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Biomedical subjects

H Tomiyama

Publications and source records attributed to H Tomiyama.

At least 73 records · Page 4Linked to original sources
PubMed1996

Use of the in vitro induced antibody production test (IVIAP) to elucidate inconclusive status of HIV-1 infection.

Studies have demonstrated the diagnostic usefulness of in vitro production of virus-specific antibodies by peripheral blood mononuclear cells (PMBC) from HIV-infected subjects. We evaluated the IVIAP (in vitro induced antibody production) by lympocytes from peripheral blood of 30 adult patients. Samples included 10 patients with inconclusive status of HIV-1 infection on previous serologic screening (2 blood donors, 8 with high risk behavior), 10 AIDS patients (CDC II-IV), and 10 known seronegative subjects. Positive IVIAP results were obtained on 2 of 10 inconclusive cases, earlier than seroconversion would demonstrate. The 8 remaining cases resulted in a negative outcome on IVIAP test, even in 2 seronegative homosexuals presenting Kaposi's sarcoma. Results showed 100% concordance either with a clinical/serological follow-up done after IVIAP tests or PCR performed for Kaposi's cases. Also, no false-positive or false-negative was detected on control groups. We concluded that IVIAP could identify the real status of HIV infection in a shorter time and with low cost compared to conventional serological methods currently available. The IVIAP test is easily performed so that can be considered as a routine supplemental test.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Prospective studies on left ventricular geometric patterns and exercise tolerance in unmedicated men with borderline and mild hypertension.

OBJECTIVE: This study was designed and conducted to assess the clinical significance of left ventricular geometric patterns and physical fitness in subjects with untreated borderline and mild hypertension. METHODS: Symptom-limited maximal treadmill stress testings and echocardiographic examinations were administered to 192 previously unmedicated men. Left ventricular geometric patterns were determined by the combined criteria of left ventricular mass index and relative wall thickness. Subjects whose left ventricular mass index was < 125 g/m2 were followed up for more than 3 years. RESULTS: Normalized treadmill time was lower and pressure rate products at peak exercise were higher in patients with concentric hypertrophy than in those with normal geometry. Of the 77 patients who revealed left ventricular mass index at baseline < 125 g/m2 and who were successfully followed without medication for more than 3 years, 18 demonstrated concentric hypertrophy at the final follow-up examination. During the follow-up period, these 18 patients had significant further augmentation of concentric geometric features, significant decreases in both cardiac output and normalized treadmill time, and significant increases in casual blood pressure and total peripheral resistance compared with those at baseline. CONCLUSION: Patients with concentric hypertrophy exhibited slightly but significantly impaired levels of physical fitness and cardiac work efficiency, and the progression of concentric hypertrophy demonstrated further impairments of these conditions. Therefore, not only lowering blood pressure, but also improving left ventricular hypertrophy, cardiovascular hemodynamics, and physical fitness might be required in patients with concentric hypertrophy.

Adult↗
PubMed1996

Left ventricular hypertrophy in mild essential hypertension. Its progression, prediction and treatment strategy.

Since the pathogenesis of left ventricular hypertrophy (LVH) in hypertension is thought to be multifactorial, the antihypertensive strategy also has to be multifaceted. Diagnosis of LVH is more reliable than ever with echocardiography either of the M-mode or 2D method. Diagnostic criteria have already been proposed by Ganau et al who classified LV morphology into 4 different sectors based on the standard values of left ventricular mass index (LVMI) and relative wall thickness in diastole (RWTd); normal, concentric remodeling, concentric hypertrophy and eccentric hypertrophy. The concentric hypertrophy pattern is the most risky with regard to prognosis. Therefore, its detection and prediction for further progression have to be conducted with relatively easy routine work-up procedures such as echocardiography and maximal exercise testing. The prediction of LVH progression has already been proposed based on several studies conducted in patients with borderline or mild hypertension. The following two predictors were defined as LVMI > 124 g/m2 and peak Ps at maximal exercise testing > 200 mmHg. Therefore, the patient who meets these criteria has to be treated with medications that are appropriately selected on an individualized basis. Both hyperinsulinemia and insulin resistance are thought to be involved in the initiation, promotion and potentiation of remodeling of the LV in hypertension. Physical fitness also seems to be decreased in a parallel manner. Selection of the most appropriate drug for a given patient has to be individually determined based on the risks that have to be corrected. Finally, arteriosclerosis, which is almost always initiated and progresses in concert with hypertension, must also be targeted with regard to such prognostic aspects as cardiovascular morbidity and mortality. Arteriosclerosis is pathogenetically independent from hypertension, but usually behaves in concert with it. Selection of medication must be focussed on an individualized basis not only for LVH, but also for improvement in arterial elasticity. Further clinical research is still needed to provide more reasonable approaches to patients with hypertension.

Angiotensin II↗
PubMed1996

In vitro induced antibody production for the diagnosis of herpes simplex virus infection in immunosuppressed patients.

We developed and evaluated a specific test for herpes simplex virus (HSV) infection based on the secretion of HSV-specific antibodies by lymphocytes stimulated in vitro with HSV-1 antigens. The in vitro induced antibody production (IVIAP) test was used for the diagnosis of HSV infection in 43 seropositive selected subjects: 9 healthy subjects (controls), 30 symptomatic patients (26 of them immunocompromised and 4 immunocompetent) and 4 patients with varicella zoster infection. Anti-HSV antibodies were detected by an immune assay using an anti-human IgG peroxidase conjugate. The test showed a sensitivity of 93% (15/16) and specificity of 92% (1/13) which were confirmed by positive culture or clinical and laboratory follow-up. One AIDS patient had a false-negative result and one false-positive result (1/9) was obtained among the healthy subjects. All patients infected with varicella zoster virus were negative to the IVIAP test. The test is rapid, inexpensive, easy to interpret and can be used for the diagnosis of HSV infections, especially in immunocompromised patients.

Antibodies, Viral↗
PubMed1996

Identification of multiple HIV-1 cytotoxic T-cell epitopes presented by human leukocyte antigen B35 molecules.

OBJECTIVE: To identify HIV-1 cytotoxic T lymphocyte (CTL) epitopes presented by human leukocyte antigen (HLA)-B35 molecules that are associated with the accelerated progression of AIDS using a reverse immunogenetic approach. METHODS: 8-mer to 11-mer sequences carrying two anchor residues at position 2 and the carboxy-terminus were selected from HIV-1SF2 strain. Sixty-four peptides matched to these sequences were synthesized and tested by a peptide binding assay using RMA-S-B*3501 cells. Peripheral blood lymphocytes (PBL) from two HIV-1-infected donors carrying HLA-B35 were stimulated once-weekly with each HLA-B*3501 binding peptide. The CTL activity of the cultured cells for the HLA-B35-positive target cells loaded with the corresponding peptides was examined after the second and fourth stimulation. Furthermore, the CTL activity of the cultured cells possessing HLA-B*3501-restricted HIV-1 peptide-specific CTL activity were examined for the HLA-B*3501-positive target cells infected with the recombinant vaccinia virus containing corresponding HIV-1 gene. RESULTS: HIV-1 peptide-specific HLA-B*3501-restricted CTL was induced in PBL of HIV-1 infected donors by in vitro stimulation with 11 out of 27 HLA-B*3501-binding HIV-1 peptides. The specific CTL induced with 10 peptides killed the cells infected with recombinant vaccinia virus expressing the corresponding HIV-1 proteins. Out of these HIV-1 peptide epitopes, two epitopes were also presented by HLA-B51 molecules. CONCLUSION: In addition to the four HLA-B35-restricted HIV-1 CTL epitopes that have been previously reported, nine HLA-B35-restricted HIV-1 CTL epitopes were identified in the present study. These multiple epitopes will be useful in studies for immunopathogenesis of AIDS.

Antigen Presentation↗
PubMed1996

Safety and effectiveness of exercise training in patients with silent myocardial ischemia.

The effectiveness of exercise training in patients with silent myocardial ischemia was examined. Forty patients with coronary heart disease (mean age 55 +/- 8 years) were recruited for a 12-week exercise training program. All patients underwent treadmill exercise stress testing, exercise thallium-201 single photon emission computed tomography and left heart catheterization. They were divided into three groups based on the symptoms and the results of exercise thallium scintigraphy, i.e., painful myocardial ischemia (PMI group), silent myocardial ischemia (SMI group), and non-myocardial ischemia (NMI group). Normalized treadmill time was longer in the SMI group (108 +/- 24%) than in the PMI group (86 +/- 14%, p < 0.05). All 40 patients, 14 from the PMI group, 16 from the SMI group and 10 from the NMI group, completed the whole exercise training program. A significant prolongation of treadmill time was attained in all three groups after exercise training [PMI group: from 494 +/- 105 to 632 +/- 78 sec (p < 0.05), SMI group: from 609 +/- 147 to 746 +/- 137 sec (p < 0.05), NMI group: from 572 +/- 112 to 739 +/- 13 sec (p < 0.05)]. The improvement of myocardial ischemia following exercise training was similar in the SMI and PMI groups. No adverse effects were detected throughout the program. The exercise training program adopted in this study proved safe and effective in patients with silent myocardial ischemia.

Adult↗
PubMed1995

Inhibition of gamma delta T cell recognition by receptors for MHC class I molecules.

NK cells have receptors for MHC class I molecules that inhibit cytotoxicity against target cells. We show that recognition of gamma delta CTL is negatively regulated by receptors for MHC class I molecules. Cytolysis of C1R cells by gamma delta CTL clones was inhibited by the expression of polymorphic HLA class I molecules on target cells and was restored by blocking with anti-HLA class I mAb, suggesting the presence of inhibitory receptors for HLA class I molecules. The receptors for HLA class I molecules on gamma delta T cells were heterogenous. The immune responses to various Ags may be regulated via these inhibitory receptors on T cells and NK cells.

Clone Cells↗
PubMed1995

Isolation of a human allo-peptide presented by HLA-B51 molecules.

Recent studies have demonstrated directly that alloreactive mouse CTL recognize peptides presented by MHC class I molecules. However, there is no direct evidence that human alloreactive CTL recognize peptides presented by HLA class I molecules. We have isolated an HLA-B51 alloreactive CTL clone, 2B3, that did not kill the TAP defective cell lines T2 and .174, whereas it killed the TAP-positive cell line T1 and .174 cells transfected with TAP genes. These findings suggested that this clone recognizes a TAP-dependent allo-peptide. We attempted to isolate the human allo-peptide recognized by the 2B3 clone from HLA-B51 molecules. A naturally occurring HLA-B*5101 binding peptide isolated from T1 cells was recognized by the 2B3 clone. The peptide was also isolated from HLA-B*5101 molecules purified from C1R-B*5101 cells. In the present study, we directly demonstrated that a human alloreactive CTL clone recognizes peptide presented by HLA class I molecules.

Antigen Presentation↗
PubMed1995

Changes in the E/A ratio induced by handgrip-exercise are related to changes in the plasma atrial natriuretic peptide level, but not to changes in brain natriuretic peptide in mild essential hypertension.

We investigated the relationship between changes in atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) and changes in cardiac function during mild exercise in patients with mild hypertension. The handgrip test (HGT) was performed by 21 untreated, mildly hypertensive patients, mean age 45 +/- 5 years. M-mode and pulse Doppler echocardiograms were recorded before and during HGT. In 7 patients (Group A), diastolic function, which was determined by the peak early velocity and peak atrial velocity (E/A) ratio using Doppler echocardiography was attenuated during HGT (1.19 +/- 0.21 TO 1.04 +/- 0.16, p < 0.05). There was no change in diastolic function in the remaining 14 patients, left atrial diameter, cardiac index, ejection fraction, plasma renin activity, plasma norepinephrine, blood pressure, nor heart rate were different between the two groups. While ANP was increased in Group A during HGT (from 41.0 +/- 18.2 to 54.0 +/- 24.1 pg/ml, p < 0.05) it was unchanged in Group B (36.8 +/- 16.3 to 33.5 +/- 11.9 pg/ml). BNP did not change in either Group (Group A: 2.9 +/- 3.1 to 3.0 +/- 3.4 pg/ml, Group B: 2.6 +/- 1.6 to 3.6 +/- 4.8 pg/ml). The percent change in ANP during HGT did not correlate with the percent change in BNP. Thus, the impairment of cardiac functional reserve appeared to influence ANP excretion in patients with mild hypertension.

Adult↗
PubMed1994

Kinins contribute to the improvement of insulin sensitivity during treatment with angiotensin converting enzyme inhibitor.

Although angiotensin converting enzyme inhibitors and alpha 1-blockers have been reported to improve insulin sensitivity, their mechanisms of action have not been elucidated. To investigate the role of kinins in insulin sensitivity, we treated 4-week-old spontaneously hypertensive rats with either an angiotensin converting enzyme inhibitor (enalapril), an alpha 1-blocker (doxazosin), or an angiotensin II antagonist (losartan) for 3 weeks. A control group received no drugs. In addition, 18 rats treated with enalapril or doxazosin received a simultaneous administration of a kinin antagonist (Hoe 140). Glucose clamp testing was performed in each group. Enalapril (128 +/- 1 mmHg) and doxazosin (132 +/- 2 mmHg) decreased mean blood pressure compared with control levels (148 +/- 1 mmHg) (P < .01). The glucose requirement for the clamp test during the administration of enalapril (25.8 +/- 0.5 mg/kg per minute) or doxazosin (28.6 +/- 0.7 mg/kg per minute) was higher than that of the control group (19.8 +/- 0.5 mg/kg per minute) (P < .05). Although Hoe 140 did not alter the glucose requirement of doxazosin (27.8 +/- 0.5 mg/kg per minute), it decreased that of enalapril (22.6 +/- 0.9 mg/kg per minute) (P < .05) without affecting the changes in mean blood pressure induced by enalapril. In addition, losartan decreased mean blood pressure but did not affect the glucose requirement. Thus, the improvement in insulin sensitivity produced by an angiotensin converting enzyme inhibitor is mostly dependent on kinins but not on angiotensin II antagonism, and an alpha 1-blocker improves insulin sensitivity irrespective of kinins.

Analysis of Variance↗
PubMed1992

Blood pressure response to hyperinsulinemia in salt-sensitive and salt-resistant rats.

We investigated the role of insulin in salt-sensitive hypertension in Dahl salt-sensitive and salt-resistant rats. The rats were kept in metabolic cages, and sodium intake and urinary sodium excretion were measured. In salt-sensitive rats receiving a 0.3% NaCl diet, sodium retention was significantly greater at weeks 1 and 2 in rats that received an insulin infusion than in those receiving a saline infusion. Mean arterial blood pressure and plasma norepinephrine levels were significantly higher at week 3 in insulin-treated rats than in saline-treated rats (mean arterial pressure, 137 +/- 3 mm Hg versus 119 +/- 3 mm Hg, p < 0.05; plasma norepinephrine, 0.40 +/- 0.02 ng/ml versus 0.27 +/- 0.01 ng/ml, p < 0.05). Insulin did not influence sodium retention, mean arterial pressure, or plasma norepinephrine in salt-resistant rats. Coadministration of an alpha-blocker (bunazosin, 10 mg/kg per day for 3 weeks) in salt-sensitive rats abolished the insulin-induced elevations in mean arterial pressure and sodium retention. When salt-sensitive rats were fed a low salt diet (0.03% NaCl), insulin did not raise mean arterial pressure. Thus, insulin elevated blood pressure only in the salt-sensitive model. The sympathetic nervous system and sodium retention in the early phase of insulin overload may contribute to elevation of mean arterial pressure in this model.

Animals↗
PubMed1991

Role of sympathetic activity in blood pressure reduction with low calorie regimen.

To investigate the effects of a low calorie regimen on sympathetic function and its relation to blood pressure response, 22 untreated obese essential hypertensive patients (50 +/- 2 years, body mass index 29 +/- 1 kg/m2) were hospitalized and a diet was prescribed of 2,000 kcal/day for 5 days (control period) followed by 800 kcal/day for 21 days without changing salt intake (8-10 g/day). The dose of intravenous phenylephrine infusion needed to elevate systolic blood pressure 20 mm Hg (CD20) and the 24-hour urinary excretion of norepinephrine (UNE) were measured. During the low calorie period, blood pressure normalized in 14 patients (responder group, 124 +/- 3/79 +/- 4 mm Hg) and eight remained hypertensive (poor responder group, 158 +/- 6/103 +/- 3 mm Hg). At the control period, blood pressure and body mass index were similar, but the responder group had higher UNE (134 +/- 15 micrograms/day) and CD20 (127 +/- 11 micrograms) than the poor responder group (89 +/- 6 micrograms/day and 79 +/- 13 micrograms, respectively). During the low calorie period, both UNE (87 +/- 15 micrograms/day) and CD20 (74 +/- 10 micrograms) decreased in the responder group; no change was seen in the poor responder group. Changes in UNE and systolic blood pressure were correlated (r = 0.6, p less than 0.05). In conclusion, suppression of sympathetic activity plays a role in blood pressure reduction during moderate caloric restriction.

Blood Pressure↗
PubMed1990

Renal effects of Fab fragments of kinin antibodies on deoxycorticosterone acetate-salt-treated rats.

The role of the renal kallikrein-kinin system in the regulation of renal function is not completely understood. Intrarenal kinins can influence renal function by acting as paracrine hormones at basolateral, luminal, or both sites in the distal nephron. To examine the role of intrarenal kinins in deoxycorticosterone acetate-salt-treated rats, which have high renal kallikrein, Fab fragments of antibradykinin antibody or DArg[Hyp3Thi5,8DPhe7]bradykinin, a kinin antagonist, were used to block kinins. At the dose used, the antibody (25 mg) and kinin antagonist (10 micrograms/min/rat) inhibited the hypotensive effect of intra-arterially injected bradykinin (100 ng) by 70% and 52%, respectively. The antibody appeared in the urine within 30 minutes after administration. Urinary volume was lowered from 9.4 +/- 0.2 to 6.7 +/- 0.4 microliters/min/g kidney wt (p less than 0.001, paired t test) by the antibody and from 8.5 +/- 0.3 to 6.8 +/- 0.4 microliters/min/g kidney wt (p less than 0.004, paired t test) by the kinin antagonist. The antibody lowered urine sodium excretion from 1.11 +/- 0.04 to 0.88 +/- 0.06 mueq/min/g kidney wt (p less than 0.001, paired t test), whereas the kinin antagonist had no significant effect. Neither altered blood pressure, renal blood flow, or glomerular filtration rate. These data suggest that in deoxycorticosterone acetate-salt-treated rats, excretion of water and sodium is regulated in part by kinins. The antidiuretic effect of the antibody and kinin antagonist might be due to blockade of kinins in the vascular-interstitial space of the kidney, since the kinin antagonist is likely hydrolyzed in the proximal tubule and does not reach the lumen of the distal nephron.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

[Studies on evaluation of the oxygen transport system function with multistage treadmill stress testing: comparison between normal control subjects and patients with coronary heart disease].

The oxygen transport system (OTS) function was evaluated with multistage treadmill stress testing on 171 normal control subjects and 80 patients with coronary heart disease (CHD). After Bruce's definition, OTS function was expressed with functional aerobic impairment (FAI), left ventricular impairment (LVI) or myocardial aerobic impairment (MAI), heart rate impairment (HRI) or chronotropic reserve impairment (CRI) and peripheral circulatory impairment (PCI). All subjects were monitored on heart rate, blood pressure, electrocardiogram and endtidal O2 and CO2 before and every one minute during the symptom limited maximal stress testing. Seventy three of 80 coronary patients were subjected to the coronary arteriography and were classified into four groups; 31 with single vessel disease (SVD), 20 with double vessel disease (DVD), 15 with triple vessel disease (TVD) and 7 with A-C bypass surgery. Comparison between normal control subjects and the CHD patients with regard to the relation of age and VO2max derived from the linear regression analysis disclosed the identical age-related decrease in VO2max in both groups. The age corrected VO2max in the CHD patients, however, was 2.2 METS less than that of normal control subjects. Therefore, the level of VO2max in CHD patients was determined not only by disease, but also by ageing process itself. Comparisons among three CHD groups with regard to FAI, LVI, HRI and PCI clearly demonstrated different functional impairments paralleling to the severity of the disease process. On the other hand, the patients with A-C bypass surgery revealed almost identical functional impairment to the patients with SVD. In conclusion, these simple and noninvasive evaluations of the oxygen transport system could give us valuable informations reasonably differentiating the clinical status of the patients with CHD.

Adult↗