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Biomedical subjects

H Takashima

Publications and source records attributed to H Takashima.

At least 163 records · Page 9Linked to original sources
PubMed1991

Highly potent and selective inhibition of human immunodeficiency virus type 1 by a novel series of 6-substituted acyclouridine derivatives.

In the search for novel derivatives of 1-[2-(hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT), we have found that several 5-ethyl-6-(3,5-dimethylphenylthio)uracil and 5-ethyl-6-(3,5-dimethylbenzyl)uracil analogues are exquisitely potent and selective inhibitors of human immunodeficiency virus type 1 (HIV-1) replication in a variety of cell culture systems. Of this series, 5-ethyl-1-ethoxymethyl-6-(3,5-dimethylbenzyl)uracil (E-EBU-dM) emerged as the most active congener. Its 50% inhibitory concentration for HIV-1 (HTLV-IIIB) in MT-4 cells and peripheral blood lymphocytes is 2.2 and 0.45 nM, respectively. These concentrations are more than 10(5)-fold lower than the 50% cytotoxic concentrations of E-EBU-dM for the host cells. All compounds proved equally inhibitory to a number of clinical HIV-1 isolates, including a 3'-azido-2',3'-dideoxythymidine-resistant variant. However, as previously noted for HEPT, they do not inhibit human immunodeficiency virus type 2 replication. Reverse transcriptase assays have revealed that these HEPT derivatives act specifically on HIV-1 reverse transcriptase, according to a mechanism that is different from that of the dideoxynucleosides.

Antiviral Agents↗
PubMed1990

Impairment of cell-mediated immune responses in HTLV-I-associated myelopathy.

In order to assess in vivo cell-mediated immune functions in HTLV-I-associated myelopathy (HAM), we immunized 18 HAM patients with dinitrochlorobenzene (DNCB). Of 18 patients, the skin reaction to DNCB was negative in 15. All those 15 patients also showed anergy to PPD-tuberculin and 9 of 15 patients had a persistent lymphocytopenia (less than 1500/mm3). In vitro lymphoproliferative responses to mitogens, assayed by a flow fluorocytometric method, were also significantly depressed in HAM patients when compared to normal controls. The results thus indicate that cell-mediated immune functions are significantly impaired in HAM patients.

Deltaretrovirus Antibodies↗
PubMed1990

Anti-human immunodeficiency virus type 1 activities and pharmacokinetics of novel 6-substituted acyclouridine derivatives.

The novel 6-substituted acyclouridine derivatives 1-[(2-hydroxyethoxy)methyl]-6-phenylthiothymine (HEPT), 1-[(2-hydroxyethoxy)methyl]-6-(3-methylphenylthio)thymine (HEPT-M), 6-cyclohexylthio-1-[(2-hydroxyethoxy) methyl]thymine (HEPT-H), and 1-[(2-hydroxyethoxy)methyl]-6-phenylthio-2- thiothymine (HEPT-S) have proved to be potent and selective inhibitors of human immunodeficiency virus type 1 (HIV-1) replication in a variety of cell systems, including peripheral blood lymphocytes. They are not inhibitory to the replication of HIV-2. HEPT-S emerged as the most active congener, with a 50% inhibitory concentration of 1.6 microM for HIV-1 (human T-cell lymphotropic virus type IIIB) in MT-4 cells. We also examined the pharmacokinetics of the compounds following oral administration to rats. The pharmacokinetic profile varied considerably from one compound to another. The highest concentration in plasma (7.4 micrograms/ml, or 22.8 microM) was achieved by HEPT-S within 30 min after administration of an oral dose of 20 mg/kg of body weight. HEPT-S can be considered a promising candidate for the treatment of HIV-1 infections.

Animals↗
PubMed1990

[Treatment of HTLV-I-associated myelopathy with alpha-interferon and high-dose of gamma-globulin].

We administered alpha-interferon (alpha-IFN) and gamma-globulin (gamma-gl) to patients with HTLV-I-associated myelopathy (HAM). Patients selected for this study fulfilled the diagnostic criteria of HAM by Osame et al. As for alpha-IFN, 12 patients were injected intramuscularly with a dose of 3 X 10(6) IU/day of alpha-IFN for 28 days. As for gamma-gl, 10 patients were injected intravenously with a dose of 10 g/day of human gamma-gl for 5 days. alpha-IFN exerted therapeutic effects in 7 of 12 patients and gamma-gl in 6 of 10. The therapeutic effects were shown by the improvement in time for a 20-meter walk, muscle power of lower limbs and urinary frequency. All patients having a history of improvement by corticosteroid therapy showed beneficial responses to both treatments with alpha-IFN and gamma-gl. Contrarily, patients who had not improved by corticosteroid therapy did not show any improvement after gamma-gl and alpha-IFN administration. The therapeutic effects of gamma-gl and alpha-IFN were observed predominantly in cases with shorter duration of illness, more marked abnormality in cerebral MRI findings and higher CSF antibody titers to HTLV-I. There was no correlation between the therapeutic efficacy and clinical severity or serum antibody titers to HTLV-I. We conclude that therapies with alpha-IFN and gamma-gl were safe and effective for the treatment of HAM.

Adult↗
PubMed1990

Synthesis of novel 6-substituted acyclouridine derivatives and their anti-HIV-1 activity.

To improve the anti-HIV activity of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT), a variety of its analogues were synthesized. Introduction of SR group to the C-6 position was carried out based on LDA lithiation followed by the reaction of aryl- or alkyl disulfide. An addition-elimination reaction of a 6-phenylsulfinyl derivative was used for synthesizing the analogues having OR or NHR group at the C-6 position. The C-5 modified derivatives were synthesized mainly based on LTMP lithiation of a 6-phenylthio derivative. Modification at the 2- or 4-position was also carried out. Some compounds prepared in the present study showed higher activity than HEPT.

Antiviral Agents↗
PubMed1990

[A case of food-dependent-exercise induced anaphylaxis possibly induced by shellfish (Sulculus Supertexta and Turbo Cornutus)].

A 17 years old girl experienced an anaphylactic reaction of urticaria, dyspnea, syncope and hypotension while riding a bicycle 55 minutes after eating shellfish Lapas shellfish which was a-like Sulculus Supertexta (SS). She recovered within several hours after the emergency treatment. Another attack occurred 3 months later while she was running with a dog 30 minutes after eating shellfish (Turbo Cornutus; TC). RAST scores were 4 for Lapas and 2 for TC. RAST inhibition test by ELISA showed a high crose-reaction between keyhole limpet hemocyanin (KLH) and Lapas, and between KLH and TC, while the cross reaction between Lapas and TC was low. Gel chromatography with sephacryl G-200 revealed that both Lapas and TC had several allergens with different molecules which were detected by ELISA. Exercise challenge produced an immediate fall of FEV1 and a significant increase in plasma histamine levels for 45 minutes.

Adolescent↗
PubMed1990

Hemodynamic response to ibopamine in acute myocardial infarction.

To determine the effects of ibopamine on hemodynamic parameters, 9 patients with cardiac dilation after acute myocardial infarction were studied. Although there were no significant changes in mean blood pressure, heart rate and rate pressure product after administration of ibopamine, cardiac index and urine volume increased significantly. These data indicate that ibopamine exerts a positive inotropic effect on the myocardium and vasodilating effect on renal vasculature without increasing myocardial oxygen consumption. However, pulmonary capillary wedge pressure increased significantly at 30 min after ibopamine and decreased to the control value at 120 min. A significant increase in heart rate was observed in 3 patients which was followed by chest pain. In addition to increase in cardiac contractile force and decrease in subendocardial perfusion from elevated left ventricular end diastolic pressure, increase in heart rate would decrease diastole time, while increase in oxygen consumption results in aggravation of ischemia especially in patients with multivessel coronary disease. From these findings it is considered that ibopamine should be administered with care to patients with multivessel coronary disease.

Aged↗
PubMed1989

Oxygen delivery, oxygen consumption and hemoglobin-oxygen affinity in acute myocardial infarction.

The interrelations of oxygen delivery (DO2), oxygen consumption (VO2) and hemoglobin-oxygen affinity assessed by P50 were investigated in 43 patients with acute myocardial infarction. As DO2 declined due to low cardiac output, a significant decrease in VO2 (r = 0.75, p less than 0.001) and a significant increase in P50 (r = -0.74, p less than 0.001) were observed. In the DO2 range between 300 and 450 ml/min/m2, in which the DO2 of 32 survivors and 11 nonsurvivors overlapped, the P50 of nonsurvivors was significantly higher than that of survivors (31.5 +/- 1.6 vs 27.9 +/- 1.5 torr, p less than 0.001), but there were no significant differences in any other oxygen transport variable. As a result of differences in P50, VO2 in this range was significantly higher in nonsurvivors compared to survivors (169 +/- 17 vs 148 +/- 13 ml/min/m2, p less than 0.001). These data suggest that a normal or increased VO2 alone does not ensure survival in patients with acute myocardial infarction, and increased P50 leads to an increase in VO2. Nevertheless, the interpretation of an increased P50 in patients with acute myocardial infarction must be made with caution, even with adequate DO2 and VO2, because it may imply a precarious oxygen transport/requirement balance in peripheral tissue and, hence, a fatal outcome.

Aged↗
PubMed1989

Clinical values for an index predicting postoperative residual liver function by pre-operative liver-scintigraphy in patients with liver disease.

Hepatic resection is essential in treating hepatocellular carcinoma. However, before an operation, it is difficult to predict the functional reserve in the remnant following massive resection. We devised an original method by which effective liver volume was measured by liver scintigraphy. In order to predict the residual liver function before hepatic resection in a preoperative radiocolloid study, we obtained a predictive index by combining the K values with effective liver volumes which seemed to have the estimated residual liver function. Twenty-one patients with liver or biliary tract disease were selected at random for the present study. We divided them into 3 groups in accordance with prognosis after hepatic resection. There were statistically significant difference between the deceased group who died from hepatic failure and the group who died from causes other than hepatic failure; and between the deceased group who died from hepatic failure and the living group in the preictive index (p less than 0.01). Our data suggest that if the predictive index is above 0.45, the probability of hepatic failure after hepatic resection is low. We concluded that our predictive index is useful to use in preoperative prediction of post-hepatectomic residual liver function.

Aged↗
PubMed1989

Simultaneous measurement of alpha-human atrial natriuretic factor (hANF) and NH2-terminal fragment of pro-hANF in essential hypertension.

A radioimmunoassay specific for the N-terminal fragment of prohuman atrial natriuretic factor (hANF) was established with the use of antiserum for pro-hANF (1-30). Plasma levels of alpha-hANF-like immunoreactivity (LI) and pro-hANF (1-30)-Ll in patients with severe hypertension who were receiving a normal sodium diet were 56 +/- 5 pg/ml and 2710 +/- 118 pg/ml, respectively; these levels were significantly higher than control values. Levels of these peptides in patients with mild hypertension were similar to those of control subjects. Mean blood pressure correlated closely with alpha-hANF-Ll levels (r = 0.56, p less than 0.001) and pro-hANF (1-30)-Ll levels (r = 0.66, p less than 0.001) in patients receiving a normal sodium diet. Plasma alpha-hANF-Ll and pro-hANF (1-30)-Ll levels were significantly decreased 3 days in mild hypertension and 7 days in severe hypertension after initiation of a low-sodium diet with a decrease in blood pressure as compared to the initial values. These results suggest that plasma N-terminal fragment levels are elevated in proportion to the degree of hypertension, and they can be reduced by means of effective antihypertensive treatment.

Adult↗
PubMed1989

Fragile X chromosome in institutionalized male adults with mental retardation.

A clinical and cytogenetical study of mentally retarded male adults with an IQ of below 35 has been carried out in the Ranzan Colony for Mental Retardates, Saitama, Japan. The study showed one fragile X-positive retardate with IQ 23 in the 53 residential retarded patients, giving a hemizygote prevalence of 1.9% (1/53). Macroorchidism and elongated ears, practical markers for the clinical diagnosis of fragile X-linked mental retardation, were also detected in this 43-year-old subject with fra(X)(q27.3). He is amiable and no autistic behavior has been observed. The subject, however, has been suffering from epilepsy since childhood and has cataract in both eyes.

Adult↗
PubMed1989

Clinical study of asthma in adolescents and in young adults. Correlation between laboratory findings and severity of asthma.

Fifty-eight mite-allergic asthmatic patients ages 15 to 22 years were examined. Low respiratory threshold to acetyl-choline (RT-Ach), high maximal histamine release (HR) by mite and anti-IgE, high serum IgE levels and high eosinophil counts were highly associated with the severity of asthma. RT-Ach correlated inversely with HR to mite and anti-IgE. The maximal histamine release from leukocyte caused by anti-IgE also correlated highly with the severity of asthma.

Adolescent↗
PubMed1989

[Outbreaks of asthma attacks and meteorological parameters--multivariate analysis].

The correlation between patient visits and meteorological parameters was analyzed among asthmatic children who visited the out-patient emergency clinic at the Teikyo University Hospital during the three years from 1984 to 1986. Data were analyzed with the method of multivariate analysis (quantification theory type II). The major factors affecting the frequency of visits were an air temperature at more than 15 degrees C, a relative humidity at more than 65%, a vapor pressure at more 1013 mb and a wind speed at less than 3.5 m/sec. Multivariate analysis of seven meteorological parameters, the four parameters shown above plus sea level pressure, cloud density and precipitation, revealed that discrimination ratios with the Lag 3, Lag 2, Lag 1 and Lag 0 values were 63.8%, 68.5%, 68.5% and 63.6%, respectively. These results indicate that asthma forecast is possible by the multivariate analysis of meteorological conditions.

Asthma↗
PubMed1989

[Evaluation of a modified latex agglutination inhibitory reaction method for the quantitation of urinary estriol in pregnant women].

This study evaluated a modified latex agglutination inhibitory reaction method for the quantitation of urinary estriol in women during normal and abnormal pregnancy. The urinary levels of estriol in pregnant women measured by this method correlated with urinary and serum levels measured by radioimmunoassay. The urinary level of estriol rose during pregnancy and reached a peak at the time of delivery, after which it returned to the control level in a few days. In contrast, the urinary level of estriol in women with abnormal pregnancy did not rise during pregnancy. This method is useful to detect impaired function of the placenta in pregnant women.

Estriol↗
PubMed1988

Resistance to ischemic conduction block of the peripheral nerve in hyperglycemic rats: an electrophysiological study.

Resistance to ischemic conduction block (RICB) was studied in rats with streptozotocin (STZ) induced hyperglycemia, hyperglycemia by glucose injection, and glycerin-induced hyperosmolarity. Ischemia was produced by tight ligation at the base of the tail. The time required for nerve action potentials (NAP) to disappear was defined as the disappearance time of NAP (DT-NAP). Both STZ and glucose rats showed a marked prolongation of DT-NAP at 2 hours after injection of STZ (up to 120 minutes) or glucose (up to 95 minutes), as compared with the control rats (less than 45 minutes). Hyperosmolar rats showed no prolongation of DT-NAP. The amplitude of NAP remained at the initial level for at least 2 hours after ligation of the sciatic nerve, whereas NAP disappeared within 45 minutes after ligation of the abdominal aorta. These findings indicate that the RICB can be produced by means of hyperglycemia without the presence of diabetic neuropathy and is the most sensitive indicator of hyperglycemia.

Action Potentials↗
PubMed1988

[The clinical evaluation of the serum SCC antigen levels with "SCC RIABEAD" by immunoradiometric assay].

The clinical significance of serum SCC antigen level was evaluated by the monoclonal antibody method (SCC.RIABEAD Dinabot Co. Ltd). Patients with squamous cell carcinoma showed a high positive SCC antigen level and positive rate elevated with the advance of the clinical stage. The serum SCC antigen level was decreased by treatment, and it increased again before obvious clinical recurrence was recognized. The results suggest that measurement of serum SCC antigen level is useful as a follow up of cancer treatment.

Antibodies, Monoclonal↗