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Biomedical subjects

T Honma

Publications and source records attributed to T Honma.

At least 109 records · Page 6Linked to original sources
PubMed1995

Novel angiotensin II receptor antagonists. Design, synthesis, and in vitro evaluation of dibenzo[a,d]cycloheptene and dibenzo[b,f]oxepin derivatives. Searching for bioisosteres of biphenylyltetrazole using a three-dimensional search technique.

Three-dimensional substructure searching (3D search), using the program MACCS-3D, was utilized for designing novel angiotensin II receptor antagonists which contain a bioisostere of the biphenylyltetrazole moiety of DuP 753. A 3D query was prepared from an overlay model of substructures of several potent AII antagonists. The search system retrieved 139 compounds from the database MDDR-3D, which consisted of 29,400 medicinal patent compounds. A tricyclic compound was selected from the retrieved compounds and then evolved by considering steric fitness to the overlay model and synthetic feasibility. Finally, various novel AII antagonists having dibenzo[a,d]cycloheptene or dibenzo[b,f]oxepin were designed and synthesized. The receptor binding activity (Ki) for several members of this series was in the 10(-10) M range, demonstrating the ability of 3D search technique to explore new lead structures.

Angiotensin II↗
PubMed1995

Acute effects of inhalation exposure to carbon monoxide on schedule-controlled operant behavior and blood carboxyhemoglobin levels in rats.

The acute effects of carbon monoxide (CO) exposure on a steady-state operant behavior (bar-pressing under a VI 60-sec schedule of food reinforcement) were repeatedly measured in (a) rats exposed to various concentrations of CO (500, 1,000, 1,500 and 2,000 ppm) for 1 h and (b) rats exposed to 1,500 ppm for different periods (1, 2 and 4 h). Measurements were made continuously before, during and after the exposure period. Abrupt cessation of the response was produced by exposure to 1,000 ppm or higher concentrations of CO. Recovery from the effects of CO exposure was observed as sudden resumption of responding during the post-exposure period. The duration of exposure required to produce response inhibition was closely correlated with the exposure concentration. The post-exposure interval required for response recovery was also correlated with the exposure concentration. This post-exposure response recovery interval, however, was constant and independent of the duration of exposure when the concentration was fixed at 1,500 ppm. In order to correlate these behavioral changes with an internal index of CO exposure, blood carboxyhemoglobin (HbCO) levels were determined under several exposure conditions corresponding to those of the behavioral observations. It was found that HbCO levels were within a certain range (33-43%) when response recovery occurred, suggesting the existence of a critical HbCO level (threshold) associated with the drastic behavioral change. Hence, these results support the view that blood HbCO is an important determinant of the acute behavioral effects of CO.

Administration, Inhalation↗
PubMed1995

Increased serum angiotensin I-converting enzyme activity in patients with mixed connective tissue disease and pulmonary hypertension.

The relationship between serum angiotensin I-converting enzyme (ACE) activity, a possible marker of pulmonary endothelial injury, and the occurrence of pulmonary hypertension (PH) in patients with mixed connective tissue disease (MCTD) was investigated. Before corticsteroid therapy, the mean serum ACE level was 26.4 +/- 14.0 mU/ml in patients with MCTD and PH (n = 6), 16.8 +/- 4.1 mU/ml in patients with MCTD but without PH (n = 18), 16.8 +/- 4.1 mU/ml in patients with undifferentiated connective tissue disease (n = 14), and 16.5 +/- 3.9 mU/ml in controls (n = 18). No significant difference in the enzyme activity was found among the groups. However, 4 patients with MCTD showed increased ACE levels (> 28.3 mU/ml), and all of them had PH. Our results suggest that elevation of serum ACE activity may be related to the occurrence of PH in patients with MCTD.

Adolescent↗
PubMed1995

[Outcome of patients with chronic systemic lupus erythematosus].

We analyzed data on 69 Japanese patients who had been affected with systemic lupus erythematosus (SLE) for more than 10 years to clarify the clinical and social features of the chronic phase of this disease. There were 3 men and 66 women. Mean age at disease onset was 24.3 years, and the mean duration of disease was 17.4 years. In these patients, the mean number of relapses was 1.5, and the mean duration of the relapse was 4.7 years. These patients were receiving prednisolone at a mean dosage of 9.2 mg/day. While only 4 patients were thought to be in the active disease stage at the time of evaluation, hypercholesterolemia was present in 33.3% (20 patients out of 60) and 64. 3% (27 patients out of 42) showed a decrease in bone mineral content by DEXA method. Ten patients out of 69 patients (14.5%) had aseptic necrosis of the head of the femur (ANF). ANF was related to the relapse and the administration of immunosuppressant in the initial therapy. Seventeen female patients had gotten married after the onset of SLE and 14 patients became pregnant and gave birth. Of the 9 deaths that occurred, only 3 cases were thought to be due to SLE. Two patients died suddenly, and there was 1 case of acute heart failure. Mean age at death was 39.8 years old. However, data suggest that many patients in the chronic phase of SLE may have a reasonably high quality of life, despite the disease.

Adolescent↗
PubMed1995

[Resection of lung cancer complicated by pleural empyema].

In a 53-year-old man, carcinoma of the lung was resected and was complicated by pleural empyema. Two days after fiberoptic bronchoscopy, he developed a high fever and was found to have pleural empyema. After thoracic drainage and other palliative treatment, the right lower lobe and empyema cavity were resected. The postoperative course was uneventful and he was discharged 3 weeks after the operation, but he died of cervical and intrathoracic lymph node recurrence 5 months later. Surgical treatment of malignant lung cancer complicated by pleural empyema has been reported 10 times, including 3 reports from Japan. According to those reports, post-operative complications are rare, and long survival is possible. Therefore, surgical resection is indicated in some cases.

Carcinoma, Squamous Cell↗
PubMed1995

Electron microscopic observation of erythema nodosum with the eosinophilic infiltration. A case report.

The presence of eosinophils localized within an inflammatory skin lesion of a patient with erythema nodosum has been studied by electron microscopy. Among the intact eosinophils seen in the cellular infiltration, some underwent necrosis and released membrane-bound, free eosinophil granules into the interlobular septa of the subcutaneous fat. Such granules, identified by their central crystalline cores, often showed granular changes with core dissolution and were found scattered in the edematous space between the collagen bundles. A few intact eosinophils that showed minor alterations of cytoplasmic granules were also present. The significance of these findings, which may enhance endothelial permeability, is discussed.

Adult↗
PubMed1995

Combined drug therapy with diltiazem, dextran, and hydrocortisone (DDH therapy) for late cerebral vasospasm after aneurysmal subarachnoid hemorrhage: assessment of efficacy and safety in an open clinical study.

Late cerebral vasospasm after subarachnoid hemorrhage (SAH) is a disastrous phenomenon for the patients and a definite treatment has not been established. We studied 48 consecutive patients receiving high-dose diltiazem (5 micrograms/kg/min) injection combined with dextran and hydrocortisone to late cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH). All but 2 patients underwent surgery within 72 hours after SAH. Diltiazem was continuously given via a central venous line for up to 2 weeks in conjunction with simple cisternal drainage. 5% of dextran solution (500 ml/day) was infused for 7-10 days. Hydrocortisone was given 1,600 mg on the first day, then the dose was gradually decreased over 14 days. Symptomatic vasospasm (SVS) occurred in 5 patients (10.4%), 4 patients recovered, but 1 had severe neurological deficit. A low density area on CT-scan was observed in 2 patients. Thirty patients (62.5%) had good recovery, 10 patients (20.8%) had moderate disability, 3 (6.3%) had severe disability and 3 (6.3%) had vegetative survival. Two patients died of the initial brain damage. There were no severely hypotensive side effects. However, 3 patients showed atrioventricular blockage on electrocardiogram. These side effects subsided after the dose of the drug was decreased or administration was stopped altogether. These findings show that high-dose calcium antagonist diltiazem therapy combined with dextran and hydrocortisone injection is safe and effective for prevention of late cerebral symptomatic vasospasm after SAH.

Adult↗
PubMed1994

Proliferating cell nuclear antigen/cyclin expression in small adenomas of the large intestine in relation to size and macroscopic appearance.

Sixty-two colorectal adenomas 10 mm or less in diameter, resected endoscopically and fixed in formalin for 3 days or less, were evaluated with antiproliferating cell nuclear antigen/cyclin (PCNA) monoclonal antibody to investigate the cell proliferation kinetics. All lesions were tubular adenoma with low-grade atypia. These lesions were classified by macroscopic type as: I; polypoid (n = 14), IIa; flat or hemispherically elevated (n = 28), IIb; plain, flat (n = 6), IIc; depressed (n = 9), and IIa+IIc slightly elevated with a central depression (n = 5). The distribution patterns of PCNA-positive cells were divided into two types; diffuse distribution of positive cells throughout the crypts (diffuse type) and localized distribution, mainly in the upper portions of the crypts (superficial type). The distribution pattern of proliferating cells was correlated with the size and macroscopic type of adenoma. Type IIc, IIa+IIc, IIb, smaller (< or = 5 mm) IIa and smaller (5 mm) I adenomas showed the superficial type pattern. Larger (> 5 mm) adenomas of type I and IIa had the diffuse type pattern. The formation of a proliferative zone in small adenomas, as in normal mucosa, but in opposite locations, suggested a lower cell proliferation activity. In the elevated type (I and IIa) adenomas, however, the change in the distribution pattern of proliferating cells from the superficial to the diffuse type would lead to growth in size.

Adenoma↗
PubMed1994

Development of a sensitive two-site immunoradiometric assay for parathyroid hormone-related peptide: evidence for elevated levels in plasma from patients with adult T-cell leukemia/lymphoma and B-cell lymphoma.

We have developed a sensitive immunoradiometric assay for PTH-related peptide (PTHrP) using a monoclonal antibody against PTHrP(1-34) and a polyclonal antibody against PTHrP(50-83), with recombinant human PTHrP(1-87) as the standard. The detection limit of the immunoradiometric assay was 0.5 pmol/L, and plasma PTHrP(1-87) concentrations in 110 healthy subjects were 0.8 +/- 0.01 pmol/L, with the upper limit of the normal range being 1.1 pmol/L. Increased circulating PTHrP(1-87) concentrations were demonstrated in all 46 cancer patients with hypercalcemia, but not in patients with primary hyperparathyroidism, chronic renal failure, or hypoparathyroidism. Normalization of serum calcium levels after resection of tumors was shown to correlate well with that of plasma PTHrP(1-87) concentrations in 2 cancer patients. High circulating PTHrP(1-87) levels were also demonstrated in 12 out of 13 hypercalcemic patients with adult T-cell leukemia/lymphoma and in 7 out of 8 hypercalcemic patients with non-Hodgkin's lymphoma especially of B-cell type. These results suggest that PTHrP is a major humoral factor responsible for the hypercalcemia frequently associated with adult T-cell leukemia/lymphoma and also with B-cell lymphoma.

Adult↗
PubMed1994

Behavioral evidence for modified receptor sensitivity in rat brain induced by methyl bromide exposure.

To clarify the neurochemical basis of methyl bromide toxicity in rats, we measured changes in the sensitivity of cerebral monoamine, dopamine (DA) and norepinephrine (NE) receptors, using abnormal behavior and locomotor activity as indicators of receptor sensitivity. Apomorphine and clonidine were used as specific agonists of DA (D1 and D2) and NE (alpha 2) receptors, respectively. In the first experiment, rats were exposed to methyl bromide gas at 25-200 ppm for 8hr once or to methyl bromide at 5-50 ppm 8hr a day for 7 days. The intensity of stereotyped oral (STO) behavior produced by an injection of apomorphine, 0.5 mg/kg i.p., was rated over the following 28 days. The STO behavior of rats exposed to methyl bromide (MB rats) was much more intense than in air-exposed (control) rats. This finding strongly suggests that the sensitivity of striatal DA, D1 and D2, receptors to apomorphine was increased by methyl bromide exposure. In the second experiment, rats were exposed to 50 ppm methyl bromide for 8hr once or to 10-50 ppm methyl bromide 8hr a day for 7 days. Seven days after the final exposure, rats were injected with a small dose of apomorphine, 0.3 mg/kg i.p., and the counts of apomorphine-induced locomotor activity (ALA) were recorded. The ALA counts of MB rats were markedly higher than in the control rats. This finding suggests that the DA receptors in the nucleus accumbens of MB rats are more sensitive to apomorphine than those of control rats. In the third experiment, rats were exposed to 50 ppm methyl bromide, 8hr a day for one day or 7 consecutive days, and the degree of attenuation of locomotor activity following clonidine injection (CLA) was rated. CLA counting was performed 7 days after the final exposure. CLA counts in MB rats were not attenuated as much as in the control rats. This indicates that the cerebral NE receptors, i.e., alpha 2-adrenoceptors, of MB rats may be less sensitive to clonidine than those of control rats. Increased behavioral sensitivity to apomorphine was observed in rats even when exposed to 5 ppm (TLV) methyl bromide.

Animals↗
PubMed1994

Neurochemical profile of effects of 28 neurotoxic chemicals on the central nervous system in rats (1). Effects of oral administration on brain contents of biogenic amines and metabolites.

We investigated the effects of oral administration of 28 organic chemical agents, all of which possess neurotoxicity and most of which are used as industrial solvents, on monoamine neurotransmitters and metabolites in the rat brain. Each chemical was administered to rats singly at a dose of one-quarter the LD50 value. Two hours after administration, acetylcholine, 3,4-dihydroxyphenylalanine (DOPA), dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), norepinephrine, 3-methoxy-4-hydroxyphenylglycol (MHPG), serotonin, and 5-hydroxyindoleacetic acid (5HIAA) contents in the small-brain regions were measured. Twenty-one of the 28 chemicals increased acetylcholine in the hippocampus, a ratio (21/28) far higher than the 0.5 expected were these chemicals to have no tendency to increase or decrease acetylcholine. This ratio was calculated for each brain substance. Large differences from 0.5 were also obtained for DOPAC (higher), and for 5HIAA and three neurotransmitters (dopamine, norepinephrine, and serotonin) in the hypothalamus (all lower). The ratios for MHPG and 5HIAA in the medulla oblongata were very high. In the hypothalamus, the concentrations of brain substances were easily altered by the test chemicals, and the turnover rates of hypothalamic norepinephrine and serotonin in the medulla oblongata seemed to be accelerated. Several lines of evidence obtained in previous studies suggest that the increased acetylcholine content in the brain homogenate induced by organic solvents such as toluene may be due to a decrease in acetylcholine release from nerve terminals. Based on the results of the present experiment and previous studies, this acetylcholine suppressing property appears to be common to solvents which possess anesthetic properties.

Administration, Oral↗
PubMed1994

[Sudden deafness in the elderly].

We investigated the clinical features of 64 cases of sudden deafness in patients more than 60 years of age. Forty-eight cases (75%) had profound deafness, 13 moderate and three mild deafness. The audiograms of 25 cases showed a flat pattern, 13 a gradually descending curve, and 13 total deafness. In 60 cases, the unaffected ear also had hearing impairment of variable severity. Fifty-one of these 60 cases demonstrated a physiological hearing threshold shift termed presbycusis in the unaffected ear. Hearing impairment in 35 cases (55%) was cured or improved by medical treatment including steroids. But in the majority of cases, the hearing threshold level of the affected ear did not improve above that of the unaffected ear when the unaffected ear had a hearing impairment. In particular, hearing impairment in five cases with total deafness in the unaffected ear did not improve. The elderly often had various systemic complications, including nine cases of diabetes and seven of hypertension. We treated patients with diabetes using steroids under the consultation of diabetic specialists. As a result, there was no case of complications induced by steroids. We consider the effect of treatment of sudden deafness in the elderly to be best judged in various degrees of hearing impairment in the unaffected ear.

Aged↗