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Biomedical subjects

T Yamazaki

Publications and source records attributed to T Yamazaki.

At least 181 records · Page 10Linked to original sources

Left cervical aortic arch with aortic coarctation and saccular aneurysm.

Cervical aortic arch is a very rare malformation and is occasionally accompanied by other cardiovascular anomalies. A 48-year-old male patient had a left cervical aortic arch with aortic coarctation and saccular aneurysm distal to the coarcted segment. The major clinical manifestations were upper body hypertension with a 50-mmHg discrepancy between the upper and lower limbs and a loud continuous murmur in the upper chest and back. Magnetic resonance angiography successfully depicted the anomalous aorta, and the aortic coarctation and aneurysm were surgically resected and the thoracic aorta was reconstructed. The discrepancy in blood pressure diminished after the operation, but antihypertensive medication was continued to satisfactorily control the hypertension.

Aorta, Thoracic↗

Studies on the mechanism of action of the gastric H+,K(+)-ATPase inhibitor SPI-447.

3-Amino-5-methyl-2(2-methyl-3-thienyl)- imidazo[1,2-a]thieno[3,2-c]pyridine, SPI-447, is a potent gastric H+,K(+)-ATPase inhibitor, but a detailed mechanism of the inhibition is unknown. This study was designed to investigate the mechanism by which SPI-447 inhibits gastric H+,K(+)-ATPase. For this purpose, the inhibitory action of SPI-447 on gastric H+,K(+)-ATPase from porcine gastric mucosa was compared with that of omeprazole (an irreversible inhibitor) and SCH28080 (a reversible inhibitor). All compounds produced dose-dependent inhibition of gastric H+,K(+)-ATPase, and the inhibitory intensities were increased under acidic conditions. The anti-H+,K(+)-ATPase actions of SPI-447 and SCH28080 were attenuated by dilution, but not influenced by glutathione pretreatment. In contrast, that of omeprazole was not influenced by dilution, but was suppressed by glutathione pretreatment. KCl addition reversed the inhibition of H+,K(+)-ATPase-mediated H(+)-transport by SPI-447 and SCH28080, but had no effect on that by omeprazole. The anti-gastric H+,K(+)-ATPase action of SPI-447 was additive with that of SCH28080. SPI-447 and SCH28080 had no effect on Na+,K(+)-ATPase activity. These findings indicated that the inhibitory mechanism of SPI-447 on gastric H+,K(+)-ATPase was similar to that of SCH28080, but different from that of omeprazole; i.e., 1) reversible, 2) SH-group independent, 3) K(+)-competitive, and 4) highly specific against gastric H+,K(+)-ATPase.

Animals↗

Deletion of the yhhP gene results in filamentous cell morphology in Escherichia coli.

The Escherichia coli yhhP gene was predicted to encode a small hypothetical protein of 81 amino acids, the cellular function of which is not known. To gain insight into the function of this uncharacterized YhhP protein, genetic and biochemical studies were done. We first tried to express and purify the YhhP protein to prepare an anti-YhhP antiserum. Western blotting showed that the hypothetical yhhP gene is indeed transcribed and translated as a minor cytoplasmic protein. YhhP-deficient (delta yhhP) cells formed colonies poorly on a rich medium (e.g., Luria-Bertani medium) containing a relatively low concentration of NaCl, while they can grow normally either in LB containing 3% NaCl or in a synthetic medium (e.g., M9-glucose). During exponential growth in rich medium, an early step of cell division was inhibited in delta yhhP cells, forming filaments. For the YhhP-deficient filamentous cells, the FtsZ-ring formation was analyzed with immunofluorescence microscopy. The FtsZ-ring formation did not occur normally in the delta yhhP filaments, although the filamentous cells contained the FtsZ protein at a certain level comparable to that in the wild-type cells. The ftsZ gene was found to function as a multicopy suppressor of the delta yhhP mutant. Another multicopy suppressor gene was identified as the dksA gene. Provided that either the ftsZ or dksA gene was introduced into the mutant cells with its multicopy state, the resulting transformants were capable of growing in rich medium, formed wild-type short rods. These results are discussed with regard to the presumed function of this ubiquitous protein.

Amino Acid Sequence↗

Screening for cardiac dysfunction in asymptomatic patients by measuring B-type natriuretic peptide levels.

Early diagnosis and treatment of heart failure lead to improved survival; pre-clinical detection would thus be beneficial. A non-invasive biochemical testing method would indeed be ideal to screen for the condition. In the present study, we sought to determine whether circulating levels of B-type natriuretic peptide (BNP) correlate with cardiac function in asymptomatic subjects. 294 consenting asymptomatic subjects were examined. BNP levels in elevated patients (> 18.4 pg / ml) showed significant correlation with echocardiographic parameters of the systolic and diastolic functions (EF r = -0.51, FS r = -0.50, E/A r = 0.42, p < 0.01). Moderate correlation with the CTR on chest X-ray was also seen (r = 0.23, p < 0.01). Multiple regression analysis showed numerous echocardiographic and hemodynamic parameters including those of systolic and diastolic function in addition to left ventricular wall thickness, blood pressure and serum creatinine levels to be significantly associated with raised BNP levels. Elevated BNP levels reflect cardiac function (both systolic and diastolic) in the asymptomatic population. Detection of cardiac dysfunction by the non-invasive biochemical test may prove useful in early pre-clinical diagnosis of heart failure.

Atrial Natriuretic Factor↗

Hyponatremia with increased plasma antidiuretic hormone in a case of hypothyroidism.

We report a 70-year-old woman with hypothyroidism and severe hyponatremia. Her plasma antidiuretic hormone (ADH) level was inappropriately high for her low plasma osmolality. Her low serum sodium level was gradually corrected by water restriction and sodium supplementation prior to the initiation of thyroid hormone replacement. After a diagnosis of Hashimoto's thyroiditis had been made, the patient was treated with levothyroxine. Following this treatment, the patient's serum sodium level increased drastically. It is suggested that the elevated plasma ADH level played an important role in the development of hyponatremia in this case.

Adrenal Glands↗

Geko, a novel gene involved in olfaction in Drosophila melanogaster.

To characterize genes involved in olfactory responses to chemical attractants, we screened 3000 P-element-tagged lines for their attraction to ethanol. Ten lines showed reduced levels of response, and revertants of these lines were obtained by excising the inserted P-element. The olfactory response of one line reverted to wild-type behavior compared to the original mutant line. The gene affected by this P-lacW insertion was named geko (gk). A 1.3-kb transcript was found to emanate from close to the P-insertion site, and the 5' upstream region was interrupted by the P-element. The amount of mRNA of gk gene in the P-lacW inserted line was about half that of the control strain. The response to ethanol of the gk(1) mutant was restored by transforming the genomic region containing this transcription unit. lacZ expression (stemming from this reporter-gene's presence in the transposon) was observed in the antenna and the antennal-maxillary complex (the olfactory organ of adults and larvae, respectively). gk mRNA was detected at the antenna and from other parts of the body. The deduced gk product showed no overall similarity to any reported amino-acid sequences.

Animals↗

[Copper supplement with cocoa for copper deficiency in patients with long-term enteral nutrition].

Copper deficiency (normal serum copper level: 78-136 micrograms/dl) has been reported in patients with long-term enteral nutrition, caused by a copper deficit in enteral nutrition. Occasionally, this leads to anemia and leukopenia. We used Hershey's pure cocoa that is rich in copper (content 3.8 mg/cocoa 100 g) for copper deficiency. A total of 86 (40 men and 46 women, mean age 69 years) patients on enteral nutrition were studied. The primary diseases were cerebral vascular disease in 71 patients, neurological disease in 5 and others in 10. Those who showed serum copper levels of 20 micrograms/dl or less (N = 8) were given 30-45 g of cocoa (copper content 1.14-1.71 mg) per day for about 40 days. Among them, two patients could not continue because of vomiting and diarrhea and were excluded from this study. Mean serum copper levels increased from 8.7 +/- 6.2 to 99.0 +/- 25.4 micrograms/dl (N = 6). Those who showed serum copper levels 20-77 mg/dl (N = 31) were given 10 g of cocoa (copper content 0.38 mg) per day for about 40 days. When mean serum copper levels increased from 50.5 +/- 19.3 to 89.0 +/- 12.9 micrograms/dl with cocoa administration, anemia and neutropenia caused by copper deficiency showed a tendency to improve. After completing the study period, cocoa was reduced to 5 g (copper content 0.19 mg) per day in 23 patients. The mean serum copper levels increased from 90.7 +/- 10.4 to 100.6 +/- 17.1 micrograms/dl for about 100 days. Recently, the amount of daily copper requirement for adults has been reported to be 1.28-2.5 mg per day. We showed that 10 g of cocoa (0.6 mg total copper: 0.38 mg in cocoa and 0.22 mg in other nutrients) is sufficient to treat copper deficiency, and 5 g of cocoa (0.37 mg total copper: 0.19 mg in cocoa and 0.18 mg in other nutrients) is enough to maintain the normal level of serum copper in patients with long-term enteral nutrition.

Aged↗

Clinical significance of tenascin-C expression in osteosarcoma: tenascin-C promotes distant metastases of osteosarcoma.

Tenascin-C (TN-C) is one of extracellular matrix glycoproteins. We have immunohistochemically examined the TN-C expression of 33 primary osteosarcoma paraffin-embedded samples. The TN-C expression of the patient group with metastases was higher than that of the group without metastases at significant difference, and the survival curves show a tendency for poor outcome in the high grade staining group. Moreover, the supplemental TN-C had an effect of easier migration of a human osteosarcoma cell line (HOS) in vitro. The results may suggest that TN-C help osteosarcoma cells to migrate and to metastasize.

Adolescent↗

[Usefulness of Doppler echocardiography in patients with ischemic cerebrovascular disease].

We carried out transthoracic Doppler echocardiography on 213 patients with ischemic cerebrovascular disease to examine cardiac functions. The prevalence of valvular regurgitation, left ventricular diastolic function (E/A ratio), and ejection fraction (EF) of each patient were studied by transthoracic Doppler echocardiography. In patients with embolic strokes, the prevalence of valvular regurgitation of the left ventricular system such as mitral regurgitation was significantly higher than that of normal controls. In contrast, there was no significant difference in the prevalence of valvular regurgitation in the right ventricular system. Although there was no significant difference in the ejection fraction between groups, the E/A ratio in patients with ischemic cerebrovascular disease showed a significantly lower value than that in normal controls. Patients with ischemic cerebrovascular disease showed a tendency to have an atherosclerotic change in the systemic arteries including cerebral and coronary arteries, reflecting an aggravation of cardiac wall compliance and diastolic dysfunction resulting in lowering of the E/A ratio. Thus, transthoracic Doppler echocardiography was useful to evaluate cardiac diastolic dysfunction and valvular regurgitation in patients with ischemic cerebrovascular disease.

Acute Disease↗

Severe factor VII deficiency caused by a novel mutation His348 to Gln in the catalytic domain.

Factor VII is a vitamin K-dependent zymogen that plays a key role in the initiation of the extrinsic pathway. A severe factor VII deficiency was identified in a 45-year old male whose plasma factor VII antigen was less than 60 ng/ml and expressed 5.2% of normal factor VII activity. DNA sequence analysis of the patient's factor VII gene showed a thymidine to guanine transversion at nucleotide 10968 in exon VIII that results in a novel amino acid substitution of His348 to Gln. The patient was homozygous for this mutation, whereas some of his family members were heterozygous. Both wild type and mutant factor VII were transiently expressed in COS-1 cells. The level of secreted mutant factor VII antigen was only 11.0% of the level of wild type factor VII. In CHO cells stably transfected with the mutant factor VII, only 37.3% of the total labeled FVII was secreted into the conditioned media and the remainder was retained inside the cells. These data suggest this mutation leads to factor VII deficiency due to the impaired secretion of the molecule.

Amino Acid Sequence↗

[Phenotypic classification of malignant lymphoma].

The phenotypic characters of the lymphoma cell are important in the diagnosis of this disease. We recently tested whether the flow cytometry with fresh biopsy sample might be useful in the diagnosis of the lymphoma. In our date, 1. a rise and fall of the surface immunoglobulin kappa/lambda ratio indicated the monoclonal proliferation of the B-cell, 2. the increased proportion of the CD5/CD23 double positive cells indicated B-cell chronic lymphocytic leukemia or small lymphocytic lymphoma, 3. the decreased proportion of the CD2 positive cells and the increased proportion of the CD19 positive cells indicated B-cell lymphoma. These findings suggest that the flow cytometry is of adjunctive importance in making a diagnosis of the lymphoma.

Flow Cytometry↗

[Treatment of intermediate and high grade non-Hodgkin's lymphoma].

Since the study by SWOG in 1993, CHOP regimen has been the standard therapy for patients with advanced stage intermediate-grade or high-grade non-Hodgkin's lymphoma. Three-year estimated survival for all patients was about 50%. However, five-year disease free survival of the patients with high or high-intermediate risk by age-adjusted international prognostic index(IPI) is less than 30%. For the patients with low and low-intermediate IPI, high cure rate can be achieved by CHOP, or modified CHOP therapy. For the patients in high or high-intermediate risk groups, the CHOP regimen is not satisfactory. High-dose chemotherapy with haematopoietic stem cell rescue has been tried for those patients. We are conducting pilot study of high-dose chemotherapy with peripheral blood stem cell transplant(PBSCT) following induction with double CHOP regimen. Although the results are encouraging, confirmation with randomized prospective trials are necessary.

Antineoplastic Combined Chemotherapy Protocols↗

[Absence of cross resistance between an irinotecan plus cisplatin combination and raltitrexed (ZD1694) in two patients with advanced colorectal cancer].

Two patients with advanced colorectal cancer were consecutively administered two different chemotherapeutic regimens. The first patient showed an initial response to combination treatment with irinotecan plus cisplatin, but then progressed. He subsequently responded to treatment with a novel thymidylate synthase (TS) inhibitor, raltitrexed. The second patient, who progressed after exhibiting a response to raltitrexed, subsequently responded to irinotecan/cisplatin combination therapy. In conclusion, no clinical cross resistance between the regimens of irinotecan/cisplatin combination therapy and raltitrexed was observed in these patients with advanced colorectal cancer.

Antimetabolites, Antineoplastic↗

[Antimicrobial susceptibility testing for Mycobacterium tuberculosis by the bioluminescence assay of mycobacterial ATP using filamentous cell treatment].

The antimicrobial susceptibility testing for Mycobacterium tuberculosis by the bioluminescence assay of adenosine triphosphate(ATP) derived from living mycobacteria was improved introducing filamentous cell treatment(FCT) reported for beta-lactam susceptibility test of Pseudomonas aeruginosa by Hattori. Before ATP extraction, bacterial cells were treated with the FCT reagent for 30 minutes at room temperature. Adenosine phosphate deaminase in the FCT reagent simultaneously digested the extracted ATP and released ATP in a liquid culture of M. tuberculosis H37Rv and the RLU level was decreased markedly. Using this improved ATP method, we determined the ATP contents of M. tuberculosis inoculated into Middle-brook 7H9 broth medium with or without drugs. In ethambutol(EB) susceptibility, the ATP method reported previously, showed false-resistance when judged within 7 days. To eliminate false-resistance in EB susceptibility we applied the modified ATP method with FCT treatment to strains determined EB susceptible by reference methods. Using this modified ATP method, we could judge EB susceptibility of 5 ATCC reference strains within 3 days, and these of 15 clinical isolates of M. tuberculosis within 5 days. And all the results obtained were coincident between the ATP method and the reference methods. The reproducibility of this modified ATP method was evaluated with six ATCC reference strains at the concentrations of 0.1 microgram/ml of isoniazid(INH), 2.0 micrograms/ml of rifampicin(RFP), 2.5 micrograms/ml of EB, 2.0 micrograms/ml of streptomycin(SM), and 5.0 micrograms/ml of kanamycin(KM). The test was repeated six times. Reduction of ATP contents were observed in susceptible strains but not in resistant ones within 3 days of cultivation and susceptibilities to drugs could be determined within 3 days at every time when combined FCT to the ATP method. And highly reproducible results were obtained. It is strongly suggested that this modified method is simple, rapid, highly reproducible and nonradiometric, and could be used for the assessment of drug susceptibility for M. tuberculosis.

Adenosine Triphosphate↗

[Cardiac function estimated by Doppler echocardiography in patients with hypertensive intracerebral hemorrhage].

We carried out transthoracic Doppler echocardiography on 38 patients with hypertensive intracerebral hemorrhage(ICH) to examine cardiac functions. The ratio of myocardial hypertrophy and the prevalence of valvular regurgitation were investigated. The E/A ratio which reflects left ventricular diastolic function and the ejection fraction(EF) of each patient were also studied to demonstrate cardiac functions in patients with hypertensive ICH. Myocardial hypertrophy was found in 39.5% of patients with hypertensive ICH. The aortic regurgitation showed a trend to have a higher prevalence in patients with hypertensive ICH when compared to normal volunteer group. Although there was no significant differences in the ejection fraction between groups, the E/A ratio in patients with hypertensive ICH showed a significantly lower value than in normal volunteer group. Therefore, transthoracic Doppler echocardiography demonstrated that patients with intracerebral ICH showed a trend to have a myocardial hypertrophy, aortic valvular regurgitation, and the lower ventricular diastolic function. Thus, transthoracic Doppler echocardiography is useful to evaluate cardiac functions in patients with hypertensive ICH.

Adult↗

[Correlation of pulmonary perfusion volume analysis with pulmonary function in emphysema].

Pulmonary perfusion single photon emission tomography with 99mTc MAA was performed on 13 pulmonary emphysema patients and 6 controls. We calculated perfusion volume with lower 10%, 20%, 30%, 40% and 50% of the highest counts/boxels in the lung cut-off. And perfusion index (PI) was defined as follows; PI = ((A% cut-off volume) - (B% cut-off volume))/(A% cut-off volume); A and B take 10 to 50, A < B. The correlation of each PI and pulmonary function test results (FEV1, FEV1%, VC, VC%, FVC, FVC%, PaO2 and PaCO2) was examined. There were significant correlation between every PI and FEV1 or FEV1% (p < 0.05), and any PI had no significant correlation with other functional results. When A = 10 and B = 40, the PI showed the best correlation with FEV1 (r = 0.680) and FEV1% (r = 0.830). And the PI showed an increasing tendency along with the rise of the emphysema severity. The PI may have the clinical utility of the evaluation of pulmonary function. Moreover, we showed the lung CT painted the area where the uptake counts/boxels was more than 10% and less than 40% of the highest counts/boxels. This makes it easy to understand the severe emphysematous area.

Adult↗

[A case of acute urticaria from hydroxyzine hydrochloride used for preanesthetic medication].

We report a case of acute urticaria probably caused by hydroxyzine hydrochloride. A 66-year-old male was scheduled for cardiac cystectomy by thoracic endoscopy. The patient was premedicated with atropine and hydroxyzine intramuscularly 30 min before arrival in the operating room. Abrupt general exanthema was observed when intravenous infusion was started. Although his general condition was stable, the operation was postponed. Three days later, the skin test was performed using several drugs. Only hydroxyzine hydrochloride gave positive result. It is assumed that hydroxyzine hydrochloride may have caused his urticaria.

Acute Disease↗