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Biomedical subjects

T Tsuchiya

Publications and source records attributed to T Tsuchiya.

At least 289 records · Page 16Linked to original sources

Abnormal expression of sphingomyelin acylase in atopic dermatitis: an etiologic factor for ceramide deficiency?

Previously, we demonstrated that there is a marked reduction in the amount of ceramide in the stratum corneum of both lesional and nonlesional forearms in atopic dermatitis (AD), suggesting that an insufficiency of ceramides in the stratum corneum is an etiologic factor in atopic dry and barrier-disrupted skin. In this study, we investigated, as a possible mechanism involved in the ceramide deficiency, whether sphingomyelin (SM) metabolism is altered in AD as compared to normal controls. In stripped stratum corneum and biopsied whole epidermis of patients with AD, SM hydrolysis as measured at pH 4.7 using [choline-methyl-14C]sphingomyelin as a substrate were markedly increased by 27- and 7-fold, respectively. Radio-thin-layer chromatography of the reaction products revealed that, whereas the SM hydrolysis in age-matched normal controls were associated with sphingomyelinase (SMase) that degrades SM to yield ceramides and phosphorylcholine (PC), most of the SM hydrolysis detected in AD were attributable not to the SMase but to a hitherto undiscovered epidermal enzyme, SM acylase, which releases free fatty acid and sphingosyl-PC (Sph-PC) instead of ceramides. The potential of this acylase-like enzyme to generate Sph-PC through SM hydrolysis was corroborated by thin-layer chromatographic analysis of the reaction products obtained using porcine kidney acylase, followed by high-performance liquid chromatography-mass spectrometry. Furthermore, Sph-PC was also detected by high-performance liquid chromatography-mass spectrometry after incubation of SM with atopic stratum corneum samples. On the other hand, the stratum corneum of patients with contact dermatitis or chronic eczema exhibited neither increased SM hydrolysis nor the generation of Sph-PC upon radio-thin-layer chromatographic analysis. These findings suggest that SM metabolism is altered in AD, resulting in a decrease in levels of ceramides, which could be an etiologic factor in the continuous generation of atopic dry and barrier disrupted skin observed in AD.

Amidohydrolases↗

Double atrial responses to a single ventricular impulse in long RP' tachycardia.

Double atrial responses (DARs) to a single ventricular impulse have been described in patients with long RP' tachycardia. To define the determinants for the occurrence of DARs, 8 cases with long RP' tachycardia were examined. The mechanism of long RP' tachycardia was the orthodromic atrioventricular reciprocating tachycardia (AVRT) involving a slow conducting concealed accessory pathway in 4 cases and uncommon (fast-slow) type of atrioventricular nodal reentrant tachycardia (AVNRT) in the other 4 cases. Programmed and rapid ventricular pacing was performed during sinus rhythm and also rapid ventricular pacing during tachycardia (i.e., entrainment). The retrograde effective refractory period (ERP) and the retrograde maximal 1:1 conduction rate of the fast and slow conducting pathways were examined. In 1 of the 4 cases with AVRT, DARs were observed during programmed and rapid ventricular pacing, performed during sinus rhythm and also during entrainment. In 1 of the 4 cases with AVNRT, DARs were observed only during entrainment. The determinants of DARs in cases with long RP' tachycardia were: (1) presence of two different retrogradely conducting pathways; (2) short ERP of the retrograde fast and slow conducting pathways and a short minimal pacing cycle length at which 1:1 ventriculoatrial conduction occurs via these pathways; (3) crucial conduction delay in the slow conducting pathway; and (4) preexisting antegrade unidirectional block in the slow conducting pathway or the antegrade block in the slow conducting pathway produced by collision with a previous retrograde impulse during entrainment.

Adult↗

Apolipoprotein A-IV synthesis in proximal jejunum is stimulated by ileal lipid infusion.

Biosynthesis of apolipoprotein A-IV (apo A-IV) is stimulated by dietary lipid, but the precise mechanisms involved are not clearly understood. Using an intestinally infused rat model, we compared the effect of delivery of lipid into different intestinal sites on mucosal synthesis of apo A-IV in the jejunum and ileum to determine 1) the effect of lipid delivered to one region of the intestine on apo A-IV synthesis in another region of the gut, and 2) whether any such effect is dependent on the presence of lipid in the latter region. Duodenal infusion of triolein emulsion (40 mumol/h) increased jejunal apo A-IV synthesis and mRNA levels by two- to threefold but had no effect on ileal apo A-IV synthesis or mRNA abundance. Ileal infusion of lipid emulsion containing monoolein (20 mumol/h) + oleic acid (40 mumol/h) stimulated apo A-IV synthesis in both ileum and proximal jejunum. Retrograde (orad) transport of ileally infused lipid was not a likely explanation for the ileal effect on jejunal apo A-IV synthesis, because there was negligible luminal and mucosal recovery of [14C]oleic acid in the jejunum after ileal infusion. Total bile diversion did not block the effect of ileal lipid on jejunal apo A-IV synthesis. Ileal, but not duodenal, lipid infusion stimulated apo A-IV synthesis in a jejunal Thiry-Vella fistula, and perfusion of an ileal Thiry-Vella fistula marginally stimulated proximal jejunal apo A-IV synthesis. Thus administration of lipid to the distal gut produces an increase in mucosal synthesis of apo A-IV in both proximal and distal gut. This effect appears to be independent of direct jejunal presence of lipid, suggesting that lipid in the distal intestine may elicit a signal capable of stimulating jejunal synthesis of apo A-IV.

Animals↗

Ileal transposition into the upper jejunum affects lipid and bile salt absorption in rats.

To determine whether ileal transposition affects absorption and transport of lipids and bile salts, we studied the absorption and lymphatic transport of triglyceride, cholesterol, and sodium taurocholate in rats with the distal quarter of their small bowel transposed to the proximal jejunum and in control rats whose intestines were transected and reanastomosed without transposition. Three weeks after transposition or sham surgery, rats were equipped with duodenal or jejunal and intestinal lymph duct cannulas and then given continuous duodenal or jejunal infusions of lipid emulsion containing triolein (40 mumol/h + [3H]triolein) and cholesterol (7.8 mumol/h + [14C]cholesterol) for 8 h. Lymph lipid output was measured; after 8 h of lipid infusion, luminal and mucosal radioactive lipid distribution was also quantified. Transposition had no effect on triglyceride absorption and transport, but cholesterol absorption and transport were both significantly attenuated in the transposed rats. In a separate study we examined whether ileal transposition would alter the kinetics of bile salt absorption. Six weeks after either transposition or sham surgery, rats were given a duodenal bolus injection of 14C-labeled sodium taurocholate mixed in rat bile, and the output of radiolabeled bile salt through a bile fistula was measured. Appearance of radiolabeled taurocholate was gradual in the control rats, peaking at approximately 90 min after administration. Appearance of labeled bile salt was rapid in the transposed rats, peaking within 60 min after administration. In conclusion, ileal transposition has no effect on triglyceride absorption but attenuates cholesterol absorption and transport, possibly by promoting premature absorption of bile salts.

Animals↗

Estrogen receptor-mediated transcriptional activation by 17 beta-estradiol and its analogs.

We investigated the effects of natural and synthetic estrogens on estrogen receptor-mediated signal transduction and transcription. To assess estrogen receptor-dependent gene expression, we constructed a reporter plasmid that can express the luciferase gene under the control of the estrogen-responsive element. A transcriptional assay was performed by transfection of the reporter plasmid into estrogen-responsive MCF-7 cells. Transcription was completely dependent on the natural estrogen, 17 beta-estradiol (E2), in a dose-dependent manner. Retinoic acids and other steroid hormones had no effect on gene expression. The effect of synthetic estrogens on estrogen receptor-mediated signal transduction was also examined using the specific reporter assay system. A synthetic estrogen, diethylstilbestrol, exhibited higher activity than E2 at lower concentrations. In addition, transcriptional activities of the (+)- and (-)-enantiomers of indenestrol A, a metabolite of diethylstilbestrol, could be distinguished using the reporter assay system.

Diethylstilbestrol↗

Protective effects of chlorogenic acid on paraquat-induced oxidative stress in rats.

The protective effects of chlorogenic acid on paraquat-induced oxidative stress were examined in rats. The activities of erythrocytes and liver glutathione peroxidase, and of both liver catalase and glutathione reductase, which were increased by feeding paraquat, declined to the levels in the control rats by supplementing chlorogenic acid to the paraquat diet. The activity of superoxide dismutase was not changed by dietary paraquat or by supplementing chlorogenic acid to the paraquat diet. Paraquat in the diet markedly decreased the liver triacylglycerol and phospholipid concentrations, as well as the food intake and body weight gain, while chlorogenic acid protected against these decreases. These in vivo results and the in vitro superoxide anion scavenging activity of chlorogenic acid suggest that chlorogenic acid acted preventively against paraquat-induced oxidative stress.

Administration, Oral↗

[Asthma-like symptoms due to thoracic aneurysm].

We describe a case of positional dyspnea due to compression of the tracheobronchial tree by an extensive thoracic aneurysm. In a 77-year-old woman with long-standing systemic hypertension, intermittent anterior chest pain gradually developed over several years. She had no history of asthma or thoracic trauma. She was admitted to our hospital because of sudden, severe shortness of breath. The breathlessness was markedly worse when she lay on her back or on her right side. On physical examination, she was in acute respiratory distress with cyanosis, severe hypertension (180/110 mmHg), tachycardia, and inspiratory stridor. A chest X-ray film showed loss of volume and nearly complete radiopacity of the left hemithorax. Arterial blood gas analysis revealed an arterial oxygen partial pressure of 54.8 mmHg, a carbon dioxide partial pressure of 39.8 mmHg, and an oxygen saturation of 84.5 percent on room air. Computed tomographic examination of the thorax showed dilation of the aortic arch and descending aorta, and marked compression of the trachea and the left main bronchus. Examination with a fiberoptic bronchoscope revealed extrinsic compression of the trachea just proximal to the carina. The patient's symptoms stabilized. However, she did not undergo surgery because of her age and because of the size of the aneurysm. She died due to rupture of the aneurysm.

Aged↗

[Death due to pulmonary tuberculosis--a comparison between 1984-88 and 1989-93].

Pulmonary tuberculosis (TB) remains the single leading cause of death from any single infectious agent in the world. We reviewed the case records and chest radiographs of patients with pulmonary tuberculosis who died between 1984 and 1993. Of 2333 patients discharged from National Nishi-Niigata Hospital, 86 (3.7%) died during that period. Comparison between the data for 1984-88 and for 1989-93 showed an increase in the number of elderly patients, TB-related deaths, and complication of TB by malignancy. Thirty-nine of the 86 patients died within 2 months of admission: a spread of TB over a wide region and low performance scores were noted in these patients. Multiple-drug-resistant Mycobacterium tuberculosis was often the cause of death. These results encourage us to pursue early detection in elderly people, to improve management during initial treatment such as with steroids, and to develop new and more effective drugs to treat TB.

Aged↗

[Pneumothorax from a nasogastric feeding tube].

An 83-year-old woman was admitted to our hospital because of fever and disturbance of consciousness. Pneumonia and multiple organ failure were diagnosed from symptoms, a chest X-ray film, and laboratory findings. With the administration of antibiotics and an antiprotease inhibitor, the pneumonia and multiple organ failure began to resolve, but consciousness remained disturbed. A nasogastric feeding tube was inserted to provide parenteral nutrition. Neither abnormal resistance nor reflex coughing were noted during insertion. Bubbling rales were not heard on auscultation, and a chest X-ray film revealed that the tube had traversed the right bronchial tree, perforated the lung, coiled up in the right pleural vavity, and caused a right pneumothorax. The tube was immediately removed. The pneumothorax was treated with an intercostal drainage tube for 1 day and resolved without further problems. This case shows one of the dangers involved in inserting nasogastric feeding tubes. The medical community should be aware that pulmonary complications may develop after such tubes are inserted in patients with risk factors.

Aged↗

[An evaluation of the incidence of hyperparathyroidism after 131I treatment for Basedow disease (Part I)].

It is known that external radiation can act as a developing factor in hyperparathyroidism (HPT). To clarify whether or not 131I acts as a factor of developing HPT or not, levels of calcium and parathyroid hormone in the blood were studied in 2,954 cases of patients treated with 131I (RI group) and 530 cases treated with antithyroid drugs (ATD group). The calcium level was measured in all cases treated with 131I and/or antithyroid drugs. PTH-M (parathyroid hormone) was measured in 262 cases of the RI group and 29 cases of the ATD group which showed levels over 10 mg/dl of calcium. Fifty-eight cases (2.50%) in the RI group and three cases (1.19%) in the ATD group showed over 560 pg/ml PTH-M, which is the highest normal value. The increase in incidence of cases with over 560 pg/ml PTH-M in the RI group versus that of the ATD group is statistically significant. However, there is no statistically significant difference in the annual incidence when the follow-up period is taken into account, because the follow-up period differed between the two groups. The incidence of cases with 560 pg/ml of PTH-M was higher in the older patients than in the younger patients. These results suggest that 131I treatment for Basedow disease affects increase in the development of HPT after treatment and that the age factor is also important in the above fact.

Adult↗

[An evaluation of the incidence of hyperparathyroidism after 131I treatment for Basedow disease (Part II)].

The authors reported in a previous paper that 131I treatment for Basedow disease tends to increase in development of hyperparathyroidism (HPT) after therapy, from results showing that the measurement of levels of parathyroid hormone and calcium in the blood showed higher levels in the 131I-treated (RI) group than in the anti-thyroid drugs (ATD) group after therapy for Basedow disease. In the present work, the incidence of HPT was studied in patients with HPT that developed after treatment with 131I and/or ATD for Basedow disease at Ito Hospital. Fifteen of nineteen HPT patients had been treated with 131I and the other four had been treated with ATD. Basedow patients of the same age and sex with HPT and treated in the same year at Ito Hospital were selected as the control population for this study. The populations were 223 cases treated with 131I and 199 cases with ATD. The incidence of HPT in the RI and ATD groups was 6.7 percent and 2.0 percent, respectively. The incidence in the RI group was apparently higher than that in the ATD group. The average latent periods in the RI group and in the ATD group were 13.5 years and 4.1 years respectively. In the RI group 11 cases underwent follow-up periods of more than 10 years and 4 cases were followed up for less than 10 years. For the ATD group 3 of 4 HPT cases were followed up for less than 3 years. In the population the average follow-up periods for the RI group and the ATD group were 5.9 years and 5.3 years respectively. A relationship between radiation dose and development of HPT was demonstrated in these 15 cases of HPT. These findings suggest that 131I treatments for Basedow disease may result in development of hyperparathyroidism but the length of the follow-up period may also be an important factor in the incidence.

Adult↗

[II. multidisciplinary analysis of chronic excretors of Mycobacterium tuberculosis bacilli].

For the most patients with pulmonary tuberculosis, treatment are successful and the chemotherapy can be finished within a year. Few patients, though receiving standard anti-tuberculous chemotherapy, expectorate tubercle bacilli continuously for more than a year. They are named "chronic excretors of mycobacterium tuberculosis bacilli" or "intractable tuberculosis patients". Being suspected that this phenomenon is produced by many factors, it is necessary to correspond suitably to these patients for eradication of tuberculosis. This symposium was organized to search for some factors on the bacterium and on the host, which caused patients to be the chronic excretors or intractable patients. We hope that our discussion may contribute to take the appropriate measures for such hard diseases. The main results are summarized as follows. 1) Dr. TSUCHIYA conducted a epidemiologic study by questionaire method to 33 Japanese national sanatoriums. The total number of tuberculosis patients admitted to these hospitals on a optimal day from September to October 1994 were 1,295. Numbers of patients who had expectorated bacilli continuously for more than 12 months were 85 (6.6%). The male/female ratio was about 3, their average age was 64. They had a tendency of thin-physique and most of them had past histories of tuberculosis, being the refractory cases. The average clinico-epidemiologic conditions of the patients came before our eyes. 2) Dr. OGATA analysed the results of drug sensitivity tests of mycobacterium tuberculosis bacilli from 2,630 pulmonary tuberculosis patients which contained 179 chronic excretors. The only 2.2% of bacilli from the chronic excretors were sensitive to RFP (50 gamma). The 99.4% of bacilli showed to be resistant to INH (0.1 gamma). The 39.1% of bacilli were sensitive to streptomycin (20 gamma). To EB (2.5 gamma) 34.1% of bacilli were sensitive. However, the ratio of chronic excretors in tuberculosis patients was not increased in these 17 years, and for many cases of these chronic excretors, they are all inexperienced in PZA, multi-sensitive-drug chemotherapy including PZA and OFLX were useful. Some of them underwent lobectomy combined for effective chemotherapy. The chronic excretors are likely to be affected multidrug-resistant bacilli, and it is important for such cases to treat intensively with several kinds of sensitive drugs. 3) Dr. FUJIWARA studied Interleukin-10 (IL-10) producing function of monocytes stimulated by Mycobacterium tuberculosis (M-TB). The IL-10 usually down-regulates a number of different macrophage functions, including microbicidal activity against intracellular bacteria such as Mycobacterium species. They found that the mean IL-10 production by peripheral blood mononuclear cells (PBMC) obtained from a healthy tuberculin-reactor stimulated with multidrug-resistant M-TB was greater than that with drug-sensitive M-TB. The IL-10 producing cells were monocytes, not T-lymphocytes. They moreover found that PBMC from intractable tuberculosis patients secreted greater amounts of IL-10 than those of healthy subjects. These data may give a hint for development of new immunotherapeutic methods for multi-drug-resistant tuberculosis patients. 4) Dr. HARA analysed clinical courses of 580 consecutive cases of bacilli positive pulmonary tuberculosis admitted in his hospital from a point of underlying diseases. All of dead 24 cases had some underlying diseases; diabetes mellitus 3, chronic liver diseases 4, others 17 (malignant neoplasms, central nerve vascular diseases, malnutritional condition, etc). (ABSTRACT TRUNCATED)

Chronic Disease↗

[Epidemiologic study of the actual investigation of chronic excretors of Mycobacterium tuberculosis bacilli].

Of 1,295 patients with tuberculosis who were admitted in 33 Japanese national sanatoriums from September to October, 1994, actual investigation of patients with persistent expectorate tubercle bacilli continuously for more than 12 months was carried out by questionnaire. From the result, numbers of patients who had persistently expectorated bacteria were 85 (6.6% of inpatient). The rate of male and female was 3:1, and mean age was 63.5 years old. Many slim type patients (less than 90% of the standard body weight) were observed at the rate of 55.8%. The rate of the inpatient whose admission period was for more than 10 years were found in 22%. The past history of the tuberculosis and surgical therapy were existent at the rate of 83.3% and 18.8% respectively. The chief complications such as diabetes mellitus (12.4%), pyothorax (10.1%), alcoholism (10.1%) and hepatic dysfunction (6.7%) were observed at the respective rate. As chest X-ray findings on admission, severe cases with cavity of I or II 3 by the classification of the Japanese society for tuberculosis were found in 32.2%, and many cases with much amount persistently excreted bacteria such as more than number 7 of Gaffky scale (24.7%) or 3+ by culture (55.8%) were detected by sputum-test on admission. From the result drug-resistance, resistance of the main drugs early found from initial medication, and high degree resistance of isonicotinic acid hydrazide (INH; 80%), rifampicin (RFP; 94.4%), ethambutol (EB; 85.6%) and streptomycin (SM; 76.4%) was found. As intractable causes which were indicated by doctor in charge, drug-resistance, drug allergy, disorder of life, unfavorable medication-compliance and unsuitable treatment were considered.

Adult↗

Synthesis of 5-deoxy-5-epifluoro derivatives of arbekacin, amikacin, and 1-N-[(S)-4-amino-2-hydroxybutanoyl]tobramycin (study on structure--toxicity relationships).

As part of a study on fluorination--toxicity relationships for aminoglycoside antibiotics, 5,3'-dideoxy-5-epifluorokanamycin B (10), 5,3',4'-trideoxy-5-epifluorokanamycin B (11), 1-N-[(S)-4-amino-2-hydroxybutanoyl]-5-deoxy-5-epifluorotobramyc in (19), 5-deoxy-5-epifluoroarbekacin (20), and 5-deoxy-5-epifluoroamikacin (21) have been prepared. The acute toxicities of these three 5-deoxy-5-epifluoro compounds showed values almost identical or similar to those for arbekacin (ABK) and amikacin (15), making a sharp contrast with the toxicities of the corresponding 5-deoxy-5-fluoro derivatives. This fact is explained on the basis of basicity changes (retention for the 5-epifluoro derivatives and reduction for the 5-fluoro derivatives) at the H2N-3 groups of the fluorinated compounds compared to the parent compounds; this hypothesis was substantiated by the pKa values at the H3N(+)-1, 3 groups (determined by the shift changes depending on pD values at C-2 and C-4, 6 in their 13C NMR spectra) of 2,5-dideoxy-5-epifluorostreptamine (23) and 2,5-dideoxy-5-fluorostreptamine (24), chosen as model compounds, and 2-deoxystreptamine (DST).

Amikacin↗

A unique chromosome translocation, t(11;12;18)(q21;q13;q21) [correction of t(11;12;18)(q13;q13;q12)], in primary lung lymphoma.

A 54-year old man with a primary lung lymphoma of mucosa-associated lymphoid tissue (MALT) origin whose tumor cells had a t(11;12;18)(q13;q13;q12) chromosome abnormality is described. The morphologic, immunologic, and molecular biologic investigations showed that the patient's lung tumor consisted of small lymphoid cells that expressed monoclonal IgM, kappa-type immunoglobulin, and immunoglobulin gene (JH and C kappa) rearrangements. Cytogenetic study revealed that the tumor cells contained a unique chromosome translocation, t(11;12;18)(q13;q13;q12), that has not been reported previously in lymphoma.

Chromosome Aberrations↗