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Biomedical subjects

T Okubo

Publications and source records attributed to T Okubo.

At least 217 records · Page 12Linked to original sources

Pure red cell aplasia after major ABO-incompatible bone marrow transplantation: two case reports of treatment with recombinant human erythropoietin.

A 34-year-old man with acute myelocytic leukemia (AML: MO) and a 32-year-old woman with AML: M2 developed pure red cell aplasia (PRCA) after receiving a major ABO incompatible bone marrow transplant (BMT). The first patient responded to recombinant human erythropoietin (rhEPO) therapy, while the second did not. The second patient also received methylprednisolone (m-PSL) but developed reticulocytosis and hemolysis after the administration of m-PSL. Plasmapheresis was then performed and the patient promptly recovered from hemolysis and PRCA. We conclude that close attention must be paid when treating PRCA following major ABO-incompatible BMT with rhEPO and m-PSL, as there is always the potential for massive hemolysis.

ABO Blood-Group System↗

DNA topoisomerase II inhibitors enhance random integration of transfected vectors into human chromosomes.

To study the involvement of DNA topoisomerase (topo) II on nonhomologous (illegitimate) recombination, we examined the effect of topo II inhibitors on random integration of exogenous vectors into human chromosomes. We transfected human cell lines PA1, HeLa and EJ-1 with linearized plasmid pSV2neo by electroporation, treated with topo II inhibitors and determined the frequency of Geneticin-resistant (G418r) colonies. We found that three topo II inhibitors, etoposide (VP-16), ICRF-193 and amsacrine (m-AMSA), greatly enhanced the frequency of G418r colonies. These effects were maximally expressed by as little as 12 hrs treatment with the drugs. Similar enhancements were found with different vectors (closed-circular and linear), different cell types, or by different transfection methods (calcium precipitation and lipofection). In contrast, the inhibitor treatments did not affect the transient expression of chloramphenicol acetyltransferase and beta-galactosidase activity following transfection with pSV2CAT and pCH110, respectively. Southern blot analysis revealed that the integration pattern of transfected pSV2neo into PA1 chromosomes was random and not characteristic for each inhibitor. These results suggest that topo II inhibitors directly act at a nonhomologous recombination reaction, promoting the integration process of transfected vectors into human chromosomes. We discuss the enhancement mechanism with a special emphasis on DNA strand breaks induced by the inhibitors.

Amsacrine↗

Surgical treatment of a sacral nerve root cyst with intermittent claudication in an 85-year-old patient: case report.

The following presents a case of an 85-year-old woman with intermittent claudication of a sacral nerve root cyst. The cyst wall was incised and oversewn while preserving the surrounding nerve fibers by microscopic procedures. All symptoms were eliminated following the operation. The syndrome of intermittent claudication may possibly arise while walking from the transient influx of cerebrospinal fluid into a cyst in a relatively narrow sacral canal. The present case may indicate that a sacral nerve root cyst is curable even in aged patients through thorough evaluation and management.

Age Factors↗

Novel synthetic peptides from the C-terminal heparin binding domain of fibronectin with heparin binding activity.

To identify a minimal peptide ligand that participates in recognition of heparin, we synthesized peptides extending a 29-kDa fragment in the C-terminal heparin binding domain of fibronectin. We obtained evidence that two peptides (designated D5 and D1) exhibit inhibitory activity on binding of the 29-kDa fragment to heparin-Sepharose CL 6B. It dose inhibitory studies, peptide D5 showed the potent inhibitory activity with IC50 of 210 +/- 37 microM. A new heparin binding site in the C-terminal heparin binding domain of fibronectin is demonstrated and provides a rationale for understanding the mechanism of cell adhesion and spreading.

Binding Sites↗

Expression of an epithelial membrane glycoprotein by neurons arising from the human olfactory plate through development.

Human terminal-vomeronasal neural crest cells began to express a 34,000 molecular weight epithelial membrane glycoprotein, which was detected by the mouse monoclonal antibody Ber-EP4 soon after their migration into the olfactory plate. Expression of this antigen continued in neurons arising from these cells, which were olfactory sensory neurons and luteinizing hormone-releasing hormone-producing neurons migrating into the brains of the embryos of approximately 44-52 postovulatory days. Ber-EP4 immunoreactivity appeared over the entire surface membranes of these neurons, including their processes, not only in their extracerebral portions, but also within the brain parenchyma from 48 to 53 postovulatory days. Ber-EP4 immunoreactivity of these migrating neurons became weaker as they matured into luteinizing hormone-releasing hormone-producing neurons and disappeared from the postnatal hypothalamic neurons; however, it remained in the primary sensory nerve fibers throughout postnatal life. Except for the neurons arising from the olfactory plate, no other human neurons express this epithelial antigen during the course of development. The mechanism and significance of the expression of this antigen in mature sensory neurons remains unclear, but the intramucosal location and morphological kinship of these neurons to epithelial cells may be related to this phenomenon. The results of the present study indicate that neurons arising from the olfactory plate are distinct from other neurons by having a 34,000 molecular weight epithelial membrane glycoprotein that can be detected by the mouse monoclonal antibody, Ber-EP4, during the embryonic stage. This antigen disappears from the luteinizing hormone-releasing hormone-producing neurons concomitant with maturation, but is preserved in the olfactory primary sensory nerve throughout postnatal life.

Antibodies, Monoclonal↗

Human herpesvirus-6-associated exanthema in a patient with acute lymphocytic leukaemia.

SUMMARY: We report the first case of human herpesvirus-6 (HHV-6) associated exanthema in a patient with acute lymphocytic leukaemia (ALL). We analysed DNA extracted from an exanthematous lesion using the polymerase chain reaction (PCR). DNA was positive for HHV-6 but negative for herpes simplex virus, varicella zoster virus, and cytomegalovirus. Immunohistochemical staining of the skin with monoclonal antibody against (HHV-6 confirmed the infection. The possibility of HHV-6 infection should be considered when an atypical skin rash is seen in patients with ALL.

Adult↗

Detection of genes regulating beta-lactamase production in Enterococcus faecalis and Staphylococcus aureus.

Four beta-lactamase-producing clinical isolates (WH245, WH257, CH570, and DEL) of Enterococcus faecalis were examined for the presence of the staphylococcal beta-lactamase regulatory genes (blaR1 and blaI) by PCR using six primer pairs. All isolates produced small amounts of beta-lactamase constitutively. In WH245, CH570, and DEL, the corresponding regions of the regulatory genes have lost sequences of various lengths. However, the regulatory genes in WH257 appeared to be the same as those in staphylococcal plasmid pI258. The beta-lactamase genes could be transferred to enterococcal and staphylococcal recipients from WH257 and DEL by conjugation or transformation with selection for gentamicin resistance. After transformation, the expression of beta-lactamase from DEL was still constitutive, whereas the gene from WH257 showed inducible expression in Staphylococcus aureus. The gene coding for inducible beta-lactamase production from pI258 showed constitutive expression in E. faecalis. These findings suggest that constitutive beta-lactamase production in E. faecalis is due not only to the absence of functional regulatory genes but to some other factor(s) as well.

Conjugation, Genetic↗

A bibliometric study of the trend in articles related to epidemiology published in occupational health journals.

OBJECTIVES: To study the role assumed by epidemiology in occupational health literature and characterise its change over the years. METHODS: A bibliometric study was conducted with a MEDLINE search to evaluate 9024 articles published in eight representative occupational health journals for the period 1980-93. Articles related to epidemiology were found by descriptors indexed in the articles and their numbers and proportions among all published articles was tabulated for the study period. RESULTS: The proportion of source items indexed by epidemiology as a descriptor increased over threefold from 7.9% (42/534) in 1980 to over 25% after 1990. Epidemiology was indexed most frequently as a subheading associated with other descriptors-for example, occupational diseases-epidemiology. Cohort studies had the largest increase in the descriptors that indicated epidemiological type of studies during the period studied. CONCLUSION: Epidemiology is assuming increasing importance in occupational health literature. This was shown quantitatively and qualitatively by the use of descriptors in the MEDLINE database.

Abstracting and Indexing↗

Effects of surfactant on the in vivo alveolar surface-to-volume ratio.

To investigate how pulmonary surfactant influences alveolar structure in vivo, we examined the alveolar surface area-to-lung volume (S/V) ratio of the lung parenchyma of a live dog by light-scattering stereology before and after saline lavage. We measured the backscattered light pattern produced by applying a laser beam to the pleural surface of a ventilated animal and obtained the S/V [equivalent to the inverse of the optical mean free path (lambda)]. After saline lavage, V at transpulmonary pressure (P) of 30 cmH2O (defined as total lung capacity) decreased by 11.1 +/- 3.1% (SD) and the P-V curve shifted to a lower V. The lambda-V curve was shifted to a higher lambda and to a lower V after saline lavage. S/V decreased after saline lavage (lambda increased by 38 +/- 27% on the deflation limb at a V of 80% of control total lung capacity). The alveolar surface tension increased after saline lavage, and the increase in surface tension was greater on inflation than on deflation. We conclude that depletion of pulmonary surfactant increases the alveolar surface tension in vivo, resulting in a decrease in S/V.

Animals↗

Effects of fenoterol on inspiratory effort sensation and fatigue during inspiratory threshold loading.

We studied the effects of a single dose of fenoterol on the relationship between inspiratory effort sensation (IES) and inspiratory muscle fatigue induced by inspiratory threshold loading in healthy subjects. The magnitude of the threshold was 60% of maximal static inspiratory mouth pressure (PI,mmax) at functional residual capacity, and the duty cycle was 0.5. Subjects continued the threshold loaded breathing until the target mouth pressure could no longer be maintained (endurance time). The intensity of the IES was scored with a modified Borg scale. Either fenoterol (5 mg) or a placebo was given orally 2 h before loading in a randomized double-blind crossover protocol. The endurance time with fenoterol (34.4 +/- 8.6 min) was longer than that with the placebo (22.2 +/- 7.1 min; P < 0.05). The ratio of high- to low-frequency power of the diaphragmatic electromyogram (EMGdi) decreased during loading; the decrease was less with fenoterol (P < 0.05). The EMGdi also decreased with loading; the decrease was greater on fenoterol treatment (P < 0.01). The PI,mmax and maximal transdiaphragmatic pressure (Pdi) were similarly decreased after loading on either treatment. The intensity of the IES rose with time during loading in both groups but was lower with fenoterol than with the placebo (P < 0.05). The ratio of Pdi to integrated activity of the EMGdi increased with fenoterol (P < 0.05). Fenoterol treatment increased both superimposed Pdi twitch and Pdi twitch of relaxed diaphragm and decreased the value of (1-superimposed Pdi twitch/Pdi twitch of relaxed diaphragm). Thus we conclude that in normal subjects fenoterol reduces diaphragmatic fatigue and decreases the motor command to the diaphragm, resulting in a decrease in IES during inspiratory threshold loading and a prolongation of endurance.

Adult↗

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↗

Estimation of the optimal cut off point in a new immunological faecal occult blood test in a corporate colorectal cancer screening programme.

OBJECTIVE: To estimate the optimal cut off point in a new immunological method (OC-Hemodia) for faecal occult blood testing (FOBT). SETTING: A corporate colorectal cancer screening programme in Japan. METHOD - The screening programme targeted colorectal cancer and adenomatous polyps > or = 10 mm, and was conducted on 27 860 participants (age > or = 40 ) during 1991-92. The follow up consisted of diagnostic management by total colonoscopy on positive screened subjects exceeding the manufacturer recommended cut off level of 50 ng/ml faecal haemoglobin, and the identification of false negative cases by health insurance claims. The optimal cut off point was estimated by the positive predictive value, receiver operating characteristic (ROC) curve, and a cost effectiveness analysis. In this study evaluation was carried out only for cancer as the target disease. RESULTS: - At the current cut off level of 50 ng/ml the sensitivity and specificity were 86.5% and 94.9%. When the optimal cut off point was estimated the highest positive predictive value was obtained at 250-350 ng/ml. The ROC curve showed that the sum of sensitivity and specificity is maximised at 50 ng/ml, but evaluation of the ratio, change in sensitivity/change in false positive rate, pointed to higher optimal cut off points, showing marked changes occurring at about 200 ng/ml. The average cost per case was lowest at 250-300 ng/ml. Overall, the optimal cut off point was estimated to be about 200 ng/ml, at which the sensitivity and specificity of the test would be 77.5% and 98.9%, respectively. CONCLUSION: The optimal cut off point of the new immunological method of FOBT was estimated to be about 200 ng/ml, a value which, more than the current cut off value, favours specificity over sensitivity.

Adenoma↗

Effect of estrogen replacement therapy on hepatic triglyceride lipase, lipoprotein lipase and lipids including apolipoprotein E in climacteric and elderly women.

Estrogen provides beneficial effects on hyperlipidemia in climacteric and elderly women. In this study of 68 women (37 to 67 years old), hepatic triglyceride lipase (HTGL), lipoprotein lipase (LpL) serum lipids and apolipoproteins were analyzed to investigate the effects of estrogen replacement therapy (ERT). After menopause, LpL, total cholesterol, low-density lipoprotein (LDL)-cholesterol, and apolipoprotein B increased. But ERT suppressed total cholesterol, LDL-cholesterol, apolipoprotein B, and especially apolipoprotein E in menopausal women. The mechanism was thought that ERT significantly suppressed HTGL, but LpL was not affected. Estrogen also increases hepatic LDL receptors and accelerates transfer of serum LDL-C (and TC). It was said that HTGL accelerates conversion of intermediate-density lipoprotein (IDL) to LDL. The suppression of HTGL by the ERT may decrease conversion of IDL to LDL and lower LDL-C (and TC). These estrogen's beneficial effects on lipids, may prevent the atherosclerosis. In addition, apolipoprotein E increases senile plaques in senile dementia-Alzheimer's type. The decrease in apolipoprotein E with ERT may be related to cognitive functions of elderly women.

Adult↗

Lymphoproliferative disorder of granular lymphocytes (natural killer cell type) with interstitial pneumonia in a patient with familial pancytopenia.

A 50-year-old woman is presented here with natural killer (NK) cell type lymphoproliferative disorder of granular lymphocytes. She was admitted to the hospital because of dyspnea on exertion. Chest X-ray revealed bilateral reticular shadows. Open lung biopsy demonstrated usual interstitial pneumonia (UIP). Her white blood cell count was 3,900/mm3, of which 55% was large granular lymphocytes (LGLs). The LGLs were CD3- CD16+CD56+, and the clonality of them was not confirmed. Despite steroid therapy, she died from exacerbation of UIP complicated with opportunistic infection. The patient, her father and son had pancytopenia. Congenital immunological abnormality might cause both large granular lymphocytosis and UIP.

Female↗

A human T-cell lymphotropic virus type-I carrier with chronic renal failure, aplastic anemia, myelopathy, uveitis, Sjögren's syndrome and panniculitis.

A 53-year-old female infected with human T lymphotropic virus type-I (HTLV-I) suffered from chronic renal failure, aplastic anemia, myelopathy, uveitis, Sjögren's syndrome and Weber-Christian disease. Although HTLV-I antibody was negative in cerebrospinal fluid, she was diagnosed as HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP) based on clinical and histological findings. Though to date there is no direct evidence, other complications have also been reported to be HTLV-I related diseases. This case provided the unique opportunity to observe various HTLV-I related diseases.

Anemia, Aplastic↗

[Successful therapy with cyclosporine in a case with interstitial pneumonitis associated with polymyositis].

We describe a case of interstitial pneumonitis associated with polymyositis who responded well to cyclosporine therapy. In October, 1993, a 49-year-old female was admitted to our hospital because of fever, muscle weakness and progressive dyspnea. Interstitial pneumonitis with polymyositis was diagnosed and daily oral steroid therapy was started. As the therapy was ineffective, pulse intravenous steroid therapies followed by oral cyclophosphamide and steroid therapy was given. Whereas serum levels of muscle enzymes decreased, she became progressively hypoxemic. No effect was observed in series of therapy including additional pulse steroid therapy, pulse intravenous cyclophosphamide therapy, oral azathioprine and oral bethametazone therapy. In April, 1994, oral cyclosporine was started. After daily oral cyclosporine was combined with steroid, her symptoms, chest X-ray, chest CT and pulmonary function tests significantly improved. Her disease became stable and there was no signs of recurrence since then. It is suggested that cyclosporine is useful for the treatment of progressive interstitial pneumonitis associated with polymyositis.

Cyclosporine↗

Effects of weight cycling on coronary risk factors.

Interest in the health hazards of weight loss and regain (weight cycling) is growing. This study examined the relationship between weight cycling during ages 21 to 35 and changes in coronary risk factors (systolic blood pressure, diastolic blood pressure, total cholesterol, and HDL cholesterol) during ages 35 to 40. We followed up 264 blue-collar workers from the time they were 21 to 40 years of age working for one company. Analysis of covariance was applied including the number of weight cycles during ages 21 to 35 as the independent variable and the changes in coronary risk factors between age 35 and 40 as the dependent variables. The covariates were adjusted for body mass index (BMI) at age 35, increase in BMI between ages 35 and 40, value of coronary disease risk factors at age 35, and smoking status at age 40. The results showed that increase in systolic and diastolic blood pressure was not significantly related to the number of weight cycles. For total and HDL cholesterol, interaction was seen between smoking status and the number of weight cycles, and the effects of weight cycle on cholesterol levels were examined by smoking status. The change in total cholesterol among frequent cyclers was not significantly different from that among non-cyclers. Though the increment of HDL cholesterol in frequent cyclers was significantly larger than that in non-cyclers for non-smokers, an inverse relationship was seen for heavy smokers (not significant). Our results showed the effects of weight cycling on changes in coronary risk factors only for HDL cholesterol based on analysis by smoking status. As the present study was conducted on a small population, interaction between weight cycling and smoking status on HDL cholesterol should be confirmed using a larger population.

Adult↗

Effect of mizoribine on pulmonary lesions in MRL/lpr/lpr mice.

The present study was made to investigate the effect of mizoribine (MZR), an imidazole nucleoside immunosuppressant, on pulmonary lesions and immunological mode of action of MRL/lpr/lpr mice. Four-week-old female MRL/lpr/lpr mice were injected subcutaneously with 20 mg/kg body weight of MZR every other day. For control, mice were given phosphate-buffered saline (PBS) every other day. MZR caused the delay in the histological development of peribronchial and perivascular lymphocytic infiltrations in the lungs of MRL/lpr/lpr (MRL/lpr) mice. And then, MZR suppressed the number of immunoglobulin (Ig) (IgG and IgM) secreting B cells and anti-DNA-secreting B cells in the spleen of MRL/lpr/lpr mice. The above data indicate that MZR could be useful for the treatment of pulmonary lesions associated with autoimmune disorders such as systemic lupus erythematosus (SLE).

Animals↗