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Biomedical subjects

Y Takahashi

Publications and source records attributed to Y Takahashi.

At least 19 recordsLinked to original sources
PubMed1995

Expression of vascular endothelial growth factor and its receptor, KDR, correlates with vascularity, metastasis, and proliferation of human colon cancer.

We studied the correlation between expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and their receptors with vascularity, metastasis, and proliferative index of human colon cancers. Immunohistochemical analyses using antibodies against VEGF, bFGF, their receptors (KDR, flt-1, bek, and flg), factor VIII, and proliferating cell nuclear antigen were carried out on archival specimens of 52 human colon carcinomas and 10 adenomas. Vessels were quantitated by light microscopy (x200), and the intensity of staining for VEGF and bFGF was assessed on a scale of 0-3+. The presence or absence of immunostaining for KDR, flt-1, bek, and flg was evaluated in endothelial cells, and proliferation was determined by counting the number of proliferating cell nuclear antigen-positive cells per 500 tumor cells. Expression of VEGF and KDR was higher in metastatic than in nonmetastatic neoplasms and directly correlated with the extent of neovascularization and the degree of proliferation, whereas expression of bFGF, flt-1, bek, and flg did not differ among tumor types. Vessel counts were greater in metastatic tumors than in nonmetastatic tumors. These findings support the hypothesis that VEGF is an important angiogenic factor in primary and metastatic human colon cancer. VEGF expression and vessel counts may aid in predicting patients at risk for metastasis from colon cancer.

Adenoma↗
PubMed1995

Role of age on transmitral flow velocity patterns in assessing left ventricular diastolic function in normal infants and children.

This study demonstrated that both peak E and flow velocity integral of early diastole increased to reach the older children's values by 36 months of age and leveled off thereafter, whereas both peak A and flow velocity integral of atrial contraction had little change. These results suggest that age-related changes in E wave reflect the maturational or developmental alterations in LV diastolic properties, especially in the relaxation process.

Adolescent↗
PubMed1995

Identification of auxin-responsive elements of parB and their expression in apices of shoot and root.

Detailed analysis of transgenic tobaccos containing a series of chimeric parB promoter/beta-glucuronidase (GUS) gene constructs allowed us to define two auxin-responsive elements (AREs) of 48 bp and 95 bp (positions -210 to -163 and -374 to -280) in the parB promoter. The two AREs responded independently to physiological concentrations of auxin. Gel retardation assays revealed binding of nuclear protein(s) to the sequence conserved between ARE I and ARE II. The auxin responsiveness of the parB promoter did not mediate the pathway through the as-1 element and transcription factor ASF-1. AREs I and II were responsive to auxin at physiological concentrations, whereas as-1 responded only to higher concentrations of auxin which may be interpreted as stress, though as-1 had been reported to be a minimal ARE [Liu, X. & Lam, E. (1994) J. Biol. Chem. 269, 668-675]. Histochemical staining of transgenic tobacco that contained a parB promoter/GUS construct demonstrated the expression of GUS activity in the shoot apex as well as in the root tips, suggesting the involvement of parB expression in meristematic activity or differentiation. The drastic change in auxin responsiveness in the transgenic plants between the 6th and 10th day after imbibition of seeds implies the development or the activation of auxin signal transduction systems during plant development.

Bacterial Proteins↗
PubMed1995

Rat genomic structure of amidophosphoribosyltransferase, cDNA sequence of aminoimidazole ribonucleotide carboxylase, and cell cycle-dependent expression of these two physically linked genes.

Genomic structure of rat amidophosphoribosyltransferase (ATase; EC 2.4.2.14), which catalyzes the first committed step in de novo purine nucleotide synthesis, was determined by polymerase chain reaction (PCR)-based methods. There are 11 exons and all exon-intron boundaries were conserved among rat, human, and chicken ATase genes. A rat aminoimidazole ribonucleotide carboxylase (AIRC) cDNA encoding a bifunctional enzyme of AIRC (EC 4.1.1.21) at step 6 and SAICAR synthetase (EC 6.3.2.6) at step 7 in de novo purine nucleotide synthesis was cloned and sequenced. The size of the cloned rat AIRC cDNA was 1329 bp, and amino acid identity with human and chicken AIRC was 96 and 85%, respectively. The intergenic sequence using a phage clone and the PCR product disclosed that ATase and AIRC genes are physically linked with the 736 bp sequence between the translation start sites, and the determination of the transcriptional start sites by the primer extension assay for these genes disclosed that distance between the two major transcriptional start sites is 585 bp. The amount of mRNAs of both genes showed approx. 5-6-fold increase in G1/S phase of the cell cycle over those in G0 phase in synchronized rat 3Y1 fibroblasts.

Amidophosphoribosyltransferase↗
PubMed1995

A mutant strain of Chlamydomonas reinhardtii lacking the chloroplast photosystem II psbI gene grows photoautotrophically.

The product of the chloroplast psbI gene is associated with the photosystem II reaction center. To gain insights into the function of this polypeptide, we have disrupted its gene in Chlamydomonas reinhardtii with an aadA expression cassette that confers resistance to spectinomycin through biolistic transformation. The transformants are still able to grow photoautotrophically in dim light, but not in high light, and they remain photosensitive when grown on acetate containing medium. The amounts of photosystem II complex and oxygen evolving activity are both reduced to 10-20% of wild-type levels in these psbI-deficient mutants. It appears that the PsbI polypeptide plays a role in the stability of photosystem II and possibly also in modulating electron transport or energy transfer in this complex.

Amino Acid Sequence↗
PubMed1995

The utility of chelating agents as antidotes for nephrotoxicity of gold sodium thiomalate in adjuvant-arthritic rats.

The effects of 2,3-dimercaptopropane sulphonate (DMPS) and N-(2-mercapto-2-methylpropanoyl)-L-cysteine (bucillamine) against the renal damage induced by gold sodium thiomalate (AuTM) in adjuvant-arthritic rats were studied. Arthritic rats induced by adjuvant using Mycobacterium butyricum were injected intraperitoneally with a chelating agent (0.6 mmol/kg) immediately after intramuscular injection of AuTM (0.066 mmol/kg) every other day for 21 days. Treatment with DMPS and bucillamine prevented increases in the urinary excretion of protein, aspartate aminotransferase, and glucose and blood urea nitrogen level after AuTM injection. AuTM prevented the increase in both adjuvant-injected and uninjected hind-feet volumes. The prevention of these inflamed lesions by AuTM was not affected by DMPS and bucillamine. These chelating agents decreased the gold concentration in the kidney and liver after AuTM administration, but did not affect the hepatic and renal concentrations of copper, zinc, iron, and calcium except the renal copper level after AuTM. These findings suggest that DMPS and bucillamine are very useful antidotes for gold toxicity.

Animals↗
PubMed1995

Aceruloplasminemia: molecular characterization of this disorder of iron metabolism.

Ceruloplasmin is an abundant alpha 2-serum glycoprotein that contains 95% of the copper found in the plasma of vertebrate species. We report here on the identification of a genetic defect in the ceruloplasmin gene in a patient previously noted to have a total absence of circulating serum ceruloplasmin in association with late-onset retinal and basal ganglia degeneration. In this patient T2 (transverse relaxation time)-weighted magnetic resonance imaging of the brain revealed basal ganglia densities consistent with iron deposition, and liver biopsy confirmed the presence of excess iron. Although Southern blot analysis of the patient's DNA was normal, PCR amplification of 18 of the 19 exons composing the human ceruloplasmin gene revealed a distinct size difference in exon 7. DNA sequence analysis of this exon revealed a 5-bp insertion at amino acid 410, resulting in a frame-shift mutation and a truncated open reading frame. The validity of this mutation was confirmed by analysis of DNA from the patient's daughter, which revealed heterozygosity for this same 5-bp insertion. The presence of this mutation in conjunction with the clinical and pathologic findings demonstrates an essential role for ceruloplasmin in human biology and identifies aceruloplasminemia as an autosomal recessive disorder of iron metabolism. These findings support previous studies that identified ceruloplasmin as a ferroxidase and are remarkably consistent with recent studies on the essential role of a homologous copper oxidase in iron metabolism in yeast. The clinical and laboratory findings suggest that additional patients with movement disorders and nonclassical Wilson disease should be examined for ceruloplasmin gene mutations.

Amino Acid Sequence↗
PubMed1995

Factors influencing growth rate of recurrent stomach cancers as determined by analysis of serum carcinoembryonic antigen.

BACKGROUND: Although there are many reports regarding the growth rate of human tumors, those discussing stomach cancer are rare due to the difficulty in evaluating the growth rate of stomach cancer. Stomach cancers grow with either a large central depression or through severe invasion. Metastatic sites of stomach cancer, however, grow expandingly, as with pulmonary tumors. METHODS: The reported doubling time estimate, based on the serum level of carcinoembryonic antigen (CEA), agreed with the actual tumor doubling time investigated in 112 previously untreated patients with recurrent gastric cancers. The influencing factors of the CEA doubling time were studied clinicopathologically, and a possible correlation between postoperative survival and the CEA doubling time was noted. RESULTS: The CEA doubling time ranged from 12 to 105 days, with a mean of 37.5 +/- 20.5 days (mean +/- standard deviation) and a median of 32 days. The CEA doubling time did not differ significantly between sexes or between patients of varying ages. However, the CEA doubling time was significantly shorter in patients with papillary adenocarcinoma than in those with well or moderately differentiated tubular adenocarcinoma. The CEA doubling time of patients with poorly differentiated adenocarcinoma was divided into two groups--a shorter one and a longer one. The doubling time was also significantly shorter in patients with liver metastasis than in those with lymph node metastasis or peritoneal dissemination. Furthermore, among patients who did not receive any chemotherapy, a significant correlation was observed between the CEA doubling time and postoperative survival time. Most treated patients survived longer than untreated patients. CONCLUSION: The influencing factors on growth rates in recurrent stomach cancers were histologic type and metastatic sites. This growth rate plays an important role in determining the degree of biologic malignancy and may be influenced by some chemotherapeutic regimens.

Adenocarcinoma↗
PubMed1995

Multiple epiphyseal dysplasia with small head, congenital nystagmus, hypoplasia of corpus callosum, and leukonychia totalis: a variant of Lowry-Wood syndrome?

We report on a boy with multiple epiphyseal dysplasia (MED), mild short stature, small head, mental retardation and congenital nystagmus associated with other visual problems. These manifestations were similar to those seen in Lowry-Wood syndrome (LWS). He also had hypoplasia of the corpus callosum and leukonychia totalis, which were not described in the previous cases.

Abnormalities, Multiple↗
PubMed1995

Structure-activity relationship of bromoeudistomin D, a powerful Ca2+ releaser in skeletal muscle sarcoplasmic reticulum.

Bromoeudistomin D and 9-methyl-7-bromoeudistomin D which have a beta-carboline skeleton are powerful Ca2+ releasers from skeletal muscle sarcoplasmic reticulum exhibiting caffeine-like properties. We examined the effects of bromoeudistomin D analogues on Ca(2+)-induced Ca2+ release from skeletal muscle sarcoplasmic reticulum. Among bromoeudistomin D analogues, the Ca(2+)-releasing activities of carboline derivatives were higher than those of carbazole derivatives, suggesting that a carboline skeleton is significantly important for the manifestation of Ca(2+)-releasing activity and Ca2+ sensitivity of Ca(2+)-induced Ca2+ release. On the contrary, the analogues which have a carbazole skeleton and bromine at C-6 inhibit both Ca(2+)- and caffeine-induced Ca2+ release. 9-Methyl-substitution of the analogue elevated its Ca(2+)-releasing activity. Moreover, there is a close correlation between the enhancement of [3H]ryanodine binding to sarcoplasmic reticulum by the analogues and the activation of Ca2+ release by them. Bromoudistomin D analogues may provide valuable information about the structure-function relationship of the ryanodine receptor/Ca2+ release channels in skeletal muscle sarcoplasmic reticulum.

Animals↗
PubMed1995

Chemotactic agonists induce cytokine generation in eosinophils.

Recent studies have shown that eosinophils are capable of generating and releasing cytokines, providing a novel biologic aspect of eosinophils for regulating allergic inflammation by an autocrine or paracrine mechanism. Eosinophils synthesize various cytokines; however, the physiologic stimuli that trigger eosinophils to generate cytokines have not been fully elucidated. We examined the effect of chemotactic agonists on eosinophil cytokine generation by employing the determination of IL-8 as the main parameter. Both C5a and FMLP stimulated eosinophils to release IL-8, whereas platelet-activating factor and C-C chemokines did not exert any significant effects. On a molar basis, C5a was two orders of magnitude more potent than FMLP. The generation of IL-8 by chemoattractants was absolutely dependent on the presence of cytochalasin B. Pertussis toxin completely attenuated C5a- and FMLP-induced IL-8 production, indicating the involvement of pertussis toxin-sensitive G-proteins in the signal-transduction process leading to these responses. Experiments of in situ hybridization and PCR amplification revealed that both C5a and FMLP promoted eosinophil IL-8 production through transcriptional gene activation. Pyrrolidine dithiocarbamate completely abrogated chemoattractant-induced IL-8 production, indicating the involvement of NF-kappa B in the cytoplasmic/nuclear signal-transduction process. Furthermore, chemoattractant-induced cytokine production was not limited to IL-8; C5a and FMLP but not platelet-activating factor induced significant secretion of granulocyte-macrophage-CSF from eosinophils. These results indicate that C5a and FMLP stimulate eosinophils to elaborate cytokines, which could be an important mechanism in the regulation of allergic inflammation.

Base Sequence↗
PubMed1995

Diabeteslike proliferative retinal changes in galactose-fed dogs.

OBJECTIVE: To determine whether diabeteslike lesions associated with the proliferative stage of diabetic retinopathy develop in galactose-fed dogs, since studies designed to define the complex biochemical effects of prolonged hyperglycemia on retinal vessels have been hampered by the lack of an animal model that mirrors both the early and advanced stages of diabetic retinopathy. METHODS: Eyes from 9-month-old male beagles fed a daily diet containing either 30% nonnutrient filler (control diet) or 30% galactose (galactose diet) for up to 84 months were enucleated and histologically examined. RESULTS: Retinal vessel changes associated with the proliferative stage were observed in two of nine galactose-fed dogs while the remainder demonstrated retinal changes that included the appearance of microaneurysms, acellular capillary beds associated with areas of nonperfusion, and intraretinal microvascular abnormalities. Proliferative changes were evidenced by the formation of preretinal fibrous membranes and the appearance of fibrovascular membranes on the retinal surface and on the posterior hyaloid membrane. No retinal lesions were observed in similar dogs fed a control diet for up to 84 months. CONCLUSION: The galactose-fed dog appears to be the first animal model that can develop diabeteslike retinal vessel changes associated with both the early and advanced stages of retinopathy, including the proliferative stage.

Animals↗