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Biomedical subjects

T Baba

Publications and source records attributed to T Baba.

At least 397 records · Page 22Linked to original sources
PubMed1989

High invasiveness associated with augmentation of motility in a fos-transferred highly metastatic rat 3Y1 cell line.

We previously reported that v-fos transfer to a src-transformed rat 3Y1 cell line enhanced lung metastasis. To clarify the mechanism of this enhancement, we compared various biological factors related to metastatic potential between a fos-transferred highly metastatic cell line (fos-SR-3Y1-202) and the control cell line transferred with genetic marker (pSV2-neo) plus pBR322, neo-SR-3Y1-200. Lung arrest, the effect of lung extract on cell growth, or sensitivity to natural killer cells could not explain the higher metastasis of fos-SR-3Y1-202, compared to findings with neo-SR-3Y1-200. The invasiveness, assessed by penetration through a Matrigel-coated filter was about 5 times higher in fos-SR-3Y1-202 than in neo-SR-3Y1-200; high invasiveness in vitro was also observed in a fos-transferred mixed-population cell line (fos-SR-3Y1-200) and fos-transferred highly metastatic clones. Histopathological evidence of an in vivo tumor also showed the high invasiveness of fos-SR-3Y1-202 cells. To elucidate the causes of the increased invasiveness of fos-SR-3Y1-202, attachment of the cells to Matrigel and its components, such as laminin and type IV collagen, type IV collagenase activity, and motility were examined. Attachment of the cells to the substrate coated on Petri dishes or the activity of type IV collagenase did not differ significantly. On the other hand, cell motility, determined by a new method to directly quantitate alteration of cell shape continuously, using video image analysis and computer techniques, was higher in fos-SR-3Y1-202 than in neo-SR-3Y1-200. Thus, the fos-transferred cell line, fos-SR-3Y1-202 has a high invasiveness, in association with augmentation of motility, hence the enhancement of metastatic potential.

Animals↗
PubMed1989

Enhancement of colony forming ability in the lung by transfer of the v-fos oncogene into a ras-transformed rat 3Y1 cell line.

Transfer of the v-fos oncogene into a rat 3Y1 cell line transformed by v-H-ras, which is tumorigenic but non-metastatic, enhanced lung metastasis, depending on the amount of fos-related transcripts. Enhancement of the metastatic potential was associated with increases in tumor growth rate i.m. of inoculated cells but not the rate of in vitro cell growth, irrespective of the addition of tissue (e.g. lung) extract to the regular medium. These results suggest that the v-fos oncogene increased the malignancy by altering biological factors of the recipient cells responsible for cell growth and/or survival rate in vivo.

Animals↗
PubMed1989

Differential expression of smooth muscle alpha-like actin between benign and malignant human pigment tissues.

When examining proteins in human pigment tissues, we found that a third actin-like protein, in addition to beta- and gamma-actin was more frequent and in a larger amount in benign tissues such as blue nevus and nevus pigmentosus, than in malignant melanoma. This third actin-like protein was immunologically stained with monoclonal antibodies reacting with several actin species and specific for smooth muscle alpha-actin. We propose that this third actin-like protein is probably smooth muscle alpha-actin and that different expressions of this third actin may possibly serve as a sensitive biochemical marker for the diagnosis of human malignant melanoma.

Actins↗
PubMed1989

Nucleotide sequence of the maltotetraohydrolase gene from Pseudomonas saccharophila.

The nucleotide sequence of the Pseudomonas saccharophila gene encoding maltotetraohydrolase (G4-forming amylase) has been determined. The coding region for the G4-forming amylase precursor contained 1653 nucleotides. The deduced precursor protein included an N-terminal 21-residue putative signal peptide; the deduced mature form of G4-forming amylase contains 530 amino acid residues with a calculated molecular mass of 57 740 Da. Sequence similarities between the G4-forming amylase and other amylolytic enzymes of species ranging from prokaryotes to eukaryotes are quite limited. However, three regions, which are involved in both the catalytic and substrate-binding sites of various amylolytic enzymes, are highly conserved in the G4-forming amylase of P. saccharophila.

Amino Acid Sequence↗
PubMed1989

Efficacy of two-route chemotherapy using cis-diamminedichloroplatinum(II) and its antidote, sodium thiosulfate, in combination with angiotensin II for rat liver tumor.

To improve the therapeutic effects of conventional TRC using i.a. CDDP plus simultaneous i.v. STS in a rat liver tumor, we made use of the AT-II-induced hypertension method, in combination with TRC. The decrease in tumor area (-15%), measured 8 days after the TRC using CDDP 12 mg/kg i.a. plus i.v. post-administration (5 min later) of STS 1,264 mg/kg, was much greater than that (+ 13%) seen in the conventional TRC, but BUN level was elevated (44.9 mg/dl). AT-II (15 micrograms/kg) administered i.a. simultaneously with CDDP normalized the BUN level (20.3 mg/dl) and further decreased (-15% to -31%) the tumor area (modified TRC). The modified TRC also exhibited a higher anti-tumor effect than did CDDP 3 mg/kg with AT-II i.a. (5%) at a similar BUN level (22.2 mg/dl). Loss of body weight, decrease in WBC count and changes in serum transaminases of rats treated with the modified TRC were tolerable. The improved therapeutic effect of the modified TRC was explained as follows: during AT-II-induced hypertension, (I) CDDP delivery to the tumor was increased by 150% and (2) CDDP delivery to the kidney was decreased by 35%. The latter effect of AT-II made feasible the post-administration of STS to CDDP.

Angiotensin II↗
PubMed1989

Activation and maturation mechanisms of boar acrosin zymogen based on the deduced primary structure.

We have isolated cDNA clones encoding boar acrosin, a serine protease participating in the initial stage of fertilization, from boar testis lambda gt11 cDNA libraries. Nucleotide sequencing of the overlapping clones indicates that the composite cDNA inserts contain 1,391 base pairs coding for a 5'-untranslated region, an open reading frame, a stop codon, a 3'-untranslated region, and a poly(A)+ tail. A polyadenylation signal, AATAAA, is located 33 bases upstream from the start of the poly(A)+ tail. The amino acid sequence deduced from the cDNAs shows that boar acrosin is initially synthesized as a prepro-protein with a 16-residue signal peptide at the NH2 terminus. This signal sequence is followed by a 399-residue sequence corresponding to the acrosin zymogen. COOH-terminal sequence analysis of boar sperm 55-kDa proacrosin and its processed forms indicates that the mature acrosin molecule contains 322 amino acid residues in two polypeptide chains, a 23-residue light chain and a 299-residue heavy chain, with a combined molecular mass of 35,735 Da, and that the 55-kDa proacrosin molecule has 14-, 18-, and 43-residue segments as COOH-terminal extensions that are removed during proacrosin maturation. The COOH-terminal 43-residue segment is rich in proline residues, including an unusual repeat of 23 consecutive prolines. The deduced amino acid sequence of boar acrosin shows a high degree of identity with major portions of other serine proteases, including the active site region and the location of cysteine residues. We conclude that boar acrosin is synthesized as a single-chain polypeptide with the regions corresponding to the light and heavy chains covalently connected by two disulfide bonds, and that the single-chain molecule is autoactivated by cleavage of the Arg23-Val24 bond after removal of the COOH-terminal 14-residue segment, resulting in the formation of the light and heavy chains. This two-chain molecule is then converted to the mature enzyme by removal of the COOH-terminal 18- and 43-residue segments.

Acrosin↗
PubMed1989

Proacrosin activation in the presence of a 32-kDa protein from boar spermatozoa.

A 32-kDa protein was purified from acrosomal extracts of ejaculated boar spermatozoa as a complex with 55- and 53-kDa proacrosins. In the presence of the 32-kDa protein, these proacrosins were sequentially converted by autoactivation to a 49-kDa intermediate, a 43-kDa intermediate, and then a 35-kDa mature acrosin. This activation process was consistent with that in the absence of the 32-kDa protein, but differed in producing the 49-kDa form as the predominant acrosin intermediate. Thus, the 32-kDa protein may be a regulatory protein for proacrosin activation. The 49-kDa intermediate was a two-chain polypeptide with the amino-terminal sequences corresponding to those of the light and heavy chains of mature acrosin, whereas the carboxyl-terminal sequence of its heavy chain was identical with that of the 53-kDa proacrosin. These results suggest that the 49-kDa intermediate is produced from 53-kDa proacrosin during proacrosin activation by the cleavage of the peptide bond between Arg-23 and Val-24, which results in the formation of the light and heavy chains.

Acrosin↗
PubMed1989

Primary structure of human proacrosin deduced from its cDNA sequence.

cDNA clones encoding proacrosin, the zymogen of acrosin, were isolated from a human testis cDNA library by using a fragment of boar acrosin cDNA as a probe. Nucleotide sequencing of the longest cDNA clone has predicted that human proacrosin is synthesized with a 19-amino-acid signal peptide at the N-terminus. The cleavable signal sequence is followed by a 23-residue segment corresponding to the light chain and then by a 379-residue stretch that constitutes the heavy chain containing the catalytic site of the mature protease. The C-terminal portion of the deduced sequence for the heavy chain is very rich in proline residues, most of which are encoded by a unique repeat of CCCCCA. The active-site residues including histidine, aspartic acid, and serine are also predicted to be located at residues 69, 123, and 221, respectively.

Acrosin↗
PubMed1989

Activation of boar proacrosin is effected by processing at both N- and C-terminal portions of the zymogen molecule.

A mixture of 55 and 53 kDa boar proacrosins was autoactivated at pH 8.5 to produce a 43 kDa intermediate form and a 35 kDa mature acrosin, and each of four forms of (pro)acrosins was isolated. Analysis of the N-terminal sequences of the two proacrosins indicated the existence of a segment corresponding to the acrosin light chain at the N-terminal end of the zymogen. Two N-terminal sequences identical with those of the light and heavy chains were found in the intermediate form and mature acrosin. The proacrosins and the intermediate contained many more proline residues than the mature enzyme. These results indicate that the activation of boar acrosin zymogen is achieved by the removal of a C-terminal segment rich in proline residues and by the cleavage of the Arg23-Val24 bond leading to the formation of the light and heavy chains.

Acrosin↗
PubMed1989

Comparison of the renal effects of angiotensin converting enzyme inhibitor and calcium antagonist in hypertensive type 2 (non-insulin-dependent) diabetic patients with microalbuminuria: a randomised controlled trial.

Seven of eight hypertensive Type 2 (non-insulin-dependent) diabetic patients with microalbuminuria completed a randomised crossover trial to compare the renal effects of angiotensin converting enzyme inhibitor (enalapril) and calcium antagonist (nicardipine). Four-week fixed oral maintenance dosages of enalapril (10-20 mg/day) and nicardipine (60-120 mg/day) significantly (p less than 0.05) lowered the systolic and diastolic blood pressures without altering renal blood flow, glomerular filtration rate and filtration fraction. Both drugs significantly reduced (p less than 0.05) urinary albumin excretion rate and fractional clearance of albumin to similar extents. Total renal vascular resistance decreased significantly by nicardipine (p less than 0.05) and non-significantly by enalapril. Plasma osmotic pressure, plasma aldosterone concentration, total serum protein concentration, serum electrolytes and HbA1c remained unchanged by these drugs, whereas plasma renin activity was significantly higher (p less than 0.05) in the enalapril than in the control and nicardipine phases. These results suggest that both drugs have similar renal function preserving effects with a concomitant hypotensive action in hypertensive Type 2 diabetic patients with microalbuminuria, and that the angiotensin converting enzyme inhibitor may not have advantageous renal effects when compared to the calcium antagonist and vice versa. Both drugs might be useful for treatment of high blood pressure in hypertensive diabetic patients, if long-term studies of these drugs can be shown to benefit the patients over other conventional antihypertensive therapies.

Aged↗
PubMed1989

"Two-route chemotherapy" using cis-diamminedichloroplatinum(II) and its antidote, sodium thiosulfate, combined with angiotensin II is effective against peritoneally disseminated cancer in rats.

"Two-route chemotherapy" (TRC) using cis-diamminedichloroplatinum(II) (DDP) and its antidote, sodium thiosulfate (STS), combined with the angiotensin II (AT-II)-induced hypertension method was evaluated for its efficacy against peritoneally disseminated tumors in rats. A bolus i.p. injection of DDP (15 mg/kg) was given 1 min after the initiation of an AT-II (16.5 micrograms/kg) i.v. infusion lasting 11 min. Immediately after the termination of the AT-II infusion, 1,580 mg/kg STS was injected i.v. over a further 5 min. This modified TRC significantly improved the antitumor effect, evaluated by survival (increase in life span, 273%), compared with that achieved with other treatments, as follows: 15 mg/kg DDP i.p. and the concomitant i.v. infusion of 1,580 mg/kg STS (conventional TRC), 153% increase in life span; 5 mg/kg DDP i.p. with or without AT-II i.v. (167% and 107% increases in life span, respectively). As an index of nephrotoxicity, blood urea nitrogen (BUN) levels seen after modified TRC (21.1 mg/dl) were as low as those observed after conventional TRC (19.1 mg/dl), despite the postadministration of STS, and were much lower than those seen after DDP alone or DDP plus AT-II (35.6 and 35.7 mg/dl, respectively). Further evaluation of the effectiveness of modified TRC using various doses of DDP gave similar results. The feasibility of the administration of STS 10 min after DDP treatment was explained by the significant inhibition of DDP delivery to the kidney during the AT-II-induced hypertension. Thus, TRC combined with AT-II has a superior therapeutic effect against peritonitis carcinomatosa induced in rats.

Angiotensin II↗
PubMed1989

Selective enhancement of intratumoural blood flow in malignant gliomas: experimental study in rats by intracarotid administration of adenosine or adenosine triphosphate.

We studied the effect of intravenous and intracarotid infusion of adenosine and adenosine triphosphate (ATP) on the regional blood flow of intracerebrally transplanted RG-C6 tumours in rats, using the hydrogen clearance method. The intracarotid administration of adenosine or ATP selectively increased blood flow in the tumour, but did not produce any significant change either in the regional cerebral blood flow of the extratumoural ipsilateral hemisphere or in the ipsilateral hemisphere without tumour. The intracarotid administration of ATP at a dose of 10 micrograms/kg/min produced the most effective increase in the tumour blood flow (+51.5 +/- 16.8%). In contrast, both the intravenous administration of adenosine and that of ATP failed to increase tumour blood flow. These results may possibly indicate that intracarotid administration of the adenosine or ATP might contribute in selectively enhancing the delivery of anti-cancer agents to malignant brain tumours.

Adenosine↗
PubMed1989

Urinary dopamine, noradrenaline and adrenaline in type 2 diabetic patients with and without nephropathy.

We measured the urinary excretions of dopamine, noradrenaline and adrenaline, their conjugated metabolites, urinary excretion of sodium and creatinine clearance simultaneously in 21 patients with Type 2 (non-insulin-dependent) diabetes and 6 normal subjects. The mean (+/- SEM) value for urinary excretion of dopamine (52.4 +/- 8.8 micrograms/day) in diabetic patients with nephropathy (Group C, n = 12) was significantly lower (P less than 0.01) than in the normal subjects (Group A, 179.7 +/- 15.5 micrograms/day) and in diabetic patients without nephropathy (Group B, n = 9, 131.5 +/- 16.5 micrograms/day). The mean values for the urinary excretions of noradrenaline and adrenaline were also significantly lower (P less than 0.01) in Group C than in Groups A and B. In addition, the mean urinary excretion of conjugated metabolite of dopamine in Group C was significantly lower (P less than 0.05) than in Group A. There was a trend toward the observation that the mean 24-h urinary excretion of sodium in Group C (121.6 less than 12.9 mEq) was lower as compared with that in Group A (140.8 +/- 8.9 mEq) or B (150.7 +/- 17.9 mEq). A multiple regression analysis revealed that the 24-h urinary excretion of dopamine correlated significantly with creatinine clearance, systolic (P less than 0.01) and diastolic (P less than 0.05) blood pressures. The results indicate that synthesis or secretion of renal dopamine might decrease with a progression of diabetic nephropathy.(ABSTRACT TRUNCATED AT 250 WORDS)

Creatinine↗
PubMed1989

Thermally adaptive changes of mycolic acids in Mycobacterium smegmatis.

The effect of growth temperature on mycolic acid composition in eight strains of Mycobacterium smegmatis was investigated by gas chromatography/mass spectrometry. A change in growth temperature from 45 to 20 degrees C caused a shift in the subclass and molecular species composition of mycolic acids. The relative amount of alpha'-mycolic acids to alpha-mycolic acids decreased, and that of hydroxy mycolic acids increased at lower temperatures. Moreover, the proportion of shorter-chain species of alpha-mycolic acids increased, and those of longer-chain species of alpha-mycolic and hydroxy mycolic acids decreased. This observation seems to be due to the changes of the chain length of meromycolates because the alpha-alkyl chain unit of mycolic acids was not affected. The ratio of odd to even carbon-numbered alpha-mycolates decreased as the growth temperature was lowered. In contrast, the molecular species composition of alpha'-mycolic acid was not influenced by the growth temperature.

Adaptation, Physiological↗
PubMed1989

Altered expression of a third actin accompanying malignant progression in mouse B16 melanoma cells.

The expression of actin was examined and compared in several mouse B16 melanoma cell lines with different metastatic ability, by the use of two-dimensional gel electrophoresis or horizontal isoelectric focusing. In the mouse B16 melanoma cell lines, the expression of newly found AX actin (Mr = 43,000, pI = 5.2) decreased with the increase in in vitro and in vivo selection cycles (F number) for high-metastatic cells. On the contrary, the metastatic ability of each mouse cell line, assessed by lung colony-forming ability following iv administration, increased with increase in the F number. The half life of AX actin was much the same as that of beta- and gamma-actin and the different expressions of AX actin between the low- (F = 1) and high-metastatic (F = 10) cell lines were attributed to differences in the rate of synthesis but not in the decay rate of AX actin. The AX actin was incorporated into the cytoskeletal fraction with the same efficiency as beta- and gamma-actin. The invasiveness of the cells, assessed in vitro using matrigel, was increased with the decrease in AX expression. The actin stress fibers, observed staining with rhodamine-conjugated phalloidin, were organized better in a low-metastatic cell line (F = 1) than in a high-metastatic one (F = 10). These results suggest to us that depression of AX actin is involved in disorganization of the cytoskeletal system, the cellular flexibility and motility are enhanced and there is a consequent increase in the invasiveness and metastatic potential.

Actins↗
PubMed1989

Efficacy of two-route chemotherapy using intraperitoneal neocarzinostatin and its antidote, intravenous tiopronin, for peritoneally disseminated tumors in mice.

We assessed the efficacy of "two-route chemotherapy (TRC)" using neocarzinostatin (NCS) given ip and its antidote, N-(2-mercaptopropionyl)-glycine (tiopronin), given iv for peritoneally disseminated tumors in mice. Whether or not the single iv administration of tiopronin (800 mg/kg) at various times after NCS ip would decrease the lethal toxicity induced by NCS ip was given attention. When compared with the LD50 (4.4 mg/kg) of NCS ip alone, simultaneous or postadministration of tiopronin together with NCS ip increased the LD50 of NCS ip by 2.8 to 7.6 fold in a time-dependent manner. Chemotherapy experiments on ip disseminated tumors in mice were done to compare the antitumor effects of the following treatments, at two dose levels (75 and 100% of LD10) of NCS, with or without tiopronin: treatment with NCS ip alone and combined chemotherapy using NCS ip plus tiopronin iv, simultaneously or postadministered. Based on the survival time of the treated mice, the groups given NCS plus tiopronin (postadministration, 15 or 25 min later) showed a significantly superior survival time to that of the group given NCS ip alone. The side effects, evaluated in terms of the changes in body weight and number of WBC of the mice, were not significantly different among the groups treated with 100% of LD10 of NCS.

Animals↗