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Biomedical subjects

T Okada

Publications and source records attributed to T Okada.

At least 487 records · Page 27Linked to original sources

Single basic amino acid substitutions at position 302 or 320 in the V3 domain of HIV type 1 are not sufficient to alter the antiviral activity of dextran sulfate and heparin.

The third variable domain (V3 domain) of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp120 contains a substantial number of positively charged amino acid residues. We previously demonstrated that mutation of basic amino acid residues at position 303, 306, 309, 313, and 325 in the V3 domain of HIV-1 strain NL4-3 resulted in a dramatic elimination of both virus infectivity and syncytium-inducing ability. Mutations of arginine at position 302 to serine (R302S) or lysine at position 320 to glutamine (K320Q) had variable effects on infectivity for a panel of T cell lines tested. These mutations are located on opposite sides of the Gly-Pro-Gly-Arg-Ala sequence in the center of the V3 domain. The R302S and K320Q mutations allowed us to determine if these basic residues are important for virus neutralization by polyanionic compounds. Dextran sulfate and heparin inhibited the cytopathogenicities of both mutants for MT-4 cells, although their 50% antiviral effective doses were slightly higher than those required to achieve complete protection against wild-type HIV-1NL4-3 replication. This result emphasizes that the basic amino acids of Arg302 and Lys320 are not essential for the inhibitory effect of dextran sulfate and heparin on HIV-1 infection.

Amino Acid Sequence↗

Origin of CD57+ T cells which increase at tumour sites in patients with colorectal cancer.

Human T cells carrying natural killer (NK) markers, CD57 or CD56 antigens, appear to be distinguishable from other T cell subsets in terms of their granular lymphocyte morphology and their numerical increase in patients with AIDS and in recipients of bone marrow transplantation. At the beginning of this study, we observed that CD57+ T cells as well as CD56+ T cells were abundant at tumour sites in many patients with colorectal cancer. Since all these findings for CD57+ T cells are quite similar to those of extrathymic T cells seen in mice, we investigated how CD57+ T cells are distributed to various immune organs in humans. They were found to be present mainly in the bone marrow and liver, but to be completely absent in the thymus. Similar to the case of extrathymic T cells in mice, they were observed to consist of double-negative CD4-8- subsets as well as single-positive subsets (preponderance of CD8+ cells), and to contain a considerable proportion of gamma delta T cells. These features are striking when compared with those of CD57- T cells, which are characterized by an abundance of CD4+ subsets and alpha beta T cells. Not only at tumour sites but also in the peripheral blood, some patients with colorectal cancer displayed elevated levels of CD57+ cells. These results suggest that CD57+ T cells may be of extrathymic origin, possibly originating in the bone marrow and liver, and may be associated with tumour immunity, similar to another extrathymic population of CD56+ T cells in humans.

Adult↗

A new clustering system for protein sequences and its application to constraints discovery in protein evolution.

A conceptual clustering system, CLUSMOL/S, has been developed to classify protein sequences from a user-defined point of view. Given a grouping of amino acids as a viewpoint, the system constructs taxonomic trees of sequences based on minimum information criterion. Every tree node expresses itself as a generic consensus sequence that consists of specific consensus amino acids insertion/deletion points, and generic amino acids with a specified character. The resulting tree and generic sequences show the similarity-based relationships among sequences and their characteristics. Application to vertebrate cytochromes c yields an acceptable cladrogram only when amino acids are grouped by volume and length of sidechains. The result indicates that the steric factor is the most important constraint in the process of protein evolution.

Amino Acid Sequence↗

Changes in various tissues in the arterial wall of spontaneously hypertensive rats.

1. Using stroke-prone spontaneously hypertensive rats (SHRSP), stroke-resistant spontaneously hypertensive rats (SHRSR) and Wistar-Kyoto rats (WKY), vascular complications and the longevity of rats were investigated. 2. SHRSP aged more than 9.5 months tended to suffer from severe vascular complications such as periarteritis nodosa (PN) of mesenteric artery, while SHRSR very rarely showed severe vascular complications and WKY did not show any complications, because of the different level of systolic blood pressure. 3. Among some tissues PN tended to occur early in the small arteries of the testes and then in mesenteric artery, when these tissues of SHRSP were investigated microscopically. 4. Concerning the influence of systolic blood pressure on arterial smooth muscle layer, the deviation force of this layer was larger in SHRSR compared to WKY (44.7 times in Y axis), which was calculated mathematically and physically using computer analysis. 5. The arterial wall area of PN was enlarged, resulting in the low ratio of lumen/wall. The ratio of arterial lumen/wall was lower in SHRSP when compared to the age-matched WKY. 6. In search for myocardial ischaemia, ECG was recorded. There were positive correlations between PQ interval or SV1 + RV5 and age in the three strains of rats. ST depression more than 1 mm on ECG was most prevalent in old SHRSP, indicating probably the presence of myocardial ischaemia.

Animals↗

Magnesium, calcium and trace elements in spontaneously hypertensive rats.

1. Using three strains, which showed severe hypertension, mild hypertension and normotension, respectively, the relationships between electrolytes or trace elements and vascular complications combined with the factor of ageing were investigated. 2. In ash materials of some tissues old female SHRSP and old WKY showed a decrease of selenium in many tissues when compared to adult female SHRSP and WKY, respectively. 3. In cellular supernatant fraction, SHRSP showed a decrease of magnesium in many tissues and an elevation of the calcium to magnesium ratio when compared to age-matched WKY and SHRSR. 4. In diabetic rats induced by streptozotocin, myocardial magnesium decreased, resulting in an elevation of the myocardial calcium to magnesium ratio. 5. Alpha tocopherol concentration was lower in both the myocardium and cerebrum of old female SHRSR when compared to that of adult female SHRSR. 6. From these findings the elevation of calcium to magnesium ratio was found in old rats and SHRSP, indicating the tendency of tissue deterioration in these rats. 7. Tissue selenium also decreased in old rats and SHRSP and this decrement was probably related to the peroxidation in tissue damage.

Aging↗

Beta-thalassemia with the IVS-I-1 (G-->T) mutation in a Japanese girl.

We analyzed the hemoglobins of a Japanese girl with beta-thalassemia and those of her immediate family. DNA sequencing of the cloned beta-globin gene from this patient revealed a point mutation at the IVS-I position 1 (G-->T). This rare point mutation has been found in Asian Indians, but this is the first reported Japanese case.

Base Sequence↗

Interferon-alpha potentiates priming-dependent FMLP-induced neutrophil superoxide generation in a patient with chronic myeloid leukemia.

A 13 year old girl diagnosed as having chronic myeloid leukemia (CML) was treated with interferon-alpha (IFN-alpha) alone and 4 months later hematological remission was obtained. In the course of the IFN-alpha treatment there was neither infectious sign nor side effects. In this study we have examined the effect of IFN-alpha on superoxide O2- generation by polymorphonuclear neutrophils (PMN). The PMN of the patient generated less O2- than PMN from normal controls. When patient PMN were cultured in the presence of 1000 U/mL IFN-alpha, enhancement of the formyl-methionyl-leucyl-phenylalanine induced O2- generation following priming with tissue necrosis factor-alpha was observed. Over the course of the IFN-alpha therapy, such O2- generation was gradually restored. It is suggested that CML PMN are in the resting condition in terms of their ability to generate O2- and that IFN-alpha is effective in inducing O2- generation by CML PMN.

Adolescent↗

Bronchial hyper-responsiveness to inhaled histamine in children with congenital heart disease.

In order to assess bronchial responsiveness in patients with congestive heart failure secondary to congenital heart disease, we performed a histamine inhalation test while monitoring transcutaneous oxygen tension and compared the respiratory threshold to histamine with that obtained in patients with bronchial asthma. The inhalation test was performed by doubling concentrations of histamine solution for 2 min at 1 min intervals. The respiratory threshold of histamine was defined as the minimal concentration causing a drop in transcutaneous oxygen tension greater than 10% from baseline. Six of 10 patients with congenital heart disease and all of 12 patients with bronchial asthma had bronchial hyper-responsiveness to histamine. The mean of histamine concentration was 2750 micrograms/mL and 937 micrograms/mL, respectively. During the histamine inhalation test, respiratory resistance gradually increased in congenital heart disease patients. This was measured by the linear slope of transcutaneous oxygen pressure (-1.08 +/- 0.75 mmHg/min), whereas in the bronchial asthma patients it rapidly decreased at the infection point (-4.19 +/- 1.86 mmHg/min). We conclude that children with congestive heart failure had bronchial hyper-responsiveness. We suggest bronchial hyper-responsiveness to inhaled histamine in congestive heart failure was caused by the gradual increased respiratory resistance, which was different from that of bronchial asthma.

Blood Gas Monitoring, Transcutaneous↗

Lipoprotein (a) and apolipoprotein A-1 and B in schoolchildren whose grandparents had coronary and cerebrovascular events: a preliminary study of 12-13 year old Japanese children.

The aim of this study was to evaluate the relationship between the serum levels of lipoprotein (a) [Lp (a)] and apolipoproteins (apo A-1 and apo B) in schoolchildren with a history of coronary and cerebrovascular events in their grandparents. We measured serum concentrations of Lp (a) and apoliproteins immunochemically in 289 schoolchildren aged 12-13 years and questioned parents about coronary and cerebrovascular events in the children's grandparents. In boys and girls, mean +/- s.d. levels of apo A-1, apo B and Lp (a) were 134 +/- 20.3 and 136 +/- 17.4 mg/dL, 61 +/- 16 and 66 +/- 15 mg/dL and 12.5 +/- 15.3 and 12.5 +/- 15.1 mg/dL, respectively. There were no significant sex differences in the levels of apo A-1, apo B, and Lp (a). The Lp (a) levels (mean +/- s.d., 12.5 +/- 15.2 mg/dL; median 7.5 mg/dL, n = 289) were not affected by other variables. The Lp (a) distribution was strongly positively skewed and 75% of schoolchildren had very low levels. In the total 289 schoolchildren, thirty-two grandparents who had had coronary vascular events (21 myocardial infarction, 11 angina pectoris) and twenty-three grandparents who had had cerebrovascular events were recorded. By the boxplot statistical analysis, no difference was found in Lp (a) levels in children whose grandparents had myocardial infarction compared with those whose grandparents had no such history, or compared with those whose grandparents had suffered cerebrovascular events.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Intra-abdominal fat in obese children.

We investigated the distribution of abdominal fat accumulation in obese children to know whether a clustering of coronary risk factors was demonstrated in visceral fat obesity as reported in adults. The relative indicator of intra-abdominal fat accumulation was obtained from computed tomography scans at the umbilicus level in 36 obese subjects (24 males, 12 females). There was no visceral fat obesity in this study by reported criteria. All metabolic variables except triglyceride did not correlate significantly with intra-abdominal fat accumulation. We conclude that visceral fat obesity is a rare status and has no close relationship to coronary risk factors in childhood.

Abdomen↗

Acute renal failure after exercise in a child with renal hypouricemia.

We describe a 15 year old boy with renal hypouricemia who developed acute renal failure after a school athletics meeting, accompanied by appendicitis. During acute renal failure, the highest level of uric acid was 5.0 mg/dL, creatinine 7.9 mg/dL and urea nitrogen 58.6 mg/dL. After recovery, the serum uric acid fell to 0.9 mg/dL and the fractional excretion of uric acid (FEuA) exceeded the normal range. The probenecid and pyrazinamide tests showed that the patient had a total defect of uric acid reabsorption. This case suggested that strenuous exercise could be responsible for acute renal failure in patients with renal hypouricemia.

Acute Kidney Injury↗

Changes in apolipoproteins during the acute phase of Kawasaki disease.

To determine disturbances of lipid metabolism in patients with Kawasaki disease, we investigated changes in the serum levels of apolipoproteins and serum lipids. Results were as follows. Total serum cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C) decreased during the early stage of Kawasaki disease. The apo A-I and A-II levels were low until the 2nd week of illness. Apo B decreased during the 1st week of illness, but rose slightly during the 2nd and 3rd weeks. The apo B/apo A-I ratio and the apo B/TC ratio were high in the early stages of illness. The group of patients with coronary artery lesions showed low levels of TC and HDL-C, and low levels of apo A-I, A-II and B during the early stages, compared with the group without coronary artery lesions. The apo B/TC ratio was significantly higher in the patients with coronary artery lesions during the 2nd week of illness. Our findings suggest an association between changes in serum lipids and apolipoproteins and coronary artery involvement in Kawasaki disease. These abnormalities may indicate the presence of early coronary arteriosclerosis.

Acute Disease↗

Fetal valproate syndrome with reduction deformity of limb.

A case is reported of a female infant having multiple anomalies, including epicanthic folds, hypertelorism, bifid nasal bridge, shallow philtrum, low-set ears, brain atrophy, cleft palate, hemangioma on the chest, and reduction deformity of the left upper limb. This is the first case where an infant who was exposed to sodium valproate intra-uterine has a reduction deformity of the upper limb.

Abnormalities, Drug-Induced↗

Effects of Bordetella bronchiseptica dermonecrotizing toxin on bone formation in calvaria of neonatal rats.

The effects of Bordetella bronchiseptica dermonecrotizing toxin on bone formation were investigated using a purified toxin preparation. Single injection of 4.3 ng of the toxin into the subcutaneous tissue overlying the calvariae of neonatal rats necrotized periosteum of parietal bone and degenerated osteoblasts within two days. Nine days after the injection, the lesion of the bone tissue became severe; the bone matrix became thin and fragmented. These observations indicate that dermonecrotizing toxin without other factors produced by the organisms impairs bone formation.

Animals↗

Detection of monocyte chemotactic and activating factor (MCAF) and interleukin (IL)-6 in human seminal plasma and effect of leukospermia on these cytokine levels.

PROBLEM: To demonstrate whether monocyte chemotactic and activating factor (MCAF) and interleukin-6 (IL-6) are present in the seminal plasma, and whether these presence is modulated by leukospermia. METHODS: Semen samples from 53 men were obtained by masturbation and examined for the presence of MCAF and IL-6 by enzyme immunoassay (EIA). Semen samples were obtained from 28 infertile men without leukospermia, 16 infertile men with leukospermia, and nine proven-fertile men. The correlation between the amount of MCAF in the seminal plasma with some spermiogram parameters and other cytokines such as IL-6 and IL-8 was statistically evaluated. RESULTS: Immunoreactive MCAF was detected in the seminal plasmas of all 53 subjects. The MCAF titer in the seminal plasma of patients with leukospermia (11.19 +/- 2.75 micrograms/l) was significantly higher than that in the seminal plasma of the patients without leukospermia (3.24 +/- 0.53 micrograms/l) and the fertile men (2.78 +/- 0.35 micrograms/l) (P < 0.001). The IL-6 titer in the seminal plasma of the patients with leukospermia (21.05 +/- 4.49 ng/l) was also significantly higher than that in the seminal plasma of the patients without leukospermia (8.77 +/- 1.92 ng/l) and the fertile men (6.94 +/- 1.27 ng/l) (P < 0.01). There was a high degree of correlation among the levels of MCAF, IL-6 and IL-8 in the seminal plasma. CONCLUSIONS: These findings demonstrated the presence of MCAF and IL-6 in the seminal plasma, and that the levels of these cytokines were elevated in the seminal plasma of the infertile patients with leukospermia.

Chemokine CCL2↗

A fast transient outward current in cultured cells from human pulmonary artery smooth muscle.

A voltage-dependent transient outward current (I(to)) was observed in cells cultured from human pulmonary artery smooth muscle when K+, but not Cs+, was the dominant cation in the pipette solution. In 30% of cells investigated using the Cs+ pipette solution, a tetrodotoxin-sensitive inward current (I(in)) dependent on extracellular Na+ was evoked from depolarizations positive to -30 mV.Iin showed voltage-dependent inactivation with a membrane potential at 50% of the evoked current (V50%) of -75.53 +/- 0.81 mV and slope factor potential (Vs) of -10.73 +/- 0.01 mV. In the presence of 1 microM tetrodotoxin, I(to) was rapidly evoked by depolarizations positive to -40 mV and decayed with a single exponential time course (tau = 9.9 +/- 1.1 ms, pulse potential = +50 mV). I(to) also showed voltage-dependent inactivation with a V50% of -70.9 +/- 2.63 mV and Vs of -7.7 +/- 0.03 mV. I(to) was inhibited concentration dependently by the K+ channel blocker, 4-aminopyridine (4-AP), with a concentration of 4-AP at which I(to) was reduced to 50% of control of 36.5 +/- 2.8 microM. These cells possess voltage-dependent currents characteristic of the K(+)-selective fast transient outward and Na(+)-selective inward currents of smooth muscle cells.

4-Aminopyridine↗