Search PubMed⌕ Search

Biomedical subjects

H Baba

Publications and source records attributed to H Baba.

At least 199 records · Page 11Linked to original sources
PubMed1996

Response of phosphoenolpyruvate cycle activity to fasting and to hyperinsulinemia in human subjects.

We have used a new isotopic tracer technique to investigate the physiological role of the phosphoenolpyruvate (PEP) cycle in metabolic adaptation to fasting and to hyperinsulinemia. The forward direction of the PEP cycle is the conversion of oxaloacetate (OAA) to PEP, and the net flux of the cycle is the rate at which PEP from OAA goes on to form glucose or glycogen, as opposed to being recycled to pyruvate and then OAA. Normal volunteers (n = 6) were studied after an overnight fast and then again after 3 days of fasting, and five additional subjects were studied during a hyperinsulinemic clamp (insulin concentration = 568 +/- 25 microU/ml, glucose infusion = 14.2 +/- 0.55 mg.kg-1.min-1). After an overnight fast, 35.4 +/- 6.7% of PEP from OAA was recycled to pyruvate-lactate. Short-term fasting caused a significant increase in the conversion of OAA to PEP and also a drop in the percentage of PEP from OAA that went to pyruvate-lactate to 15.2 +/- 4.0%. The principal response to hyperinsulinemia was a decrease in the recycling of OAA to lactate, because there was no significant change in the conversion of OAA to PEP. We conclude that changes in both directions of the PEP cycle are important in regulating gluconeogenic-glyconeogenic flux.

Fasting↗
PubMed1996

The 69-84 amino acid region of the parathyroid hormone molecule is essential for the interaction of the hormone with the binding sites with carboxyl-terminal specificity.

We evaluated the competitive inhibitory effect of intact PTH, the amino-terminal PTH(1-34) fragment, and a series of truncated carboxyl-terminal PTH fragments on the binding of internally 35S-labeled human PTH(1-84) ([35S]hPTH(1-84)) to osteoblastic cells (ROS 17/2.8), in order to identify the minimum and critical elements within the PTH molecule for the interaction with the binding sites specific for the carboxyl-terminal region of the hormone. When the amino-terminal region of the PTH molecule was truncated stepwise, hPTH(35-84), hPTH(53-84) and hPTH(69-84), but not hPTH(70-84), significantly inhibited the [35S]hPTH(1-84) binding. On the other hand, the simple deletion of the carboxyl-terminal glutamine at position 84 of hPTH(53-84) [hPTH(53-83)] resulted in blunting the inhibitory effect of the peptide on the [35S]hPTH(1-84) binding. Furthermore, hPTH(35-84), hPTH(53-84) and hPTH(69-84), but not hPTH(70-84) nor hPTH(53-83), augmented the inhibitory effect of the amino-terminal PTH fragment [hPTH(1-34)] on the [35S]hPTH(1-84) binding. Of special interest was that the combination of hPTH(1-34) and hPTH(35-84) reproduced the inhibitory effect of unlabeled hPTH(1-84) on the [35S]hPTH(1-84) binding, on an equimolar basis. The 69-84 region of the PTH molecule thus appears to be crucial for binding to the carboxyl-terminal specific binding sites for PTH in osteoblasts. The interaction of the amino-terminal and carboxyl-terminal regions of a PTH molecule with their own respective binding sites seemed to occur in a fairly independent manner.

Alkaline Phosphatase↗
PubMed1996

[Heterogeneity of GTPase-activating proteins for Ras in the regulation of Ras signal transduction pathway].

The proto-oncogene ras is an essential gene for the growth and the differentiation for various types of cells. Ras, ras gene product, is a GTP binding protein which controls the signal transduction by GTP hydrolysis. The ras gene is frequently activated by point mutations in various types of human cancers, which results in a decrease in the GTPase activity of its product. A GTPase-activating protein p120 (p120GAP) was identified as a factor which stimulates the GTPase of normal ras gene product p21 but not of the mutated. An NF1 gene was identified as a gene whose loss of function causes an onset of human disorder, neurofibromatosis type I. The NF1 gene encodes a protein which contains a region with a similarity to the catalytic domain of p120GAP. We recently purified a novel Ras GAP whose molecular weight and immunogenecity are different from those of p120GAP and NF1. We named the novel mammalian Ras GAP as Gap1m. Isolation and sequencing of Gap1m cDNA revealed that Gap1m is indeed a novel Ras GAP. We also succeeded in isolation of another novel Ras GAP gene, GapIII/Gap1IP4BP, which is closely related to Gap1m. Recently, it is shown that GapIII/Gap1IP4BP binds inositol-tetrakis phosphate compounds. The overview of these Ras GAP molecules is described.

Amino Acid Sequence↗
PubMed1996

Adjuvant cyclophosphamide, methotrexate and 5-fluorouracil versus cyclophosphamide plus futraful for premenopausal patients with stage I-II and one- to three-node-positive breast cancer: results of a prospective randomized study.

A prospective randomized study was conducted to compare the adjuvant efficacy of 12 cycles of low-dose CMF (cyclophosphamide: CPA, methotrexate; MTX, 5-fluorouracil; 5-FU) with that of orally administered CPA plus FT (futraful) in premenopausal patients with stage I-II and one- to three-node-positive breast cancer. The 12-cycle CMF group (91 patients) received, 100 mg CPA orally on days 1 to 14 plus 20 mg MTX and 500 mg 5-FU intravenously (iv) on days 1 and 8 of each cycle. The CPA plus FT group (85 patients) received 100 mg CPA and 600 mg FT orally each day for one year. The background characteristics of the two groups were comparable. At 5 and 10 years, there were non-significant trends towards better disease-free and overall survival rates in the CMF group. Both treatments were well tolerated, but more patients in the CPA plus FT group refused to continue chemotherapy because of continuous gastrointestinal disturbances. No clear benefit of adding low-dose MTX to CPA and fluoropyrimidines was observed in this subgroup of Japanese patients. Further studies will be required to clarify the superiority of conventional-dose of CMF treatment to orally administered CPA plust FT treatment.

Adult↗
PubMed1996

[Advances in the treatment of colorectal cancer].

Colorectal cancer is one of the most serious diseases of our time. Recent progress in its treatment is reviewed in this paper. There are many approaches for treating colorectal cancer; extended surgery to function-preserving surgery. The aim of surgical treatment is to excise the tumor completely, so extended surgery has been performed for curative resection of colorectal cancer. However, the quality of life (QOL) of the patients has been extremely impaired. In recent years, surgical treatments for avoiding colostomy, and urinary and sexual difficulties have been widely carried out, and QOL of the patients could be maintained in the postoperative period. Stage-oriented therapy is accepted as the concept of surgical treatment of colorectal cancer. For further improving the clinical results of colorectal cancer, we advocated "type-oriented therapy" which is based on the biological characteristics of colorectal cancer, by determining i.e., p53 abnormalities of cancer cells, serum p53 antibodies, micrometastasis in the bone marrow and/or sensitivity to anticancer drugs.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

[Traumatic atlanto-occipital dislocation: a case report with survival].

We reported a case of a patient who survived anterior atlanto-occipital dislocation. A seven-year-old girl was admitted to our hospital due to disturbed consciousness after being involved in a traffic accident. With gradual improvement of consciousness, she showed bilateral abducens nerve palsy, quadriparesis and cervical instability. Lateral plain film showed anterior atlanto-occipital dislocation. MRI showed severe compression of the cervical cord and disruption of supporting ligaments of the cervicomedullary junction. After 4 months, cervical instability continued and posterior fixation was carried out with bone grafts. Her postoperative course was uneventful.

Accidents, Traffic↗
PubMed1996

[Application of oculokinetic perimetry in examination of the eye].

Oculokinetic perimetry was performed using the same protocol at four health screening facilities to determine its usefulness for identifying visual field abnormalities including glaucoma during complete physical screenings in Japan. Ophthalmoscopy of the optic disc, 26-point oculokinetic perimetry (OKP), and applanation tonometry were performed in 2,768 eyes. If any one of the tests yielded an abnormal result, the eye was then examined with a Humphrey visual field analyzer (HVFA, program 30-2). After the tests were completed, the results were evaluated by ophthalmologists for evidence of primary open-angle glaucoma and normal tension glaucoma and were classified into one of 3 groups: confirmed glaucoma, suspected glaucoma, and no glaucoma. OKP detected abnormalities in the visual field in 96 eyes (3.5%). Of these 96 eyes, 29 eyes had confirmed glaucoma, 52 eyes were suspected of having glaucoma and 15 eyes had no glaucoma. The remaining 15 eyes had no glaucoma, but in 7 of them other ophthalmological disease was diagnosed. The sensitivity, specificity, positive predictive value, and negative predictive value of OKP for detecting glaucomatous visual field defect were 0.46, 0.99, 0.84 and 0.96, respectively. The high specificity and negative predictive value show that OKP is unlikely to produce false positive results, but its low sensitivity suggests that it is not suitable for the early detection of glaucoma. However, OKP identified advanced glaucoma and other ophthalmological diseases associated with visual field abnormalities, suggesting that it is a useful screening test.

Adult↗
PubMed1996

[Continuous hepatic arterial infusion chemotherapy with low-dose CDDP plus 5-FU for liver metastases from colorectal carcinoma].

Seven patients with unresectable liver metastases from colorectal carcinoma were treated with low-dose CDDP plus 5-FU continuous hepatic arterial infusion chemotherapy. A hepatic artery catheter was placed into the gastroduodenal artery at laparotomy or percutaneously placed into the proper hepatic artery via left subclavian artery. Through an injection port placed beneath the skin, 5-FU (300 mg/m2/day) was continuously infused for 5 days; CDDP (6 mg/m2/day) was infused for 5 successive days a week. One cycle consisted of 4 weeks. The response rate was 71% (1 CR, 4 PR, 2 NC). The CEA level decreased in all cases. The median survival was 17 months. Major toxicities were abdominal pain and appetite loss due to extrahepatic perfusion of the drugs. Failure in maintaining the catheter was a problem in most cases. The pharmacokinetic study demonstrated high hepatic extraction of CDDP and 5-FU (40% and 90%, respectively). These results suggest that continuous hepatic arterial infusion chemotherapy with low-dose CDDP plus 5-FU is effective for patients with unresectable liver metastases from colorectal carcinoma.

Adult↗
PubMed1996

Characteristics and mechanism of the ossification of posterior longitudinal ligament in the tip-toe walking Yoshimura (twy) mouse.

To elucidate the mechanism of ossification of the posterior longitudinal ligament (OPLL), we examined the serial changes in the intervertebral disc of tip-toe walking Yoshimura (twy) mouse. At the age of 6 weeks, the volume of the nucleus pulposus increased in all intervertebral discs causing anterior and posterior herniation. Secondary to this herniation, the cartilagineous tissue of the annulus fibrosus was disrupted and showed regenerative proliferation with PCNA-positive cartilagineous cells. These cells were S-100 positive and the matrix was positive for chondroitin-4-sulfate proteoglycan, indicating the development of calcification. At the age of 15 weeks, the regenerative cartilagineous tissue of the annulus fibrosus reached the posterior longitudinal ligament together with neovascularization and appearance of PCNA-positive proliferating primitive mesenchymal cells. These cells were considered to be osteoblasts since they were positive for alkaline phosphatase and the matrix contained type I collagen. Using electron microscopic X-ray analysis, vesicles present in the matrix of regenerative cartilagineous cells of the annulus fibrosus were confirmed to contain calcium phosphate crystals, also indicating the development of calcification. In conclusion, our serial analysis indicates that ossification of posterior longitudinal ligament in twy mouse was triggered by enlargement of the nucleus pulposus followed by herniation, disruption and regenerative proliferation of annulus fibrosus cartilagineous tissues. Enchondral ossification of the new annulus fibrosus cartilagineous cells and membraneous ossification by primitive osteoblasts proceed to the final ossification of the posterior longitudinal ligaments.

Alkaline Phosphatase↗
PubMed1996

[A case of coronary perforation after directional coronary atherectomy].

Directional coronary atherectomy was performed on a 69-year-old female with angina pectoris. She suffered from coronary perforation as a result of cardiac tamponade and shock. Pericardial drainage and hemostasis were performed immediately using a perfusion catheter. The patient was transferred to the operating room for perforation repair and coronary artery bypass grafting to the distal portion of the left anterior descending artery. The procedure was performed successfully. Although acute coronary perforation associated with directional coronary atherectomy is rare, it can be managed temporarily by a perfusion catheter and we successfully performed coronary artery bypass grafting.

Aged↗
PubMed1995

Role of A delta afferent fibers in modulation of primary afferent input to the adult rat spinal cord.

To address the question of whether fine myelinated and unmyelinated primary afferent fibers contribute to the mechanism of presynaptic inhibition in the spinal cord, we studied dorsal root-evoked dorsal root potentials (DR-DRPs) using a newly developed longitudinal spinal cord slice preparations in the adult rat. Single stimuli applied to the L6 dorsal root elicited a DR-DRP in the L5 dorsal root which had an amplitude of 50-150 microV and had a half decay time of 20-66 ms. The DR-DRP was depressed by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10-20 microM), while DL-2-amino-5-phosphonovaleric acid (APV, 50-100 microM) had no significant effect. DR-DRP was markedly depressed by bicuculline or picrotoxin. The evoked DR-DRP was unchanged in rats treated with capsaicin which eliminated the majority of unmyelinated C afferent fibers. Taken together with the higher voltages (> or = 1.9 V) required to elicit DR-DRP, this observation strongly suggests that the A delta afferent fibers are primarily responsible for producing and receiving the DR-DRP. The present study shows that the DR-DRP mediated by the A delta fibers in the slice preparation is analogous to those described for larger myelinated fibers in vivo. This pathway may contribute importantly to synaptic modulation of somatosensory information, including nociception at the superficial dorsal horn through an interneuronal connection which are mediated by the non-NMDA and GABAA receptors.

Afferent Pathways↗
PubMed1995

GapIII, a new brain-enriched member of the GTPase-activating protein family.

Ras GTPase-activating proteins (GAPs) are negative regulators of ras, which controls proliferation and differentiation in many cells. Ras GAPs have been found in a variety of species from yeast to mammals. We describe here a newly identified mammalian GAP, GapIII, which was obtained by differential screening of a rat oligodendrocyte cDNA library. GapIII putatively encodes a 834 amino acid protein with a predicted molecular weight of 96 kDa, which contains a consensus GAP-related domain (GRD). The protein encoded by this cDNA has high homology with Gap1m, which was recently identified as a putative mammalian homolog of Drosophila Gap1. These proteins contain three structural domains, an N-terminal calcium-dependent phospholipid binding domain, GRD, and a C-terminal PH/Btk domain. Because of the sequence homology and the structural similarities of this protein with Gap1m, we hypothesize that GapIII and Gap1m may be members of a mammalian GAP gene family, separate from p120GAP, neurofibromin (NF1), and IQGAP. To confirm the GapIII protein activity, constructs containing different GapIII-GRD domains were transformed into iral mutant yeast to determine their relative ability to replace IRA1 functionally. Constructs that contained essentially the full-length protein (all three domains), the GRD alone, or the GRD plus PH/Btk domain suppressed heat shock sensitivity of ira1, whereas constructs that contained the GRD with part of the PH/Btk domain had only a weak ability to suppress heat shock sensitivity. These results suggest that the GapIII GRD itself is sufficient to down-regulate ras proteins in yeast. Expression of GapIII mRNA (4.2 kb) was examined by Northern analysis and in situ hybridization. This mRNA was expressed at highest levels in the brain, where its expression increased with development. Lower levels of the mRNA were expressed in the spleen and lung. Among neural cells, GapIII mRNA was expressed in neurons and oligodendrocytes, but not in astrocytes. Interestingly, the expression pattern in brain is reminiscent of type 1 NF1 expression reported by Gutmann et al. (Cell Growth Differ in press, 1995). We propose that in addition to p120GAP and neurofibromin, the GapIII/Gap1m family may be important for modulating ras activity in neurons and oligodendrocytes during normal brain development and in particular in the adult brain.

Animals↗
PubMed1995

A serine protease in Alzheimer's disease cells cleaves a 16K-peptide with flanking residues upstream to beta-amyloid-N-terminus as natural substrate.

A serine protease which cleaves an oligopeptide at the beta-amyloid (beta A4) N-terminus was identified and purified from extracellular fluid of familial Alzheimer's disease (FAD) lymphoblastoid cells. In order to search for a natural substrate that stands for a direct precursor of beta A4, C-terminal fragments of beta-amyloid precursor protein (APP) were prepared by immunoprecipitation of cytosol proteins with beta A4-specific antibody. The 16 kDa peptide with N-terminus 30 amino acids upstream from the beta A4-N-terminus, also existing in other hematopoietic cells, was proved to be a natural substrate for the protease in human lymphoid cells. Its cleaved fragment with beta A4-N-terminus was thought to be less amyloidogenic on the basis of its property of self-aggregation in acidic pH. The results suggest the significance of the unique cleavage site at beta A4-upstreams in generation and accumulation of beta A4.

Alzheimer Disease↗
PubMed1995

Inhibitory action of nm23 proteins on induction of erythroid differentiation of human leukemia cells.

We recently identified a differentiation inhibitory factor (I-factor) in mouse myeloid leukemia M1 cells as a murine homolog of the human nm23-H2 gene product. nm23 genes encode proteins that participate in tumor metastasis regulation and in various fundamental cellular processes, although their mechanisms of action are still unknown. Although all nm23 proteins contain nucleoside diphosphate (NDP) kinase activity, it has not been established that the enzyme activity mediated the various functions of nm23 proteins. In the present experiment, we examined the effect of nm23 proteins on various differentiation induction systems of human leukemic cells including HL-60, U937, HEL/S, KU812F, K562, and HEL cells. Native human erythrocyte NDP kinase protein inhibited the induction of erythroid differentiation of HEL, KU812 and K562 cells, but not the induction of monocytic or granulocytic differentiation of HL-60, U937 and HEL/S cells. The erythroid differentiation of HEL cells was inhibited by recombinant human nm23-H1, -H2, mouse nm23-M1, and -M2 proteins. Moreover, both the mutant nm23-H2His protein and truncated nm23-H2 protein containing N-terminal (1-60) peptide, which do not have NDP kinase activity, also inhibited erythroid differentiation of HEL cells. These results suggest that (1) the differentiation inhibitory activity of I-factor/nm23 protein is not restricted to monocytic differentiation of M1 cells, (2) the inhibitory activity is exhibited without species specificity, and (3) the differentiation inhibitory activity of the nm23/NDP kinase protein is independent of its enzyme activity and requires the presence of N-terminal peptides.

Base Sequence↗
PubMed1995

Two isotypes of murine nm23/nucleoside diphosphate kinase, nm23-M1 and nm23-M2, are involved in metastatic suppression of a murine melanoma line.

A series of sublines of a murine melanoma B16 of C57BL/6 origin were established and examined regarding their metastatic capacity and expression of nm23. The number of pulmonary metastases developed by these sublines was inversely correlated with the expression of two isotypes of nm23, nm23-M1 and nm23-M2. The cDNAs of nm23-M1, nm23-M2, and a combination of both were transfected into the highly metastatic melanoma subline FE7, with low nm23 expression. FE7 transfectants of any of these cDNAs expressed transfected genes, and their metastatic capacity was suppressed when compared with parental FE7 or FE7 transfected with a control neo gene. These cell lines, however, did not change in terms of in vitro growth in the presence of 3 or 10% fetal bovine serum and in vivo growth when injected s.c. into C57BL/6-nu/nu mice. Similar experiments were also performed using FE7 transfectants of human nm23 genes. Transfectants of nm23-H1, nm23-H2, and their combination did not present altered metastatic potential. These findings indicated that two murine isotypes of nm23 but not those of humans are intimately related with the suppression of metastasis in the murine body.

Animals↗