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Biomedical subjects

K Abe

Publications and source records attributed to K Abe.

At least 865 records · Page 48Linked to original sources

Cloning and expression of the quaking gene in the zebrafish embryo.

The responsible gene for hypomyelinating quaking deficiency, qkI, encoding a KH RNA binding protein, is expressed abundantly in the developing mouse nervous system, whereas who/how/struthio, a homologue of the qkI in Drosophila, is expressed predominantly in the mesoderm. Here we describe the isolation and early developmental expression of a zebrafish homologue of qkI. The zebrafish quaking cDNA, zqk, exhibits striking conservation with qkI across the coding region, accompanied by a unique 123 nucleotide insertion sequence. Maternal and zygotic zqk transcripts are ubiquitously distributed during cleavage and blastula periods, and then accumulate in the dorsal midline of the body trunk during gastrulation. During segmentation and pharyngula periods zqk transcripts are expressed in the neural tissue of the head region, and in the paraxial mesoderm of the body trunk. Subsequently they diminish until the hatching period, when they are expressed only in the cardiac sac and pectoral finbuds. We also found that the zqk transcript is alternatively spliced with the transcript containing a 123 nucleotide additional segment localized in neural tissue in the head region, but not in the paraxial mesoderm in the body trunk. The data suggest that the quaking gene family originated in the mesoderm and evolved to become expressed in the nervous system in lower vertebrates. The insertion of the 123 nucleotide sequence could be related to the acquisition of a neural function for the gene.

Alternative Splicing↗

Synthesis and pharmacological properties of ureidomethylcarbamoylphenylketone derivatives. A new potent and subtype-selective nonpeptide CCK-B/gastrin receptor antagonist, S-0509.

A novel series of CCK-B/gastrin receptor antagonists-ureidomethylcarbamoylphenylketone derivatives-were designed, synthesized, and evaluated for activity. Structure-activity relationship studies revealed the importance of a carboxylic acid at substituent R2 and tert-butoxycarbonyl group at R1 in structure A. Compound 7a (S-0509) showed remarkable affinity for the CCK-B/gastrin receptor and a subtype selectivity profile in vitro. Administration (id) of 7a led to excellent inhibition of gastric acid secretion induced by pentagastrin in anesthetized rats with an ED50 value of 0.014 mg/kg. Furthermore, 7a proved to have poor blood-brain permeability by its small effect on enhancement of morphine analgesia. Thus, S-0509 has an increase in selectivity for the peripheral effects of gastrin antagonism from the central effects of CCK-B antagonism.

Animals↗

Biologically active oligodeoxyribonucleotides--IX. Synthesis and anti-HIV-1 activity of hexadeoxyribonucleotides, TGGGAG, bearing 3'- and 5'-end-modification.

We have determined that hexadeoxyribonucleotides (5'TGGGAG3'), with modified aromatic groups such as a trityl group at the 5'-end, have anti-HIV-1 activity in vitro. The 6-mer bearing a 3,4-dibenzyloxybenzyl (3,4-DBB) group at the 5'-end had the most potent activity and the least cytotoxicity. When the 3'-end of the 5'-(3,4-DBB)-modified 6-mer was substituted with a 2-hydroxyethylphosphate, a 2-hydroxyethylthiophosphate, or a methylphosphate group at the 3'-end, anti-HIV-1 activity increased. Moreover, among various 3'- and 5'-end-modified 6-mers that were tested, the 6-mer (R-95288) bearing a 3,4-DBB group at the 5'-end and a 2-hydroxyethylphosphate group at the 3'-end was the most stable, when incubated with mouse, rat, or human plasma. Therefore, R-95288 was chosen as the best candidate for possible use in therapy on the basis of its anti-HIV-1 activity.

Animals↗

Numb chin syndrome as an initial symptom of acute lymphocytic leukemia: report of three cases.

This article describes three cases of acute lymphocytic leukemia that presented with mental neuropathy, or so-called "numb chin syndrome," as the initial symptom of the disease. This symptom heralded the initial progression of the disease in the first and second cases and the recurrence of the disease in the third case. In these cases tenderness in the mental foramen, percussion pain of the teeth, loosening and extrusion of the teeth, and radiographic abnormalities were also, if not always, observed in association with mental neuropathy. The radiographic abnormalities included a disappearance of the mandibular canals, an enlarged periodontal ligament space, a loss or thinning of the lamina dura, and a destruction of the alveolar crestal bone. This report indicates that oral manifestations can therefore occasionally play an extremely important role in the early recognition of acute lymphocytic leukemia. The unexplained oral abnormalities such as numbness of the chin and lower lip must thus be considered, potentially ominous indication of acute lymphocytic leukemia.

Adolescent↗

Patients in phase I trials of anti-cancer agents in Japan: motivation, comprehension and expectations.

We attempted to characterize the motivation, comprehension and expectations of patients who had given informed consent to participate in phase I trials of anti-cancer agents at the National Cancer Center of Japan. Thirty-three patients were given a simple multiple-choice questionnaire and asked to return it at a later date. The completed survey was returned by 32 patients. The patients were surveyed before they had received any investigational phase I agents. Nineteen per cent of patients were motivated to participate in the phase I trials by the possibility of therapeutic benefit, 9% because participation seemed a better choice than no treatment and only 6% for altruistic reasons. Most patients comprehended the major features of a phase I trial, namely its investigational nature, the unknown effects of the agent investigated and the unclear benefit to the patients themselves. Fifty-nine per cent of the patients anticipated that they might suffer severe or life-threatening side-effects if they participated in the phase I trial, and 43% were able to indicate accurately the purpose of the phase I trial as a dose determination study. Although only a minority of the patients indicated that their motivation to participate was possible treatment benefit to themselves, when answering questions regarding expectations, more than half indicated that there might be personal benefits of varying degrees by participation.

Antineoplastic Agents↗

Tyrosine kinase, phosphatidylinositol 3-kinase, and protein kinase C regulate insulin-stimulated NaCl absorption in the thick ascending limb.

We have previously shown a direct stimulatory effect of insulin on NaCl absorption in the medullary thick ascending limb of Henle's loop (mTAL). To further investigate the signal transduction involved, we determined whether tyrosine kinase, phosphatidylinositol 3-kinase (PI3-kinase), and/or protein kinase C (PKC) regulate insulin-stimulated NaCl absorption in the mTAL by in vitro microperfusion methods. In control experiments, insulin increased transepithelial voltage (V(te)) and net lumen-to-bath Cl- flux (J(Cl)). Genistein and methyl 2,5-dihydroxycinnamate, two specific tyrosine kinase inhibitors, abolished the effects of insulin. Wortmannin, a specific PI3-kinase inhibitor, inhibited the action of insulin. The effects of insulin also were inhibited by staurosporin and calphostin C, which are dissimilar inhibitors of PKC. These results indicate that insulin stimulates NaCl absorption in the mTAL through tyrosine kinase, PI3-kinase, and PKC-mediated mechanisms. Moreover, because we have reported previously that insulin causes no detectable change in cytosolic free Ca2+ in the mTAL cells, the present results also suggest that insulin-induced PKC activation is not related to inositol 1,4,5-triphosphate (IP3) production.

Absorption↗

Double adenomas with different pathological and hormonal features in the left adrenal gland of a patient with Cushing's syndrome.

We report a 52-year-old women with Cushing's syndrome who presented with two adenomas in the left adrenal gland. One tumour appeared dark brown and the other appeared yellow on the cut surface. The non-neoplastic adrenal demonstrated marked cortical atrophy. Upon histological examination, the brown tumour was found to be composed of both compact and clear cells. In contrast, the yellow tumour was composed of clear cells associated with pseudoglandular formation and marked degeneration. Immunohistochemical studies demonstrated positive immunostaining of cytochrome P-450 specific for 17 alpha-hydroxylation (P-450c17) in the brown but not the yellow tumour. Other steroidogenic enzymes except for dehydroepiandrosterone sulphotransferase were detected in both tumours. The biochemical activities of 21-hydroxylase, 17-hydroxylase and 11 beta-hydroxylase in the brown tumour (6.10 nmol/mg protein/4 minutes, 1.87 nmol/mg protein/2 minutes and 5.71 mumol 11-OHCS formed/g protein/10 minutes, respectively) were much greater than those in the yellow tumour. Gel-supported three-dimensional native-state primary culture of the tumours demonstrated a much higher concentration of cortisol in the culture medium for the brown tumour (5750 nmol/l on 4th day). Vimentin expression was detected in both tumours but cytokeratin expression was detected only in the yellow tumour. The Ki67 labelling index in the brown tumour was greater than that in the yellow tumour. These results indicated that these two adenomas had different biological characteristics and the brown tumour was primarily involved in over-production of cortisol in this patient. When analysing unilateral multiple adrenocortical lesions, approaches using immunohistochemical studies for steroidogenic enzymes, enzyme activity assays and cell culture can help to define the steroidogenesis of individual adrenocortical lesions.

Adenoma↗

The development of transient hypothyroidism after iodine-131 treatment in hyperthyroid patients with Graves' disease: prevalence, mechanism and prognosis.

OBJECTIVE: Recovery of thyroid function in patients following hypothyroidism induced by 131I therapy for Graves' disease has been described, but only a few detailed clinical and biochemical studies of this phenomenon (transient hypothyroidism) have been published. The prevalence, mechanism, and final outcome of transient hypothyroidism in 260 patients with Graves' disease treated with 131I was studied. DESIGN: A retrospective study. PATIENTS: Two hundred sixty patients with Graves' disease, treated with 131I between 1 and 15 years previously, were categorized into 4 groups according to their thyroid function during and 1 year after therapy (Group 1: permanent hypothyroidism, 28 patients; Group 2: transient hypothyroidism, 39 patients; Group 3: euthyroidism without transient hypothyroidism, 83 patients; Group 4: hyperthyroidism, 110 patients). MEASUREMENTS: We compared total T4, total T3, TSH, anti-thyroglobulin (TGHA) and anti-microsomal (MCHA) antibodies, the TSH-binding inhibitory immunoglobulin (TBII) index, thyroid weight, dose of 131I, and 24-hour 131I uptake as pretreatment variables. The mean time for permanent hypothyroidism to develop was estimated by the Kaplan-Meier product limit method. The TBII index and thyroid stimulating antibody (TSAb) activity were measured in seven patients from Group 1 and in nine patients from Group 2 at the time that they became hypothyroid. RESULTS: Hypothyroidism developing within 12 months of therapy was transient in 58% (39/67) of patients. No pretreatment variables were found to differ between patients with and without transient hypothyroidism. The mean estimated time between therapy and the development of permanent hypothyroidism was 96 months in Group 2; this time interval was significantly shorter than 126 months in Group 3 and 129 months in Group 4 (P < 0.05, P < 0.01, respectively). TSAb activity was > 500% In 78% (7/9) of patients from Group 2, which was significantly higher than that found (14%, 1/7) in Group 1. CONCLUSIONS: These results indicate that (1) more than half the patients who developed hypothyroidism within 6 months after 131I treatment for Graves' disease recovered spontaneously, (2) TSAb activity might play some role in the recovery of transient hypothyroidism, and (3) the development of transient hypothyroidism may influence long-term thyroid function.

Adult↗

A 900 bp genomic region from the mouse dystrophin promoter directs lacZ reporter expression only to the right heart of transgenic mice.

In order to study the regulatory mechanism of developmental and tissue-specific expression of the muscle type dystrophin gene in mice, transgenic mice were generated carrying the 900 bp genomic fragment derived from the muscle type dystrophin promoter region fused to the bacterial lacZ gene. Six independent transgenic mouse lines showed specific reporter gene expression in the right heart, but not in skeletal or smooth muscle. The reporter gene expression was first detected in the presumptive right ventricle of the embryos at 8.5 days post coitum and the expression continued only in the right ventricle throughout the development and at the adult stage. The results indicate that the 900 bp genomic fragment contains the regulatory element required for expression of dystrophin only in the right heart, suggesting that distinct elements are responsible for the expression in the left and right compartments of the heart, and/or in skeletal and smooth muscle cells. Based on these findings, the relationship between defects in muscle type promoter and the diseases caused by abnormal dystrophin expression is discussed.

Animals↗

Nanomolar amyloid beta protein-induced inhibition of cellular redox activity in cultured astrocytes.

It has been previously reported that Alzheimer's amyloid beta protein (A beta) induces reactive astrocytosis in culture. In the present study, we found that A beta potently inhibits cellular redox activity of cultured astrocytes, as determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction assay. The following comparative studies revealed several differences between these two actions of A beta on astrocytes. First, A beta-induced reactive morphological change was suppressed by the presence of serum or thrombin, and A beta inhibition of cellular redox activity was observed in either the presence or the absence of serum. Second, micromolar concentrations (10 microM or more) were required for A beta to induce reactive astrocytosis, whereas nanomolar concentrations (0.1-100 nM) were sufficient to inhibit cellular redox activity. Third, the effect of micromolar A beta was virtually irreversible, but nanomolar A beta-induced inhibition of cellular redox activity was reversed by washing out A beta. Furthermore, as it has been reported that A beta neurotoxicity is mediated by reactive oxygen species, we also examined if similar mechanisms are involved in astrocytic response to A beta. However, neither A beta-induced morphological change nor inhibition of redox activity was blocked by antioxidants, suggesting that these effects are not caused by oxidative stress.

Amyloid beta-Peptides↗

Upregulation of protein-tyrosine nitration in the anterior horn cells of amyotrophic lateral sclerosis.

Spinal cords of sporadic cases with amyotrophic lateral sclerosis (ALS) and normal controls were immunohistochemically examined using antibodies for nitrotyrosine (NT), Cu/Zn superoxide dismutase (SOD), and nitric oxide synthase (NOS) of brain, endothelial, and inducible forms. Immunoreactivity for NT was densely detected in the motor neurons of ALS while it was not or was only minimally detected in those of controls. The staining was also found in the axons of motor neurons of ALS, but was not found in the controls. In contrast, although immunoreactivity for Cu/Zn SOD of the motor neurons was dense in the motor neurons, it was not different between the ALS and controls. Immunoreactivities for bNOS and eNOS in the motor neurons of ALS were stronger than those of controls, and were also found in degenerated axons in the anterior horn of ALS. However, the immunoreactivity for inducible NOS was only minimally detected in the motor neurons of ALS and controls, and was not detected in the degenerated axons of ALS. These results suggest that nitration of protein-tyrosine residue is upregulated in motor neurons of the spinal cord of ALS with selective increases of brain NOS- and endothelial NOS-like immunoreactivities.

Amyotrophic Lateral Sclerosis↗

Increase of ciliary neurotrophic factor (CNTF) in the ischemic rat brain as determined by a sensitive enzyme-linked immunoassay.

To study the distribution of ciliary neurotrophic factor (CNTF) in the rat brain under physiological as well as pathological conditions, a sensitive sandwich enzyme linked immunoassay (EIA) for rat CNTF was developed using rabbit anti-CNTF antibody. This method detected as little as 10 pg ml-1 CNTF with a good linearity and accuracy. Analysis of various regions of rat brain and peripheral nerves showed a high content of CNTF in the sciatic nerves, spinal cord, optic nerves, and olfactory bulb. Transient focal ischemia of rat brain caused by middle cerebral artery occlusion significantly and specifically increased CNTF levels in the cerebral cortex and hippocampus regions in the ischemic hemisphere.

Animals↗

Genetic remodeling of gangliosides resulted in the enhanced reactions to the foreign substances in skin.

Several lines of transgenic mice with gangliosides GM2/GD2 synthase gene were established, and the expression levels of the transgene in brain, liver, spleen and thymus were analyzed by comparing with those in their litter mates. Among four tissues, brain and skin showed markedly high expression levels of the transgene in Northern blotting. Particularly, transgenic mice skin showed about 10-fold higher expression of GM2/GD2 synthase gene than the wild type mice skin. Therefore, alterations in the morphology, glycolipid components, and responses to the exogenous stimulations in the transgenic mice skin were examined. Gangliosides in the transgenic skin were dramatically converted from GM3 to GM1, whereas no morphological changes were observed. However, when skin flap test was performed with insertion of nylon membranes under the skin flaps, much stronger inflammatory reactions consisting of edema, marked thickness, and cell infiltration were observed in the transgenic mice compared with the wild type. Similar enhanced inflammatory reaction was also observed in the skin injected by silicon gel, and in the peritoneal reaction to the injected casein. Main cell population in these inflammatory reactions consisted of neutrophils, suggesting an increased sensitivity of neutrophils to chemotactic factors in the transgenic mice.

Animals↗

Characterization of a gene family encoding cysteine proteinases of Sitophilus zeamais (maize weevil), and analysis of the protein distribution in various tissues including alimentary tract and germ cells.

We have identified and characterized a gene family comprising at least four genes encoding cathepsin L-like cysteine proteinases (SCPs) in Sitophilus zeamais, Coleoptera. A cDNA clone corresponding to a major mRNA species of the gene family in adult insects codes for a cysteine proteinase (CP) of 338 amino acid residues, and two genomic clones code for similar CPs of 331 residues whose COOH-terminal structures are seven amino acids shorter. These three SCPs show high sequence similarity to one another as well as to other insect and mammalian cathepsin L-like proteinases. A polyclonal antibody raised against bacterially expressed SCP was used as a probe to examine the molecular forms and distribution of the enzyme. SCP exists in both proenzyme and mature forms in larvae, pupae, and adults, and the proenzyme converts in vitro into the mature form at acidic pH. Immunohistochemical analysis showed that SCP is present in several tissues including alimentary organs and germ cells. In alimentary organs, SCP is distributed in the gastric caeca, but not the midgut. SCP is also present in genital organs, especially in oocytes and nurse cells, where it exists at high levels. These results indicate that SCP plays a variety of physiological roles including a role in food digestion.

Amino Acid Sequence↗

Prediction of mortality by ambulatory blood pressure monitoring versus screening blood pressure measurements: a pilot study in Ohasama.

OBJECTIVE: To compare the prediction of mortality by ambulatory blood pressure monitoring and screening blood pressure measurements in a general population. DESIGN: A prospective cohort study. PATIENTS AND METHODS: We obtained blood pressure data for 1542 subjects (565 men and 977 women) aged > or = 40 years who were followed up for up to 8.1 years (mean 5.1 years). Subjects were subdivided into five groups according to their ambulatory and screening blood pressure levels. The prognostic significance of blood pressure for mortality was examined by the Cox proportional hazards regression model. RESULTS: The association between blood pressure level and mortality was more distinctive for the ambulatory blood pressure than it was for the screening blood pressure. The risk of cardiovascular mortality increased significantly for the highest quintiles of 24 h ambulatory blood pressure, whereas there was no significant association between the screening blood pressure and the cardiovascular mortality. When both 24 h and screening blood pressure values were included in the Cox model, only the systolic ambulatory blood pressure was related significantly to the increased risk of cardiovascular mortality. CONCLUSIONS: The ambulatory blood pressure had a stronger predictive power for mortality than did the screening blood pressure. This appears to have been the first study of the prognostic significance of ambulatory blood pressure monitoring versus screening blood pressure measurements in a general population.

Adult↗

Recurrent brief depression in Prader-Willi syndrome: a case report.

Prader-Willi syndrome is caused by a deletion of 15q11-13 or maternal disomy of chromosome 15. A female patient with Prader-Willi syndrome, who was 19 years of age at the first onset of her recurrent brief episodes, is described. The episodes showed a near-monthly rhythm and were followed by a spontaneous remission in 7-18 days. The symptoms during the episodes were anorexia, insomnia, guilt feelings, ideas of being doomed, ostracized and persecuted, and stupor alternating with agitation.

Adult↗