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Biomedical subjects

Y Hirota

Publications and source records attributed to Y Hirota.

At least 397 records · Page 22Linked to original sources
PubMed1986

[Clinical investigation of the therapeutic effects of cefmenoxime in the treatment of infections complicated by hematological diseases].

Therapeutic effects on cefmenoxime hemihydrochloride (CMX, Bestcall), a new synthetic cephem antibiotic, were examined in the treatment of various infections complicated with hematological diseases. The number of patients treated with CMX was 37 including 5 cases of sepsis or suspected sepsis, 14 cases of pneumonia or suspected pneumonia, 5 cases of upper respiratory diseases, 2 cases of urinary tract infections and 11 cases of other infections. All of these infections were complicated with hematological diseases: Acute leukemia, 13 cases; chronic myelocytic leukemia, 1 case; adult T cell leukemia, 3 cases; malignant lymphoma, 8 cases; Hodgkin's disease, 2 cases and myeloma, 3 cases. CMX were administered by a single intravenous injection or by a drip infusion. The dose was between 2 and 6 grams per day. Good to excellent clinical results were obtained in 25 out of 37 cases, total effective rate of 67.6%. No clinical side effects or abnormal laboratory findings attributable to CMX were observed except for light diarrhea in 2 cases. By the clinical investigation, it was demonstrated that CMX was one of safe and effective antibiotics for treating infections in the compromised hosts complicated with hematological diseases.

Acute Disease↗
PubMed1986

Phase I clinical and pharmacokinetic study of N4-behenoyl-1-beta-D-arabinofuranosylcytosine.

A phase I study of N4-behenoyl-1-beta-D-arabinofuranosylcytosine (BHAC) was conducted in 66 patients, 41 with solid tumors and 25 with hematological malignancies. The patients received either a 2-h single intravenous (i.v.) drip infusion (Schedule 1) or consecutive daily 2-h i.v. infusions (Schedule 2). In Schedule 1 the daily dose was initiated with 1.5 mg kg-1 which was escalated up to 7 mg kg-1. Side-effects were mild, and included nausea, vomiting, epilation, and hot flushes. Because of the presence of the solvent vehicle, HCO-60 and in consideration of the mechanism of action of BHAC, the dose escalation was stopped at 7 mg kg-1. In Schedule 2, the daily dose was started with 1.5 mg kg-1 which was escalated up to 8 mg kg-1 and given for 2-16 days. Myelosuppression was found to be dose-limiting toxicity. The maximum tolerated dose (MTD) in patients with non-hematological solid tumors was assumed to be 5 mg kg-1 daily X 5 days. The plasma disappearance curve of BHAC looked biphasic, and when 4 mg kg-1 of BHAC were administered the half-lives of the initial phase (t1/2 alpha) and the second phase (t1/2 beta) were calculated as 0.798 and 5.76 h respectively. In Schedule 2 complete remission was observed in 5 out of 21 patients with acute leukemia, one partial remission in Hodgkin's disease, and one 1-B response (Karnofsky) in thyroid papillary adenocarcinoma.

Adult↗
PubMed1986

[The natural history of dilated cardiomyopathy and pathophysiology of congestive heart failure].

To clarify the natural history and mechanisms of compensation and decompensation in dilated cardiomyopathy (DCM), the hemodynamic and follow-up data of 52 patients who underwent cardiac catheterization between April 1976 and July 1984 were evaluated. The symptoms of the majority of 42 patients who were in severe congestive heart failure (CHF) (New York Heart Association Functional Class IV) on admission were improved. Two were in Class I, 22 in Class I, 22 in Class III, only six remaining in Class IV at the times of their catheterizations one to two months post admission. The patients were categorized as compensated (Class I and II) and decompensated (Class III and IV), and their data were compared with those of 30 normal subjects. Cardiac status was evaluated at the end of August 1984, and the mean follow-up period was 44 months. The hemodynamic and angiographic characteristics of DCM consisted of an enlarged and poorly contracting left ventricle, with an increased left ventricular (LV) muscle mass, low LV systolic pressure, reduced cardiac output, and elevated systemic vascular resistance. LV volume was larger, and the ejection fraction (EF) was more reduced in the decompensated group in association with elevated preload and afterload. Preload and afterload were within the normal range in the compensated group. LV wall thickness tended to decrease in the decompensated group, and the LV muscle masses did not differ between these two groups. There was a significant inverse correlation between afterload and EF (r = -0.57, p less than 0.01) in DCM. There were five sudden deaths and five CHF deaths, and cardiac symptoms improved in the majority of the survivors. One, two and five year survival rates were 91.2%, 79.8%, and 72.5%, respectively. No hemodynamic variables could be available to predict the prognosis except for the LV end-diastolic pressure and stress. It is concluded that the absence of adequate compensatory hypertrophy and the inappropriate elevation of afterload, or so-called "afterload mismatch" plays an important role in the development of CHF, in addition to depressed contractility in DCM. Persistent elevation of preload despite vigorous medical treatment indicates a poor prognosis. No other hemodynamic variables were good indicators of prognosis.

Blood Pressure↗
PubMed1985

Treatment of acute myelogenous leukemia in adults with N4-behenoyl-1-beta-D-arabinofuranosylcytosine.

Forty-five previously-untreated adult patients with acute myelogenous leukemia (AML) were treated with N4-behenoyl-1-beta-D-arabinofuranosyl-cytosine (BHAC) in a multi-institutional cooperative study. Among 41 evaluable patients, 15 (36.6%) achieved complete remission (CR) and 10 (24.4%) achieved partial remission by daily administration of 3 to 8 mg/kg of BHAC. Higher daily doses (5 mg/kg or more) produced higher CR rates, and all of the CR were observed among the patients receiving a total BHAC dosage of 50 mg/kg or more in a period of 10 days or more. The side effects were mild and acceptable: nausea-anorexia was observed in 27% of the patients and vomiting in 17%. The results of this study thus indicate BHAC to be effective for remission induction of AML, and to deserve further clinical trials in combination with other anti-leukemic drugs.

Adolescent↗
PubMed1985

Sites of dnaA protein-binding in the replication origin of the Escherichia coli K-12 chromosome.

On the basis of the observation that dnaA protein binds preferentially to DNA fragments carrying the Escherichia coli chromosomal replication origin (oriC), the binding sites were investigated by DNase I footprinting. As a result, three strong binding sites were identified in the minimal oriC sequence. The respective binding sites were 16 to 17 base-pairs long, and contained a common sequence (5') T-G-T-G-(G/T)-A-T-A-A-C (3') in the middle, although their polarities were not the same. Since mutants defective in function for autonomous replication have been isolated in the corresponding positions of the common sequence at each binding site, dnaA protein-binding at these sites seems to be significant for replication initiation.

Bacterial Proteins↗
PubMed1985

Purification and sequencing of the active site tryptic peptide from penicillin-binding protein 1b of Escherichia coli.

This paper reports the sequence of the active site peptide of penicillin-binding protein 1b from Escherichia coli. Purified penicillin-binding protein 1b was labeled with [14C]penicillin G, digested with trypsin, and partially purified by gel filtration. Upon further purification by high-pressure liquid chromatography, two radioactive peaks were observed, and the major peak, representing over 75% of the applied radioactivity, was submitted to amino acid analysis and sequencing. The sequence Ser-Ile-Gly-Ser-Leu-Ala-Lys was obtained. The active site nucleophile was identified by digesting the purified peptide with aminopeptidase M and separating the radioactive products on high-pressure liquid chromatography. Amino acid analysis confirmed that the serine residue in the middle of the sequence was covalently bonded to the [14C]penicilloyl moiety. A comparison of this sequence to active site sequences of other penicillin-binding proteins and beta-lactamases is presented.

Amino Acids↗
PubMed1985

Enhancement of erythroid progenitor cell growth in medium conditioned by a human cancer cell line, KONT.

Erythroid-potentiating activity (EPA) was detected in culture medium conditioned by a human cancer cell line (KONT) that produces colony-stimulating activity (CSA), using erythroid colony formation in vitro. EPA in the medium conditioned by the KONT cells (KONT-CM) was markedly heat stable. After treating KONT-CM at 80 degrees C for 30 min, 30% EPA remained, while CSA was completely inactivated. Both EPA and CSA appeared in approximately the same fractions of the gel filtration, indicating a molecular weight of approximately 30,000 daltons. EPA bound partially to Concanavalin-A Sepharose, whereas CSA almost did not bind. Our results indicate that EPA can be separated from CSA based on heat stability and binding to Concanavalin-A Sepharose.

Cell Division↗
PubMed1985

Binding of penicillin to thiol-penicillin-binding protein 3 of Escherichia coli: identification of its active site.

In order to determine the active site of penicillin-binding protein 3 of Escherichia coli (PBP3), the serine residue at position 307 was replaced with alanine, threonine or cysteine by oligonucleotide-directed site-specific mutagenesis. Since a unique BanII site exists at the position corresponding to serine-307, BanII digestion of the plasmid DNA after mutagenesis resulted in significant enrichment of the mutant plasmids. For mutagenesis, the gene coding for PBP3 (ftsI) was inserted into the expression cloning vector pIN-IIB. The hybrid protein produced was able to bind penicillin while mutant PBP3 in which serine-307 was replaced with either alanine or threonine did not lead to any detectable binding. However, contrary to the report of Broome-Smith et al. (1985) thiol-penicillin-binding protein 3, in which serine-307 was replaced with cysteine, was still able to bind penicillin. Replacement of serine-445 with an alanine residue had no effect on penicillin binding to PBP3.

Acyltransferases↗
PubMed1985

Dispensability of either penicillin-binding protein-1a or -1b involved in the essential process for cell elongation in Escherichia coli.

A strain of Escherichia coli lacking the entire ponB gene and a strain lacking the proximal part of the ponA gene were constructed by substitution with a drug resistance gene. These strains lost either penicillin-binding protein(PBP)-1b or -1a totally and their growth was apparently normal at 30 degrees C and 42 degrees C except that growth of the ponB deletion strain was poor on a nutrient agar plate containing no NaCl at 30 degrees C as well as at 42 degrees C. Transductional experiments to introduce the ponB deletion into the ponA deletion strain, and vice versa, showed that the ponA ponB double deletion was lethal unless the deletion was functionally compensated, e.g., by the presence of a plasmid carrying either gene. Thus, either PBP-1b (ponB) or PBP-1a (ponA), but not both, is dispensable for cell viability, at least under ordinary culture conditions. Transductional experiments also suggested that the gamma component of PBP-1b or the PBP-1b lacking the C-terminal portion encoded in the distal region to the SphI site on the ponB was sufficient for supporting growth of the E. coli cell.

Acyltransferases↗
PubMed1985

Electron-microscopic and immunohistochemical studies on endomyocardial biopsies from a patient with eosinophilic endomyocardial disease.

Light- and electron-microscopic studies and immunohistochemical procedures were carried out on blood eosinophils and left ventricular endomyocardial biopsies from a 68-year-old man with an eosinophilia of 8.2 X 10(9)/l and congestive cardiac failure due to eosinophilic endomyocardial disease. Some blood eosinophils were vacuolated and degranulated, and reversal of the normal staining pattern of eosinophil granules was seen by means of electron microscopy. The biopsies showed degenerative changes in the cardiac myocytes, with interstitial fibrosis and infiltration by numerous eosinophils, mast cells, and macrophages. Eosinophils infiltrating the myocardium showed a decrease in the number of granules, many of which were indistinct or contained dissolving crystalloids, which occasionally were seen to be discharged onto the surface of adjacent cardiac myocytes. Immunohistochemical studies of the endomyocardial biopsies with a monoclonal antibody, which is specific for activated eosinophils and binds to the secreted forms of eosinophil cationic protein (ECP) and eosinophil protein-X (EP-X), demonstrated that the lesions contained numerous activated eosinophils and secreted ECP and EP-X. These findings support the concept that in eosinophilic endomyocardial disease, activated eosinophils infiltrate and degranulate in the myocardium, releasing eosinophil cationic proteins which then damage adjacent myocardial cells.

Aged↗
PubMed1985

Factors discriminating survivors and nonsurvivors in alcoholic heart disease.

Eighteen patients with dilated cardiomyopathy and a history of excessive ethanol intake were monitored for 3-98 months (mean 23 months). Six patients died (mean age 43.7 +/- 9.2 years) and 12 patients survived (mean age 48.8 +/- 9.5 years). Of the echocardiographic findings taken during heart failure, only the relative wall thickness to the internal dimension of the left ventricle (t/r ratio) differed significantly (survivors 0.33 +/- 0.77 vs. nonsurvivors 0.25 +/- 0.04, P less than 0.05). Of the hemodynamic data obtained after treatment of heart failure, left ventricular end-diastolic pressure differed significantly (survivors 6 +/- 2 vs. nonsurvivors 12 +/- 4 mmHg, P less than 0.001). The two groups could not be differentiated by ejection fraction, cardiac output, end-diastolic or end-systolic volumes, or semi-quantitative analysis of histologic findings obtained by right ventricular endomyocardial biopsy (light microscopy). Only two of six nonsurvivors (33%) succeeded in abstaining from alcohol, while eight of twelve survivors (67%) became teetotalers (P less than 0.05). Total abstinence from alcohol seems to be essential but was not necessarily followed by recovery in the most severe cases. Thus, the absence of adequate hypertrophy and high left ventricular filling pressure may predict the prognosis in alcoholic heart disease.

Adult↗
PubMed1985

Alterations in circulating thyroid hormones and thyrotropin in euthyroid patients with Graves' disease after total thyroidectomy: comparison between responders and nonresponders to TSH-releasing hormone.

Eleven euthyroid patients with severe exophthalmos of Graves' disease who had been treated with antithyroidal drugs for one to three years prior to total thyroidectomy were studied. All patients were clinically and biochemically euthyroid at the time of operation. According to their responses of TSH to TRH prior to operation, the patients were divided into two groups: (1) five responders and (2) six nonresponders. In group 1, serum TSH levels increased significantly on the third day after thyroidectomy (from 1.5 +/- 0.3 to 8.6 +/- 1.4 microU/mL: P less than 0.05); serum T4 concentrations decreased significantly and were in the hypothyroid range by the third day. In group 2, serum TSH levels rose from 0.5 +/- 0.01 to 3.2 +/- 0.5 microU/ml (P less than 0.05) on the ninth postoperative day; serum T4 concentrations decreased on the third day after operation but did not attain hypothyroid levels until the 12th day. Thus after total thyroidectomy the following are concluded: (1) serum TSH levels even in treated euthyroid patients with Graves' disease, rose more gradually in TRH-nonresponders in comparison with TRH responders; (2) the time when serum TSH elevation occurs is dependent upon serum concentrations of thyroid hormones (serum T3 and T4).

Adult↗
PubMed1985

Clinicopathological study of the heart and coronary arteries of autopsied cases from the community of Hisayama during a 10-year period. Part V. Comparison of autopsy findings with electrocardiograms--Q.QS items of the Minnesota Code.

In a longitudinal study of a general population in Hisayama, Japan, 339 persons aged 40 years or over at death were autopsied during the period November 1, 1961-October 31, 1971. In 308 of these people, electrocardiograms taken at the periodic examinations were available, and Q.QS items of the Minnesota Code were recorded in 49 persons. The sensitivity of item 1-1 to autopsy-proven old myocardial infarction was 0.32 and the specificity was 0.95. Using the estimated prevalence of old myocardial infarction in this community--77 per 100,000--the proportion of persons without old myocardial infarction among those with item 1-1 in the general population (PF+) was 0.9954 and the proportion of persons with old myocardial infarction among those without item 1-1 (PF-) was 0.0005. The sensitivity of items 1-1 and 1-2 to old myocardial infarction was 0.43 and the specificity was 0.94. PF+ of items 1-1 and 1-2 was 0.9949 and PF- was 0.0005. These large values of PF+ mean that more than 99 per cent of persons with these items are probably false positives if these items are used as a screening test for this disease in the general population of this community, i.e., that these items cannot be defined as a definite myocardial infarction.

Aged↗
PubMed1985

Identification of the active site in penicillin-binding protein 3 of Escherichia coli.

We report the sequence of the active site tryptic peptide of penicillin-binding protein 3 from Escherichia coli. Purified penicillin-binding protein 3 was labeled with [14C]penicillin G and digested with trypsin, and the resulting radioactive peptides were isolated by a combination of gel filtration and high-pressure liquid chromatography. The major radioactive peak from high-pressure liquid chromatography was sequenced, and the peptide Thr-Ile-Thr-Asp-Val-Phe-Glu-Pro-Gly-Ser-Thr-Val-Lys, which comprises residues 298 to 310 in the amino acid sequence, was identified. This sequence is compared with the active site sequences from other penicillin-binding proteins and beta-lactamases.

Acyltransferases↗
PubMed1985

Immunogenetics of Hashimoto's and Graves' diseases.

Haplotypes of the human major histocompatibility complex (HLA) and the immunoglobulin allotype (Gm) were analyzed in all 243 members of 37 families in which 2 or more first degree relatives had Graves' disease. In 10 families with 70 members where 1 or more first degree relatives had Hashimoto's disease, 26 (37%) had Graves' disease, and 14 (20%) had Hashimoto's disease. In the other 27 families, consisting of 173 members, 70 (40%) had Graves' disease, and none had Hashimoto's disease. The disease-associated haplotypes of HLA and Gm for each family were identified by determining the haplotypes concordant in 2 members with Graves' disease. In 10 families with Graves' and Hashimoto's diseases, all 14 members with Hashimoto's disease had the same disease-associated haplotypes of both HLA and Gm as had members with Graves' disease in each family. Among 96 members with Graves' disease in 37 families, 74 were used for the determination of the disease-associated haplotypes. In the remaining 22 members with Graves' disease, 21 had both disease-associated haplotypes in their families. Our findings in these families suggest that 1) in Hashimoto's disease as in Graves' disease, two genes linked to HLA and Gm, respectively, control the susceptibility of the disease; 2) common immunogenetic factors are involved in the pathogenesis of both Hashimoto's and Graves' disease, and 3) those who do not have immunogenetic factors are very unlikely to develop Hashimoto's or Graves' disease.

Female↗
PubMed1985

A long term clinical, immunological, and histological follow-up study of patients with goitrous chronic lymphocytic thyroiditis.

Goiter size, thyroid function, antimicrosomal and antithyroglobulin antibodies, and thyroid histology were compared in 43 patients with goitrous chronic lymphocytic thyroiditis (Hashimoto's disease) confirmed by biopsy before and after an interval of 10-20 yr. Although all were given thyroid hormone therapy, 13 patients took it infrequently, and are considered untreated. Among these 13 patients, 5 (38%) became hypothyroid, and 1 became thyrotoxic. Goiter size decreased in 17 (57%) of 30 patients during therapy and in 3 (23%) of 13 untreated patients, and the incidence of reduction was greater in treated than in untreated patients (P less than 0.05). However, in 13 (43%) of the patients, goiter size did not decrease even during treatment. Titers of antithyroid antibodies decreased in only 8 (21%) of 38 patients. There was no significant correlation between changes in antibodies and the size of goiter, and treatment with thyroid hormone did not decrease the titers of antibodies. In patients whose goiters were initially diffusely enlarged and regressed significantly in size during the follow-up period, the initial biopsies showed histological changes in diffuse lymphocytic infiltration and diffuse epithelial changes. Comparative studies of histological differences between patients who were treated with thyroid hormone and those who were not were made in the patients who had no change in goiter size during the observation period, which was greater than 10 yr. The histological changes were similar in both groups at the beginning of the study, and no significant histological changes during the period of greater than 10 yr were found in either group. In one patient who developed thyrotoxicosis after 20 yr and was rebiopsied, the histological picture was that of thyroid hyperplasia and lymphocytic thyroiditis. These data indicate that goitrous chronic lymphocytic thyroiditis changes little as a function of time in many patients regardless of whether thyroid hormone is administered.

Autoantibodies↗