Biomedical subjects

M Shiota

Publications and source records attributed to M Shiota.

At least 19 recordsLinked to original sources

PubMed2001

Study on the role of G1 cyclins in Epstein-Barr virus-associated human lymphomas maintained in severe combined immune deficiency (SCID) mice.

Five Epstein-Barr virus (EBV)-positive human lymphoma cell lines maintained in severe combined immune deficiency (SCID) mice were used to investigate the role of G1 cyclins in EBV-induced lymphomagenesis. All the primary tumors had been negative for EBV but became positive after establishment in SCID mice, with monoclonal immunoglobulin gene rearrangement and EBV monoclonality. To compare the expression status of G1 cyclins, these EBV-associated lymphoma lines (6 EBV[-] human SCID mouse lymphoma lines, 13 human B cell lymphomas and 8 samples of human tonsil tissue) were examined by reverse transcription-polymerase chain reaction-Southern blotting, Western blotting and immunohistochemistry. mRNA expression of cyclin D1 (CCND1), cyclin D2 (CCND2), cyclin E (CCNE), cyclin-dependent kinase 2 (CDK2) and 4 (CDK4) was found in all 3 types of lymphomas. Western blotting demonstrated identical results. Immunohistochemistry revealed CCND1 to be negative in all lymphomas. CCND2 was positive and restricted to the nuclei in all EBV(+) SCID mouse lymphoma lines, whereas it was limited to the cytoplasm in half of the EBV(-) counterparts. CCNE was positive in the nuclei in all EBV(+) but negative in all EBV(-) SCID mouse lymphoma lines. Immunoprecipitation of EBV(+) and (-) SCID mouse lymphomas for CCND1, CCND2 and CCNE vs. p21, PCNA and CDK2 or CDK4 demonstrated that, in EBV(+) SCID lines, CCND2/CDK4 complexes were present without binding to p21, suggesting independence from p21 regulation. In EBV(-) SCID mouse lymphomas, half of the cases showed complex formation of CCND2/CDK4 without binding of p21. In contrast, CCND1/CDK4 and CCNE/CDK2 were under regulation of p21 in both EBV(+) and (-) lymphomas. These results suggest that differential expression of CCNDs, CCNE and CDKs, as well as variation in their subcellular localization and association with CDK-inhibitor protein, could explain differences in cell proliferation between EBV(+) and EBV(-) lymphomas.

Animals↗

PubMed2001

Influenza virus RNA polymerase PA subunit is a novel serine protease with Ser624 at the active site.

BACKGROUND: Influenza virus RNA polymerase is a multifunctional enzyme that catalyses both transcription and replication of the RNA genome. The function of the influenza virus RNA polymerase PA subunit in viral replication is poorly understood, although the enzyme is known to be required for cRNA --> vRNA synthesis. The protease related activity of PA has been discussed ever since protease-inducing activity was demonstrated in transfection experiments. RESULTS: PA protein was highly purified from insect cells infected with the recombinant baculovirus carrying PA cDNA, and a novel chymotrypsin-type serine protease activity was identified with the synthetic peptide, Suc-LLVY-MCA, in the PA protein. [3H]DFP was crosslinked with PA and a mutational analysis revealed that serine624 was as an active site for the protease activity. CONCLUSIONS: These results constitute the demonstration of protease activity in PA subunit of the influenza virus RNA polymerase complexes.

Amino Acid Sequence↗

PubMed2001

Mini-plasmin found in the epithelial cells of bronchioles triggers infection by broad-spectrum influenza A viruses and Sendai virus.

Extracellular cleavage of virus envelope fusion glycoproteins by host cellular proteases is a prerequisite for the infectivity of mammalian and nonpathogenic avian influenza viruses, and Sendai virus. Here we report a protease present in the airway that, like tryptase Clara, can process influenza A virus haemagglutinin and Sendai virus envelope fusion glycoprotein. This protease was extracted from the membrane fraction of rat lungs, purified and then identified as a mini-plasmin. Mini-plasmin was distributed predominantly in the epithelial cells of the upward divisions of bronchioles and potentiated the replication of broad-spectrum influenza A viruses and Sendai virus, even that of the plasmin-insensitive influenza A virus strain. In comparison with plasmin, its increased hydrophobicity, leading to its higher local concentrations on membranes, and decreased molecular mass may enable mini-plasmin to gain ready access to the cleavage sites of various haemagglutinins and fusion glycoproteins after expression of these viral proteins on the cell surface. These findings suggest that mini-plasmin in the airway may play a pivotal role in the spread of viruses and their pathogenicity.

Amino Acid Sequence↗

PubMed2001

Cell-specific roles of glucokinase in glucose homeostasis.

Mutations in the glucokinase (GK) gene cause two different diseases of blood glucose regulation: maturity onset diabetes of the young, type 2 (MODY-2) and persistent hyperinsulinemic hypoglycemia of infancy (PHHI). To gain further understanding of the pathophysiology of these disorders, we have used both transgenic and gene-targeting strategies to explore the relationship between GK gene expression in specific tissues and the blood glucose concentration. These studies, which have included the use of aCre/loxP gene-targeting strategy to perform both pancreatic beta-cell- and hepatocyte-specific knockouts of GK, clearly demonstrate multiple, cell-specific roles for this hexokinase that, together, contribute to the maintainance of euglycemia. In the pancreatic beta cell, GK functions as the glucose sensor, determining the threshold for insulin secretion. Mice lacking GK in the pancreatic beta cell die within 3 days of birth of profound hyperglycemia. In the liver, GK facilitates hepatic glucose uptake during hyperglycemia and is essential for the appropriate regulation of a network of glucose-responsive genes. While mice lacking hepatic GK are viable, and are only mildly hyperglycemic when fasted, they also have impaired insulin secretion in response to hyperglycemia. The mechanisms that enable hepatic GK to affect beta-cell function are not yet understood. Thus, the hyperglycemia that occurs in MODY-2 is due to impaired GK function in both the liver and pancreatic beta cell, although the defect in beta-cell function is clearly more dominant. Whether defects in GK gene expression also impair glucose sensing by neurons in the brain or enteroendocrine cells in gut, two other sites known to express GK, remains to be determined. Moreover, whether the pathophysiology of PHHI also involves multitissue dysfunction remains to be explored.

Animals↗

PubMed2001

Alpha- and beta-cell responses to small changes in plasma glucose in the conscious dog.

The responses of the pancreatic alpha- and beta-cells to small changes in glucose were examined in overnight-fasted conscious dogs. Each study consisted of an equilibration (-140 to -40 min), a control (-40 to 0 min), and a test period (0 to 180 min), during which BAY R3401 (10 mg/kg), a glycogen phosphorylase inhibitor, was administered orally, either alone to create mild hypoglycemia or with peripheral glucose infusion to maintain euglycemia or create mild hyperglycemia. Drug administration in the hypoglycemic group decreased net hepatic glucose output (NHGO) from 8.9 +/- 1.7 (basal) to 6.0 +/- 1.7 and 5.8 +/- 1.0 pmol x kg(-1) x min(-1) by 30 and 90 min. As a result, the arterial plasma glucose level decreased from 5.8 +/- 0.2 (basal) to 5.2 +/- 0.3 and 4.4 +/- 0.3 mmol/l by 30 and 90 min, respectively (P < 0.01). Arterial plasma insulin levels and the hepatic portal-arterial difference in plasma insulin decreased (P < 0.01) from 78 +/- 18 and 90 +/- 24 to 24 +/- 6 and 12 +/- 12 pmol/l over the first 30 min of the test period and decreased to 18 +/- 6 and 0 pmol/l by 90 min, respectively. The arterial glucagon levels and the hepatic portal-arterial difference in plasma glucagon increased from 43 +/- 5 and 4 +/- 2 to 51 +/- 5 and 10 +/- 5 ng/l by 30 min (P < 0.05) and to 79 +/- 16 and 31 +/- 15 ng/l by 90 min (P < 0.05), respectively. In euglycemic dogs, the arterial plasma glucose level remained at 5.9 +/- 0.1 mmol/l, and the NHGO decreased from 10 +/- 0.6 to -3.3 +/- 0.6 pmol x kg(-1) x min(-1) (180 min). The insulin and glucagon levels and the hepatic portal-arterial differences remained constant. In hyperglycemic dogs, the arterial plasma glucose level increased from 5.9 +/- 0.2 to 6.2 +/- 0.2 mmol/l by 30 min, and the NHGO decreased from 10 +/- 1.7 to 0 pmol x kg(-1) x min(-1) by 30 min. The arterial plasma insulin levels and the hepatic portal-arterial difference in plasma insulin increased from 60 +/- 18 and 78 +/- 24 to 126 +/- 30 and 192 +/- 42 pmol/l by 30 min, after which they averaged 138 +/- 24 and 282 +/- 30 pmol/l, respectively. The arterial plasma glucagon levels and the hepatic portal-arterial difference in plasma glucagon decreased slightly from 41 +/- 7 and 4 +/- 3 to 34 +/- 7 and 3 +/- 2 ng/l during the test period. These data show that the alpha- and beta-cells of the pancreas respond as a coupled unit to very small decreases in the plasma glucose level.

Alanine↗

PubMed2001

Glucokinase gene locus transgenic mice are resistant to the development of obesity-induced type 2 diabetes.

Transgenic mice that overexpress the entire glucokinase (GK) gene locus have been previously shown to be mildly hypoglycemic and to have improved tolerance to glucose. To determine whether increased GK might also prevent or diminish diabetes in diet-induced obese animals, we examined the effect of feeding these mice a high-fat high-simple carbohydrate low-fiber diet (HF diet) for 30 weeks. In response to this diet, both normal and transgenic mice became obese and had similar BMIs (5.3 +/- 0.1 and 5.0 +/- 0.1 kg/m2 in transgenic and non-transgenic mice, respectively). The blood glucose concentration of the control mice increased linearly with time and reached 17.0 +/- 1.3 mmol/l at the 30th week. In contrast, the blood glucose of GK transgenic mice rose to only 9.7 +/- 1.2 mmol/l at the 15th week, after which it returned to 7.6 +/- 1.0 mmol/l by the 30th week. The plasma insulin concentration was also lower in the GK transgenic animals (232 +/- 79 pmol/l) than in the controls (595 +/- 77 pmol/l), but there was no difference in plasma glucagon concentrations. Together, these data indicate that increased GK levels dramatically lessen the development of both hyperglycemia and hyperinsulinemia associated with the feeding of an HF diet.

Animals↗

PubMed2000

Prognostic significance of CD56 expression for ALK-positive and ALK-negative anaplastic large-cell lymphoma of T/null cell phenotype.

Anaplastic large cell lymphoma (ALCL) is a distinct entity of non-Hodgkin lymphoma, characterized by a proliferation of pleomorphic large lymphoid cells that express CD30. Recent studies have found that a subset of ALCL aberrantly expresses a chimeric anaplastic lymphoma kinase (ALK) protein as a result of t(2;5)(p23;q35) or variant translocations. ALK-positive ALCLs feature good prognosis, but some of them lead to poor outcomes. Since CD56 is expressed in some ALCLs, its clinical significance was examined in a series of T/null cell type ALCLs. Of 143 patients, 83 (58%) showed ALK-positive staining, and of 140 patients, 25 (18%) expressed CD56. The ALK-positive subgroup was characterized by a younger age of onset (P <.0001), lower serum lactate dehydrogenase level (P =.01), better performance status (P =.03), less frequent extranodal involvement (P =.01), lower international prognostic index (IPI) categories (P =.002), and superior survival (P =.0009) in comparison with the ALK-negative group, suggesting that ALK is a specific marker defining a distinct subtype. CD56(+) cases showed a significantly poor prognosis overall (P =.002) as well as in both ALK-positive and ALK-negative subgroups (P =.02 and P =.04, respectively). Multivariate analysis confirmed that CD56 is independent of other prognostic factors, including IPI. Although CD56(+) cases showed a higher incidence of bone involvement, no other differences in clinicopathologic parameters were found between the CD56(+) and CD56(-) groups. These findings suggest that CD56 is not a marker to identify a distinct subtype of ALCL, but a strong clinical prognostic factor. Effective therapeutic approaches should be explored for high-risk ALCL patients, who can be identified by means of a prognostic model, including CD56.

Adolescent↗

PubMed2000

Tumor necrosis factor alpha 5'-flanking region, tumor necrosis factor receptor II, and HLA-DRB1 polymorphisms in Japanese patients with rheumatoid arthritis.

OBJECTIVE: New polymorphisms affecting transcriptional activity were recently reported within the 5'-flanking region of the tumor necrosis factor alpha gene (TNFalpha). In addition, genome-wide linkage screening indicated 1p36 as one of the candidate chromosomal regions where the TNF receptor II gene (TNFR2) is located. In the present study, HLA-DRB1, TNFalpha promoter, and TNFR2 genotypes were determined to examine whether these polymorphisms are associated with rheumatoid arthritis (RA), either independently or in combination. METHODS: Genotypes of HLA-DRB1, TNFalpha upstream promoter, and TNFR2 codon 196 were determined in 545 Japanese patients with RA and 265 healthy controls. Association of these genes with susceptibility to RA was analyzed both independently and after stratification by one of the genotypes. RESULTS: As expected, the HLA-DRB1 shared epitope was strongly associated with RA. In addition, a significant negative association of DRB1*1405 and 1302 was observed. Furthermore, DRB1*1405 was suggested to possess a protective role for the development of RA in DRB1*0405-positive individuals. A significant increase in TNFalpha-U02 in RA was detected, which was not independent of DRB1*0405. A significant association was not observed between TNFR2-196M/R polymorphism and RA. CONCLUSION: Among the 3 genes examined in this study, HLA-DRB1 was considered to be most strongly associated with RA.

Antigens, CD↗

PubMed2000

Cognitive and neurophysiological evaluation of Japanese dyslexia.

Seven Japanese dyslexic boys were evaluated as to their pedagogic performance on the pupil rating scale (PRS), and psychological and neurophysiological characteristics. One of them suffered from severe English dyslexia despite that his Japanese dyslexia was feeble. PRS did not successfully reveal their reading difficulties. Psychological examination (WISC-R and K-ABC) revealed their cognitive dysfunction, but the results were heterogeneous. The Token test was most useful for detecting their poor reading comprehension. Electroencephalogram (EEG) coherence analysis showed high inter- and intra-hemispheric values. These findings may imply hyperconnectivity of the cerebral white matter in dyslexia. We assumed that the Token test demonstrates the discrepancy between reading and hearing comprehension best of all among these psychological tests and that connectivity between non-functional cortical lesions remains in dyslexic children.

Adolescent↗

PubMed2000

Mast cell tryptase from pig lungs triggers infection by pneumotropic Sendai and influenza A viruses. Purification and characterization.

A novel trypsin-type serine proteinase, which processes the precursors of the envelope fusion glycoproteins of pneumotropic Sendai and human influenza A viruses, was purified to homogeneity from pig lungs. On SDS/PAGE, the purified enzyme gave a protein band corresponding to about 32 kDa, and has an apparent molecular mass of 120 kDa, as determined by gel permeation chromatography. Immunohistochemical staining with antibodies against this enzyme revealed that the enzyme is located in pig lung mast cells. The N-terminal 44-amino-acid sequence of the enzyme exhibits about 80% identity with those of mast cell tryptases from other species. Of the inhibitors tested, di-isopropyl fluorophosphate, antipain, leupeptin, benzamidine and a few proteinaceous inhibitors, such as mucus protease inhibitor and aprotinin, inhibited this enzyme activity. Heparin stabilized the enzyme, but high-ionic-strength conditions did not, unlike for human mast cell tryptase. The purified enzyme efficiently processed the fusion glycoprotein precursor of Sendai virus and slowly processed hemagglutinin of human influenza A virus, and triggered the infectivity of Sendai virus in a dose-dependent manner, although human mast cell tryptase beta and rat mast cell tryptase (rat MCP-7) from lungs did not process these fusion glycoproteins at all. These results suggest that mast cell tryptase in pig lungs is the possible trigger of the pneumotropic virus infections.

Amino Acid Sequence↗

PubMed2000

Phosphoenolpyruvate carboxykinase is necessary for the integration of hepatic energy metabolism.

We used an allelogenic Cre/loxP gene targeting strategy in mice to determine the role of cytosolic phosphoenolpyruvate carboxykinase (PEPCK) in hepatic energy metabolism. Mice that lack this enzyme die within 3 days of birth, while mice with at least a 90% global reduction of PEPCK, or a liver-specific knockout of PEPCK, are viable. Surprisingly, in both cases these animals remain euglycemic after a 24-h fast. However, mice without hepatic PEPCK develop hepatic steatosis after fasting despite up-regulation of a variety of genes encoding free fatty acid-oxidizing enzymes. Also, marked alterations in the expression of hepatic genes involved in energy metabolism occur in the absence of any changes in plasma hormone concentrations. Given that a ninefold elevation of the hepatic malate concentration occurs in the liver-specific PEPCK knockout mice, we suggest that one or more intermediary metabolites may directly regulate expression of the affected genes. Thus, hepatic PEPCK may function more as an integrator of hepatic energy metabolism than as a determinant of gluconeogenesis.

Alleles↗

PubMed2000

Combined intraportal infusion of acetylcholine and adrenergic blockers augments net hepatic glucose uptake.

Portal glucose delivery in the conscious dog augments net hepatic glucose uptake (NHGU). To investigate the possible role of altered autonomic nervous activity in the effect of portal glucose delivery, the effects of adrenergic blockade and acetylcholine (ACh) on hepatic glucose metabolism were examined in 42-h-fasted conscious dogs. Each study consisted of an equilibration (-120 to -20 min), a control (-20 to 0 min), and a hyperglycemic-hyperinsulinemic period (0 to 300 min). During the last period, somatostatin (0.8 microg. kg(-1). min(-1)) was infused along with intraportal insulin (1.2 mU. kg(-1). min(-1)) and glucagon (0.5 ng. kg(-1). min(-1)). Hepatic sinusoidal insulin was four times basal (73 +/- 7 microU/ml) and glucagon was basal (55 +/- 7 pg/ml). Glucose was infused peripherally (0-300 min) to create hyperglycemia (220 mg/dl). In test protocol, phentolamine and propranolol were infused intraportally at 0.2 microg and 0.1 microg. kg(-1). min(-1) from 120 min on. ACh was infused intraportally at 3 microg. kg(-1). min(-1) from 210 min on. In control protocol, saline was given in place of the blockers and ACh. Hyperglycemia-hyperinsulinemia switched the net hepatic glucose balance (mg. kg(-1). min(-1)) from output (2.1 +/- 0.3 and 1.1 +/- 0.2) to uptake (2.8 +/- 0.9 and 2.6 +/- 0.6) and lactate balance (micromol. kg(-1). min(-1)) from uptake (7.5 +/- 2.2 and 6.7 +/- 1.6) to output (3.7 +/- 2.6 and 3.9 +/- 1.6) by 120 min in the control and test protocols, respectively. Thereafter, in the control protocol, NHGU tended to increase slightly (3.0 +/- 0.6 mg. kg(-1). min(-1) by 300 min). In the test protocol, adrenergic blockade did not alter NHGU, but ACh infusion increased it to 4.4 +/- 0.6 and 4.6 +/- 0.6 mg. kg(-1). min(-1) by 220 and 300 min, respectively. These data are consistent with the hypothesis that alterations in nerve activity contribute to the increase in NHGU seen after portal glucose delivery.

Acetylcholine↗

PubMed2000

[Clinical study on risk management for dental implant treatment--Part 1. Clinical retrospective study on the medically compromised patients at clinic for oral implant].

A retrospective study on medically compromised patients was made using 1,000 outpatients who visited the Clinic for Oral Implant, University Hospital, Faculty of Dentistry, Tokyo Medical and Dental University between April 1995 and June 1998. The results were as follows: 1. 35.3% (353 patients: 140 males and 213 females) of the outpatients were medically compromised. 2. The greatest number of medically compromised patients was in the 50-59 age group (118 cases), followed by those in the 40-49 and 60-69 age groups. 3. The highest ratio of medically compromised patients was in the 60-69 age group (48.2%), followed by those in the 70-79 and 50-59 age groups. 4. Among the 353 patients, 96 (27.2%) underwent surgical treatment such as insertion of implant (68 cases), removal of implant, extraction of tooth, and free gingival graft. 5. Among the 68 patients who underwent insertion of implant, in a classification by type of disease, the patients with cardiovascular diseases were the most numerous (33.9%), followed by metabolic and digestive tract diseases. 6. All surgical treatments of implant insertion were performed under local anesthesia, while monitoring cardiac and respiratory function, and SpO2. Among the 68 patients, 9 underwent operation under intravenous sedation and 2 under nitrous oxide inhalation sedation. All 11 patients had hypertension. The results suggested that identification of preoperative risk factors, precise recognition of general condition, and establishment of control system are important to manage medically compromised patients for dental implant treatment.

Adult↗

PubMed2000

[Distribution in normal subjects of performance in Token test: a basic study for the diagnosis of learning disabilities].

For the diagnosis of specific reading disorder (SRD) we studied the distribution in 187 elementary school children of the scores of Token test. Token test was performed under two conditions: listening and reading by presenting the same sentences. The diagnosis required a normal score under the listening condition, an abnormally low score under the reading condition and significantly large discrepancy between them. This test is valid and convenient for the diagnosis of SRD.

Acoustic Stimulation↗

PubMed2000

[A patient with recurrent uterine cervical cancer successfully treated by combined modality therapy including local injection of anticancer agents based on CDDP].

The patient was a 77-year-old woman who had undergone total abdominal hysterectomy and bilateral salpingo-oophorectomy following the diagnosis of uterine cervical cancer at the age of 57. A recurrent tumor was detected on the anterior surface of the right iliopsoas muscle and fine needle aspiration of the tumor revealed squamous cell carcinoma. A needle was inserted into the tumor under transabdominal ultrasound guidance, and anticancer agents, chiefly cis-diamminedichloroplatinum [II] (CDDP), were injected. The patient also received systemic chemotherapy (CAP therapy) and radiotherapy. Subsequently, computed tomography showed a 73% reduction in the size of the tumor. A mass 7 cm in diameter was still present on the anterior surface of the iliopsoas after treatment, but tumor markers fell to normal levels. The patient is presently receiving UFT (600 mg/day) as maintenance therapy. At 48 months after recurrence, there has been no increase in the tumor size or tumor marker levels, and the performance status is grade 0. In conclusion, a good outcome was achieved by local injection of anticancer agents combined with systemic chemotherapy and radiotherapy, and there were few side effects.

Aged↗

PubMed1999

Dual roles for glucokinase in glucose homeostasis as determined by liver and pancreatic beta cell-specific gene knock-outs using Cre recombinase.

Glucokinase (GK) gene mutations cause diabetes mellitus in both humans and mouse models, but the pathophysiological basis is only partially defined. We have used cre-loxP technology in combination with gene targeting to perform global, beta cell-, and hepatocyte-specific gene knock-outs of this enzyme in mice. Gene targeting was used to create a triple-loxed gk allele, which was converted by partial or total Cre-mediated recombination to a conditional allele lacking neomycin resistance, or to a null allele, respectively. beta cell- and hepatocyte-specific expression of Cre was achieved using transgenes that contain either insulin or albumin promoter/enhancer sequences. By intercrossing the transgenic mice that express Cre in a cell-specific manner with mice containing a conditional gk allele, we obtained animals with either a beta cell or hepatocyte-specific knock-out of GK. Animals either globally deficient in GK, or lacking GK just in beta cells, die within a few days of birth from severe diabetes. Mice that are heterozygous null for GK, either globally or just in the beta cell, survive but are moderately hyperglycemic. Mice that lack GK only in the liver are only mildly hyperglycemic but display pronounced defects in both glycogen synthesis and glucose turnover rates during a hyperglycemic clamp. Interestingly, hepatic GK knock-out mice also have impaired insulin secretion in response to glucose. These studies indicate that deficiencies in both beta cell and hepatic GK contribute to the hyperglycemia of MODY-2.

Albumins↗

PubMed1999

Mice lacking alpha-calcitonin gene-related peptide exhibit normal cardiovascular regulation and neuromuscular development.

alpha-Calcitonin gene-related peptide (alphaCGRP) is a pleiotropic peptide neuromodulator that is widely expressed throughout the Central and peripheral nervous systems. CGRP has been implicated in a variety of physiological processes including peripheral vasodilation, cardiac acceleration nicotinic acetylcholine receptor (AChR) synthesis and function, testicular descent, nociception, carbohydrate metabolism, gastrointestinal motility, neurogenic inflammation, and gastric acid secretion. To provide a better understanding of the physiological role(s) mediated by this peptide neurotransmitter, we have generated alphaCGRP-null mice by targeted modification in embryonic stem cells. Mice lacking alpha CGRP expression demonstrate no obvious phenotypic differences from their wild-type littermates. Detailed analysis of systemic cardiovascular function revealed no differences between control and mutant mice regarding heart rate and blood pressure under basal or exercise-induced conditions and subsequent to pharmacological manipulation. Characterization of neuromuscular junction in morphology including nicotinic receptor localization, terminal sprouting in response to denervation, developmental regulation of AChR subunit expression, and synapse elimination also revealed no differences in alphaCGRP-deficient animals. These results suggest that alphaCGRP is not required for the systemic regulation of cardiovascular hemodynamics or development of the neuromuscular junction.

Aging↗

PubMed1999

Identification of the gene variations in human CD22.

CD22, a member of the immunoglobulin superfamily, is a B-cell transmembrane glycoprotein that acts as an accessory-signaling component of the B-cell antigen receptor (BCR). Recent evidence indicating the role of CD22 as a negative regulator of BCR signal transduction prompted us to test the possibility that genetic variations of human CD22 may be associated with autoimmune diseases. In this study, variation screening of the entire CD22 coding region was performed, and possible association with rheumatic diseases was tested, using the genomic DNA from 207 healthy Japanese individuals, 68 patients with systemic lupus erythematosus (SLE), and 119 patients with rheumatoid arthritis (RA). Through the variation screening, seven non-synonymous and four synonymous substitutions were identified. In addition, single base substitutions were found in two introns flanking exon-intron junctions. Among these variations, Q152E substitution within the second extracellular domain was observed with a marginally higher frequency in the patients with SLE (3/68, 4.4%) than that in healthy individuals (1/207, 0.5%) (P=0.048. SLE vs healthy individuals), although this difference was no longer significant after correction for the number of comparisons (Pc=0.62). No significant association was observed between any of the variations and RA. These findings indicate that a number of genetic variants are present in CD22, and suggest that CD22 could be considered a candidate for the susceptibility genes to autoimmune diseases.

Adolescent↗