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Biomedical subjects

T Okubo

Publications and source records attributed to T Okubo.

At least 253 records · Page 14Linked to original sources

Expression of nm23-H1 gene product in thyroid, ovary, and breast cancers.

The nm23 gene product is one of several possible mediators of cancer invasion and metastasis. As the amounts of nm23-H1 mRNA and gene product are reduced in metastatic lymph nodes from patients with papillary carcinoma of the thyroid, we examined the expression of nm23 gene product in 115 thyroid cancers, 78 ovarian cancers, 63 breast cancers, and metastatic lymph node tissues by immunohistochemistry. It was found that nm23-H1, but not nm23-H2 gene product, was expressed in primary sites of thyroid, ovarian, and breast cancers, except for medullary and anaplastic carcinomas of the thyroid, but expressed only weakly or poorly in metastatic lymph nodes. Although nm23-H1 gene product expression was lower in anaplastic and medullary carcinomas of the thyroid, there was no significant difference in nm23-H1 gene product expression among histological types of ovarian and breast cancers. Our data indicate that the nm23-H1 gene product may play a role in metastasis in these hormone-producing organs and that other factors may be involved in metastasis of anaplastic and medullary carcinomas of the thyroid.

Breast Neoplasms↗

Attenuation of acetylcholine-induced vasoconstriction by L-arginine is related to the progression of atherosclerosis.

To determine if L-arginine, a precursor of the endothelium-derived relaxing factor, restores endothelium-dependent dilation in human coronary arteries, we studied 21 patients in whom the lumina of the coronary arteries were angiographically smooth or slightly irregular and in whom there was a constrictor response to acetylcholine (ACh) in the left anterior descending coronary artery or the circumflex coronary artery. We examined the response to intracoronary ACh before and after infusion of L-arginine by measuring coronary diameter with quantitative angiography. Intracoronary injection of ACh produced vasoconstriction in the majority of patients with coronary risk factors. The percentage diameter change in smooth segments in patients with entirely smooth coronary arteries (group 1, n = 44) from baseline was -20.7% +/- 17.4%. During systemic infusion of L-arginine, the constrictor response to ACh in these segments was significantly attenuated (-2.2% +/- 15.1% from baseline, p < 0.01, ACh alone vs ACh during L-arginine infusion). In smooth segments in patients with luminal irregularities in the other coronary arteries (group 2, n = 19), ACh produced a marked constriction (-32.5% +/- 22.5% from baseline, p < 0.05, group 1 vs group 2). Infusion of L-arginine also attenuated ACh-induced vasoconstriction in these segments (-9.7% +/- 14.1% from baseline, p < 0.01, ACh vs ACh during L-arginine infusion). In segments with irregular lumina (group 3, n = 26), ACh produced more prominent vasoconstriction. The percentage diameter change was -40.9% +/- 26.5% from baseline (p < 0.01 vs group 1).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

Synthetic peptides demonstrate RGD-independent platelet glycoprotein IIb/IIIa recognition site in cell binding domain of human fibronectin.

Fibronectin binds to platelet membrane glycoprotein (GP) IIb/IIIa in both an Arg-Gly-Asp (RGD)-dependent and -independent manner. The identification of an RGD-independent binding domain(s) that interacts with GPIIb/IIIa may be the key to understand the mechanism of thrombus formation. A recombinant fibronectin fragment containing the residues from Ile1359 to Ser1436 (lacking the RGD sequence) had been shown to bind to GPIIb/IIIa in a divalent cation- and activation-dependent manner. To identify a minimal peptide ligand that participates in the recognition of GPIIb/IIIa, we synthesized peptides extending this region, which consist of 12 amino acid residues in length and overlapping by six amino acids. We obtained evidence that two 12-residue peptide sequences from this region (residues 1371-1382 and 1377-1388) inhibit fibronectin binding to GPIIb/IIIa by interacting directly with this receptor, with IC50s of 95 +/- 16 and 104 +/- 19 microM, respectively. These peptides inhibited the binding of fibrinogen to GPIIb/IIIa, as well as ADP-induced platelet aggregation. These results indicate that an RGD-independent GPIIb/IIIa binding site in the cell binding domain of fibronectin was localized within the residues His1377-Ile1382.

Adenosine Diphosphate↗

Predicting relapse of chronic myelogenous leukemia after allogeneic bone marrow transplantation by bcr-abl mRNA and DNA fingerprinting.

Fourteen patients treated by allogeneic bone marrow transplantation for chronic myelogenous leukemia (CML) were evaluated by the polymerase chain reaction (PCR) for bcr-abl-specific transcripts. Nine patients were transplanted in the first chronic phase, three in the second chronic phase, and two in the accelerated phase. All patients achieved a complete cytogenetic and hematologic remission after bone marrow transplantation. Twelve patients are alive (median, 18 months; range, 5-54 months) and two patients died early. bcr-abl mRNA was persistently detectable for 6 to 54 months in four patients (patients 1, 3, 4, 6). From two of them, DNA fingerprint analysis showed only donor type DNA although bcr-abl mRNA was detectable. bcr-abl mRNA was never detectable posttransplant in three patients (patients 2, 5, 13). Six patients had detectable bcr-abl mRNA (patients 8-12, 14): by 6 months, all of these patients were bcr-abl mRNA negative. One patient (patient 7) had detectable full bcr-abl mRNA again at 12 months, but was then negative at 20 months. Ten patients (patients 2, 4-8, 10-13) had never detectable Philadelphia (Ph1) chromosome t(9.22) translocation, whereas four patients had detectable Ph1 (patient 1, 3, 9, 14); by 6 months, three of four cases were negative. One patient (patient 1) had detectable Ph1 at 44 months, but was negative at 50 months. Three of six patients who initially had bcr-abl mRNA detectable posttransplant (patient 7-9) became negative for bcr-abl mRNA at the time of development of chronic graft-versus-host disease (GVHD). These results suggest that the detection of subclinical Ph1 positive cells by PCR is not associated with imminent clinical or cytogenetic relapse. Moreover, graft-versus-leukemia (GVL) activity may contribute to the treatment of minimal residual disease in CML after allogeneic bone marrow transplantation.

Adolescent↗

Health status, health habits, utilization behaviour and health care utilization in an actively employed Japanese population.

Healthcare utilization data from 1 February 1986 to 31 January 1992 for 18,601 local public service employees were analysed in relation to data on their perceived health status, health habits, health care utilization behaviour and health-related worries which were obtained from a questionnaire survey conducted in 1988. The results showed health care utilization behaviour as defined by the questionnaire responses to be the most important predictor of health care utilization as defined by claim rate and group utilization rate, followed by perceived health status and certain health habits (ie caring about sleep, food and diet, watching body weight). Health-related worries, when used as a group variable, were not an independent predictor of utilization. The co-existence of 'active' utilization behaviour or the above-mentioned health habits with fair/poor perceived health status was associated with the highest health care utilization. The implication of these findings is that if utilization behaviour modification is incorporated into various worksite health programmes that aim at improving employee health and containing health care utilization and costs, greater reduction can be achieved in employee health care utilization and costs.

Adult↗

Acquired von Willebrand disease associated with multiple myeloma; characterization of an inhibitor to von Willebrand factor.

Acquired von Willebrand disease (vWD) has been described in a few patients with multiple myeloma. The present study characterizes an inhibitor of von Willebrand factor (vWF) isolated from a patient with multiple myeloma (IgG-kappa). Multimeric analysis of vWF from this patient's plasma showed a reduction in multimers of all sizes. The inhibitor (IgG) detected only the vWF subunit from plasma of normal individuals. It reacted with intact vWF subunit and a 39/34kDa dispase-digested fragment of vWF (residues; Leu480/Val481-Gly718), but did not react with platelet membrane glycoproteins (GPs) or adhesive proteins. The binding of vWF to GPIb mediated by ristocetin and by botrocetin was inhibited by the patient's IgG with an IC50s of 0.3 mg/ml and 0.48 mg/ml, respectively. The platelet aggregation induced by ristocetin or botrocetin was also inhibited by the IgG. These results indicate that this inhibitor may recognize the binding region of vWF to GPIb. Therefore, the antibody to vWF appears to represent the likely pathophysiological mechanism responsible for the acquired vWD in this patient.

Autoantibodies↗

[Clinico-pathological aspect of HIV-sero positive inpatients].

To describe the clinico-pathological aspect of HIV/AIDS inpatients, we reviewed HIV/AIDS inpatients in our hospital since 1988. We evaluated risk factors, CD4 counts, CD4/8 ratio, cause of death and the survival time after diagnosis of AIDS. A total of 13 HIV sero-positive subjects were admitted to our hospital, including 11 cases (85%) with AIDS. One patient was a foreigner. All cases were male; age range 18-70 years. Hemophiliacs and sexually transmitted patients account for 62% and 38% of cases, respectively. There were no cases of intravenous drug users. In all cases with AIDS, CD4+ cells and CD4/8 ratio significantly decreased with median value of 73/microns and 0.18, respectively. Six cases (54%) were decreased and autopsy were done in four cases. Findings of autopsy revealed HIV encephalopathy and systemic various infection, including Pneumocystis carinii, cytomegalovirus, papilloma virus and pox virus. Cytomegalovirus infection was found in all cases; one had innumerable inclusion bodies in lung, adrenal gland and intestines. The median survival time after diagnosis of AIDS were 26 months.

AIDS-Related Opportunistic Infections↗

Effects of fenoterol on ventilatory responses to hypoxia and hypercapnia in normal subjects.

BACKGROUND: The effects of beta 2 adrenergic agonists on chemoreceptors remain controversial. This study was designed to examine whether fenoterol, a beta 2 adrenergic agonist, increases the ventilatory responses to hypercapnia (HCVR) and hypoxia (HVR) in normal subjects. METHODS: HCVR was tested with a rebreathing method and HVR was examined with a progressive isocapnic hypoxic method in 11 normal subjects. Both HCVR and HVR were assessed by the slope of occlusion pressure (P0.1) or ventilation (VE) plotted against end tidal carbon dioxide pressure and arterial oxygen saturation, respectively. Respiratory muscle strength, spirometric values and lung volume were measured. After a single oral administration of 5 mg fenoterol or placebo HCVR and HVR were evaluated. RESULTS: Fenoterol treatment did not change the specific airway conductance or forced expiratory volume in one second. Respiratory muscle strength did not change. Fenoterol increased the slope of the HCVR of both P0.1 (from 0.251 (0.116) to 0.386 (0.206) kPa/kPa, average increase 71%) and VE (from 10.7 (3.4) to 15.1 (4.2) l/min/kPa, average increase 52%), and shifted the response curves to higher values. For the HVR fenoterol increased the slopes of both P0.1 and VE (from -4.06 (2.00) x 10(-3) to -7.99 (4.29) x 10(-3) kPa/%, an average increase of 83%, and from -0.221 (0.070) to -0.313 (0.112) l/min/%, a 44.5% increase, respectively), and shifted the response curves to higher values. CONCLUSION: Acute administration of fenoterol increases the ventilatory responses to both hypercapnia and hypoxia in normal subjects.

Adult↗

Expiratory muscle training and sensation of respiratory effort during exercise in normal subjects.

BACKGROUND: The sensation of respiratory effort may increase as expiratory muscles become fatigued during expiratory loading. A study was performed to determine whether expiratory muscle training (EMT) affects the sensation of respiratory effort during exercise in healthy subjects. METHODS: Six subjects performed EMT for 15 minutes twice daily for four weeks using a pressure threshold device; another six subjects served as a control group. The expiratory threshold was set at 30% of the individual's maximum expiratory mouth pressure (PEmax). The sensation of respiratory effort was evaluated during a progressive exercise test using the Borg scale. RESULTS: After EMT PEmax increased by 25% in the training group. The Borg score increased as exercise grade increased before and after EMT, but scores for each grade were lower after EMT. Minute ventilation during exercise decreased after EMT, as did the breathing frequency during exercise, while the expiratory time increased. Although there was no difference in the relationship between Borg score and minute ventilation before or after EMT, the curve shifted to a lower Borg score after EMT. There were no changes in PEmax, Borg score, minute ventilation, or breathing pattern after the four week study period in the control group. CONCLUSION: These findings suggest that EMT increases expiratory muscle strength and reduces the sensation of respiratory effort during exercise, presumably by reducing minute ventilation.

Abdominal Muscles↗

Enhancement of the intracranial arterial wall at MR imaging: relationship to cerebral atherosclerosis.

PURPOSE: To investigate the relationship between intracranial arterial wall enhancement and atherosclerosis. MATERIALS AND METHODS: Intracranial vertebral arteries of 30 patients and carotid arteries of 62 patients were studied with spin-echo magnetic resonance imaging with contrast enhancement and spatial presaturation. Arterial wall enhancement was graded as follows: stage 1, no substantial enhancement; stage 2, faint or thin area of enhancement; stage 3, definite and thick area of enhancement. RESULTS: In vertebral arteries, stage 3 enhancement was seen in 11 patients (mean age, 73.7 years) and stage 1 in eight (mean age, 56.4 years). In carotid arteries, stage 3 enhancement was seen in 13 patients (mean age, 71.0 years) and stage 1 in 21 patients (mean age, 39.0 years). In both arteries, stage was well correlated with age (P < .05). CONCLUSION: Arterial wall enhancement is related to aging and is probably due to neovascularity in association with atherosclerotic plaques. This finding may permit assessment of intracranial atherosclerosis and other vascular diseases.

Adult↗

Return to work after stroke. A follow-up study.

BACKGROUND AND PURPOSE: Few studies have reported the longitudinal trend of return to work after stroke. The purpose of our study was to evaluate the longitudinal trend of proportion of patients who return to work after stroke and further to examine the predictors of return to work while taking follow-up periods into consideration. METHODS: We conducted a retrospective cohort study on the association between characteristics of stroke patients at admission and return to work after first stroke, taking length of follow-up period into consideration (n = 183). The patients were all younger than 65 years and were working at the time of their stroke. A follow-up questionnaire evaluated return to work and related information. Data were analyzed using the Kaplan-Meier method for curves of the proportion of return to work and Cox's proportional hazards model for odds ratios of return to work. RESULTS: The curve of proportion of return to work had two steep slopes, and the proportion was at a maximum at 18 months from patient admission. The adjusted odds ratios of return to work for patients with normal muscle strength versus severe weakness, without apraxia versus with apraxia, and with white-collar versus blue-collar occupations were 5.16 (P < .05), 4.16 (P < .05), and 1.43 (.05 < P < .10), respectively. CONCLUSIONS: The increase of proportion of return to work after stroke was nonlinear, and this trend was referable to the social security systems available to the patients included in this study. Normal muscle strength and absence of apraxia were significant predictors of return to work after stroke. White-collar occupation showed a tendency to promote return to work.

Adolescent↗

[ILO conventions on occupational safety and health with reference to ratification status of Japan].

This paper grouped together recent ILO conventions relevant to occupational safety and health (OSH) in order to clarify their characteristics and form an overview. There are 13 such conventions adopted by ILO during the period 1960-1993. Each of these conventions have distinct goals to cover respective areas of OSH, which was contrasted with each other. Conventions are subject to ratification, thus the ratification status of Japan was statistically compared to that of ILO and OECD member states. As at June 1993, Japan ratified three of such conventions, which was slightly higher than the average number ratified by all ILO member states and ranked 11th among 24 OECD member states. The relative ratification status of Japan on ILO Conventions fared better with those relevant to OSH than others. ILO Conventions are inter-related by reference and note, thus ratification of basic conventions such as C. 155 (Occupational Safety and Health Convention) and C. 148 (Working Environment Convention), neither of which is ratified by Japan, should be prioritized to further promote ratification status in the OSH area.

International Agencies↗

[Intermittent-dose ara-C/daunomycin therapy combined with cyclosporin-A and G-CSF led to a fourth remission in a patient with acute promyelocytic leukemia].

A 50-year-old female was admitted with acute promyelocytic leukemia (APL) in August, 1988. She was treated with behenoyl-ara-C, daunomycin, 6-mercaptopurine and prednisolone (BH-AC.DMP), which led to a complete remission. Thereafter, she was treated with 2 courses of BH-AC.DM and discharged from hospital. Intensification therapy was performed twice a year, with 1 course of BH-AC.DM and 5 courses of intermittent-dose ara-C/mitoxantrone which ended in March, 1992. She had a relapse in September, 1993 and was treated with all-trans retinoic acid, which led to a second remission. A second relapse occurred in May, 1994, and intermittent-dose ara-C/mitoxantrone, combined with granulocyte colony-stimulating factor (G-CSF), led to a third remission. However, she had a third relapse in September, 1994. She was treated with a trial of G-CSF (300 micrograms/body, day 1-7), to stimulate dormant leukemic cells to enter the cell cycle, and cyclosporin-A (78 mg/kg, day 2-5), in order to overcome daunomycin resistance in refractory leukemia, combined with daunomycin (45 mg/m2, day 3-5) and ara-C (1.4 g/m2, day 3-7), after obtaining informed consent. The fourth remission needed 46 days after combination chemotherapy because of severe myelosuppression. It was suggested that intermittent-dose ara-C/daunomycin therapy combined with G-CSF and cyclosporin-A may be useful for relapsed and refractory leukemia.

Antineoplastic Combined Chemotherapy Protocols↗

[Three cases of adult intrapulmonary sequestration].

Three cases of adult intrapulmonary sequestration were presented. They were all females ranging from 22 to 49-year-old (mean age 35 yrs.). Chest X-rays showed abnormal shadows in the right or left lower lobe. Aortograms showed aberrant arteries in each cases, and the diagnosis of pulmonaly sequestration was made preoperatively. Lobectomies were performed in all cases because of recurrent bronchopulmonary infections. We could not classify our cases based on Pryce's classification by unclear margins between sequestrated lungs and normal pulmonary tissues. All cases had no histories of infantile bronchopulmonary infections which supported the theory of acquired origin.

Adult↗

Successful pregnancy after allogeneic bone marrow transplantation following conditioning with total body irradiation.

A 23-year-old woman had a normal full-term delivery 78 months after BMT for ALL. Conditioning therapy was Ara C 1.4 g/m2 x 4, CY 60 mg/kg x 2 and TBI 2.5 Gy x 5 at a dose rate of 3.5 cGy/min. Despite GVHD prophylaxis with short-term MTX and CsA, she developed grade I acute GVHD, but showed no evidence of chronic GVHD. Following amenorrhea for 4 years, menstruation recommenced spontaneously. She had a normal pregnancy 6 years after BMT resulting in a healthy infant with simple hypospadias. This and previous reports indicate that normal pregnancy is possible after BMT with TBI in excess of 10 Gy.

Acute Disease↗

[Hypoplastic leukemia achieved long-term remission with low-dose cytosine arabinoside].

A 74-year-old woman was admitted in October 1988 with anemia and leukocytopenia. Hematologic investigations established a diagnosis of hypoplastic acute leukemia. She received a low dose of cytosine arabinoside (LDAC: 10 mg/m2 every 12 hours) subcutaneously for 21 days and achieved complete remission (CR) one month later. After one course of LDAC of 14 days, she received LDAC of 21 days every 5 to 6 months as maintenance therapy till April 1993. She has been in remission for 6 years. Intensification therapy with LDAC every 5 to 6 months might be useful in maintaining remission for hypoplastic acute leukemia.

Aged↗

p53 gene mutation and loss of heterozygosity are associated with increased risk of disease progression in adult T cell leukemia.

Although the prototype of adult T cell leukemia (ATL) is an aggressive T cell neoplasm, ATL manifests four major clinical subtypes, acute, lymphoma, chronic, and smoldering. We studied the relationship between p53 gene alteration and clinical features in 34 patients with ATL, 14 acute type, 15 chronic type, and five crisis type transformed from chronic type. Using a polymerase chain reaction/single strand conformation polymorphism (PCR/SSCP) assay, followed by nucleotide sequencing, we detected mutations of the p53 gene in six of the 14 acute type patients, two of the five crisis type, and one of the 15 chronic type patients. Gene dosage studies, using PCR amplification and Southern blotting, showed loss of heterozygosity (LOH) of the p53 gene in four of the 14 acute type patients, two of the five crisis type, and one of 14 chronic type patients examined. These observations indicated that the frequency of p53 gene alterations in the acute and crisis types of ATL was markedly higher than that in chronic type, suggesting that p53 gene alteration plays a role in the disease progression of ATL.

Adult↗

[Optic neuropathy in systemic lupus erythematosus (SLE)--analysis of 54 cases including our case].

A 46-year old woman with systemic lupus erythematosus (SLE) who had been treated with oral administration of prednisolone (7.5 mg/5 mg on alternate days) at our outpatient clinic suddenly developed a loss of visual acuity, visual field defect, and photophobia on Dec. 15th, 1993. When she was admitted three days later, she was diagnosed as having optic neuropathy, and immediate treatment with methylprednisolone (1 g/day for three days) followed by prednisolone (50 mg/day) resulted in complete disappearance of the above symptoms by Feb. 9th, 1994. As far as we know, fifty-three cases of SLE with optic neuropathy have been reported previously. The result of analysis of the 54 cases including our case indicates that rapid diagnosis and corticosteroid treatment in an early phase of optic neuropathy leads to significant improvement.

Female↗