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Biomedical subjects

Y Homma

Publications and source records attributed to Y Homma.

At least 217 records · Page 12Linked to original sources

[Clinical criteria for definition of idiopathic interstitial pneumonia (IIP)].

Clinical criteria for definition of IIP proposed in 1991 by the Project Team for Diffuse Lung Diseases Organized by Japanese Ministry of Health and Welfare are reviewed. After the clinical roentgenological, and pathological researches of 92 IIP patients, we concluded that IIP patients were grouped into two clinical types, acute and chronic, by their clinical courses and characteristic pathological findings. The latter is, moreover, grouped into two types, typical and atypical, by their morphological characteristics. The acute type are represented by alveolitis with marked edema and cell infiltration of alveolar wall, and by hyaline membrane formation. "Typical" of chronic types only have typical pathologic changes of interstitial pneumonia and/or fibrosis represented by honeycombing. "Atypical" have both those interstitial changes and intra-alveolar scar formation and fibrosis due to organized pneumonia and secondarily occurred emphysema such as bulla as well. The continuity in clinical courses between acute and chronic types are still obscure.

Acute Disease↗

Highly conserved eight amino acid sequence in SH2 is important for recognition of phosphotyrosine site.

Src homology region 2(SH2) has been demonstrated to recognize phosphotyrosine site. To clarify the precise mechanism of the recognition, we developed in vitro binding assay system using EGF receptor and SH2/SH3 region of phospholipase C(PLC) gamma 1. Phosphorylated EGF receptor bound to immobilized SH2/SH3 of PLC gamma 1 in Sepharose beads, while nonphosphorylated EGF receptor did not bind. In SH2 domain of PLC gamma 1, there are several highly conserved amino acid sequences that are common in a variety of SH2-containing proteins. Especially the eight amino acid sequence, G(S/T)FLVR(E/D)S is highly conserved in these proteins. We synthesized several peptides related to these sequences and examined the effect of peptides on the binding of EGF receptor to SH2 of PLC gamma 1. P1, GSFLVRES was the most effective inhibitor to suppress the binding. P2, GSFLVAES in which one amino acid, arginine of P1 is substituted by alanine is still effective. But a peptide, P3, SFLVRE in which two amino acids are deleted from P1 did not inhibit markedly. Moreover, P1 peptide immobilized in Sepharose beads also bound phosphorylated EGF receptor. These data suggest that highly conserved amino acid sequence GSFLVRES is the minimum essential unit to recognize tyrosine phosphorylated site.

Amino Acid Sequence↗

A short sequence responsible for both phosphoinositide binding and actin binding activities of cofilin.

Cofilin is a widely distributed actin-modulating protein that has abilities to bind along the side of F-actin and to depolymerize F-actin. Both abilities of cofilin can be inhibited by phosphoinositides such as phosphatidylinositol, phosphatidylinositol 4-monophosphate, and phosphatidylinositol 4,5-bisphosphate (PIP2). We have previously shown that the synthetic dodecapeptide corresponding to Trp104-Met115 of cofilin is a potent inhibitor of actin polymerization (Yonezawa, N., Nishida, E., Iida, K., Kumagai, H., Yahara, I., and Sakai, H. (1991) J. Biol. Chem. 266, 10485-10489). In this study, we have found that the inhibitory effect of the synthetic dodecapeptide on actin polymerization is canceled specifically by phosphatidylinositol, phosphatidylinositol 4-monophosphate and PIP2. We further show that the dodecapeptide as well as cofilin binds to PIP2 molecules and inhibits PIP2 hydrolysis by phospholipase C. Thus, the actin-binding dodecapeptide sequence of cofilin may constitute a multifunctional domain in cofilin.

Actin Depolymerizing Factors↗

[Evaluation of muscle layer of the uterine body by dynamic MRI].

Gd-DTPA enhanced dynamic MR imaging was performed in 11 normal uteri using a 1.5-T MR unit in order to analyze normal dynamic patterns. After intravenous bolus administration of Gd-DTPA, dynamic study was performed with serial imaging-gradient echo (FLASH). In most cases of normal uteri, early enhancement was shown in peripheral zone that was similar to be junctional zone, forming inner region of muscle layer.

Contrast Media↗

Two types of phosphatidylinositol 3-kinase from bovine thymus. Monomer and heterodimer form.

Two types of phosphatidylinositol (PI) 3-kinase (PI3K) have been purified 6250-fold (PI3KI) and 1250-fold (PI3KII) from the cytosol fraction of bovine thymus. Purified PI3KI and PI3KII were found to have apparent molecular masses of 110 and 190 kDa, respectively, by gel filtration. On the other hand, on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, while the molecular mass of PI3KI was again estimated as 110 kDa, PI3KII showed two bands with apparent molecular masses of 110 and 85 kDa, suggesting a heterodimer form. Peptide mapping analysis demonstrated that the 110-kDa protein in PI3KII was the same protein as PI3KI. The specific activity of PI3KI was calculated as 250 nmol/min/mg of protein, while that of PI3KII was 50 nmol/min/mg of protein. The product of PI phosphorylation by PI3KI and PI3KII were confirmed as phosphatidylinositol 3-phosphate by PartiSphere Sax column chromatography. The results show that there are two types of PI 3-kinase in bovine thymus. One exists as a monomer and the other as a heterodimer form. Furthermore, the biochemical properties of these two PI 3-kinases are markedly different. These two types of PI 3-kinase may be regulated differently under physiological conditions.

1-Phosphatidylinositol 4-Kinase↗

Effects of probucol on plasma lipoprotein subfractions and activities of lipoprotein lipase and hepatic triglyceride lipase.

The effects of 12 weeks treatment with probucol on plasma lipoprotein subfraction levels and on LPL and HTGL activities were investigated. Plasma VLDL-C, VLDL-TG, VLDL-apo B levels were not changed. Probucol significantly reduced plasma IDL-C and IDL-apo B levels by 26.7% and 23.8%, respectively. Plasma cholesterol and apo B levels of large light LDL (LDL1) were decreased significantly by 27.8% and 23.2% by probucol treatment. Plasma cholesterol and apo B levels of small heavy LDL (LDL2) remained unchanged. Probucol markedly reduced plasma HDL2 levels. The reduction rates of plasma TC, TG and apo A-I levels of HDL2 were 43.0%, 43.6% and 47.0%. Probucol significantly decreased HDL3-C and HDL3-apo A-I levels by 18.0% and 19.2%. LPL activities in the post-heparin plasma were decreased significantly from 2.53 +/- 0.71 mumol free fatty acids (FFA)/ml/h to 1.71 +/- 0.71 mumol FFA/ml/h by probucol while HTGL activities remained unchanged. We conclude that probucol suppresses LPL activity and decreases plasma IDL, LDL1 and HDL2 levels due to disturbances of VLDL conversion to LDL1 via IDL and of HDL3 conversion to HDL2.

Aged↗

Effects of eicosapentaenoic acid on plasma lipoprotein subfractions and activities of lecithin:cholesterol acyltransferase and lipid transfer protein.

The effects of 12 weeks eicosapentaenoic acid (EPA) administration (2.7 g/day) on plasma lipoprotein subfraction levels and on activities of lecithin: cholesterol acyltransferase (LCAT) and lipid transfer protein (LTP) were investigated. Plasma VLDL-C, VLDL-TG, VLDL-PL, VLDL-apo B, VLDL-apo C-II and VLDL-apo C-III levels were decreased by 32.8% (P less than 0.05), 31.2% (P less than 0.01), 31.5% (P less than 0.05), 32.5% (P less than 0.05), 34.7% (P less than 0.05) and 34.1% (P less than 0.05), respectively. EPA did not change plasma IDL-TC, IDL-TG, IDL-PL and IDL-apo B levels. Plasma large, light LDL (LDL1)-TC, LDL1-PL and LDL1-apo B levels were decreased by EPA by 18.7% (P less than 0.02), 19.1% (P less than 0.01) and 23.3% (P less than 0.01) while LDL1-TG level was not changed. Plasma small, heavy LDL (LDL2)-TC level was increased by 25.7% (P less than 0.02) while LDL2-TG, LDL2-PL and LDL2-apo B levels were not altered. Plasma HDL2-TC, HDL2-TG, HDL2-PL and HDL2-apo A-I levels stayed unchanged by EPA treatment. EPA did not affect plasma HDL3-TC, HDL3-PL and HDL3-apo A-I levels but decreased HDL3-TG level significantly (P less than 0.02). LCAT activity was not altered by EPA. LTP activity was increased by 24.8% at 4 weeks (P less than 0.02) and by 32.1% (P less than 0.001) at 12 weeks EPA treatment. We conclude that EPA reduces plasma large, light LDL levels as well as plasma VLDL amounts and stimulates LTP activities.

Adult↗

Lack of bladder carcinogenicity of dietary sodium saccharin in analbuminaemic rats, which are highly susceptible to N-nitroso-n-butyl-(4-hydroxybutyl)amine.

A previous 1-wk study measuring the agglutinability of bladder epithelial cells by concanavalin A had suggested a high susceptibility of analbuminaemic rats to bladder carcinogenesis by sodium saccharin (Honma et al., Cancer Letters 1983, 19, 7). A long-term study was conducted to confirm the results of this short-term assay. Sodium saccharin was administered at 5% in the diet to groups of 35 male analbuminaemic rats and 36 male rats of the Sprague-Dawley strain. No bladder carcinomas nor precancerous lesions were observed in any of the rats exposed to sodium saccharin. The discrepancy between the results of the agglutination assay and the long-term experiment might be attributable to a sharp increase in urine volume in analbuminaemic rats during the first week of treatment. The resultant distension of the bladder wall might make the epithelial cells more susceptible to concanavalin A agglutination. The results indicated no demonstrable bladder carcinogenicity of sodium saccharin in analbuminaemic rats and excluded the possibility that these particular mutant rats could be useful animals for shorter-duration screening for bladder carcinogens.

Administration, Oral↗

Spectral and waveform characteristics of fine and coarse crackles.

Two acoustically different types of lung crackles, fine and coarse, occur in different pathophysiological conditions. To differentiate these crackles from objective characteristics of frequency information, crackles were recorded from 16 patients with pulmonary fibrosis judged clinically to have "fine" crackles and from 10 with chronic bronchitis who had mainly "coarse" crackles. Time expanded waveforms (1/4 cycle duration, initial deflection width, two cycle duration, and 9/4 cycle duration; duration of the first 1/4, 2/4, 8/4, and 9/4 cycles of crackle waveforms) were examined and fast Fourier transform analysis (peak and maximum frequencies) was performed. All waveform measurements for fine crackles were significantly smaller than those for coarse crackles. Peak and maximum frequencies for fine crackles were significantly higher than those for coarse crackles. Although there was some overlap in these values for individual crackles between the two groups when average values of these measurements were calculated for each patient, there was no overlap between fine and coarse crackles and the two groups could be clearly separated. Log peak frequency and log maximum frequency correlated better with 9/4 cycle duration (r = 0.85, 0.84) and two cycle duration (r = 0.87, 0.86) than with 1/4 cycle duration (r = 0.66, 0.77) or initial deflection width (r = 0.67, 0.79). Early and late segments of crackles have different characteristics, probably related to the origin of the sound and the resonance of the lung respectively. These results suggest that spectral and waveform characteristics may help to improve the accuracy of pulmonary auscultation and increase knowledge of how crackles are generated.

Adult↗

[Treatment of renal cell carcinoma with human lymphoblastoid interferon alpha and UFT in combination. A prospective multicenter trial].

A cooperative study of combination of UFT (a compound of FT and Uracil) and human lymphoblastoid interferon (IFN-alpha) was conducted in the cases of metastatic renal cell cancer. IFN-alpha was administered over 3 times a week at a dose of 3 X 10(6) units in combination with UFT at a daily dose of 600 mg FT equivalent. Twenty-eight patients from 16 collaborating institutions were the subjects of the present study. The antitumor effects of the drugs were clinically evaluable in 25 cases according to the response criteria of Japan Society for Cancer Therapy. Complete responses and partial responses were observed in 3 and 2 cases, respectively, showing a response rate of 20 per cent. One complete responder had bone and liver metastases and has been alive for more than 2 years without any evidence of relapse. All of the other responders had lung metastasis. The survival durations of the other two complete responders were 716 days and 255 days. The two partial responders had been alive for more than 819 days and 471 days. The adverse effects of this combination therapy were minimal. Combination of a biological response modifier and a cancer chemotherapeutic agent seems to be a way to increase the treatment efficacy of renal cell cancer.

Antineoplastic Combined Chemotherapy Protocols↗

[The urodynamic effects of an alpha 1-adrenoceptor agonist on the bladder and urethra of female dogs].

It has been known that alpha 1-adrenoceptors play an important role in urethral contraction. The incompetence of the urethral contraction is a cause of stress incontinence. We studied the urodynamic effects of a selective alpha 1-adrenoceptor agonist (midodrine hydrochloride) on the bladder and urethra of female dogs. Under anesthesia with intravenous chloralose, four doses (0.03, 0.1, 0.3 and 1.0 mg/kg) of midodrine were administered intravenously and urodynamic studies including cystometry, urethral pressure profilometry and electromyography (EMG) of the external urethral sphincter were performed. The administration of midodrine induced a significant increase of the maximum closing pressure in the proximal portion of the urethra (p less than 0.05 at 0.03 mg/kg and p less than 0.01 at 0.1, 0.3, 1.0 mg/kg). There were no significant changes in the functional profile length, the closing pressure at the external sphincters, the maximum bladder pressure, bladder capacity and bladder compliance. The administration of 0.3 mg/kg or more of midodrine produced a significant increase in the mean arterial blood pressure. After midodrine administration, transient increases in the external sphincter EMG activities were recognized. The activities showed the synergistic pattern during the bladder contractions. In conclusion, lower dose administration of a selective alpha 1-adrenoceptor agonist (midodrine) specifically produced an increase of the closing pressure in the proximal portion of the urethra without affecting blood pressure. These results suggest that midodrine is useful for the treatment of stress incontinence in humans.

Animals↗

[Hyperthermic treatment of benign prostatic hyperplasia by a prostathermer].

Prostate thermotherapy consisting of 6 sessions of intrarectal 60 min irradiation of 915 MHz microwave generated by a prostathermer (Blodan, Isreal) was performed once or twice a week on 30 patients with benign prostatic hyperplasia. Excluding 2 cases who refused further therapy at the first session because of rectal discomfort, 28 cases were evaluated for the efficacy of the treatment. Good or fair improvement in subjective symptoms was observed in 24 (85.7%) of the cases. Nocturia was significantly relieved from 2.9 to 2.0 a night. Among the objective responses, no improvement was achieved as to residual urine or prostate size, while a significant increase of maximum or average flow rate on uroflowmetry was observed. Adverse effects were minor or moderate, including 2 cases of urethral bleeding and rectal discomfort, 2 cases of lower urinary tract infection and 1 case of hypotension, which occurred at the 5th session. The scoring criteria taking into account of both subjective and objective responses showed that the efficacy is good in 10 cases (33.3%) and fair or good in 20 cases (66.7%). These results indicated the usefulness of the prostathermer as one of non-surgical therapies for benign prostatic hyperplasia.

Aged↗

[A prospective study of lung cancer in cases of idiopathic interstitial pneumonia (IIP)].

The incidence of lung cancer in 45 patients (37 males and 8 females), who were originally diagnosed as having idiopathic interstitial pneumonia (IIP), was studied prospectively by following them 4 to 10 years. As controls, sex-, age-, and smoking history matched patients with chronic obstructive lung disease (COLD) were also surveyed for the same follow up period. In addition, the differences in clinical findings between those with and without lung cancer were examined. Eight out of 45 patients with IIP (18%) developed lung cancer (adenocarcinoma; 4, small cell carcinoma; 3, squamous cell carcinoma; 2, including one double cancer). All lung cancer patients were male smokers. Looking only at males, 8 out of 37 patients with IIP (21.6%) developed lung cancer. This incidence was significantly higher than that of the male COLD group (2.2%, less than 0.01). In clinical findings, IIP patients with lung cancer had the characteristics of the chronic type of IIP (lack of volume loss on chest radiographic milder dyspnea, not on steroid treatment) when compared with those who did not develop lung cancer.

Adenocarcinoma↗

Effects of carvedilol on serum lipids in patients with essential hypertension.

The purpose of this study was to investigate the effect of carvedilol on serum lipids in patients with mild-to-moderate essential hypertension. Twenty-one patients with blood pressure greater than or equal to 160/95 mm Hg after a 4-week placebo run-in period were initially given 10 mg of carvedilol once daily. The dose was increased to 20 mg after 4 weeks if the target blood pressure was not achieved. The duration of treatment was 12 weeks. After 12 weeks of administration, blood pressure and the pulse rate (PR) declined significantly (blood pressure from 173/105 to 142/91 mm Hg, p less than 0.001; PR from 74 to 67 beats/min, p less than 0.001); however, serum lipids [total cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein (HDL), HDL2, and HDL3], lipoprotein fraction (alpha, pre-beta, and beta), apoprotein fraction (A-I, A-II, CII, CIII, and E), and atherogenic index [(total cholesterol - HDL cholesterol) divided by HDL cholesterol] were not altered significantly. There were no side effects reported during the trial. From these results, it can be concluded that carvedilol has no adverse effect on the coronary risk profile as reflected by lipid measurements, and is an efficacious, safe, well-tolerated antihypertensive drug in patients with mild-to-moderate hypertension.

Adrenergic alpha-Antagonists↗

[Characterization of childhood onset asthma in the adult asthmatic population].

Adult asthma is composed of two groups; childhood type in which asthma begins in childhood, and adult type which starts in adult life. To characterize childhood-onset asthma in the adult asthmatic population, we selected 171 patients with asthma who were treated at Hokkaido University Hospital and examined the time of onset, atopic factors (family history of asthma, skin tests, IgE (RIST, RAST], eosinophil counts, and clinical severity. We then compared these factors between childhood type and adult type. Thirty-three patients out of 171 (19.3%) developed asthma during childhood, mostly before the age of 5. The age of onset in the rest of the 138 patients was equally distributed from 20 to 60 years. Asthma rarely begun between 10 and 15 years. In childhood type, 15 of 33 patients (45%) had continuous symptoms from childhood, and 18 of 33 patients (55%) experienced remission of their asthma and recurrence at an adult age. The group with childhood-type asthma was younger than that with adult-type asthma (32.5 +/- 13.9 (SD) and 49.7 +/- 14.2 years (mean +/- SD), respectively, p less than 0.001). There were no significant differences in atopic factors except for a higher incidence of positive skin reaction and high IgE (RAST) score in childhood type than in adult type. Steroid dependent asthma was less frequent in childhood type than in adult type (10.5% and 37.7%, respectively, p less than 0.01). These results suggest that patients with childhood type are younger and have asthma of milder severity, and it is easier to determine specific antigens in childhood type than in adult type.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗