Biomedical subjects

S Hashimoto

Publications and source records attributed to S Hashimoto.

At least 55 records · Page 3Linked to original sources

PubMed1992

Novel phenoxyalkylamine derivatives. VII. Synthesis and pharmacological activities of 2-alkoxy-5-[(phenoxyalkylamino)alkyl]benzenesulfonamide derivatives.

To find a novel alpha-blocker with high alpha-blocking selectivity against dopamine D2-receptor affinity, we performed structural modification of the alkylene chains and the substituents on two benzene rings of 2-alkoxy-5-[(phenoxyalkylamino)alkyl]benzenesulfonamide derivatives. The modification of the alkylene chain between the amino moiety in the center of the molecule and the benzene ring (ring A) was found to be the most significant. 5-[2-[[2-(5-Fluoro-2-methoxyphenoxy)ethyl]amino]propyl]-2- methoxybenzenesulfonamide (II-4), which possesses 1-methylethyl as the alkylene chain, exhibited high alpha-blocking selectivity as well as potent alpha-blocking activity.

Adrenergic alpha-Antagonists↗

PubMed1992

[Studies on early stage changes of peroxide lipid in isoproterenol-induced myocardial injury].

The amount of peroxide lipid in vivo in the early stage of the experimental model of myocardial infarction in a rat induced by the administration of isoproterenol (Isp) was measured as the value of malonic dialdehyde (MDA). The model of myocardial infarction was made by giving 75 mg/kg of Isp to the rat weighing 270 +/- 10 g. After the administration of Isp, the amounts of lipid in the serum and in the myocardial tissue were measured, and a blood chemistry test (glutamic oxaloacetic dehydrogenase, glutamic pyruvic transaminase, lactate dehydrogenase, free fatty acid, creatine kinase) was simultaneously carried out on the serum. The value of the amount of peroxide lipid in the serum began to elevate 3 h after the administration of Isp and reached a maximum value at 6 h. The value of the amount of peroxide lipid in the tissue began to elevate 30 min after the administration and reached a maximum at 3 h. Each blood chemistry disclosed the elevation 30 min after the administration. As mentioned above, the production of peroxide lipid in vivo on the myocardial disorder in the early stage after the administration of Isp and the biochemical changes showed a significant correlation. From these results it is suggested that the myocardial disorder induced by the administration of Isp has already developed at 30 min after the administration.

Animals↗

PubMed1992

In vitro pharmacological profile of the novel alpha 1-adrenoceptor antagonist HSR-175.

The pharmacological profile of HSR-175, a new alpha 1-adrenoceptor antagonist, was studied in vitro and compared with those of other alpha 1-antagonists. HSR-175, prazosin, bunazosin and yohimbine competitively antagonized the contractile responses induced by noradrenaline in the dog mesenteric arteries and the rabbit thoracic aorta. The pA2 values for HSR-175 in the dog mesenteric arteries and the rabbit aorta were 10.38 and 9.63, respectively, which were significantly higher than those for prazosin (8.39 and 8.80), bunazosin (8.44 and 8.75) and yohimbine (7.34 and 6.10). HSR-175 also inhibited the sympathetic adrenergic contraction induced by electrical transmural stimulation in the dog mesenteric arteries, and the inhibitory effect of HSR-175 was more potent than those of prazosin and bunazosin. Although HSR-175 also possessed competitive antagonist properties at pre- and postsynaptic alpha 2-adrenoceptors in the rat vas deferens and the dog saphenous veins, those affinities (pA2 = 6.41 and 7.05) were much lower than those at postsynaptic alpha 1-adrenoceptors. Furthermore, HSR-175 at concentration of 10(-6) M showed no inhibition on the contractile responses to 5-HT, histamine, KCl and angiotensin II in the rabbit thoracic aorta. These results indicate that HSR-175 is a very potent and selective alpha 1-adrenoceptor antagonist.

Adrenergic alpha-Antagonists↗

PubMed1992

[Effects of smoking and drinking habits and vitamin A intake on serum concentrations of beta-carotene and retinol].

Serum samples from 341 males aged 10 to 59 years were obtained and stored at -40 degrees C until examined for retinol and beta-carotene concentrations by HPLC, and their relationships to smoking habit, alcohol drinking habit and vitamin A intake were studied. In univariate analysis the serum beta-carotene level was significantly lower in the smokers than in the non-smokers (smokers: 4.6 micrograms/dl, non-smokers: 7.1 micrograms/dl, p less than 0.01) and lower in the drinkers than in the non-drinkers (drinkers: 4.6 micrograms/dl, non-drinkers: 7.3 micrograms/dl, p less than 0.01). The serum retinol level was not different by smoking habit but was higher in the drinkers than in the non-drinkers (drinkers: 80.4 micrograms/dl, non-drinkers: 67.0 micrograms/dl, p less than 0.01). Serum beta-carotene was higher in the group with a greater intake of vitamin A of vegetable origin (6.1 micrograms/dl) than in the group with a smaller intake of it (4.7 micrograms/dl) (p less than 0.01), but serum retinol was not different by the amount of vitamin A intake of animal food origin. To estimate the respective effects and interactions of the above factors on serum beta-carotene and retinol levels by adjusting for the confounding effects of age, serum total cholesterol, HDL-cholesterol and triglyceride, analysis of covariance was performed. For serum beta-carotene, smoking habit (p less than 0.01), drinking habit (p less than 0.01) and the amount of vitamin A intake of vegetable food origin (p less than 0.05) had significant main effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1992

[Characteristics of medical institutions visited by 30 intractable disease patients receiving financial aid for treatment].

In order to determine the characteristics of medical institutions which patients with 30 intractable diseases visited, we analyzed data of a nationwide survey conducted by the Epidemiology of Intractable Diseases Research Committee in 1989. Each of 47 prefectural governments in Japan reported information of all patients with 30 intractable diseases who received financial aid for the diseases between April 1988 and March 1989. Information collected about each patient consisted of identification numbers, which included the disease code, sex, age, the code of the municipality where the patient lived, the medical institution which treated the patient, etc. Out of 173,637 patients whose information was reported by prefectural governments, we used data of 159,910 patients whose medical institutions were reported completely. The results can be summarized as follow: 1) Of the 159,910 patients, 8.6 percent visited medical institutions outside of the prefectures where the patients lived. Many patients living in prefectures located close to large cities, such as Tokyo, visited medical institutions in large cities. 2) The proportion of patients who visited hospitals of medical schools was 27.9 percent. 3) Patients who were affected by diseases causing physical disabilities such as SMON and malignant rheumatoid arthritis tended to visit medical institutions located in their neighborhoods and were treated in small hospitals or clinics. Old patients had the same tendency as patients with such diseases. 4) Although the number of patients receiving aid in 1988, whose data we analyzed in the current study, was larger than that in 1984, the proportion of patients visiting medical institutions outside of the prefecture where the patients lived, and the proportion of patients visiting hospitals of medical schools were nearly equal to those in 1984.

Adolescent↗

PubMed1992

Thyroid hormone, L-T3, stimulates the expression of the angiotensinogen gene in cultured opossum kidney (OK) cells.

Angiotensinogen (ANG) messenger RNA is expressed in opossum kidney (OK) proximal tubular cells. To examine whether thyroid hormone, L-T3, could stimulate the expression of the ANG gene in OK proximal tubular cells, fusion genes, consisting of various lengths of the 5'-flanking region of the rat angiotensinogen gene linked to a human growth hormone reporter gene, were constructed and introduced into OK cells. As a negative control, they were introduced into a nonkidney cell line, a human choriocarcinoma cell line (JEG-3). The level of the expression of fusion genes in these cells were determined by the level of immunoreactive human growth hormone secreted into the culture medium. The expression of ANG-growth hormone (ANG-GH) fusion genes pOGH (ANG N-1498/+18), pOGH (ANG N-688/+18), pOGH (ANG N-110/+18), pOGH (ANG N-53/+18), and pOGH (ANG N-35/+18) was 226-, 4.5-, 1.0-, 12-, and 2.5-fold higher than promoterless pOGH in the expression of growth hormone activity in OK cells. No significant expression of any of these ANG-GH fusion genes over the promoterless pOGH was observed in JEG-3 cells. The addition of L-T3 stimulates the expression of pOGH (ANG N-1498/+18) in a dose-dependent manner with a maximal and half-maximal effect at 10(-7) M and at 10(-8) to 10(-9) M, respectively. Thyroid hormone (10(-7) M) also stimulates the expression of pOGH (ANG N-688/+18) but not pOGH (ANG N-110/+18), pOGH (ANG N-53/+18), or pOGH (ANG N-35/+18).(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensinogen↗

PubMed1992

Primary non-AIDS related brain lymphoma. Patterns of failure following radiotherapy.

Thirteen patients with primary brain lymphoma (PBL) were treated with radiotherapy. Three patients also had ocular involvement with retinal masses at initial presentation. All but one patient received conventional whole brain irradiation and, in addition, spinal irradiation, intrathecal methotrexate or orbital irradiation were given in two, two and four patients respectively. The radiation doses for involved sites ranged from 40 to 65 Gy, and for prophylactic sites from 30 to 50 Gy. After radiotherapy, all patients had complete regression of the tumor on computed tomography. Nine patients relapsed, 5 of them with brain recurrence. Two patients had ocular recurrence exclusively as their first relapse. The remaining two relapsing patients had bone lesions. One patient died intercurrently. As a result, only three patients are alive and free of disease after 16 to 36 months and all three received some adjuvant treatment in addition to whole brain irradiation.

Adult↗

PubMed1992

[Affected siblings with Alzheimer's disease had missense mutation of codon 717 in amyloid precursor protein gene].

Using reverse genetic techniques, the gene responsible for familial Alzheimer's disease (FAD) is one of the clues to identify the pathogenesis of Alzheimer's disease (AD). Recently a missense mutation in the APP (amyloid precursor protein) gene (generally this mutation was called APP717) was detected in 2 Caucasian AD families and the same mutation was found in 3 Japanese AD families. We experienced brother's cases who were diagnosed as AD. Both of them and one normal person of the next generation had APP717. The first symptom of the elder brother (case 1) was forgetfulness at 52 years old, then dementia was advanced. In his clinical course there were characteristic findings such as the mirror sign, pseudodialog and jargon which has been rarely described in the Japanese literature. Finally he died of pneumonia at 57 years old. He was diagnosed as AD pathologically and physical findings of brain CT, SPECT (single photon emission computed tomography) and EEG supported this diagnosis clinically. The first symptom of the younger brother (case 2) was also forgetfulness at 45 years old, then severe dementia was advanced, at last he died of pneumonia at age 53 old. On the other hand the mother of the brothers died of severe dementia, so it was suspected that brothers died of severe dementia, so it was suspected that she had had AD. The clinical courses and pathological findings were thought to be typical of AD, namely there were no significant differences in comparison with other cases of FAD and sporadic AD.(ABSTRACT TRUNCATED AT 250 WORDS)

Alzheimer Disease↗

PubMed1992

[Role of neutrophil and T cell functions in host defense mechanisms of the elderly].

We studied neutrophil functions (phagocytosis, intracellular killing and chemotaxis with or without recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) and T cell functions (lymphocyte proliferation and production of GM-CSF in response to phytohemagglutin (PHA)) to clarify host defense mechanisms in the elderly. There was no significant difference in phagocytic activity of neutrophils between the elderly and control young adults. rhGM-CSF enhanced phagocytosis by neutrophils, and a similar degree of enhancement was obtained in both groups. Killing activity of neutrophils evaluated by the new Nitroblue tetrazolium reduction test in the elderly was significantly lower than that in young adults (p < 0.001), however, pretreatment of neutrophils with rhGM-CSF resulted in an increase of killing activity in the elderly, raising their response to a level comparable to that of young adults pretreated with rhGM-CSF. There was no significant difference between the elderly and young adults in chemotaxis of neutrophils. rhGM-CSF alone did not prime chemotaxis, but primed chemotaxis in response to chemoattractant (N-formyl-methionyl-leucyl-phenylalanin) in both individuals. Lymphocyte proliferation and production of GM-CSF in response to PHA in the elderly were significantly lower than those in the young adults (p < 0.001, p < 0.05, respectively). These results indicated that impaired T cell functions may contribute, at least in part, to susceptibility to bacterial infection in the elderly.

Aged↗

PubMed1992

[A clinico-pathological study of inverted papilloma of the urinary bladder. Analysis of histogenesis].

A clinico-pathological study was conducted on 9 cases with inverted papilloma of the urinary bladder. 1. Clinical study: The incidence of inverted papillomas, when compared with transitional cell carcinoma of the urinary bladder, was much higher in men than in women in our study and in the literature dealing with this subject as well. Eight of 9 inverted papillomas were localized in the bladder neck. Cystoscopic examination revealed that all tumors were pedunculated and 8 of the 9 tumors had non-papillary surfaces. These clinical findings suggest that inverted papillomas localized in the bladder neck are very similar to posterior urethral polyps with prostatic type epithelium. Transurethral resection (TUR) was performed in all cases. Recurrence was not observed. 2. Pathological study: Inverted papillomas were classified into two types according to their histological patterns, determined by Hematoxylin-Eosin (H-E) staining. One pattern was glandular and the another was trabecular. Of the 9 cases, 2 were glandular, 5 were trabecular and the remaining 2 were a mixed type. Immunohistochemical staining with anti-prostate specific antigen antibody revealed 3 of the 9 tumors were stained positively, and these tumors were classified a glandular type. Inverted papilloma were classified into two patterns according to their histological patterns, determined by immunohistochemical staining with anti-keratin antibody, namely a bladder tumor pattern and a urethral tumor pattern. Inverted papillomas with a urethral tumor pattern were of the glandular type and included anti-PSA antibody positive staining tumors. These findings suggest that a portion of inverted papillomas may have arisen from neoplastic transformation of prostatic tissue.

Aged↗

PubMed1992

[Study on the effects of the hypocholesteremic agents, cholestyramine and compactin on the induction of renal tumors in rats by N-ethyl-N-hydroxyethyl nitrosamine].

Male Wistar rats were administered with 0.1% N-ethyl-N-hydroxyethyl nitrosamine (EHEN)-containing diet for 2 weeks, and were then Rept for further 23 weeks on basal diet. At 25 weeks, the rats were divided into three groups. Group I was fed on basal diet to 40 weeks. Group II was fed on 2% cholestyramine-containing diet to 40 weeks. Group III was fed on 0.02% compactin-containing diet to 40 weeks. At 40 weeks after the start of experiment, the rats were sacrificed and examined histologically for the incidence of renal cell tumors (RCT) and dysplastic foci (DF) of the kidney. The serum levels of total cholesterol at 40 weeks were 108.9 +/- 23.4, 78.8 +/- 12.5, 95.6 +/- 43.4 mg/dl in Groups I, II and III, respectively. The levels were significantly lower in Groups II and III (p less than 0.01, 0.05, respectively, Wilcoxon test) than Group I. The average numbers of DF were 4.5 +/- 4.1, 1.3 +/- 0.3, 2.3 +/- 2.0 per cm2 of kidney slices in Groups I, II and III, respectively. DF were significantly less in Group II than Group I (p less than 0.025, Wilcoxon test), and less in Group III than Group I (not statistically significant). There was no statistical difference between Groups II and III. RCT were observed in 9 of 34 kidneys (26%), 2 of 18 (11%), 1 of 20 (5%) in Groups, I, II and III, respectively. The ratios of kidneys with RCT were lower in Group II than Group I (not statistically significant), and lower in Group III than Group I (p less than 0.05, qui-square test). There was no statistical difference between Groups II and III. RCT were classified into gross and microscopic lesions. Four gross RCT were found in 4 rats of Group I; no gross RCT was in Groups II and III. There were 5 microscopic RCT in 5 rats, 3 in 2, 1 in 1 in Groups I, II and III, respectively. In Group I, serum levels of total cholesterol were compared between the following subgroups; the rats with RCT and/or with more than 10 DF per kidney, and the rats without RCT and with less than 10 DF per kidney. The mean level was 120.8 +/- 21.8 mg/dl in the former subgroup, which was significantly higher than that (94.1 +/- 19.6 mg/dl) in the latter subgroup (p less than 0.025, Wilcoxon test). The serum cholesterol was suggested to act as a promoter in the development of DF and RCT.

Animals↗

PubMed1992

DNA strand scissions by hydroxamic acids in the presence of Cu(II) ion under aerobic conditions.

Carbazolyloxyacetohydroxamic acid (1), 9,9'-decamethylene-bis-carbazolyloxyacetohydroxamic acid (2), benzohydroxamic acid (3), and acetohydroxamic acid (4) without reducing agent under aerobic conditions induced DNA strand scissions with increasing activities in the order of 4 > 3 > 2 > 1. The inhibition experiments indicated that hydrogen peroxide and superoxide participated in the reactions, but hydroxyl radical or singlet oxygen did not.

Animals↗

PubMed1992

Freeze-fracture studies of salivary glands.

Freeze-fracture electron microscopy was employed to study the general morphology, membrane fusion during exocytosis, intercellular junctions in adult and developing salivary glands, and morphological changes of intercellular junctions in secretory stimulation and neoplastic disorders. Intramembranous particles distributed on plasma membranes and organelle-membranes were determined on the basis of particle density per unit. Relationship between distribution and density of particles and functions of membranes and organelles was discussed. Fused membranes took the form of smooth areas of intramembranous particles free on the PF face in the submandibular acinar cells induced by isoproterenol stimulation. The sequence of membrane fusion during secretion was discussed from these freeze-fracture observations. Tight junctions which limited solute diffusion between adjacent cells formed continuous belts around the juxtaluminal region of plasma membrane. Their permeability function was regulated by the number and the geometrical pattern of the tight-junctional strands. The junction appeared late during gestational life, and its development and morphology correlated with the establishment of electrochemical tightness. Similarity in the location and morphology between developmental and neoplastic conditions might indicate reflect the function and degree of cytodifferentiation in salivary gland. Gap junctions were detected as clusters of particles, representing voltage-regulated intercellular channels connecting adjacent cells. The junctions were developmentally regulated, and their size and frequency correlated with the functional activity and with cytodifferentiation in neoplastic disorders. Desmosomes, which appeared as round or elongated clusters of particles, provided the mechanical stability necessary to maintain the organization of acini and ducts.

Animals↗

PubMed1992

[Two cases of esophageal varices complication after hepatic arterial infusion chemotherapy (HAI) for metastatic liver tumor].

Mild liver dysfunction is a well-known complication of HAI, but it has been thought to be transient and reversible in most cases. In the case, of metastatic liver disease, in particular, HAI has been performed safely because liver function is normal for the most part. We encountered 2 cases of irreversible severe liver dysfunction and esophageal varices after hepatectomy for metastatic liver tumor from colorectal cancer. They were treated with postoperative adjuvant HAI. Biliary enzyme as alkaline phosphatase elevated, and dilated intrahepatic bile ducts were observed in both patients. Fibrosis of Glissonean sheath, dilatation of intrahepatic bile ducts and intrahepatic biliary stones were observed at autopsy in both patients. One of the patients had obstruction of portal trunk. It must not be forgotten that such complications can occur even in a case with non-cirrhotic liver.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1992

[The pitfalls in the clinical diagnosis of dissecting aortic aneurysm].

It is sometimes very difficult to diagnose dissecting aortic aneurysms (DAA), particularly in its early stage, due to manifold signs and symptoms. The purpose of this study is to clarify the reasons for such erroneous diagnoses. A total of 41 patients with DAA were referred to our hospitals for further examination and/or surgery from April 1986 to August 1989. In 18 of these patients, the diagnostic possibility of an underlying DAA was overlooked by the referring physicians. Among these 18 patients, 2 were mistakenly diagnosed as uncomplicated myocardial infarction (MI), one as pneumonia, 2 as cerebral infarction, 6 as acute abdominal disease, one as cholelithiasis, 5 as thrombosis of the lower extremities, and one as malignant metastasis to the pericardium. The following is the detail: In 2 cases thought to be uncomplicated MI, an expanding dissecting ascending aorta had crushed the lumen of the left coronary artery, causing MI, in turn, wasting clinical treatment and consuming precious time. In one case, enlargement of the descending aorta on the chest radiography was overlooked and the patient's symptoms were mistakenly attributed to pneumonia. In 2 cases in which symptoms of cerebral ischemia were thought to be attributed to cerebral thrombosis, the real cause turned out to be occlusion of the brachiocephalic artery following aortic dissection. Among 6 cases which were initially considered to have only acute abdominal disease, 3 presented with symptoms and signs of ileus, and their exploratory laparotomies yielded no positive findings.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1992

[Posterior urethral polyp: a recurrent case].

A 38-year-old man was admitted to our hospital complaining of difficult, frequent urination to our hospital. Transrectal echography and digital examination showed chronic prostatitis. He was treated with medication for chronic prostatitis but his condition did not improve. Retrograde urethrography revealed an obstructive change in the prostatic urethra and urethroscopic findings showed a urethral tumor in the posterior urethra. Transurethral resection of the tumor was performed. Pathological diagnosis of the urethral tumor indicated a urethral caruncle. After one year, the patient was readmitted to our hospital with the same complaints as before. Urethroscopic findings revealed the recurrence of a urethral polyp in the posterior urethra. Transurethral resection of the polyp was performed. Pathological findings revealed that the inner structure of the polyp showed a prostatic glandular pattern that after staining with anti-prostatic acid phosphatase antibody. The final diagnosis was that the polyp had a prostatic-type epithelium in the prostatic urethra.

Acid Phosphatase↗

PubMed1992

[Phase I clinical study of 99mTc-ECD].

A phase I clinical study of 99mTc-L,L-ethyl cysteinate dimer (99mTc-ECD) was carried out in 3 normal volunteers. There was no significant change in vital signs and laboratory parameters attributing to the radiopharmaceutical. 99mTc-ECD was rapidly taken up by the brain, reaching the maximum peak activity within 1 min after the injection and remained relatively constant over several hours. The brain uptake of 99mTc-ECD at 5 min was 5.4 +/- 0.5% which decreased to 5.0 +/- 0.3% by 65 min. 99mTc-ECD cleared rapidly from other organs. The primary excretion route was through the kidneys. Cumulative 99mTc activity in the urine at 90 min and 24 hr were 60.2 +/- 7.3% and 88.5 +/- 10.3%, respectively. The critical organ was the bladder wall with an estimated radiation dose of 0.073 mGy/MBq, which was acceptable value. Clear SPECT images were obtained at 30, 90 and 150 min postinjection. In conclusion, 99mTc-ECD is a safe and promising radiopharmaceutical for the evaluation of regional cerebral blood flow.

Adult↗

PubMed1992

[Phase I clinical trial of a new myocardial imaging agent, 99mTc-PPN1011].

A new myocardial imaging agent, 99mTc-1,2-bis[bis(2-ethoxyethyl) phosphino]ethane (99mTc-PPN1011) was administered to healthy male volunteers to evaluate its safety and kinetics. No significant drug-related events were observed. After intravenous injection, blood clearance was rapid. Prompt heart uptake (1.8% of the injected dose after 5 minutes) was followed by relatively slow wash-out (1.0% remained after 3 hours). Liver and lung uptake was observed but the clearance was more rapid than in the heart. 4.7-24.0% of the injected 99mTc-PPN1011 was excreted into urine until 4 hours after injection. 99mTc-PPN1011 also seemed to be excreted through hepato-biliary system. Excellent and low-background myocardial images were obtained using either SPECT or planar imaging. We conclude that 99mTc-PPN1011 could be useful for myocardial perfusion imaging.

Adult↗