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Biomedical subjects

K Ota

Publications and source records attributed to K Ota.

At least 433 records · Page 24Linked to original sources

DNA replication in uterine cells of adult and prepubertal mice under normal and hormonally stimulated conditions detected by bromodeoxyuridine labeling method.

To confirm the utility of the bromodeoxyuridine (BrdU) labeling method in the study of cell proliferation in mouse uterine tissues, changes in the labeling index in the luminal and glandular epithelia, the periluminal, periglandular and deep stromal regions and the myometrium were surveyed in normal adult mice during the estrous cycle and early pregnancy, in prepubertal mice and in ovariectomized adult and young animals treated with estrogen and/or progesterone. All results obtained were consistent with those obtained in previous histometric and autoradiographic studies and proved the effectiveness of the BrdU labeling method in the study of the uterus as well as many other organs. A marked rise in the labeling index was found in the luminal epithelium at metestrus, as well as on the proestrous morning, indicating the occurrence of extensive cell proliferation in the absence of estrogen stimulation. The change in the labeling index in adult mice was much more evident in the luminal epithelium than in the glandular epithelium in all conditions examined. On the other hand, the change in the stroma was more eminent in the periglandular region than in the periluminal and deep regions in most conditions. In immature mice, a great increase in labeling incidence occurred not only in luminal epithelium but also in muscle layers along with the process of puberty and at the time of estrogen stimulation. A moderate increase in the incidence also occurred in all other areas of the uterus including the perimetrium. Again, the increase was more prominent in the periglandular area than in other stromal regions.

Animals↗

Effects of central osmotic stimulation on vasopressin and enkephalin release into the blood and cerebrospinal fluid and blood pressure.

To assess the central effect of hypertonic NaCl on the release of vasopressin (AVP) and methionine enkephalin-like substances into the blood and cerebrospinal fluid, and on blood pressure, ventriculocisternal perfusion (0.25 ml/min, 60 min) was performed in anesthetized dogs with artificial cerebrospinal fluid (CSF), either isotonic (300 mosmol/kg) or hypertonic (600 and 1200 mosmol/kg). The effect of central administration of a V1-AVP antagonist on the central osmotic challenge was also studied. In dogs, given 600 mosmol/kg, CSF osmolality increased with a concomitant rise in mean arterial pressure and plasma AVP concentrations. Plasma osmolality, heart rate, CSF AVP and plasma and CSF methionine enkephalin-like substances showed no significant change. In dogs, given 1200 mosmol/kg, the CSF osmolality increase was accompanied by a rise in mean arterial pressure, heart rate, plasma AVP and CSF AVP. Plasma osmolality and plasma and CSF methionine-enkephalin-like substances did not change significantly. A V1-AVP antagonist given centrally attenuated the rise in mean arterial pressure induced by osmotic challenge. In dogs, given 300 mosmol/kg, no parameters changed significantly except for a gradual fall in heart rate. These results suggest that central osmotic stimulation by hypertonic NaCl increases blood pressure, heart rate and the release of AVP, but not methionine enkephalin-like substances, into the blood and CSF, and a V1-blocker given centrally attenuates the pressor response.

Animals↗

Effects of intracerebroventricular administration of adrenoceptor-agonists on the regulation of renal water and electrolytes handling through endocrine, renal and hemodynamic function.

In order to assess the roles of central adrenoceptors in the release of atrial natriuretic peptide (ANP), aldosterone (ALD), vasopressin (AVP) and renin as well as in the regulation of renal and cardiovascular functions, either norepinephrine (NE; 0.07 microgram/kg/min), guanabenz (GB; alpha 2-agonist; 0.4 microgram/kg/min), methoxamine (MET; alpha 1-agonist; 0.4 microgram/kg/min), or isoproterenol (ISO; beta-agonist; 0.07 microgram/kg/min), dissolved in the artificial cerebrospinal fluid (ACSF), was intracerebroventricularly (i.c.v.) administered at a rate of 10 microliters/min for 30 min in anesthetized dogs. In the control study, the drugs were omitted. NE decreased mean arterial pressure (MAP), urinary osmolality (Uosm) and plasma ALD and AVP concentrations, and increased urine flow (UF). GB increased UF and urinary K excretion without any changes in urinary Na excretion, but decreased plasma ALD and AVP, heart rate, and Uosm without changes in MAP. ISO decreased MAP and plasma ALD, and increased Na and K output, renal plasma flow and UF with decreased Uosm. MET and ACSF failed to affect any of these parameters. Glomerular filtration rate, plasma ANP concentration and renin activity did not change in any of the studies. The present results suggest that central alpha 2- and beta-adrenoceptors may attenuate ALD and/or AVP release without changes in ANP and renin release, and decrease blood pressure, thereby causing a diuresis and natriuresis.

Adrenergic alpha-Agonists↗

Immunohistochemical detection of DNA replication in mouse uterine cells by bromodeoxyuridine labeling of wax- and resin-embedded tissue sections.

To apply the bromodeoxyuridine (BrdU) labeling method using a monoclonal antibody to the study of cell proliferation in the mouse uterus, methods of fixation and embedding of tissues and of immunofluorescent staining were compared in terms of the rate of detection of labeled cells and specificity and stability of fluorescence obtained. BrdU was administered intravenously 2 hr before death and uterine blocks were embedded in polyester wax and Technovit resin after fixation in formalin and periodate-lysine-paraformaldehyde, respectively. The indirect method with anti-BrdU and fluorescein isothiocyanate (FITC) conjugated antimouse IgG antisera and the direct method with FITC conjugated anti-BrdU antibody were applied to both wax- and resin-embedded sections. Labeled and total cells were counted in luminal and glandular epithelia and stomata adjoining them. Counterstaining with hematoxylin for counting total cells produced intense fluorescence over the whole of resin sections and made counting of labeled cells impossible. On wax sections, on the other hand, the results were satisfactory, although the number of labeled cells detected was decreased slightly. In wax sections fluorescence due to nuclear incorporation of BrdU in the indirect method could be easily distinguished from the cytoplasmic or extracellular emission seen in some cells by its location and characteristic color. In resin sections, however, more careful observation was needed since the second antibody used in the indirect method cross-reacted with IgG in eosinophils and produced cytoplasmic fluorescence of the same color. By the indirect method greater numbers of labeled cells were detected in wax sections than in resin sections. The difference was distinct in tissues with extensive cell proliferation. By the direct method the fluorescence obtained was weaker and apt to fade more quickly than that obtained by the indirect method; use of the direct method reduced the number of labeled cells detected in both wax- and resin-embedded sections.

Animals↗

[Clinical effect of recombinant human G-CSF on neutropenia induced by chemotherapy for lung cancer. rG.CSF Cooperation Study Group].

The therapeutic evaluation of rG.CSF has been studied on neutropenic patients receiving lung cancer chemotherapy with focusing the change in the absolute neutrophil counting (ANC) in the patients during chemotherapy and subsequent rG.CSF treatment by daily dosing either at 0.4, 2.0, 5.0 and 10.0 micrograms/kg intravenously or at 2.0 and 5.0 micrograms/kg subcutaneously. The daily rG.CSF dosing for 14 consecutive days was performed on the patients upon completion of the 28-day chemotherapy for lung cancer. As a result, remarkable recovery of ANC was observed in the patients administered at doses of more than 5 and 2.0 micrograms/kg intravenously and subcutaneously, respectively. Additionally, the shortening of the neutropenia (ANC: below 1,000/cmm) was observed in the patients at doses of not less than 2.0 micrograms/kg in both administration routes. In conclusion, rG.CSF treatment demonstrates the completion and/or shortening of the chemotherapy cycle for lung cancer at a subcutaneous dose of 2.0 micrograms/kg and at a intravenous dose of 5.0 micrograms/kg. No adverse drug effects were observed in all patients during the study.

Adult↗

Clinical application of Fragmin (FR-860) in hemodialysis: multicenter cooperative study in Japan.

A multicenter cooperative study was designed to evaluate the efficacy and safety of Fragmin (FR-860) as an anticoagulant in hemodialysis. Sixty-one stable maintenance hemodialysis patients were enrolled from 14 institutions in Japan. The study period was fixed at 2 weeks. Dosage requirements were 15.0 to 20.0 anti-Xa U/kg as bolus and 7.5 to 10.0 anti-Xa U/kg/hr as continuous infusion. The total dosage of Fragmin was 2505 +/- 127 anti-Xa U compared with 6124 +/- 190 U of conventional heparin. No differences were observed in residual blood in extracorporeal circuits between the groups. The hemostasis times at puncture sites after completion of dialysis were significantly shortened in the Fragmin group (7.9 +/- 0.7 minutes) when compared with the conventional heparin group (11.4 +/- 1.1 minutes; p less than 0.01). Plasma anti-Xa levels were 0.24 +/- 0.03 and 0.36 +/- 0.04 U/ml 1 hour after the initiation and at the completion of dialysis, respectively. ACTs, measured by the Hemochron method, were not prolonged during dialysis. APTTs varied from 34.3 +/- 1.2 before dialysis to 41.0 +/- 1.9 (p less than 0.01) 1 hour after the start of dialysis and 39.9 +/- 1.6 seconds (p less than 0.01) at the end of dialysis. Plasma AT III activity increased from 96.8 +/- 2.5% before dialysis to 113.0 +/- 3.2% (p less than 0.01) at the end of dialysis. No significant changes were observed in both ADP- and collagen-induced platelet aggregation during dialysis. Dialysis efficiency was the same for both groups. Slight itching developed in one of 61 cases. No abnormal laboratory data were observed during the study. The efficacy, safety, and utility rates were 98.4, 98.5, and 98.4%, respectively. Fragmin proved to have a higher utility rate and was a good and convenient alternative to conventional heparin as an anticoagulant in hemodialysis treatment.

Antithrombin III↗

A low CA++ level in effluent as a risk factor for the peritonitis in CAPD patients.

In vitro, some studies revealed the importance of the CA++ level in peritoneal macrophage functions in CAPD patients. We therefore retrospectively studied the relationship between the frequency of peritonitis and the concentration of Ca, Ca++, Interferon-r (IFN-gamma), Interleukin-1B (IL-1B) in the Pd effluent. Samples were taken during a peritonitis-free period. In a group of patients without peritonitis, the mean Ca++ level in the Pd effluent was 2.25 +/- 0.20 mEq/L, while in the other group with frequent episodes of peritonitis (more than one episode per 20 patient-months), the mean Ca++ level in PD effluent was 2.01 +/- 0.13 mEq/L which was significantly lower than the former (p less than 0.05). The mean Ca concentration in Pd effluent was also lower in the group with the high frequent peritonitis than the peritonitis-free group, but not significantly. The level of IFN-gamma is lower and IL-1B is higher in the group with frequent peritonitis than in the peritonitis-free group, although these differences were not significant. These evidences suggest that lower Ca++ level in the effluent of the frequent peritonitis group may impair the peritoneal macrophage function and peritoneal cell-mediated immune function and may increase a risk of the peritonitis. These results may offer a new approach for prophylaxis of peritonitis in CAPD patients.

Calcium↗

Evaluation of 117 patients with non-Hodgkin's lymphoma in the past ten years at our department.

We did a retrospective statistical study of 117 patients with non-Hodgkin's lymphoma admitted to our hospital from January 1979 to December 1988. Five-year survival was 83% for patients in stage I at diagnosis, which was significantly better than the 55% in stage II, 37% in stage III, and 34% in stage IV. Five-year survival was 74% for patients with B-cell lymphoma (74%), which was significantly better than with the 32% for T-cell lymphoma. For patients in stage I or II, five-year survival was 46% for those with nasal lymphoma, which was significantly worse than the 72% with nodal lymphoma and the 82% for those with Waldeyer's lymphoma. Sixty-eight patients were treated initially with radiation only. The relapse frequency was 20% in stage I and 40% in stage II. All of the relapses occurred outside the irradiated area treated on the other side of the diaphragm. Of all 48 patients with combination chemotherapy such as vincristine, cyclophosphamide, predonisolone, and Adriamycin (VEPA), mitoxantrone, cyclophosphamide, vincristine, and predonisolone (MCOP), and mitoxantrone, ifosfamide, vindesine, and predonisolone (MIFP), 33 (69%) achieved complete remission.

Adolescent↗

[Temperature-dependent pseudoleukocytopenia and in vitro studies on the underlying mechanism].

Spuriously low electronic white-cell count was obtained on EDTA-anticoagulated blood from a 54-year-old male suffering from liver cell carcinoma. In an attempt to understand better the phenomenon, in vitro studies were performed. The blood smear anticoagulated with EDTA revealed remarkable agglutinations of leukocytes, mainly neutrophils but not lymphocytes. The EDTA-treated blood showed maximal leukocytes-agglutinations at room temperature but no agglutination at 37 degrees C. The agglutinated leukocytes, moreover, were dispersed by incubating the blood at 37 degrees C. Although agglutination occurred in some degree in the blood anticoagulated with Na-heparin or Na3-citrate, it was much less pronounced compared to the EDTA-treated blood. Remarkable leukocytes-agglutinations were induced when EDTA-anticoagulated blood from healthy donor was mixed with serum from the patient at room temperature. These results suggest that the phenomenon of in vitro leukocyte agglutination and consequent pseudoleukocytopenia is due to leukocyte agglutinin in serum from the patient. The mechanisms were discussed comparing with pseudothrombocytopenia caused by platelet agglutinin.

Adolescent↗

[Cardiotoxicity and pulmonary toxicity of chemotherapy].

Recently, the quality of life of a cancer patient has been extensively discussed. Especially, side effects of chemotherapy are major problems of cancer patients. Cardiotoxicity of adriamycin and pulmonary toxicity of bleomycin are not common side effects of chemotherapy, but they can be devastating, particularly, when they occur in a patient who has been cured of cancer. Therefore, we tried to demonstrate the efficacy of cardiac or pulmonary monitoring in early detection of the toxicity. In conclusion, now non-invasive and invasive standard methods of monitoring have yet to be convincingly established, because most methods are either of no predictive value or too sensitive. Moreover, to date an effective prophylaxis of cardiotoxicity or pulmonary toxicity is still lacking. Exact evaluation of risk factors and thorough cardiac or pulmonary monitoring are necessary in patients under chemotherapy.

Antineoplastic Agents↗

[Resemblance of magnesium and zinc distribution in soft tissues and bone of rats fed unbalanced mineral diets in situ].

Although the role of zinc (Zn) and magnesium (Mg) in situ may be of a critical importance in replication, transcription and repair of DNA, to our knowledge, the relationship between Mg and Zn has been described. This study, therefore, was designed experimentally to investigate the relationship between Mg and Zn in soft tissues and bone of rats after fortification of unbalanced mineral diets, and minerals and metals in soft tissues and bone were determined by inductively coupled plasma emission spectrometry. In the groups fed low calcium (Ca) diet, low Ca-Mg diet and low Ca-Mg plus high Al diet, serum Mg level was lower in the group fed low Ca-Mg diet and low Ca-Mg plus high Al diet than those in the groups fed standard diet and low Ca diet. However, there was no significant difference in Mg content of CNS tissues in rats fed unbalanced and standard diets except for that in the spinal cord of rats fed low Ca-Mg plus high Al diet. Whereas, Zn content of CNS showed lower values in the unbalanced mineral diet groups, especially in all CNS regions of the low Ca-Mg plus high Al diet group, than those in the standard and the low Ca diet group. And Zn contents in heart, kidney and abdominal aorta of rats fed low Ca-Mg diet and low Ca-Mg plus high Al diet were more decreased than those of the standard and the low Ca diet groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Aluminum↗

[High-dose leucovorin and 5-fluorouracil in advanced gastric and colorectal cancer. High-Dose Leucovorin and 5-FU Study Group].

A multicenter cooperative study was conducted from June 1988 to July 1989 to evaluate the clinical efficacy of high-dose dl-Leucovorin (dl-LV) and 5-FU treatment in 61 cases of advanced gastric and colorectal cancer. The administration schedule was a 2-hour infusion of dl-LV (500 mg/m2) and an IV bolus of 5-FU (600 mg/m2), given 1 hour after the beginning of LV infusion. Patients (pts.) were treated q week x 6 then evaluated for response. Thirty one gastric cancer pts. were divided into two groups; nine pts. treated with 30 min. infusion of 5-FU, and the remaining 23 pts. treated with IV bolus. PR was obtained in 2/9 (22.2%) and in 7/22 (31.8%) of the first and second group, respectively. An overall response rate was 9/31 (29%). Thirty colorectal cancer pts. were divided the same: 13 pts. treated with 30 min. infusion of 5-FU and the remaining 17 pts. treated with IV bolus. PR was obtained in 2/13 (15.4%) and in 7/17 (41.2) of the first and second groups, respectively. An overall response rate was 9/30 (30%). Median survival time for the gastric cancer group was 9.4 months, and for the colorectal cancer group was 13.6 months. Toxicity was within acceptable limits. Toxic effects included diarrhea, stomatitis, anorexia and myelohypoplasia. Our data suggests that high dose LV and 5-FU seems to be a very promising combination and warrants a further investigation.

Adult↗

[Therapeutic effects of a combination treatment with cefmetazole and netilmicin against infections complicated with hematological disorders].

The efficacy and safety of a combination regimen using cefmetazole (CMZ) and netilmicin (NTL) were evaluated in the treatment of infections complicated with hematological disorders. Primary diseases in 31 patients included in the evaluation were acute myelocytic leukemia (3 cases), acute lymphocytic leukemia (2 cases), malignant lymphoma (14 cases), chronic myelocytic leukemia (2 cases), chronic myelocytic leukemia blast crisis (4 cases), myelodysplastic syndrome (2 cases), aplastic anemia (3 cases), and malignant histiocytosis (1 case). Complicated infections included 29 cases of suspected septicemia, 1 case of septicemia and 1 case of pneumonia. Clinical responses were excellent in 6 (19.4%), good in 12 (38.7%), fair in 1 (3.2%) and poor in 12 (38.7%). The total clinical efficacy rate was 58.1%. No significant effect of initial neutrophil counts was observed on response rates. Patients who showed increasing neutrophil counts during therapy had higher response rates than those in whom the neutrophil count decreased or remained unchanged at levels less than 500/mm3 in after neutrophil counts. No side effects were observed in any of the 31 patients. In conclusion, this combination therapy of CMZ and NTL thus appears to be useful and safe in therapies for infections complicated with hematological disorders.

Adult↗

[Distribution of calcium and magnesium in soft tissues, especially in the central nervous system, and bone of rats fed with low calcium-magnesium with or without aluminum loading diets].

Current epidemiological investigations in the Western Pacific area have suggested that the environmental factors contribute to the pathogenetic process of amyotrophic lateral sclerosis (ALS). The condition of unbalanced minerals found in soil and drinking water of ALS foci with low content of Ca and Mg plus high content of Al was experimentally mimicked in this study using rats. In the groups fed with low calcium diet, low Ca-Mg diet and low Ca-Mg plus high Al diet, serum calcium levels were lower than those in the group fed with standard diet. Also serum Mg levels were lower in the groups fed with low Ca-Mg diet and low Ca-Mg plus high Al diet than in the group fed with standard diet and low Ca diet. However, there was no significant difference in Mg content of the central nervous system (CNS) tissues of groups with unbalanced and standard diets except for that in spinal cord of rats fed with low Ca-Mg plus high Al diet, determined by inductively coupled plasma emission spectrometry. On the other hand, Ca content of CNS showed higher values in the unbalanced diet groups, especially in spinal cord of the low Ca-Mg plus high Al diet group, than those in the standard diet group. And Ca content in heart, liver, kidney and abdominal aorta of rats fed with both low Ca-Mg diet and low Ca-Mg plus high Al diet increased that those of standard and low Ca diet groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Aluminum↗