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Biomedical subjects

Y Doi

Publications and source records attributed to Y Doi.

At least 451 records · Page 25Linked to original sources

Preclinical increase in activity of muscle microsomal trypsin-like protease in murine muscular dystrophy, C57BL/10-mdx.

Preclinical alterations of protease activities in skeletal muscles from 10-day-old dystrophic mouse, C57BL/10-mdx, were examined by using 10 fluorogenic peptide substrates. Among the activities tested, only Boc-Val-Pro-Arg-MCA-hydrolyzing enzyme of the muscle microsomes showed an about 6-fold higher level of activity in mdx mouse. The increase in activity was not observed in tissues other than skeletal muscle. The enzyme had a pH optimum between 8.5 and 11.0, and was inhibited with DFP and variety of trypsin inhibitors. The enzymatic activity transiently increased at 1-2 weeks of age, the preclinical or very early stage of the disease. These results imply that the increased level of a trypsin-like protease possibly present in muscle microsomes may be closely related to the manifestation of muscular dystrophy.

Aging↗

HLA-DR2 and Dw2 in narcolepsy and in other disorders of excessive somnolence without cataplexy.

Studies on HLA antigens were conducted in several patient populations with the following findings: (a) All 135 Japanese narcoleptic patients, eight of whom were considered to have "symptomatic" narcolepsy, were found to be HLA-DR2 and HLA-DQw1 positive. All 17 members of a subgroup of the original population were also found to be HLA-Dw2-positive. It was concluded that HLA-DR2 is a prerequisite for the development of narcolepsy and that the diagnosis of narcolepsy can be excluded if HLA-DR2 or HLA-Dw2 is negative. The distinction between idiopathic and symptomatic narcolepsy needs to be reconsidered. (b) Haplotype studies in three families with narcoleptic members enabled detection of children at high risk for narcolepsy. (c) Of the 54 patients with disorders of excessive daytime sleepiness other than narcolepsy, those with essential hypersomnia (EHS) had a higher frequency of HLA-DR2; the others had a lower frequency. The DR2-positive EHS group could include members with an incomplete form of narcolepsy; the DR2-negative EHS group had disorders essentially different from narcolepsy, although both positive and negative groups manifested hypnagogic hallucinations, sleep paralysis, and sleep onset REMs. Two further studies were conducted in subgroups of the original narcoleptic population studied. In a subgroup of 30 patients who underwent lymphocyte subset studies, no T-cell abnormalities were detected; it is unlikely that an autoimmune mechanism is involved in the development of narcolepsy. In a subgroup of 33 narcoleptic patients, Southern's blot analysis of DNA using a DQ beta probe revealed three specific restriction fragments. Further studies are necessary to locate the DNA locus that carries the susceptibility gene for narcolepsy.

Alleles↗

Increased frequency of non-insulin-dependent diabetes mellitus among narcoleptic patients.

Forty-eight narcoleptic patients were randomly selected from a group of 197 narcoleptic outpatients, and a 50-g oral glucose tolerance test (OGTT) was performed. Blood glucose levels were determined by oximetry before and 30, 60, and 120 min after the glucose administration. Serum insulin concentrations (IRI) were determined by enzyme immunoassay, and an insulinogenic index (II) was calculated. (II = the ratio of IRI increment to blood glucose increment in 30 min following glucose load). From the results of the OGTT, six patients with definite diabetes mellitus (DM) were identified (12.5%, 4 men and 2 women) according to World Health Organization criteria (1980). The II of the DM patients was significantly low, with an average of 0.13 +/- 0.03. From recent data in the literature on the prevalence of DM in the general Japanese adult population (1.75-5.5%), it was concluded that the frequency of DM among our randomly selected narcoleptic patients was significantly increased. The positive results for diabetes in our six narcoleptic patients could not be attributed to obesity, because there was no difference between the obesity indices of DM and nonDM narcoleptic patients, nor was there a difference between the frequency of DM in obese and nonobese patients.

Adult↗

Mechanisms by which nephrectomy stimulates adrenal renin.

Renin has been identified in the adrenal gland by several investigators. Nephrectomy is the most potent stimulator of adrenal renin, and in the present study we investigated the mechanism by which nephrectomy stimulates adrenal renin. The pituitary plays a permissive role since hypophysectomy abolished the response of adrenal renin to nephrectomy (from 117.3 +/- 14.55 to 10.37 +/- 1.63 ng angiotensin I/mg protein/hr) and adrenocorticotropic hormone (ACTH) treatment restored the response to nephrectomy in hypophysectomized rats to 120 +/- 20.62 ng angiotensin I/mg protein/hr. However, large doses of ACTH given to intact rats did not increase adrenal renin to the high level observed after nephrectomy. Potassium also plays an important role, since prevention of hyperkalemia after nephrectomy by treatment with a cation exchange resin, sodium polystyrene sulfonate (Kayexalate), significantly reduced the adrenal renin response to nephrectomy. A third factor involved is the lack of negative feedback by plasma angiotensin II. Infusion of angiotensin II intraperitoneally prevented the rise in adrenal renin after nephrectomy (from 65.25 +/- 7.60 to 9.27 +/- 0.99 ng angiotensin I/mg protein/hr) despite an increase in plasma potassium and corticosterone. In conclusion, three factors influence the response of adrenal renin to nephrectomy: 1) the pituitary through the release of ACTH, 2) a direct stimulation by high plasma potassium levels, 3) the lack of angiotensin II feedback inhibition. Whether the high adrenal renin contributes to the high aldosterone observed in rats after nephrectomy remains to be established.

Adrenal Cortex↗

Abnormality of circulatory reflex and aldosterone response during head-up tilting in patients with primary aldosteronism.

Abnormality of the circulatory reflexes has been reported in patients with primary aldosteronism. However, changes in blood pressure, heart rate, plasma renin activity (PRA), and plasma aldosterone concentration (PAC) after head-up tilting in primary aldosteronism have not yet been reported. Seven patients with primary aldosteronism were tilted to a 65 degree head-up position which was maintained for 30 min. Systolic blood pressure decreased significantly 5 min after tilting and remained at this level during the period of tilting. Diastolic blood pressure did not change during the tilting. Heart rate increased after 5 min of tilting and this level of heart rate was maintained for 30 min. Plasma renin activity was low and did not change during tilting. However, plasma aldosterone concentration increased significantly 20 min after tilting. Plasma cortisol concentration and plasma ACTH concentration also increased significantly. These results suggest that primary aldosteronism causes abnormalities of the circulatory reflexes. The increase of endogenous ACTH may increase plasma aldosterone concentration in patients with primary aldosteronism.

Adrenocorticotropic Hormone↗

[Results of brachytherapy of tongue cancer].

One hundred thirty-two patients with primary cases of squamous cell carcinoma of the tongue treated at National Sapporo Hospital from 1972 to 1982 were reviewed. Most primary sites were treated with interstitial needle implant with or without external beam irradiation. The local control rate by needle implant for the primary tongue lesions was 85.5%. That for the single plane implant was especially notable at 92.5%. The cumulative five-year survival rate was 92.8% in stage, I, 74% in stage II, 53.2% in stage III, 12.5% in stage IV and 64% overall.

Adult↗

[Coronary artery disease detected noninvasively by dipyridamole-loading 201T1 myocardial scintigraphy in elderly patients].

To evaluate the usefulness in diagnosing coronary artery disease (CAD), dipyridamole-loading 201T1 myocardial scintigraphy was performed for 52 elderly patients (65-92 years, mean: 72 years), and the results were compared with data from the treadmill exercise tests. Thirty-five patients could not tolerate adequate exercise tests. Seven of them had reversible defects; six, fixed (irreversible) ones. Dipyridamole scintigraphy is therefore applicable in detecting CAD among patients with suspected CAD who are unable to perform adequate exercise tests. Four of 16 patients with positive exercise tests had no reversible defects; the exercise results in three were regarded as false positives. Seventeen patients experienced chest pain; 12 had ST depression during dipyridamole loading. There were no serious complications, but seven patients required aminophylline. We demonstrated previously that the sensitivity and specificity of dipyridamole scintigraphy in detecting CAD were 90% and 92%, respectively, in patients with chest pain undergoing coronary angiography. These results were superior to those of conventional exercise myocardial scintigraphy. Therefore, dipyridamole scintigraphy is regarded as a safe and useful method for detecting CAD, particularly in elderly patients who have ST and T wave abnormalities but cannot tolerate exercise test adequately.

Aged↗

[Results of several combination modalities for maxillary cancer].

Two hundred forty-six patients with the histologically proved squamous cell carcinoma of the maxillary sinus were treated at the Department of Radiology, National Sapporo Hospital, with various combined modes of surgery, irradiation and chemotherapy. Four combination modalities were used from 1966 to 1983. One hundred sixty-three (66.3%) patients were men and 83 (33.7%) were women. Five-year survival was 41.0% in T2 (16 cases), 22.3% in T3 (176 cases) and 15% in T4 (53 cases). In 72 cases treated since 1978 with tumor reduction as completely as possible, five-year survival was 43.5%. We recommand tumor reduction as complete as is possible and 40-50 Gy irradiation.

Adult↗

[Combined chemotherapy for head and neck cancer using cisplatin, methotrexate and continuous subcutaneous infusion of peplomycin].

Twenty-one patients with advanced or recurrent squamous cell carcinoma of the head and neck were treated with cisplatin, methotrexate and continuous subcutaneous infusion of peplomycin. The overall response rate was 62% (13/21) with 19% (4/21) complete response. The median duration of partial response was 2 months, while that of complete response was 3 months. Toxic effects were acceptable with no fatalities, but nephrotoxicity (33%), leukocytopenia (24%), thrombocytopenia (29%) and severe nausea and vomiting (76%) occurred. Pulmonary toxicity due to continuous subcutaneous infusion of peplomycin (15 mg/day, 4 days) was not seen.

Adult↗