/- 58 in group B0 (n = 6), 146 +/- 56 in group B2 (n = 5), and 147 +/- 49 in group B4 (n = 5). There was no significant difference between the irradiated and non-irradiated B groups. Laser irradiation was determined to stimulate neovascularization, and the possibility of a clinical application for this procedure was suggested.

Animals↗

Effect of left ventricular systolic pressure increase on ventricular arrhythmogenicity in old canine myocardial infarction.

OBJECTIVE: The aim was to examine the effect of an increase in left ventricular systolic pressure (LVSP) on ventricular arrhythmogenicity in old canine myocardial infarction. METHODS: Fourteen mongrel dogs of either sex weighing 11 to 15 kg were used. Studies were performed 28 d after creation of myocardial infarction by ligation of the anterior descending coronary artery. Electrical induction of ventricular arrhythmia and determinations of effective refractory period (ERP) and local intraventricular conduction delay (LIVCD) were performed using the extrastimulus technique with a cycle length of 300 ms in the normal and infarcted zones of the left ventricle. Heterogeneity of ERP (delta ERP) was determined as a difference between the longest and shortest ERP values in each site. LVSP was raised by constriction of the ascending aorta in a stepwise fashion (control, level A, level B). RESULTS: Incidence of electrically induced ventricular arrhythmia was increased from 28.6% at control level of LVSP [130.7(SEM 7.3) mm Hg] to 42.9% at level A [190.9(6.0) mm Hg] and to 64.3% (p < 0.05) at level B [243.3(4.0) mm Hg]. delta ERP and LIVCD were greater in the infarct zone than in the normal zone at each level of LVSP (p < 0.001). delta ERP in the infarct zone increased from 18.9(4.3) ms at control level of LVSP to 20.7(6.8) ms at level A, and to 27.1(8.1) ms at level B (p < 0.001). LIVCD in the infarct zone also increased from 22.9(6.2) ms at control level of LVSP to 26.8(4.9) ms at level A (p < 0.001), and to 36.1(6.0) ms at level B (p < 0.001). delta ERP and LIVCD in the normal zone were only slightly raised by increasing the LVSP. delta ERP and LIVCD in the infarct zone were closely correlated with incidence of electrically induced ventricular arrhythmia. CONCLUSIONS: Increasing the LVSP enhances ventricular arrhythmogenicity and pre-existing electrophysiologic abnormalities of the heart in the presence of old myocardial infarction. Thus a rise in LVSP from any cause in the old myocardial infarction can be a trigger of life threatening ventricular arrhythmias.

Animals↗

Anticellular and antitumor activity of duocarmycins, novel antitumor antibiotics.

The anticellular and antitumor activities of novel antitumor antibiotics, duocarmycins (DUMs), were examined against human and murine tumor cells. DUMs consist of five compounds, A, B1, B2, C1 and C2, which possess a pharmacophore similar to that of CC-1065, a previously isolated antibiotic. Among them, DUMA exhibited ultrapotent growth-inhibitory activity with an IC50 value of 6 pM against human uterine cervix carcinoma HeLa S3 cells. DUMA and DUMB1 also inhibited the growth of adriamycin (ADM)-resistant lines of human nasopharynx carcinoma KB cells and breast carcinoma MCF-7 cells as well as their sensitive lines. DUMs inhibited the growth of s.c.-inoculated murine tumors such as B16 melanoma, sarcoma 180, M5076 sarcoma and colon 26. DUMs were also significantly effective in increasing the lifespan of i.p.-inoculated B16 melanoma-bearing mice, although their effect was marginal against other i.p.-inoculated tumors. As a whole, DUMB1 exhibited superior activity to the other four compounds. DUMB1 rapidly inhibited the incorporation of [3H]-TdR into macromolecules of HeLa S3 cells as compared with that of [3H]UR or [3H]leucine. DNA strand breaks were detected in DUMB1-treated HeLa S3 cells by agarose gel electrophoresis with a contour-clamped homogeneous electric field apparatus. These results indicate that DUMs possess interesting biological activities as DNA-targeting antitumor antibiotics.

Animals↗

Effect of bilateral stellectomy on electrical instability of the atrium in the dog with hypokalemia.

To investigate the effect of sympathetic nerve activity on electrical instability of the atrium in the presence of hypokalemia, open chest electrophysiological study was performed before and after bilateral stellectomy (BS) in 15 dogs with hypokalemia (hypokalemia group) and in 15 dogs with normokalemia (control group). Hypokalemia was created by infusion of 5.0 g/kg of polystyrene sulfonic acid calcium into the colon. Serum level of potassium was significantly lower in the hypokalemia group (2.94 +/- 0.52 mEq/L) than in the control group (4.86 +/- 0.51 mEq/L, P less than 0.01) before BS. There was no significant change in serum level of potassium in the two groups after BS. Incidence of electrically induced atrial fibrillation (AF) was significantly higher in the hypokalemia group (80%) than in the control group (13%, P less than 0.001) before BS. It was significantly reduced in the hypokalemia group (40%, P less than 0.05), but not in the control group (6%) after BS. Dispersion of effective refractory period of the atrium (delta ERP) was significantly greater in the hypokalemia group (26.1 +/- 2.8 msec) than in the control group (22.0 +/- 3.3 msec, P less than 0.005) before BS. It was significantly decreased to 23.1 +/- 3.2 msec in the hypokalemia group (P less than 0.001) and to 20.6 +/- 2.5 msec in the control group (P less than 0.01) after BS. Maximum conduction delay in the atrium (MaxCD) was 36.1 +/- 3.5 msec before and 36.2 +/- 4.1 msec after BS in the hypokalemia group and 31.1 +/- 4.2 msec before and 32.3 +/- 4.9 msec after BS in the control group. There was a significant difference in MaxCD between the two groups before BS. Atrial fibrillation threshold (AFT) was significantly lower in the hypokalemia group (3.9 +/- 0.7 mA) than in the control group (13.8 +/- 3.1 mA, P less than 0.001) before BS. It was significantly increased both in the hypokalemia group (6.5 +/- 1.3 mA, P less than 0.001) and in the control group (15.0 +/- 2.7 mA, P less than 0.005) after BS. It is concluded that sympathetic nerve activity may play some role in the increase in electrical instability of the atrium in the presence of hypokalemia.

Animals↗

[Clinical study of albendazole therapy for strongyloidiasis].

We reported the efficacy of albendazole (ABZ) for the treatment of 27 patients with strongyloidiasis. Twenty-seven patients, 23 males and 4 females, received 200 mg of ABZ one hour before breakfast and supper for 3 days and this treatment was repeated 2 weeks later. The following results were obtained: 1) The eradication rate at 2 weeks after the initial treatment was 70.4% (19 of 27 patients) and 2 weeks after the second course was 66.7% (16 of 24 patients). 2) One patients (3.7%) complained of abdominal pain after the first treatment. Four patients (14.8%) complained of headache (n = 2), nausea (n = 1) and exanthema (n = 1) after the second treatment. But all symptoms were mild and required no treatment and subsided in a few days. 3) Positive rate of HTLV-1 antibody was 45.8% in the patients. As described above, side effects occurred in some cases, although they were mild and transient. From these results, it can be concluded that on increased dose of ABZ could be much more favorable for the treatment of strongyloidiasis.

Adult↗

Restoration of cerebrovascular CO2 responsivity by glutamine synthesis inhibition in hyperammonemic rats.

Hyperammonemia increases brain glutamine levels, causes astrocytic swelling, and depresses cerebral blood flow (CBF) responsivity to CO2. Methionine sulfoximine (MSO) inhibition of glutamine synthetase activity, known to be enriched in astrocytes, prevents ammonia-induced increases in brain glutamine and water content. We tested the hypothesis that inhibition of glutamine accumulation restores CBF responsivity to CO2 during acute hyperammonemia. Pentobarbital-anesthetized rats treated with either vehicle or MSO (150 mg/kg i.p.) received a 6-hour intravenous infusion of either sodium or ammonium acetate. With subsequent induction of hypercapnia, CBF increased from 113 +/- 14 (mean +/- SEM) to 194 +/- 9 ml/min per 100 g in control rats but was unchanged from 107 +/- 13 to 79 +/- 10 ml/min per 100 g in hyperammonemic rats. Treatment with MSO in hyperammonemic rats restored the CBF response to hypercapnia (from 73 +/- 8 to 141 +/- 14 ml/min per 100 g). With induction of hypocapnia, CBF decreased from 114 +/- 11 to 88 +/- 11 ml/min per 100 g in control rats but increased from 112 +/- 13 to 142 +/- 19 ml/min per 100 g in hyperammonemic rats. Treatment with MSO in hyperammonemic rats did not fully restore the response to hypocapnia but prevented the paradoxical increase in CBF (from 80 +/- 8 to 80 +/- 8 ml/min per 100 g). In control rats, MSO did not affect CO2 responsivity. Treatment with MSO prevented ammonia-induced increases in intracranial pressure. Hyposmotic-induced increases in brain water content and intracranial pressure attenuated the CBF response to hypercapnia but, unlike hyperammonemia, did not attenuate the response to hypocapnia. In contrast to hypercapnia, vasodilation in response to arterial hypotension was intact in hyperammonemic rats. We conclude that the grossly abnormal CBF responsivity to CO2 alterations during hyperammonemia is linked to glutamine accumulation rather than ammonia per se. Cerebral edema secondary to glutamine accumulation may contribute in part to abnormal CBF responses, although other aspects of astrocyte dysfunction are likely to be important.

Ammonia↗

Highly sensitive enzyme-linked immunosorbent assay for marograstim (KW-2228), a mutant of human granulocyte colony-stimulating factor.

An enzyme-linked immunosorbent assay (ELISA) for marograstim (KW-2228) was established. This ELISA proved to be highly sensitive with the detection limit of 0.01 ng/ml (about 0.5 fmol/ml) of KW-2228 and the assay range between 0.01 and 2 ng/ml. When 0.02 to 2 ng/ml of KW-2228 added to human plasma was determined, the variation coefficiencies of intra-day and inter-day assays were 0.4 to 7.6% and 5.2 to 15.8%, respectively, with good recoveries. These results indicate that this ELISA will be applicable to pharmacokinetic studies on KW-2228. With respect to the specificity, recombinant human granulocyte colony-stimulating factor (rhG-CSF) produced in Escherichia coli as well as KW-2228 which does not have sugar chains in its structure showed slightly less immunoreactivity toward the antibody raised against KW-2228. The rhG-CSF produced in Chinese hamster ovary cells (CHO) having sugar chains showed the lower immunoreactivity. The antigenic domains of KW-2228 were evaluated using a number of variants of hG-CSF. The variants having different amino acids from KW-2228 in the 1st to 5th residue of the N-terminus showed almost equal immunoreactivities to KW-2228. The immunoreactivities of the variants lacking 7 to 18 amino acids of N-terminus were less than 50% of that of KW-2228. No immunoreactivity was observed for the variants deleted in the area of 70th to 130th amino acids from the N-terminus. In addition, the immunoreactivity of a variant lacking the 10 amino acids from the C-terminus was 20% of that of KW-2228.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

Studies on absorption, distribution, excretion and metabolism of ginseng saponins. VIII. Isotope labeling of ginsenoside Rb2.

To clarify the pharmacokinetics of absorption, distribution and excretion of ginsenoside Rb2 (Rb2), one of the major saponins of the root of Panax ginseng, following oral administration to rats, a tritium (3H) labeling of Rb2 was examined. The C-12 position of Rb2 was labeled with 3H-sodium borohydride (3H-NaBH4) and 12-3H Rb2 and 12-3H-epi Rb2 was synthesized. This method of specific position labeling of Rb2 may be applicable to other ginsenosides. In the near future, the pharmacokinetics of Rb2 in rats may be clarified with 3H labeled Rb2.

Animals↗