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Biomedical subjects

M Hashimoto

Publications and source records attributed to M Hashimoto.

At least 109 records · Page 6Linked to original sources

[Investigation of postoperative adjuvant chemotherapy in patients with transitional cell carcinoma of the upper urothelium. Nara Urooncology Research Group (NUORG)].

During the 5 years from January, 1985 to December, 1989, 88 patients with transitional cell carcinoma of the renal pelvis and/or ureter were operated curatively in the Department of Urology, Nara Medical University and the affiliated hospitals. There were 66 males and 22 females (3:1) and the mean age was 66.0 years old ranging from 34 to 82. Staging of the renal pelvic and ureteral cancer of each patient was determined by General Rule for Clinical and Pathological Studies on Renal Pelvic and Ureteral Cancer established jointly by Japanese Urological Association and The Japanese Society of Pathology in 1990. The over-all survival rates at 1 and 3 years were 91.2% and 74.0%, respectively. The 3 year survival rates of TS and TE were 80.5% and 41.7%. As for grading, the 3-year survival rates were 75.0% for G1, 70.1% for G2, and 75.2% for G3, respectively. The stage of the tumors affected the prognosis. Of 88 patients 26 (Group 1) received cisplatin based combination chemotherapy as a postoperative adjuvant therapy, and the remaining 62 (Group 2) received no such cytotoxic adjuvant chemotherapy. The 3-year survival rates were 63.3% in Group 1 and 78.9% in Group 2, however mean age of Group 1 was significantly younger than that of Group 2. In spite of the age matched trial, there were no significant differences in survival rates between both groups. Adverse effects of cisplatin based combination chemotherapy included gastrointestinal symptom, fatigue, alopecia and leukopenia, however no serious toxicity was seen. These results suggest that prospective randomized trial would be clarified the efficacy of postoperative adjuvant chemotherapy for patients with renal pelvic and/or ureteral cancer.

Adult

WF-2421, a new aldose reductase inhibitor produced from a fungus, Humicola grisea.

WF-2421 is a novel aldose reductase inhibitor produced by Humicola grisea. WF-2421 was purified from the culture filtrate by successive ion exchange chromatography and the chemical structure was assigned to be alpha-formamido-5'-(2-formamido-1-hydroxyethyl)- beta,2',6-trihydroxy-3-biphenylpropanoic acid (1) on the basis of spectroscopic evidence. The IC50 value of WF-2421 was 3 x 10(-8) M against partially purified aldose reductase of rabbit lens.

Aldehyde Reductase

Human papillomavirus type 31 DNA detected in part of the dysplasia but in no part of the squamous metaplasia in a specimen taken from one patient.

Using in situ hybridization, human papillomavirus (HPV 6, 16, 18, 31, 33) DNAs were detected in a cervical severe dysplasia accompanied by squamous metaplasia. It was found that, only HPV 31 DNA was harbored in the cervical severe dysplasia, but HPV DNAs were not identified in a lesion of squamous metaplasia. The in situ hybridization method will be of use, therefore, when dysplasia with squamous metaplasia or other lesions are examined for HPV DNA. In a cervical smear, HPV 31 DNA could be detected on the nuclei of dysplastic cells, so this method is applicable to cervical smears. If squamous metaplasia is to be considered as a precursor lesion to cervical dysplasia, the HPV DNA harbored in the dysplasia must also be detected in the accompanying squamous metaplasia. Our results suggested that not all squamous metaplasias were involved with HPV, as far as we were able to detect using five types of HPV DNA probe.

Adult

Disposition and metabolism of [14C]sparfloxacin in the rat.

Disposition and metabolism of [carbonyl-14C]sparfloxacin SPFX, 5-amino-1-cyclopropyl-7-(cis-3,5-dimethyl-1-piperazinyl)-6,8-difluoro- 1,4-dihydro-4-oxoquinoline-3-carboxylic acid, AT-4140; CAS 110871-86-8), a novel antimicrobial quinolone, were studied in rats mainly after oral administration at 10 mg/kg. SPFX was absorbed from the whole area of small intestine as shown by the loop method. The extent of absorption was around 70% when estimated by AUC, urinary excretion and biliary excretion. Plasma level of radioactivity reached Cmax of 1.32 micrograms eq/ml within 1 h after oral administration and decreased with a half-life of about 4 h. Higher levels of radioactivity than that in plasma were seen in kidney, liver, submaxillary gland, lung, trachea and many other tissues and lower levels, in eye ball, brain and some others. Most tissue levels decreased with time essentially in parallel with plasma level. In pregnant rats, levels of fetal radioactivity amounted to about 60% of maternal plasma level. In lactating rats, milk was found to contain radioactivity several times as high as plasma level, which decreased with a similar half-life. SPFX was bound to plasma protein, mainly to albumin, at about 40%. Unchanged SPFX and its glucuronide were found in the plasma, milk, bile and urine. Within 48 h, about half of the dosed radioactivity was excreted in the bile, and part of which was re-absorbed. Within 96 h, about 20 and 80% of dose were found in the urine and feces, respectively.

Animals

Disposition and metabolism of [14C]sparfloxacin after repeated administration in the rat.

Disposition and metabolism of [carbonyl-14C]sparfloxacin (SPFX, 5-amino-1-cyclopropyl-7-(cis-3,5-dimethyl-1-piperazinyl)-6,8-difluoro- 1,4-dihydro-4-oxoquinoline-3-carboxylic acid, AT-4140; CAS 110871-86-8), a novel antimicrobial quinolone, were studied in rats during and after 14 consecutive daily oral administrations at 10 mg/kg. Plasma levels after the 1st and 14th administration were similar in terms of tmax (1 h), Cmax (around 1.35 micrograms eq/ml), T1/2 (3-4 h) and AUC (about 7.3 micrograms eq h/ml). Plasma levels at 0.5 h after each administration were virtually constant in the range of 1.25-2.66 micrograms eq/ml for 14 days, but those at 24 h tended to elevate to about 0.06 micrograms eq/ml, which was an apparent steady state level after the 6th administration. Tissue distribution after the repeated administration was also similar to that after single administration: levels in the kidney, liver, pancreas, submaxillary gland, lung and many others were higher than, or similar to those in plasma, and in brain and some others, lower. Composition of radioactive metabolites in urine was not statistically different from that after single administration. About 20 and 73% of dose were excreted in daily urine and feces, respectively, for 14 days and radioactivity was almost completely excreted within 96 h after the last administration.

Animals

[Mental and physical condition group characteristics of disabled elderly living at home and principal diseases related to them].

A survival study over a period of one thousand days from July 1985 was performed on 177 cases of disabled elderly (aged 65 and over) living in Moriguchi-city, Osaka, who were enrolled as recipients of solatia for the disabled elderly. At the start of this study, subjects or family members were questioned regarding physical and mental status, clinical history and social environment of these elderly and their family. On the basis of these findings, the level of disability of the elderly was estimated by applying scores to identify physical and mental conditions: The score on physical status, named Total Functional Capacity (TFC), is equivalent to the dependent level of ADL: mental status was scored by assessing seven typical psychiatric questions relating to dementia (Mental Status Score: (MSS]. The following findings were obtained. 1) It was confirmed that mortality probability tended to increase by degrees in proportion to lower level of independent ADL which was indicated by high scores of TFC, and a greater number of psychiatric symptoms such as often observed in the case of dementia (i.e. high scores of MSS) in either sex. 2) For males, among the major diseases precipitating disability, the proportion for stroke was about 50%. In females, disability causes were distribute into various categories of diseases, but orthopedic diseases (e.g. accident or a fracture), contributed a large proportion. The percentage of elderly who became disabled due to stroke was higher in the lower age categories for females. 3) TFC scores did not correlate with age among either sex. 4) More than 40% had more than one psychiatric symptom included in the MSS score. The proportion of elderly having any one symptom tended to increase with age for either sex, and was especially significant for females. 5) Correlation was seen between TFC and MSS for only female.

Activities of Daily Living

Cadmium injury of cultured human vascular endothelial cells.

The effect of cadmium chloride (CdCl2) on cultured human vascular endothelial (HVE) cells and cultured human fibroblasts (HAIN-55 cells) was investigated. Umbilical vein-derived HVE cells were collected by enzymatic digestion with collagenase. At the concentration of 0-10 microM, Cd had hardly any effect on the cell viability of either cells. The viability of HVE cells decreased markedly at 100 microM, but not that of HAIN-55 cells. Morphologic examination by phase contrast microscopy revealed a more damaging effect of Cd on HVE cells than on HAIN-55 cells. These results suggest that Cd is more cytotoxic to HVE cells than HAIN-55 cells.

Cadmium

[A case report of Buschke-Lowenstein tumor (giant condyloma)].

A 28-year-old woman with diabetes mellitus and alcoholic hepatitis presented a rare case of Buschke Lowenstein tumor, or giant condyloma of vulva. HPV DNA of this tumor was detected by in situ hybridization using tritium labeled HPV 6 b, 16 and 18 DNA. This tumor appeared to harbour HPV 6 b DNA, but other HPV DNAs were negative. The distribution of HPV 6 b DNA was detected in the nucleus of the squamous epithelium showing koilocytosis. Total vulvectomy and resection of the clitoris were done. The postoperative course was uneventful and there has been no recurrence of tumor so far.

Adult

[Diagnosis of prosthetic mitral valve regurgitation by Doppler color flow imaging using right parasternal approach: a comparative study with transesophageal method].

Doppler color flow imaging is a useful tool in evaluating mitral regurgitation (MR). However, it is frequently difficult to assess prosthetic valve MR by the conventional transthoracic approach using left parasternal or apical echo-windows, because of the interception of ultrasound by the prosthesis or artifacts produced by its motion. The purpose of this study is to determine the usefulness of the "right" parasternal approach (RPA) in the echo diagnosis of prosthetic MR. Six patients with pathological prosthetic MR determined by transesophageal approach (TEA) were studied. Transthoracic echo was performed using both the RPA and the conventional approach, and the presence or absence and the extent of MR signals by these transthoracic approaches were compared with those by TEA. Prosthetic MR was detected in five of six patients by the RPA and the extent of MR signals by the RPA was very similar to that by TEE in each of the five patients. MR could not be detected by the RPA only in one patient, whose MR was estimated to be very mild by TEE. By the conventional approach, MR could not be detected in three patients and the degree of MR was significantly underestimated in two of the remaining three patients. Thus, the transthoracic RPA is often as useful as TEA in diagnosing prosthetic MR, which is often undetectable or underestimated by the conventional approach. Because the RPA is less invasive than TEA, the RPA should be encouraged in patients with suspected prosthetic mitral valve dysfunction.

Adult

[A case of mitral stenosis associated with cardiac sarcoidosis and left ventricular aneurysm].

We report a rare case of mitral stenosis associated with cardiac sarcoidosis and left ventricular aneurysm. A 60-year-old female was admitted with complaint of palpitation and dyspnea on exertion. Chest X-ray revealed cardiomegaly and pericardial calcification, but no bilateral hilar lymphadenopathy. Electrocardiogram showed various arrhythmia. Coronary angiography showed no stenosis in any coronary arteries. Cardioangiogram showed left ventricular aneurysm at the apex and mitral stenosis. Laboratory findings showed no evidence of sarcoidosis. Open mitral commissurotomy and left ventricular aneurysmectomy was performed. Pathological findings of the myocardium showed a remarkable degenerative change and a granulomatous inflammation. Postoperative biopsied specimens of right scalene lymph nodes revealed sarcoid reaction. The postoperative course was satisfactory, but arrhythmia remained. The patient was treated with steroids and pacemaker implantation. She has been doing well for 2 year postoperatively. An operative case of mitral stenosis associated with cardiac sarcoidosis and ventricular aneurysm due to sarcoidosis is very rare and the prognosis in patient is very poor usually.

Cardiomyopathies

[Gabexate mesilate induced remarkable transient reversal of thrombocytopenia in a ITP patient].

A 46-year-old woman was admitted to our hospital because of hemorrhagic tendency. Normal coagulation test results conflicted with the diagnosis of disseminated intravascular coagulation (DIC). Furthermore, we saw no evidence of autoantibodies, including antinuclear antibodies and splenomegaly, and there was no past history of infection or medication. Peripheral blood test showed marked decrease of platelets only. Bone marrow aspiration revealed increased megakaryocytes. Morphology of other blood components was normal. Thus, we diagnosed this case as idiopathic thrombocytopenic purpura (ITP). Administration of prednisolone and an immunosuppressants did not improve symptoms. So patient was temporarily discharged and treated with 6-MP at the outpatient department. She was rehospitalized for liver damage caused by the drug. Patient then developed sepsis from acinetobactor. We administered gabexate mesilate (FOY, 2,000 mg/day) for four days to prevent DIC. Platelet count, which was 1.5 X 10(4)/microliter before FOT administration, began increasing on the second day, reaching 25. 5 X 10(4)/microliter on the fourth. Count rapidly decreased to 2.8 X 10(4)/microliter on the seventh day after administration had been discontinued. Two-time FOY administration after patient's recovery from sepsis led to a definite, similar transient increase in platelet count. As ITP patients with transient increase in platelet count by FOY administration had not been reported, this case is thought to be an interesting case in the pathogenesis and treatment of ITP.

Female

[A study on GTP-binding protein in the activation of phospholipase C and phospholipase A2 in cultured rat luteal cells].

We have studied the possible involvement of the GTP-binding protein (G-protein) in the activation of phospholipase C and A2 in cultured rat luteal cells as a transducer of cell information. 1. Inositol phosphate production and arachidonic acid release in rat luteal cells by the stimulation of PGF2 alpha and GnRH receptors are dependent on GTP and therefore suggest the involvement of GTP binding protein. 2. When the cells were not treated with IAP, a membrane protein of 41K molecular weight was apparently labeled. The protein, with a molecular weight of 41K, which was obtained from cultured rat luteal cells without prior treatment with IAP is considered to be the alpha-subunit of GTP binding protein as reported in other cells. While alpha-subunit of G-protein was ADP-ribosylated in luteal cells too, the 41K protein from the cells pretreated with IAP was not found to be ADP ribosylated. 3. When such IAP pretreated luteal cells were stimulated by PGF2 alpha or GnRHa, the production of inositol phosphate and the release of arachidonic acid were observed with no suppression. 4. The results suggest the existence of some G-protein other than Gi between the receptor and phospholipases C and A2.

Animals

[Clinical course and prognosis in SLE patients with pulmonary hypertension: a comparative study with primary pulmonary hypertension].

Recently pulmonary hypertension (PH) has been recognized as one of life threatening complications which determine the prognosis of patients with systemic lupus erythematosus (SLE). Clinical aspects and pathology in patients with SLE complicated by PH (SLE-PH) have been reported to have a close similarity to those in patients with primary pulmonary hypertension (PPH), the prognosis of which is very poor in general. However, the long-term prognosis for patients with SLE-PH is not clear yet. Mainly because of some technical limitations for determining the severity of the PH, long-term follow-up studies have been inconclusive. In this study, 7 patients with SLE-PH and 6 patients with PPH were studied by using two-dimensional echocardiography. The interventricular septal curvature (R) was measured from the parasternal short axis view and the reciprocal value (1/R) was applied as a severity index of the PH. In 4 patients with SLE-PH and 6 with PPH, pulmonary arterial pressure was measured by cardiac catheterization concomitantly. There were no significant differences in 1/R and pulmonary arterial pressure between the two groups when PH was diagnosed for the first time. In the PPH group, the mean period of follow-up study was 25.3 months and all of the patients died during that period. In SLE-PH group, the mean period of follow-up study was 50.6 months, and only 3 patients (43%) died during that period. No patients in the PPH group showed improvement in 1/R, but 3 patients with SLE-PH improved in 1/R during a long follow-up period (60, 96 and 103 months respectively). Thus, the prognosis for SLE-PH was better than that for PPH, and there were some differences in the course and worsening behavior of PH in SLE-PH compared with that in PPH during the long-term follow-up study with reference to the echocardiographic investigation using 1/R value.

Adolescent

[Empirical study of inpatients viewed from the individual psychotherapy].

There are very few empirical studies which address the effect of psychotherapy in inpatient settings. The author extracted 45 inpatient cases which could withstand detailed statistical analysis among patients who had been admitted to the psychiatric ward of the Tokai University Hospital between 1975 and 1981. Therapists of the cases were interviewed individually and the cases were evaluated retrospectively based on the criteria proposed by the study of Menninger Foundation. Significant statistical improvements were found on every items of evaluation. Furthermore, patients who had shown good interpersonal relationships and motivation at the time of admission showed positive conditions at the time of discharge. Factor analysis of therapeutic variables yielded five factors which delineated the following characteristics of the therapists: 1) having a psychoanalytic orientation, 2) viewing the improvement of symptoms as the goal of therapy, 3) utilizing one's experiences and skills, 4) utilizing a supportive approach, and 5) giving careful attention to the structuring of the psychotherapy sessions. As for the situational variables of the patients, factor analysis yielded only one factor, and multiple regression analysis revealed no significant therapeutic effects. Two types of multiple regression analysis were conducted to determine therapeutic effects and therapeutic variables, but no significant factors were found. Thus, the cases were classified into five groups according to interpersonal relationships factors and were analyzed according to "quantification method II" (Hayashi, C.). The following results were obtained: 1) the structuring of inpatient therapy should correspond with the patient's level of responsibility, 2) as for the structure of psychotherapy, the quality of improvement depended on the closeness to the psychoanalytic structure, i.e., the closer to the psychoanalytic structure, the higher the improvement, 3) the quality of improvement was poor when transference issues (in the sessions) were not brought up during the psychotherapy sessions, 4) the quality of improvement rose according to the degree that dreams and fantasies were dealt with, 5) hospital admission periods of 101 to 120 days showed the highest of improvement, 6) the frequency of sessions did not determine the quality of improvement, 7) the personality of therapist had strong effects when it worked in a negative way, and 8) the quality of improvement corresponded to the degree of the permissive atmosphere in the therapeutic relationship.

Adolescent

[Analysis of prognostic factors in patients with carcinoma of the thoracic esophagus].

Prognostic factors in patients with carcinoma of the thoracic esophagus were analysed. From May 1972 to February 1989, 361 cases were resected in our department. Cases of histological curability 0, double cancer, death within 30 days after operation, death due to other diseases and cancer except squamous cell carcinoma were excluded, and 170 were chosen for this study. We classified these cases into two groups according to the survival period; Group 1: cases died within 2 years after operation, Group 2: cases lived more than 2 years. Factors analyzed were as follows; sex, age, location of the lesion, radiological classification, radiological vertical extension, axial deviation of the esophagus, endoscopic classification, endoscopic horizontal location, resectability, longitudinal diameter, histologic differentiation, depth of invasion, degree of lymphnode metastasis, range of lymphnode metastasis, lymphatic invasion, blood vessel invasion, intraepitherial spread, intramural metatasis, histologic stage and histologic curability. Factors related to prognosis were age, radiologic classification, depth of invasion, degree of lymphnode metastasis, histologic stage and histologic curability. In the next step, these cases were also classified into three groups according to the degree of lymphnode metastasis (n(-), n1 + 2(+), n3 + 4(+) and factors which influenced prognosis were analysed in each group. In the group without lymphnode metastasis, there was a statistical difference in survival rate between cases with intramural metastasis and cases without that. In groups with lymphnode metastasis (n1 + 2(+), n3 + 4(+), any factors such as the degree and range of metastasis or intramural metastasis had no influence on prognosis. So it was concluded that lymphnode metastasis itself was an important factor for prognosis.

Age Factors