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H Tomiyama

Publications and source records attributed to H Tomiyama.

At least 37 records · Page 2Linked to original sources
PubMed2000

A single CTL clone can recognize a naturally processed HIV-1 epitope presented by two different HLA class I molecules.

Although it is known that a single peptide can be recognized by CTL restricted to two MHC class I alleles, there is no direct evidence for presentation of a single peptide by two MHC class I molecules. Furthermore, it is unclear whether such peptides are presented to the same T cell or to different T cells. Our previous study suggested that CTL recognition of the human immunodeficiency virus-1 (HIV-1) Pol HIV-B35-SF2-24 epitope (IPLTEEAEL) occurs via both HLA-B35 and HLA-B51 restriction. Here we provide the first direct evidence that a single CTL clone can recognize this peptide presented by both HLA-B35 and HLA-B51. Furthermore, we directly purified this peptide eluted from both HLA-B*3501 and HLA-B*5101 molecules isolated from target cells infected with HIV-1 recombinant vaccinia virus. These results demonstrate that HIV-B35-SF2-24 is a naturally processed peptide which is presented by both HLA-B*3501 and HLA-B*5101. TCR analysis of one CTL clone suggested that it is a single clone. B*3501-SF2-24-tetrameric complexes inhibited both HLA-B*3501- and HLA-B*5101-restricted recognition of this clone, suggesting that the TCR of this clone cross-recognize the structure of both HLA class I-peptide complexes.

Amino Acid Sequence↗
PubMed2000

Analysis of three HLA-A*3303 binding peptide anchors using an HLA-A*3303 stabilization assay.

The affinity of 232 8- to 11-mer peptides carrying HLA-A*3303 anchor residues at position 2 (P2) (Ala, Ile, Leu, Val, Phe or Tyr) and the C-terminus (Arg) was analysed by a stabilization assay using RMA-S transfectants expressing HLA-A*3303 and human beta2-microglobulin. One hundred and nineteen of these peptides (51.3%) bound to HLA-A*3303, confirming that these residues are anchors for HLA-A*3303. Evaluation of P2 residues demonstrated that binding of peptides with Phe or Tyr at P2 is stronger than that of peptides with aliphatic hydrophobic residues at P2. This was confirmed by analysis of a panel of peptides mutated at P2. Analysis of the C-terminal mutant peptides showed that substitution of Lys for Arg had minimal influence on binding to HLA-A*3303. This implies that peptides carrying HLA-A*1101 anchor residues (Val, Ile, Phe or Tyr at P2 and Lys at the C-terminus) can bind to HLA-A*3303. However, such peptides showed lower binding for HLA-A*3303 than for HLA-A*1101. Thus, Arg at the C-terminus is much stronger anchor for HLA-A*3303 than Lys. The preference for Arg and Lys at the C-terminus by HLA-A*1101 and HLA-A*3303 respectively may be due to sequences of three residues (70, 97 and 114) forming the F-pocket of these HLA class I molecules. Statistical analysis of 232 peptides further showed a positive effect of negatively charged residues at P1 for peptide binding to HLA-A*3303. Thus, residues at P1, P2 and the C-terminus play an important role in peptide binding to HLA-A*3303.

Amino Acid Sequence↗
PubMed2000

Polarity of the P1 anchor residue determines peptide binding specificity between HLA-A*3101 and HLA-A*3303.

A previous pool sequence analysis showed that HLA-A*3101 and HLA-A*3303 binding peptides have the same anchor residues at P2 and the C-terminus, the only difference being that HLA-A*3303 binding peptides have two additional P2 anchor residues. Using a stabilization assay with RMA-S transfectants expressing HLA-A*3101 and human beta2-microglobulin, we tested the binding of 232 8- to 11-mer peptides carrying HLA-A*3303 anchor residues to HLA-A*3101. One hundred of these peptides (43.1%) bound to HLA-A*3101, confirming that these residues are also anchors for HLA-A*3101. Although aromatic hydrophobic P2 residues were previously shown to be stronger anchors than aliphatic hydrophobic P2 residues in HLA-A*3303 binding peptides, we detected no significant difference in HLA-A*3101 binding affinity between peptides carrying aromatic or aliphatic hydrophobic P2 residues. Statistical analysis previously showed a positive effect of negatively charged P1 residues and a negative effect of positively charged P1 residues for peptide binding to HLA-A*3303. In contrast such analysis demonstrated a positive effect of positively charged P1 residues and a negative effect of negatively charged P1 residues for peptide binding to HLA-A*3101. Analysis using mutated peptides confirmed these results. The present study therefore demonstrates that peptide binding specificity between HLA-A*3101 and HLA-A*3303 is determined by the polarity of the P1 anchor residue.

Amino Acid Sequence↗
PubMed2000

The effects of monotherapy or combined therapy with an angiotensin converting enzyme inhibitor following initial treatment with calcium channel blockers on residual cardiovascular abnormalities.

The effects of sequential therapy with angiotensin-converting enzyme inhibitor (cilazapril) on left ventricular (LV) mass, LV diastolic function, and carotid artery distensibility were evaluated in 90 hypertensive patients whose blood pressure controlled below 140/90 mmHg with a calcium channel blocker monotherapy. The possibility of predicting the efficacy of cilazapril based on evaluation of biochemical and genetic markers of the renin-angiotensin system was examined. Before cilazapril therapy, LV diastolic function and carotid artery distensibility were significantly impaired in 32 patients with residual LV hypertrophy compared with patients without LV hypertrophy. Cilazapril improved the LV mass in these patients with LV hypertrophy and improved LV diastolic function in a subset of 20 patients with elevated plasma renin activity. Patients with residual LV hypertrophy accompanied by cardiovascular functional abnormalities. Subsequent treatment with cilazapril significantly improved LV morphology and function in those with residual LV hypertrophy or elevated plasma renin activity.

Aged↗
PubMed2000

Effects of oral administration of L-arginine on renal function in patients with heart failure.

OBJECTIVES: Although the beneficial effects of L-arginine on systemic haemodynamics have been reported in patients with heart failure, its effect on renal function has not been examined. We evaluated the effects of oral administration of L-arginine on renal haemodynamics, sodium and water handling, and various hormonal factors in patients with chronic heart failure. SUBJECTS AND METHODS: A double-blind crossover trial was performed in 17 patients with chronic congestive heart failure (NYHA II-III, 56 +/- 12 years of age) who were randomly assigned to receive oral L-arginine (15 g/day) and placebo or placebo and arginine sequentially for 5 days each. Twenty-four hour creatinine clearance (Ccr), and 24-h urinary cyclic guanosine 5-monophosphate (GMP) excretion were determined. Saline loading was performed on day 5 of each treatment Renal blood flow, glomerular filtration rate (GFR), and urinary sodium excretion rate (UNa) were assessed before and after saline loading. RESULTS: Twenty-four hour GMP excretion (1.4 +/- 1.1 versus 0.8 +/- 0.5 micromol/day, P < 0.01) and Ccr (150 +/- 43 versus 125 +/- 42 ml/min, P < 0.05) were higher and plasma endothelin level (2.5 +/- 0.6 versus 3.1 +/- 0.8 pg/ml, P < 0.05) was lower with L-arginine treatment compared to placebo treatment In addition, the relative increase of UNa and GFR after saline loading were significantly higher in L-arginine treatment (UNa, 47 +/- 12%; GFR, 44 +/- 31%) than in placebo treatment (UNa, 34 +/- 9%; GFR, 22 +/- 29%) (P < 0.05). CONCLUSIONS: Oral administration of L-arginine has beneficial effects on glomerular filtration rate, natriuresis, and plasma endothelin level in patients with chronic congestive heart failure.

Administration, Oral↗
PubMed2000

Carotid arterial distensibility is an important determinant of improvement in autonomic balance after successful coronary angioplasty.

OBJECTIVE: To determine whether arterial distensibility influences improvement of autonomic imbalance after left ventricular wall motion (LVWM) abnormality has been improved by percutaneous transluminal angioplasty (PTCA) in patients with ischemic heart disease (IHD). METHODS AND RESULTS: The following variables were assessed before and 3 months after PTCA in 63 patients with IHD who had a successful PTCA: heart rate variability (standard deviation of all normal R-R intervals [SDNN] measured from 24 h Holter electrocardiograms), baroreceptor sensitivity (determined by the phenylephrine injection method), and carotid artery distensibility (determined by ultrasonography). Abnormalities of LVWM were assessed by cineventriculography. In a multivariate analysis, carotid artery distensibility before PTCA and changes in LVWM abnormality before and after PTCA were independently associated with changes in baroreceptor sensitivity and SDNN (P< 0.05). Patients were divided into two groups: one with impaired and one group with unimpaired initial carotid artery distensibility. After PTCA, LVWM was improved significantly in both groups, but baroreceptor sensitivity and SDNN were improved significantly (respectively from 5.0 +/- 3.3 to 5.9 +/- 3.9 ms/mmHg, P< 0.01 and from 111 +/- 47 to 128 +/- 54 ms, P < 0.01) only in patients with well-preserved carotid artery distensibility. CONCLUSIONS: The beneficial effect of PTCA on autonomic balance was greater in patients with well-preserved carotid artery distensibility than in those with impaired carotid artery distensibility. These results suggest that the pathophysiological state of arterial distensibility may modify the autonomic balance even after myocardial ischemia-related LVWM abnormalities are improved.

Adult↗
PubMed2000

Close relationship of abnormal glucose tolerance with endothelial dysfunction in hypertension.

Hypertension is frequently accompanied by left ventricular hypertrophy, endothelial dysfunction, and abnormal glucose metabolism. However, no study has examined the relative pathological significance of left ventricular hypertrophy and abnormal glucose metabolism on endothelial dysfunction in hypertension. This study was conducted to evaluate whether abnormal glucose tolerance assessed by 75-g oral glucose tolerance test or left ventricular hypertrophy is more closely associated with endothelial dysfunction in never-treated hypertensive patients without elevated fasting blood glucose. We studied 107 unmedicated hypertensive patients (mean age, 54+/-10 years) whose fasting blood glucose was <7.0 mmol/L. Endothelial function was assessed by change in brachial artery diameter in response to reactive hyperemia, and left ventricular mass index was determined by ultrasonography. Simple linear regression analysis demonstrated that endothelial function significantly correlated with left ventricular mass index and 2-hour blood glucose in 75-g oral glucose tolerance test, but not with fasting blood glucose. Multiple linear regression analysis revealed that endothelial function significantly correlated with 2-hour blood glucose (beta=-2.68, P<0.05) after we controlled for other clinical variables. Patients were divided into 3 groups according to 2-hour blood glucose levels. Endothelial function was more impaired in patients with diabetes (n=12; 4.7+/-1.8%) and in those with impaired glucose tolerance (n=31; 6.3+/-2.9%) than in those with normal glucose tolerance (n=64; 8.4+/-4.5%) (P<0.05), but left ventricular mass index was similar in these 3 groups. Abnormal glucose tolerance assessed by 75-g oral glucose tolerance test, rather than left ventricular hypertrophy, may have direct pathophysiological relevance to endothelial dysfunction in borderline to moderate hypertensive patients.

Adult↗
PubMed2000

Sympathetic fibers innervating the extraocular muscles: cells of origin in the cat superior cervical ganglion.

Cells of origin of sympathetic fibers innervating the extraocular muscles were demonstrated in the cat superior cervical ganglion (SCG) using the horseradish peroxidase (HRP) technique. Each injection of HRP into the muscles was confirmed by labeling in the oculomotor, trochlear and abducens nuclei. In all cases retrogradely labeled neurons were found to be distributed widely to the ipsilateral SCG. Labeled neurons were round or oval in shape and majority of these were medium in size. There were some large-sized neurons which frequently showed to have long dendrites expanding rostrocaudally. The labeling was characterized by localization in the rostral two-thirds of the SCG after HRP injections into the medial, lateral and inferior and superior oblique muscles. However, the labeling was found in the whole of the SCG after HRP injections into the superior rectus and inferior oblique muscles. Compared with our previous studies demonstrating cells of origin of the sympathetic fibers in the facial and hypoglossal nerves, the present experiments showed quite different pattern of distribution of labeled neurons in the SCG.

Adrenergic Fibers↗
PubMed2000

[Target-controlled propofol infusion for general anesthesia in three obese patients].

We report three cases in which the target-controlled propofol infusion technique was used in obese patients for general anesthesia. General anesthesia was induced by intravenous administration of fentanyl 150-300 micrograms and ketamine 50-80 mg and propofol 2 micrograms.ml-1 to achieve a target blood concentration by target-controlled infusion system. Anesthetic maintenance was achieved by ketamine 1 mg.kg-1.h-1 for 1 hour after the induction, propofol at target blood concentration of 2-3.5 micrograms.ml-1 and the intermittent epidural injection of 1.5% lidocaine through an epidural catheter. The surgical procedures were uneventful. The estimated blood concentrations of propofol at emergence from anesthesia calculated by ConGrace ranged from 1.49-1.69 micrograms.ml-1, and it took 230-300 seconds to emerge from anesthesia. The target-controlled propofol infusion technique appears useful to control the depth of anesthesia in obese patients.

Adult↗
PubMed2000

[Comparison between total intravenous anesthesia and inhalation anesthesia in the surgery of acute cholecystitis].

We investigated retrospectively the influence of anesthetic methods on the intraoperative managements and postoperative outcomes in 26 patients receiving emergency or early surgery for acute cholecystitis. Fourteen of the 26 patients received total intravenous anesthesia with propofol, fentanyl, and ketamine (PFK group), while the remainder received nitrous oxide and isoflurane or sevoflurane anesthesia (GO group). There were no significant differences between the groups with respect to demographic data. We found no significant differences between the groups in duration of operation and anesthesia, the incidence of intraoperative hypotension, and the use of ephedrine and dopamine during induction and maintenance of anesthesia. After surgery, the PFK group had significantly earlier bowel function than the GO group, with earlier starting of oral intake (54.0 +/- 25.1 vs 89.3 +/- 31.9 hours after surgery; P = 0.026). These data suggest that total intravenous anesthesia by propofol, fentanyl, and ketamine may provide the earlier recovery of bowel function than inhaled anesthesia after emergency or early surgery for acute cholecystitis.

Acute Disease↗
PubMed1999

Accumulation of specific amino acid substitutions in HLA-B35-restricted human immunodeficiency virus type 1 cytotoxic T lymphocyte epitopes.

HLA is one of the genetic factors that influence the clinical course of HIV-1 infection, and patients with HLA-B35 are prone to rapid disease progression. Nine viral epitopes that are recognized by cytotoxic T lymphocytes (CTLs) in an HLA-B35-restricted manner were determined. To examine how HIV-1 sequences are selected by CTLs in vivo, we sequenced the nine CTL epitopes of the virus in patient plasma. Here we show that certain amino acid substitutions at three epitopes were observed with significantly higher frequency in HLA-B35-positive patients than in HLA-B35-negative patients. By performing experiments with CTL clones established from the HLA-B35-positive patients, it was determined that one of the three substitutions was probably an escape mutation. However, concerning the other two epitopes, representative CTL clones killed target cells pulsed with mutant peptides as efficiently as those pulsed with wild-type peptides, suggesting that CTLs that can be established in vitro are not functioning properly in vivo. Amino acid sequence drift in all HLA-B35-restricted epitopes was rare during the observation period (1 year). Our results may have relevance in understanding the rapid clinical progression in HLA-B35-positive patients.

Amino Acid Sequence↗
PubMed1999

Effects of short-acting and long-acting loop diuretics on heart rate variability in patients with chronic compensated congestive heart failure.

BACKGROUND: We investigated the effects of a short-acting loop diuretic (furosemide) and a long-acting loop diuretic (azosemide) on heart rate variability, fluid balance, and neurohormonal responses in patients with mild to moderate chronic congestive heart failure. METHODS: Nineteen patients with mild to moderate chronic congestive heart failure received furosemide (40 to 60 mg/day) or azosemide (60 to 90 mg/day) for 5 days in a crossover manner. We performed time-domain and frequency-domain analyses of 24-hour Holter electrocardiographic recordings to assess heart rate variability. RESULTS: The 24-hour urinary sodium excretion was similar during the furosemide and azosemide treatment periods but was significantly greater in the first 2 hours after drug administration during furosemide treatment. Plasma renin activity and the hematocrit level increased and high-frequency power significantly decreased 2 hours after the administration of furosemide only. The standard deviation of all normal R-R intervals and the root mean square of successive differences in the R-R interval were lower with furosemide than with azosemide (P <.05). CONCLUSIONS: Furosemide, a short-acting loop diuretic, has a greater influence on heart rate variability and fluid balance than azosemide, a long-acting loop diuretic, in patients with mild to moderate chronic congestive heart failure.

Blood Pressure↗
PubMed1999

Identification of multiple HIV-1 CTL epitopes presented by HLA-B*5101 molecules.

We attempted to identify and characterize HIV-1 CTL epitopes presented by HLA-B51 which is associated with a slow progression to AIDS. HLA-B*5101 stabilization assay showed that 33 out of 172 HIV-1 peptides carrying HLA-B*5101 anchor residues bound to HLA-B*5101. Seven peptides were suggested as HIV-1 CTL epitopes presented by HLA-B*5101 because the specific CTL was induced for these peptides in PBMC from three HIV-1 seropositive individuals carrying HLA-B51 by stimulation with HLA-B*5101 binding peptides. Analysis of these epitopes using the specific CTL clones confirmed that six of seven HIV-1 peptides are epitopes presented by HLA-B*5101. Three epitopes presented by HLA-B*5101 are highly conserved among the clade B strain, suggesting that the specific CTL for these epitopes might play an important role in recognition of HIV-1 infected cells. These epitopes will be useful to analyze CTL responses in HIV-1 infected individuals.

Antigen Presentation↗