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Biomedical subjects

Y Harada

Publications and source records attributed to Y Harada.

At least 19 recordsLinked to original sources

Involvement of PIM-1 in DNA fragmentation in mouse NS-1-derived cells.

In several cell lines derived from mouse NS-1 myeloma cells, internucleosomal fragmentation of chromosomal DNA, a hallmark of apoptosis, was continuously observed. Approximately 15-20% of the cells died when isolated in a 96-well plate, and the surviving cells contained fragmented DNA ('ladder'). Among a variety of genes so far reported to be related to apoptosis, only Pim-1 was expressed at an elevated level in the NS-1 hybridomas as compared in a control myeloma cell line without 'ladder'. Transfection of a Pim-1 expression vector to a 'ladder'-non-producing myeloma line yielded similar internucleosomal DNA fragmentation. The results hence suggested that Pim-1 activates endonucleases responsible for DNA fragmentation during apoptosis and/or repress DNA repair systems to restore fragmented DNA.

Animals

Mutation frequency of the p16/CDKN2 gene in primary cancers in the upper digestive tract.

We report a highly frequent homozygous deletion of the p16/CDKN2 gene in the esophageal cancer cell line and a relatively high frequency of homozygous deletion in gastric cancer cell lines. In contrast, in primary esophageal carcinomas, mutation frequency of the p16/CDKN2 gene has been controversial (0, 21, and 52% previously reported), and no reports are available for the mutation frequency of this gene in surgical specimens of gastric carcinomas. Here we report that four (16%) of 25 primary esophageal squamous cell carcinomas were found to be mutated, one in exon 1 and three in exon 2, and that no mutations were observed in 19 surgical specimens of gastric adenocarcinomas. This is the first report showing the absence or quite low frequency of mutation in surgical specimens of gastric carcinomas.

Base Sequence

Population persistence and spatially limited social interaction.

We investigate the persistence of a population composed of socially interacting individuals living in a lattice structured habitat and the effect of spatially limited social interaction, reproduction, and migration. Both cooperative interaction (enhancing the survivorship of neighboring individuals) and competitive interaction (reducing it) are examined. Mathematical analysis based on pair approximation (or doublet decoupling approximation) and computer simulation are used. Results are: If migration rate is not very large, the population tends to form clusters of individuals (clumped distribution) due to spatially limited reproduction. Although cooperative interaction is more effective in a spatially structured population, the population is more difficult to persist than in the corresponding population without spatial structure, because the shortage of nearest neighbor vacant sites reduces reproduction. Migration of individuals reduces the clumping of the spatial pattern. Pair approximation predicts the equilibrium density fairly accurately when the predicted density is sufficiently high (i.e., more than 40% sites are occupied). If the predicted density is low however, the pair approximation overestimates the equilibrium population level. To overcome this disagreement, we examined improved pair approximation.

Bias

Characterization of cell surface antigens expressed in the HMA-1 breast cancer cell line.

This report describes the characterization of an estrogen receptor-positive breast cancer cell line, HMA-1, established from a breast cancer patient, based on the expression of tumor-associated antigens (TAAs), the HLA-DR antigen, and the c-erbB-2 proto-oncogene product. In flow cytometric and immunohistochemical analyses, HMA-1 was found to express increased levels of several TAAs including MUC1, TAG-72 (sialyl Tn), Tn, T, sialyl Le(a), Le(x), and Le(y). HMA-1 also expressed enhanced levels of the HLA-DR antigen and c-erbB-2 protein. These results indicate that HMA-1 is a unique cell line with abundant TAAs which may serve as an appropriate breast cancer cell line for application in the multidisciplinary research of breast cancer.

Amino Acid Sequence

Carcinoma of the reconstructed stomach tube following esophageal resection for a benign stricture: report of a case and review of the literature.

We report herein the case of a 60-year-old woman who presented with dysphagia and anorexia and was subsequently diagnosed as having gastric cancer of the reconstructed stomach tube 36 years after undergoing surgery for a benign esophageal stricture. Reports on carcinoma of the reconstructed stomach tube are rarely found and interestingly, all of the previous cases, which were documented only in the Japanese literature, corresponded to metachronous double cancers after esophageal malignancies. To our knowledge, this is the first case of carcinoma of the reconstructed stomach tube following esophageal resection for a benign stricture, and it is thought that the carcinoma probably developed at the site of the anastomosis a long time after the first operation. We reviewed 30 cases of carcinoma of the reconstructed stomach tube for which the clinicopathological data was complete, and we believe that this new type of cancer needs more than 10 years to develop and should be defined as "carcinoma of the gastric remnant".

Adenocarcinoma

Inheritance of mitochondrial DNA in sexual crosses and protoplast cell fusions in Lentinula edodes.

By using mitochondrial DNA (mtDNA) restriction fragment length polymorphisms (RFLPs) as genetic markers, the modes of mitochondrial inheritance in sexual crosses and protoplast cell fusions of the higher basidiomycete Lentinula edodes were examined. All newly established dikaryons from reciprocal crosses between compatible monokaryons carrying different mtDNA RFLP phenotypes retained mtDNA genotypes from one of the monokaryons, suggesting that mitochondrial inheritance is principally uniparental. In contrast, it was shown that recombinant mtDNA genomes arose in some dikaryons obtained after protoplast cell fusion. Based on these results, a possible mechanism for mitochondrial inheritance in L. edodes is discussed.

Agaricales

Can concordant criss-cross heart be ameliorated by hemodynamic changes?

A 2-year-old female child with "ameliorated" concordant criss-cross heart, complicated superior-inferior ventricles, complete transposition of great arteries, hypoplastic right ventricle, ventricular septal defect, and aortic coarctation is described. The patient underwent subclavian flap, pulmonary artery banding, and balloon atrioseptostomy at age 1 month. The ameliorated concordant criss-cross anatomy was obtained after 2 years of follow-up. This dynamic morphologic change allowed us to perform a subsequent anatomic correction.

Aortic Coarctation

Nitroxidergic vasodilator nerve in the canine nasal mucosa.

The canine nasal mucosa was studied by in vitro bioassay. Non-adrenergic, non-cholinergic (NANC) vasodilator response to transmural electrical stimulation was observed in the presence of guanethidine and atropine. This vasodilator response was abolished by NG-nitro-L-arginine (L-NA) which is an inhibitor of nitric oxide (NO) formation but not by NG-nitro-D-arginine. The inhibitory effect of L-NA was partially reversed by treatment with L-arginine but not with D-arginine. The vasodilator response was significantly suppressed by tetrodotoxin. The present results indicate that NO may mediate neurogenic vasodilation in the canine nasal mucosa.

Animals

Contrasting actions of intrathecal U50,488H, morphine, or [D-Pen2, D-Pen5] enkephalin or intravenous U50,488H on the visceromotor response to colorectal distension in the rat.

BACKGROUND: Visceral sensations are an important component of many clinical pain states. It is apparent that intrathecal pain relief may be more effective if appropriate combinations of drugs rather than a single agent can be used. The purpose of this study was to examine the relative contribution of opioid receptor subtypes to visceral antinociception using colorectal distension as a visceral pain model. METHODS: The minimum colorectal distending pressure necessary to evoke a visceromotor response (contraction of abdominal musculature) was determined before and after the administration of opioid agonists for the mu (morphine), delta ([D-Pen2, D-Pen5] enkephalin [DPDPE]), and kappa (U50,488H) opioid receptors. In addition to the three drugs administered intrathecally, U50, 488H was also administered intravenously. RESULTS: Morphine and DPDPE produced a reversible increase in threshold for activation of the visceromotor response (50% maximum possible effect [MPE] at intrathecal doses of 2.2 and 16.4 micrograms, respectively). The maximum intrathecal dose of U50,488H (100 micrograms) produced only a 20% MPE. Intravenous U50,488H produced a 50% MPE at a dose of 2.6 mg/kg. CONCLUSIONS: The results suggest that spinal mu- and delta- but not kappa-opioid receptors have a significant role in the modulation of visceral nociception induced by colorectal distension. In addition, the results indicate that activation of nonspinal kappa receptors may mediate visceral antinociception.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh

Visceral antinociceptive effects of spinal clonidine combined with morphine, [D-Pen2, D-Pen5] enkephalin, or U50,488H.

BACKGROUND: Visceral pain is an important component of many clinical pain states. The perispinal administration of drug combinations rather than a single agent may reduce side effects while maximizing analgesic effectiveness. The purpose of this study was to examine the nature of interactions between an alpha 2-adrenergic agonist (clonidine) and a mu-opioid agonist (morphine), a delta-opioid agonist ([D-Pen2, D-Pen5] enkephalin [DPDPE]), or a kappa-opioid agonist (U50,488H). METHODS: Colorectal distension was used to elicit a nociceptive visceromotor response (contraction of abdominal musculature) in rats. The ability of intrathecally administered clonidine alone or in combination with morphine, DPDPE, or U50,488H to alter thresholds for the production of the visceromotor response was examined. RESULTS: Clonidine produced dose-dependent reduction in threshold. U50,488H, at the doses tested, showed no synergistic interaction with clonidine. CONCLUSIONS: Spinal combinations of alpha 2-adrenergic and mu- or delta- but not kappa-opioid agonists may be beneficial in the control of visceral pain.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh

A specific chromosome abnormality of t(4;12)(q11-12;p13) in CD7+ acute leukaemia.

Three cases of acute leukaemia with t(4;12) (q11-12;p13) karyotypic abnormalities were analysed. They had the following common clinical and biological characteristics: (1) dysplasia of three haemopoietic lineages: (2) absent or low myeloperoxidase activity: and (3) retention of platelets in the peripheral blood and megakaryocytes in the bone marrow. There were increased numbers of basophils in the bone marrow and peripheral blood in two of the cases. In all, the blast cells displayed the unique immunophenotype CD7+CD13+CD34+HLA-DR+. The blasts analysed in one case expressed c-kit on the membrane surface. These findings suggest that the t(4;12) (q11-12;p13) abnormality is associated with a particular type of acute leukaemia, one in which the morphology and immunophenotype suggest that the translocation may have occurred at an early stage of haemopoiesis.

Acute Disease

A sea urchin homologue of the chordate Brachyury (T) gene is expressed in the secondary mesenchyme founder cells.

Chordates are thought to have emerged from some common ancestor of deuterostomes by organizing shared anatomical and embryological features including a notochord, a dorsal nerve cord and pharyngeal gill slits. Because the notochord is the most prominent feature of chordates and because the Brachyury (T) gene is essential for notochord formation, the T gene is a key molecular probe with which to explore the origin and evolution of chordates. We investigated whether the sea urchin (echinoderm) conserves the T gene and, if so, where the sea urchin T gene is expressed. A cDNA clone for the sea urchin T (HpTa) gene contained a long open reading frame that encodes a polypeptide of 434 amino acids. Although the overall degree of amino acid identity was not very high (52%, sea urchin/mouse), in the T domain of the N terminus the amino acid identity was 73% (sea urchin/mouse). The HpTa gene is present as a single copy per haploid genome. As with the chordate T gene, the expression of HpTa is transient, being first detected in the swimming blastula, maximally transcribed in the gastrula, decreasing at the prism larval stage and barely detectable at the pluteus larval stage. HpTa transcripts were found in the secondary mesenchyme founder cells, vegetal plate of the mesenchyme blastula, extending tip of the invaginating archenteron and, finally, the secondary mesenchyme cells at the late-gastrula stage.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence

Barium and strontium can substitute for calcium in stimulating nitric oxide production in the endothelium of canine coronary arteries.

We investigated whether Ba2+ and Sr2+ can substitute for Ca2+ in stimulating the nitric oxide (NO) production and cause relaxation in vascular smooth muscle. Ba2+ and Sr2+, like Ca2+, relaxed K(+)-depolarized canine coronary arteries in the presence of diltiazem. The Ba(2+)- and Sr(2+)-induced relaxation was endothelium-dependent and was largely inhibited by NG-monomethyl-L-arginine (L-NMMA) and NG-nitro-L-arginine (L-NNA), but not by indomethacin. These cations increased cyclic GMP levels in the coronary artery to a similar extent, and the increment was completely abolished by L-NMMA. The relaxation induced by each cation was attenuated in the presence of a combination of propranolol, phentolamine and atropine, and L-NNA markedly inhibited any remaining relaxation. This indicates that these cations produce endothelium-dependent relaxation through NO production as well as the relaxation mediated by neurotransmitters. The present study suggests that Ba2+ and Sr2+ can substitute for Ca2+ in the activation of the NO synthase pathway in the endothelium of canine coronary arteries.

Animals

[Age-related changes and sex differences on the serum chemistry values in Sprague-Dawley rats--I. 6-30 weeks of age].

Age-related changes of 27 items in serum chemistry were investigated in Sprague-Dawley rats of both sexes from 6 to 30 weeks of age. The following 12 items were shown as an increase in those values during growth and maturity, i.e., total protein, albumin (female only), glucose, total cholesterol, triglyceride, phospholipid (female only), beta-lipoprotein, cholinesterase (female only), asparate aminotransferase (female only), creatinine, direct-bilirubin and total-bilirubin. However, the following 4 items decreased with aging, i.e., asparate aminotransferase, alkaline phosphatase, creatine phosphokinase and inorganic phosphorus. No age-related changes were found in the values for calcium, sodium and chloride in both sexes and for alanine aminotransferase, cholinesterase and albumin in males. The sex differences were shown in the following 12 items: higher values in males were alkaline phosphatase, creatinephosphokinase, glucose and inorganic phosphorus, and higher values in females were cholinesterase, albumin, phospholipid, non-esterified fatty acid, urea nitrogen, direct-bilirubin, total-bilirubin and serum iron. No sex-related differences were found in the values for calcium, sodium, chloride and total cholesterol.

Aging

Cytoskeletal organization of the vestibular sensory epithelia.

The cytoskeletal organization of the guinea pig vestibular sensory epithelium was investigated by employing the saponin perfusion method and scanning electron microscopy. The skeletal framework of a a cell was found to consist of actin, intermediate filaments and microtubules. The membrane-bound organelles such as nucleus, mitochondria, endoplasmic reticulum, Golgi apparatus, etc. were also well documented. This made it possible to investigate the three-dimensional organization of cytoskeletons as well as their complex interaction with various membrane-bound organelles. The intermediate filaments were demonstrated not only in the supporting cells but also in the sensory cells. They are usually seen surrounding the nucleus and extending through the cytoplasm which connects the nuclear membrane to the plasma membrane, cuticular plate, reticular lamina or other cyto-organelles. The intermediate filaments are also closely related to the desmosomes. These findings suggest that the intermediate filaments provide mechanical support to the cell and its nucleus. In the sensory cells, microtubules are found mainly in the supranuclear portion of the cells, running parallel to the main axis of the cell body, which is directly connected to the cuticular plate. These findings suggest that the microtubules provide the cell with mechanical support and may be closely related to the sensory cell transduction system. Inside the supporting cells, the microtubules are closely related to the secretory granules, Golgi apparatus and intermediate filaments, which supports the idea that the microtubules may control the distribution of intermediate filaments, and also play an important role for transport of the secretory granules.

Animals

Changes in calcium distribution in the utricular supporting cells of the guinea pig.

Changes in calcium distribution in cultured utricular supporting cells following streptomycin sulfate (SM) intoxication were investigated by means of an organ culture system using potassium pyroantimonate (PA) precipitation. PA precipitation showed that calcium ions are located in the otoconia and in the secretory granules of the supporting cells. Exposure of the supporting cells to SM increased the number of lysosomes and reduced the secretory granules in the cytoplasm. These lysosomes had many granules containing calcium ion. It is suggested that calcium secretion from the secretory granules was inhibited by SM and that this might lead to reduction of otoconia.

Animals

Otoconia on the vestibular dark cells of the ampullar areas.

Morphological and metabolic differences in the otoconia on vestibular dark cells of the ampullar area before and after streptomycin treatment were studied by scanning electron microscopy and X-ray microanalyser. Young adult pigmented guinea pigs were used in this study. In the control group, distribution of the otoconia showed a regular pattern. In the SM group the otoconia decreased in numbers and the regularity of the distribution pattern seemed to disappear. Calcium content of the otoconia in SM group also decreased. From these findings, it was concluded that SM might affect not only the sensory and supporting cells but also the vestibular dark cells.

Animals

Effect of streptomycin on the supporting cells of the utricular macula.

Morphological changes in utricular supporting cells in the guinea pig following streptomycin sulfate (SM) intoxication were investigated ultrastructurally in vitro, using an organ culture system. The intracellular structures of the supporting cells, such as the nucleus, mitochondria, and Golgi apparati were well preserved after 7 days in culture. After 10 and 14 days in culture, the supporting cells degenerated. The organ culture system was applied to ototoxicity studies on the supporting cells in utricular macula within 7 days after explanation. When the utricles were exposed to 3, 10 and 30 mg/ml of SM for 3 days, the number of granules in the supporting cells decreased markedly and the number of lysosomes increased daily. The lysosomes contained mitochondria, myeloid bodies, granules and vesicles. Acid phosphatase (AcPase) activity decreased in Golgi apparati and lysosomes. When the concentration of SM was reduced to 3 and 10 mg/ml, the damage to the supporting cells was less marked than that in cells exposed to 30 mg/ml. The supporting cells showed a dose-dependent response with respect to morphological damage. After 3 days culture with 30 mg/ml of SM, the specimens were subsequently cultured for 4 days in a medium without SM. After removal of SM from the medium, lysosomes decreased in number, and the granules and the endoplasmic reticulum showed a gradual increase. The AcPase activity was determined in both lysosomes and Golgi apparatus. This study revealed that the morphological changes in the supporting cells can be reversible.

Acid Phosphatase