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Biomedical subjects

T Miki

Publications and source records attributed to T Miki.

At least 757 records · Page 42Linked to original sources

Reduced bone marrow toxicity of neocarzinostatin by conjugation with divinyl ether-maleic acid copolymer.

Neocarzinostatin (NCS) was conjugated with divinyl ether-maleic acid anhydride copolymer (pyran copolymer), and its therapeutic effect was compared with that of NCS. The conjugated NCS (pyran-NCS) with a molecular weight of about 23,000, exhibited in vitro cytotoxic activity against eight cell lines and bone marrow cells that was similar to the cytotoxic activity of NCS on a molar basis. Furthermore, both drugs had similar effects against a multidrug-resistant Chinese hamster ovary cell line (CHR C5) and its parent cell line (AUXB1) in vitro. However, pharmacological analysis showed that pyran-NCS had reduced accumulation in the spleen, and most important was three times less hematotoxic in vivo compared with NCS. Also, pyran-NCS had a 1.7-fold higher 50% lethal dose (LD50). Antitumor activity of pyran-NCS and NCS was tested against two different forms of Meth A tumor. In a solid tumor model, pyran-NCS and NCS suppressed tumor growth at three-fourths of the LD50 to 12.8 and 19.0% of the control tumor as evaluated on day 28, respectively (P less than 0.025). In an ascitic tumor model, the percentage increase in the median life span caused by pyran-NCS and NCS was more than 400 and 150% on day 60, respectively. Pyran-NCS is more effective than NCS because the reduced acute toxicity permits an increased drug dosage.

Animals↗

Solitary neurofibroma of scrotum.

We report a case of solitary neurofibroma of the scrotum. These tumors, which arise from perineural and Schwann cells, commonly occur throughout the body but they rarely have been reported to originate in the scrotum. No stigmata of von Recklinghausen's disease were identified.

Adult↗

The complete coding sequence of arg defines the Abelson subfamily of cytoplasmic tyrosine kinases.

We have previously described partial genomic sequences of arg, a human gene related to c-abl, and shown that it is expressed as a 12-kilobase transcript and is located at chromosome position 1q24-25. In this study we elucidate the complete coding sequence of arg by characterization of cDNA clones. Analysis of the predicted amino acid sequence of arg revealed that it is indeed closely related to that of c-abl. The two proteins are strikingly similar with regard to overall structural architecture as well as the amino acid sequences of their tyrosine kinase and src homologous 2 and 3 domains. In addition, arg, like c-abl, is expressed as two transcripts that result from a process of alternative splicing and encode alternative protein forms that differ only in their amino termini. The two genes define the Abelson subfamily of cytoplasmic tyrosine kinases and share a common homolog in Drosophila.

Amino Acid Sequence↗

Antigenic characterization of small, round-structured viruses by immune electron microscopy.

Small, round-structured viruses (SRSVs) detected from nonbacterial gastroenteritis outbreaks in Tokyo and Saitama Prefecture, Japan, during the period from 1977 to 1988 were tentatively classified into nine antigenic patterns from SRSV-1 (S-1) to SRSV-9 (S-9) by cross-immune electron microscopy (IEM). S-1 and S-2 appeared pattern specific, while S-3 to S-9, distinguishable from each other in their reactivity, appeared somewhat antigenically related. Their antigenic relatedness to the Norwal, Hawaii, and Otofuke agents was also examined by IEM by using antisera to these agents. S-3 appeared most closely related to the Norwalk agent. S-4 and S-5 were related to the Norwalk agent and, presumably, were distantly related to the Hawaii and Otofuke agents. S-6 and S-7 were related to the Hawaii and Otofuke agents. S-8 and S-9 were related to the Otofuke agent and, presumably, were distantly related to the Hawaii agent. The prevalence of each antigenic pattern in 38 outbreaks was examined: S-8 was implicated in 24% of the outbreaks S-5 in 16%, S-4 in 13%, S-9 in 13%, S-6 in 11%, and others in 5%.

Antigens, Viral↗

Changes in parathyroid hormone in diabetic patients on long-term hemodialysis.

Changes in parathyroid hormone (PTH) and osteocalcin over 3 years were studied in hemodialyzed patients with diabetic nephropathy (HD/DM) and hemodialyzed patients without diabetes (HD/non-DM). In HD/DM patients, concentrations of the carboxyl terminal regions of PTH and osteocalcin in the serum did not change significantly, but in HD/non-DM patients, both concentrations increased significantly. In patients in both groups, the mean concentration of the mid-region of PTH increased significantly. Secondary hyperparathyroidism in HD/DM develops slower than in HD/non-DM.

Female↗

Inhibitory effect of heparin and/or antithrombin III on intraperitoneal fibrin formation in continuous ambulatory peritoneal dialysis.

The intraperitoneal fibrin formation and its inhibition by intraperitoneal heparin and/or antithrombin III (AT III) were examined in 8 patients on continuous ambulatory peritoneal dialysis (CAPD). With 1,000 and 2,000 U/L of heparin added to inflow dialysate, the concentration of fibrinopeptide A (FPA) in plasma decreased from 39.43 +/- 5.30 (mean +/- SEM) to 8.00 +/- 2.20 and to 0.74 +/- 0.12 ng/ml, respectively. The FPA concentration in outflow dialysate decreased from 34.20 +/- 5.75 to 12.94 +/- 2.10 ng/ml (1,000 U/l of heparin) and to 4.54 +/- 0.79 ng/mg (2,000 U/l of heparin). The AT III concentration was 0.47 +/- 0.07 mg/dl in dialysate and that in plasma was 24.20 +/- 2.76 mg/dl. With 100 U/bag of AT III added to inflow dialysate, the AT III concentration increased from 0.47 +/- 0.07 to 3.36 +/- 0.17 mg/dl in outflow dialysate but did not increase in plasma. The inhibition of fibrin formation of intraperitoneal heparin was increased by addition of AT III without a systemic inhibitory effect on fibrin formation. These data suggest that intraperitoneal administration of heparin without AT III would be sufficient for the purpose of preventing fibrin formation in CAPD patients without any trouble, and additional AT III might increase inhibitory effect of heparin.

Antithrombin III↗

Dietary linoleic acid prevents the development of deoxycorticosterone acetate-salt hypertension.

The aim of this study was to elucidate the effect of dietary variations of linoleic acid on the development of deoxycorticosterone acetate (DOCA)-salt hypertension in rats. All rats were divided into three groups and fed one of the following isocaloric diets with 8% NaCl: a high linoleic acid (HLA) (20% sunflower oil), a moderate linoleic acid (5% lard oil + 15% sunflower oil), or a low linoleic acid (DLA) (20% lard oil). After 4 weeks of feeding, we determined intraerythrocyte sodium, potassium, and magnesium concentrations, intra-aortic and lymphocyte magnesium content, and erythrocyte ouabain-sensitive 22Na efflux rate constant. Cytoplasmic free calcium concentration of lymphocytes from thymus was also determined with quin-2 as a fluorescent indicator. In the HLA group, the elevation of systolic blood pressure was significantly attenuated, and intraerythrocyte sodium concentration was significantly lower than in the DLA group. There were greater intraerythrocyte potassium and magnesium concentrations, intra-aortic and lymphocyte magnesium contents, and erythrocyte ouabain-sensitive 22Na efflux rate constant in the HLA group as compared with other groups. Cytoplasmic free calcium concentration in the HLA group was significantly lower than in other groups. Systolic blood pressure significantly correlated negatively with intraerythrocyte and intra-aortic magnesium concentrations and intraerythrocyte potassium concentration, and correlated positively with cytoplasmic free calcium concentration. Erythrocyte ouabain-sensitive 22Na efflux rate constant significantly correlated positively with intraerythrocyte magnesium concentration. These findings suggest that dietary linoleic acid can attenuate the development of DOCA-salt hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Synthesis of fluorine analogues of protoporphyrin potentially useful for diagnosis and therapy of tumors.

With the aim of obtaining a porphyrin derivative useful for diagnosis and therapy of cancer, fluorine analogues of protoporphyrin, in which the vinyl group(s) were replaced by difluorovinyl group(s), were synthesized by the reaction of the formylporphyrins with sodium chlorodifluoroacetate in the presence of triphenylphosphine. Some improvements in the reported procedures for the synthesis of formylporphyrins are also described. Preliminary results of biological tests of the products showed that 8(2),8(2)-difluoroprotoporphyrin accumulates to gastric cancer more selectively than other fluorine analogues and that 3(2),3(2),8(2),8(2)-tetrafluoroprotoporphyrin is taken up by rat hepatoma cells more readily than the others.

Animals↗

Afterload mismatch in patients with hypertrophic nonobstructive cardiomyopathy.

To investigate the cardiac reserve of hypertrophic nonobstructive cardiomyopathy (HNCM), an echocardiographic study was performed before and during angiotensin II loading in 22 HNCM patients without left ventricular (LV) systolic dysfunction at rest and 8 normal subjects. LV end-diastolic dimension (LVDd) and time velocity integral (Ie) at aortic annulus were obtained as parameters of preload and forward ejection respectively. Responses of these indices to afterload stress were compared with clinical findings and right ventricular biopsy findings. Based on the reserve of forward ejection characteristics to afterload stress, 22 HNCM patients were divided into 2 groups; Group I: 9 cases with more than 15% decrease of Ie which corresponded to the value of mean - 1SD in normal subjects, Group II: 13 cases with a decrease of Ie less than 15%. There were no significant differences in echocardiographic findings between Group I and II before angiotensin II loading. On the other hand, Group I had a smaller increase of LVDd (p less than 0.05) to afterload stress, a higher incidence of ventricular tachycardia on a Holter electrocardiogram (p less than 0.05), lower maximal oxygen consumption with treadmil exercise test (p less than 0.01), and a larger value of LV end-diastolic pressure (p less than 0.05) than those in Group II, respectively. Although no difference in myocyte diameter was found between the 2 groups, myocardial fibrosis was more severe (p less than 0.001) and the incidence of moderate or severe disarray was higher (p less than 0.05) in Group I than in Group II. Thus, some HNCM patients cannot maintain forward ejection to afterload stress because of impaired preload reserve attributable to a greater stiffness of the left ventricle with severe myocardial lesion.

Adolescent↗

Clinical and exercise echocardiographic findings in patients with mitral valve prolapse.

To assess the relationship between left ventricular functional reserve and prognosis in patients with idiopathic mitral valve prolapse, ergometer exercise echocardiography was performed in 10 normal subjects and 30 patients with mitral valve prolapse having either mild, or no mitral regurgitation. These 30 patients with mitral prolapse were followed for 2 to 8 (mean 4.5) years. Increment of % fractional shortening during maximum exercise at the initial study in patients with mitral valve prolapse and normal subjects were 7 +/- 7 and 11 +/- 3%, respectively. Based on increment of % fractional shortening, patients with mitral valve prolapse were divided into 2 groups; Group I: 13 cases with delta% fractional shortening less than 5%, Group II: 17 cases with delta% fractional shortening greater than or equal to 5%. The incidence of cardiac symptoms was higher in Group I than in Group II (85 vs 41%, p less than 0.05). ST-T changes and life-threatening arrhythmias were more frequently observed in Group I. During the follow-up period, M-mode echocardiographic measurements did not vary in Group II, but left ventricular and left atrial dimensions increased significantly (p less than 0.05, p less than 0.01, respectively) and % fractional shortening decreased significantly (p less than 0.01) in Group I without any change in mitral regurgitation severity. Thus, some patients with mitral valve prolapse not having significant mitral regurgitation may develop progressive deterioration of the cardiac function, which may be predicted by exercise echocardiography.

Adult↗

A case of first trimester prenatal diagnosis of 21-hydroxylase deficiency with human complement C4 cDNA probe.

Early prenatal diagnosis of 21-hydroxylase (21-OHase) deficiency would enable treatment to be done to protect the fetus from masculinization and/or life-threatening adrenal crisis at birth. We report here the prenatal diagnosis of 21-OHase deficiency with human complement component C4 cDNA to probe DNA from chorionic villi at 10 weeks of gestation. Southern analysis with human C4 cDNA identified TaqI restriction fragment length polymorphisms (RFLPs) in the family. Family analysis with these RELPs showed that the fetus was not affected at greater than 99% probability, because the frequency of recombination between the 21-OHase B gene and the C4 gene would be extremely low.

Adrenal Hyperplasia, Congenital↗

[Upper urinary tract tumors following bladder cancer].

We treated in total 795 patients with primary transitional cell carcinoma of the urinary bladder between April, 1964 and December, 1988. Eighteen patients of them had upper urothelial cancer during the follow-up period. Thirteen of the 18 patients had received transurethral resection for the initial bladder cancer, while 3 total cystectomy and 2 segmental resection. The over-all incidence of bladder cancer patients who subsequently developed upper urinary tract tumors was 2.3 per cent. The interval between initial treatment of the bladder cancer and treatment for the upper urinary tract tumor ranged from 2 to 74 months (median 20 months). The five-year survival rate after treatment for the upper urinary tract tumor was 31.7 per cent. We conclude that the following are high risk patients for development of upper urinary tract recurrences: 1) patients with bladder cancer near orifices, 2) patients with recurrent bladder cancer under bladder preserving treatment for a long time, 3) patients with G2 multifocal bladder cancer.

Aged↗

[Production of monoclonal antibodies against human bladder cancer cells and application to immunohistochemical analysis of bladder cancer].

Two hybridomas secreting two monoclonal antibodies IgG1 B1.4 and IgG2a B1.6 were obtained by immunizing BALB/c mice with human bladder cancer cell line EJ-1. In immunohistochemical staining of cryopreserved tissues, B1.4 reacted with 0 of 9 grade 1 TCC, 6 of 11 grade 2, all of 6 grade 3 and five metastatic specimens. The antigen recognized by B1.4 was not expressed by normal urothelial cells but were expressed by vascular endothelial cells and muscle of tunica media. The target antigen of B1.6 was expressed by normal urothelial cells and all grade of TCC. In this study, it was demonstrated that poorly differentiated bladder cancer and metastatic specimens of bladder cancer express a vascular carbohydrate antigen. Taking the escape mechanism of immune surveillance, into consideration, it is possible that the antigen recognized by B1.4 is an indicator of metastatic potential of bladder cancer.

Animals↗

YS-822A, a new polyene macrolide antibiotic. I. Production, isolation, characterization and biological properties.

A new polyene macrolide antibiotic, YS-822A was isolated from the culture filtrate of a mutant strain H-8 of Streptoverticillium eurocidicum var. asterocidicus S-822. Whereas the original S-822 strain produced not only YS-822 substances but also teleocidin as by-product which is well-known as a strong carcinogenic promoter, the mutagenized H-8 strain produced the antibiotic with only a trace amount of teleocidin. Chemical and biological characterizations of the antibiotic revealed that YS-822A (molecular formula: C37H59NO14) is a new polyene macrolide with a wide antifungal spectrum and a low acute toxicity.

Animals↗

[Preliminary screening for antiviral AIDS drugs. I. Report on fiscal year 1988].

Preliminary screening for antiviral AIDS drugs has been carried out, using three different in vitro assay systems. Among 105 samples tested, 13 were found to inhibit the growth of HIV in vitro. Eleven of 13 were well-known anti-HIV chemicals, while the remaining two of plant origin were new chemicals whose anti-HIV activities have not been reported elsewhere.

Antiviral Agents↗

Specific inhibition of redox-linked proton pump activity of cytochrome oxidase by oleate hydroperoxide and involvement of ferrocytochrome c in the catabolism of hydroperoxide.

Both oleic acid and oleate hydroperoxide at concentrations below 200 nmol/mg asolectin remarkably depressed the proton pumping of cytochrome c oxidase reconstituted into liposomes but did not affect the respiratory control ratio. The inhibitory effect was comparable to that of N,N'-dicyclohexylcarbodiimide. Oleate hydroperoxide in the vesicles was reduced by ferrocytochrome c in the absence of cytochrome oxidase and converted to the hydroxy fatty acid. This non-enzymatic oxidation of ferrocytochrome c affected slightly the proton pumping and the cytochrome c oxidation by liposomal cytochrome oxidase. A physiological role of ferrocytochrome c in catabolism of the hydroperoxide of fatty acids is thus suggested.

Animals↗