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Biomedical subjects

S Umezawa

Publications and source records attributed to S Umezawa.

At least 19 recordsLinked to original sources
PubMed1992

Synthesis of 5-deoxy-5-fluoro and 5-deoxy-5,5-difluoro derivatives of kanamycin B and its analogs. Study on structure-toxicity relationships.

5-Deoxy-5-fluoro- (1), 5.3'-dideoxy-5-fluoro- (2), and 5,3',4'-trideoxy-5-fluoro-kanamycin B (3) have been prepared by treatment of 5-epihydroxyl precursors (prepared by the Mitsunobu reaction) with DAST as the key step. 5,3'-Dideoxy-5,5-difluoro- (26) and 5,3',4'-trideoxy-5,5-difluoro-kanamycin B (27) were also prepared by treatment of the corresponding 5-oxo derivatives with DAST. These 5-deoxy-5-fluoro and 5-deoxy-5,5-difluoro derivatives showed markedly decreased toxicity as compared with the parent compounds.

Carbohydrate Sequence↗
PubMed1992

Synthesis of 4'-deoxy-4'-fluorokanamycin A and B.

4'-Deoxy-4'-fluorokanamycins A (17) and B (25) have been prepared through fluorinative ring-opening of the D-galacto-3',4'-oxiranes (8 and 21) derived from kanamycin A and B with potassium hydrogenfluoride in ethane-1,2-diol. The mechanism of preponderant formation of the 4'-deoxy-4'-fluoro-D-gluco (9 and 22) over the 3'-deoxy-3'-fluoro-D-gulo derivatives was discussed. In the synthesis of 25, the unusual 3',6'-epimine (23) was the main product along with the 4'-deoxy-4'-fluoro derivative. The mechanism of this reaction is also discussed. Both 17 and 25 were active against resistant bacteria producing aminoglycoside-adenylylating enzymes for HO-4'.

Anti-Bacterial Agents↗
PubMed1992

[Report of a case with aortic regurgitation in progressive systemic sclerosis].

Aortic valve lesions in progressive systemic sclerosis (PSS) are very uncommon. To our knowledge, aortic regurgitation (AR) associated with PSS has not been reported previously. We would like to report the case of a 58-year-old woman who had PSS with AR due to Raynaud's symptom, fever, positive ANA, accelerated ESR, and diastolic blowing murmur along the left sternal border. After treatment with adreno-cortico steroid and an immunosuppressive agent, the patient improved serologically and symptomatically. However, she was later admitted to our hospital again due to heart failure with progressive AR. She died of refractory heart failure with severe AR and tricuspid regurgitation (TR). The former was caused by aortic cusp lesions and the latter by pulmonary hypertension. An autopsy confirmed the diagnosis of PSS, which was found to have involved the heart, lungs and pancreas. Vasculitis with infiltration and fibrotic changes were noted in these organs. Moreover, there were fibrotic thickenings and shortenings in the aortic cusps with cell infiltration. There were no indications of rheumatic disease. These results suggest that the cause of our patient's aortic valve disease may have been PSS vasculitis.

Aortic Valve Insufficiency↗
PubMed1991

Synthesis of 3'-deoxy-3'-fluorokanamycin A and 3',4'-dideoxy-3'-fluorokanamycin A.

3'-Deoxy-3'-fluorokanamycin A (14) has been prepared by condensation of 6-azido-2,4-di-O-benzyl-3,6-dideoxy-3-fluoro-alpha-D-glucopyranlsyl++ + bromide (8) and 6-O-(2-O-acetyl-4,6-O-cyclohexylidene-3-deoxy- 3-tosylamino-alpha-D-glucopyranosyl)-2-deoxy-1,3-di-N-tosylstre ptamine (10). Compound 8 was obtained from 3-deoxy-3-fluoro-1,2:5,6-di-O-isopropylidene-D-glucofuranose in seven steps. 3',4'-Dideoxy-3'-fluorokanamycin A (22) has been prepared from 12 through selective 4'-chlorodeoxygenation, a key reaction. Both 14 and 22 were more active than 3'-deoxykanamycin A against both sensitive and resistant bacteria.

Anti-Bacterial Agents↗
PubMed1991

[Effects of antianginal drugs on left ventricular diastolic filling in patients with ischemic heart disease].

To study the acute effects of isosorbide dinitrate (ISDN), nifedipine, propranolol and placebo on left ventricular diastolic filling in patients with myocardial ischemia, we repetitively performed exercise radionuclide angiography (RNA) following random assignment of each drug in 12 patients with effort angina pectoris, and 5 normal controls. Left ventricular time activity curves were constructed using computer technique. We obtained changes of hemodynamic parameters such as endodiastolic volume, systemic vascular resistance and ejection fraction. The peak filling rate (PFR), and filling rate in the first third of the diastolic period (1/3 FR) were used as the indexes of LV diastolic filling. 1/3 FR remained unchanged during peak exercise by the patients, while it increased significantly in normal controls. After administration of ISDN and nifedipine, 1/3 FR increased significantly during peak exercise by the patients. Especially after nifedipine, 1/3 FR improved significantly compared with the improvement after ISDN, although these two drugs had the same effects on systolic function. These findings showed that 1/3 FR was reliable as an indicator of LV diastolic filling in ischemic heart disease, and nifedipine improved LV diastolic filling not only by improving ischemic changes in myocardium but also by it's direct effect on left ventricular relaxation.

Aged↗
PubMed1990

Change in the growth hormone (GH) response to GH-releasing factor (GRF) caused by exogenous GH in short children.

To determine whether exogenous GH induces feedback of GH release in children, growth hormone-releasing factor (GRP) tests were performed before and after 10-day GH administration. Sixteen non-obese short boys, aged 5-14 yr, with normal GH response to pharmacological tests were studied. Mean basal and peak serum GH levels in GRF tests before and after exogenous GH were not significantly different. The subjects were divided into two groups, A and B, according to the percent change in integrated areas under the GH curves in GRF tests (GH AUC) before and after 10-day GH administration. Group A consisted of 6 boys with decreased GH AUC and group B consisted of 10 boys with increased GH AUC. Mean peak GH in GRF tests and mean GH AUC were significantly higher before exogenous GH in group A than in group B. The boys in group A were all prepubertal, while 4 boys in group B had begun their early pubertal change. The mean age in group A (7.8 +/- 1.8 yr) was significantly lower than that of group B (11.9 +/- 2.4 yr). GH AUC before exogenous GH showed a significant correlation with the percent change in AUC (= -0.742, p less than 0.01). These data demonstrated that the exogenous GH suppressed the GH response to GRF in prepubertal children with good response to GRF before exogenous GH, while it exaggerated the GH response to GRF in older children with relatively poor response before GH.

Adolescent↗
PubMed1990

[Effect of verapamil on myocardial infarct size estimated by serial 201-thallium single-photon emission tomography].

To investigate the effects of intravenous verapamil (V) in coronary thrombolytic therapy, we serially observed the time course of perfusion of the myocardium by 201-thallium (Tl) SPECT in patients who were successfully reperfused within 6 hours from the onset. 201-Tl SPECT was attempted serially on the 1st-2nd day, the 7th-10th day and 28th-30th day. In addition to this, we calculated the count ratio of radioactivity of 99mTc-PYP (CR) in the infarcted myocardium to sternum to evaluate intracellular uptake of calcium during reperfusion. The infarct size, estimated by % Defect decreased significantly in the patients treated with V, while it remained unchanged in the patients without it. In the patients with V, the left ventricular ejection fraction was more favourable, and exercise-induced ischemia determined by redistribution of 201-Tl SPECT in the chronic phase was found more frequently. CR showed no difference between reperfused myocardium irrespective of the treatment. In conclusion, verapamil was considered to enhance myocardial salvage carried out by reperfusion, and not to affect the influx of intracellular calcium into the injured myocytes.

Drug Evaluation↗
PubMed1989

[Urinary hGH, albumin, alpha 1 MG and beta 2 MG in normal and diabetic children].

I measured urinary hGH level in children with insulin dependent diabetes mellitus (DM) and studied the relation with urinary albumin alpha 1-microglobulin (alpha 1 MG), beta 2-microglobulin (beta 2MG) and plasma HbA1. 24-hour urine or night-time urine was collected in 54 normal children (NC) and 61 DM. Urinary hGH was estimated by using a sensitive sandwich enzyme immunoassay. Urinary albumin, alpha 1 MG and beta 2MG were measured by RIA. HGH concentration in 24-hour urine in NC significantly correlated with urinary albumin and beta 2MG concentrations (p less than 0.01). In DM, hGH concentration in 24-hour urine also correlated with urinary albumin concentration (p less than 0.05). To avoid the effects of posture and exercise, night-time urine was used in the following study. Urinary hGH concentration was significantly higher in DM for all age (p less than 0.05-0.01) than that in NC. Urinary alpha 1MG and beta 2MG concentrations were also significantly higher in DM than those in NC. HGH concentration in night-time urine in NC has not correlated with urinary albumin, alpha 1MG nor beta 2MG. In DM, however hGH significantly correlated with urinary albumin and beta 2MG. Even in DM with normal concentrations of urinary albumin and beta 2MG, urinary hGH was significantly higher than in NC. Urinary hGH in poorly controlled DM was higher than in well controlled DM. Urinary hGH concentration showed positive correlation with plasma HbA1 in DM. We conclude that urinary hGH relates to not only serum hGH concentration but also renal function. In DM with normal renal function, hGH concentration in night-time urine was higher than in NC, which suggested high serum hGH concentration in DM.

Adolescent↗
PubMed1989

A large myxoma of the right atrium demonstrated by thallium-201.

A rare case of right atrial myxoma in which thallium-201 gave a good delineation of the tumor was presented. In this case, the feeding arteries were seen to be highly developed on coronary arteriogram. The amount of blood containing thallium-201 supplied to the tumor through the feeding arteries was so great that the tumor was considered to be visualized by thallium-201 imaging.

Aged↗
PubMed1989

Heterogeneity of big-big hPRL in hyperprolactinemia.

Sera from a patient with macroprolactinoma (case 1) and from a hyperprolactinemic woman with regular menstruation (case 2) were analyzed for prolactin activity by gel filtration using Sephadex G-100, Sephadex G-200 and TSK G3000SW columns. The chromatographic profile by Sephadex G-100 showed that the percentage of immunoreactive big-big hPRL was 10.7% in case 1 and 64.1% in case 2. On Sephadex G-200 and TSK G3000SW columns, the molecular weight of big-big hPRL was estimated to be more than 500,000 daltons (big-big1 hPRL) in case 1 and approximately 250,000-300,000 daltons (big-big2 hPRL) in case 2. Big-big1 hPRL in case 1 was converted to big and little hPRLs when the serum was treated with 2-mercaptoethanol (2-ME), but part of the big-big2 hPRL in case 2 was converted to a larger molecule. Radioactive big-big hPRL generated by mixing labeled hPRL with the serum from case 1 was eluted with the void volume on Sephadex G-100 column and was not converted to the other molecular forms after 2-ME treatment. There were two radioactive big-big hPRL on TSK G3000SW column and these estimated molecular weights were more than 300,000 daltons. The data demonstrated the existence of at least two forms of big-big hPRL in the serum and indicated that radioactive big-big hPRL may be different from these hPRLs in the serum.

Chromatography, Gas↗
PubMed1989

Bioactivity of human growth hormone in urine from acromegalic patients.

Bioactivity of hGH in urine from five acromegalic patients was determined by Nb2 bioassay and IM-9 receptor modulation assay (RMA). Urine samples were concentrated by immunoadsorbent chromatography, dialysis and lyophilization. The ratio of the bioactivity by Im-9 RMA and the immunoactivity by RIA was between 0.81 and 1.24 (1.01 +/- 0.19, mean +/- SD). The ratio of the bioactivity by Nb2 bioassay and the immunoactivity ranged from 0.45 to 0.60 (1.37 +/- 0.85). Gel chromatography of hGH in urine samples measured by sensitive sandwich enzyme immunoassay showed that more than 97% of hGH activity was the 22K form. Urinary hGH from acromegalic patients was bioactive in Nb2 bioassay and IM-9 RMA and the bioactivity showed a close correlation with the immunoactivity. The major immunoactive form of hGH (22K) seems to correspond to the bioactivity.

Acromegaly↗
PubMed1989

Biological activities of synthesized 20K and 22K hGH in Nb2 bioassay and IM-9 radioreceptor assay.

We investigated the bioactivities of the recombinant DNA-derived methionyl 20K hGH (20K-Met-hGH) and methionyl hGH (22K-Met-hGH). The growth-promoting activities in Nb2 cells of 20K-Met-hGH and 22K-Met-hGH were 10.7% and 93.5% of pituitary hGH (P-hGH), respectively. In the IM-9 lymphocyte assay, the binding activities of 20K-Met-hGH and 22K-Met-hGH to hGH receptor were 29.0% and 87.1% of P-hGH, respectively. Our data demonstrate that 20K-Met-hGH may have weaker biological potency than P-hGH.

Animals↗