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At least 55 records · Page 3Linked to original sources
PubMed1998

Tissue distribution, cellular source, and structural analysis of rat immunoreactive uroguanylin.

Uroguanylin, a member of the guanylin peptide family, acts on guanylyl cyclase C (GC-C) to regulate intestinal and renal fluid and electrolyte transport through the second messenger, cGMP. Using an antiserum raised against synthetic rat uroguanylin, we established an RIA and identified three endogenous molecular forms in the intestine and kidney: a 15-amino acid uroguanylin, an 18-amino acid uroguanylin that is a monobasic processing product, and a 9.4-kDa prouroguanylin. Prouroguanylin is the major molecular form in these two tissues, whereas only 15-amino-acid uroguanylin is present in the urine. Rat uroguanylin is most abundant in the proximal small intestine, its content decreasing toward the colon. Uroguanylin is present immunohistochemically in the endocrine cells in the intestine and stomach, B cells in the pancreatic islets, and tubular epithelial cells in the kidney. Uroguanylin has a widespread tissue distribution and is located in cells that function in an endocrine, paracrine, and/or luminocrine (luminal secretion) fashion. Uroguanylin may have physiological functions other than the regulation of fluid and electrolyte transport in the intestine and kidney.

Amino Acid Sequence↗
PubMed1998

[Clinical and neuroradiological evaluation of the long-term surviving siblings of Sanfilippo syndrome A type].

The siblings of Sanfilippo syndrome type A (MPS III A) have been reported. The relationship of their parents was the first cousins. Case 1: A 30-year-old Japanese man was hospitalized because of gait disturbance and mental impairment. His early somatic and mental development was normal until 9 years of age when mental deterioration had developed. Speech and gait disturbances and double incontinence occurred at 18 years of age. He could not walk at 21 years of age. Those symptoms were slowly progressive. Case 2: A 32-year-old Japanese man, the elder brother of case 1, had a similar clinical history to that of case 1. Their neurological findings revealed mental impairment, coarse face, positive forced grasp and sucking reflexes, and pyramidal signs. Lumbar X-ray showed platyspondylitis, compression fracture of L 1 and osteoporotic changes. Brain MRI of both cases showed brain atrophy, ventricular dilatation and abnormal high intensity signals near the posterior horn of the lateral ventricles on T2 weighted image. Low perfusion images of fronto-parietal regions were seen in the early phase of SPECT using 123I-IMP. This siblings were diagnosed as Sanfilippo syndrome type A because of heparan sulfaturia and deficiency of heparan sulfate sulfamidase of the lymphocytes. Average life span of Sanfilippo syndrome type A is not so long but the age of our cases is over 30 years of age.

Adult↗
PubMed1998

[Guanylin family: new intestinal peptides regulating salt and water homeostasis].

Guanylin and uroguanylin are novel peptides that are first isolated from rat jejunum and opossum urine, respectively. They bind to and activate guanylyl cyclase-C (GC-C) to regulate intestinal and renal fluid and electrolyte transport through the second messenger, cyclic GMP. Heat-stable enterotoxins produced by pathogenic bacteria have close structural similarities to guanylin and uroguanylin, and they use this mimicry to act on GC-C, causing life-threatening secretory diarrhea. Guanylin primarily is restricted to the intestine, whereas uroguanylin is present in the stomach kidney, lung and pancreas in addition to intestine. Guanylin and uroguanylin in the intestine are secreted into the lumen and blood in response to sodium chloride administration. These peptides will function in salt and water transport in the intestine and kidney by luminocrine and/or endocrine actions. Guanylin peptide family links the intestine with the kidney and could play the physiological roles in the control of water and electrolyte balance.

Amino Acid Sequence↗
PubMed1997

Detection of three transthyretin gene mutations in familial amyloidotic polyneuropathy by analysis of DNA extracted from formalin-fixed and paraffin-embedded tissues.

We identified three different missense mutations of the transthyretin (TTR) gene in three Japanese patients with familial amyloidotic polyneuropathy by analysis of their DNAs extracted from formalin-fixed and paraffin-embedded tissues. Patient 1 carried the TTR methionine-30 (Met) mutation (G to A transition at position 1679). DNA sequencing analysis of the TTR gene from patient 2 showed a G to T transversion at position 3830 in exon 3, resulting in an amino acid replacement of serine-50 (Ser) with isoleucine (Ile). Patient 3 had the novel mutation (G to T transversion at position 7314) in exon 4, resulting in an amino acid replacement of alanine-109 (Ala) with Ser. We established DNA diagnostic methods for detecting TTR Ile50 by polymerase chain reaction (PCR)-induced mutation restriction analysis and for TTR Ser109 by PCR-restriction fragment length polymorphism. Gene analysis of archival paraffin-embedded tissues is useful for the precise diagnosis of FAP and for clarifying its molecular pathogenesis in patients for whom fresh genomic DNA is not available.

Aged↗
PubMed1997

Benefit of simultaneous rhG-CSF and methylprednisolone 'pulse' therapy for methotrexate-induced bone marrow failure in rheumatoid arthritis.

A 74-year-old female with seropositive rheumatoid arthritis developed severe bone marrow failure after the treatment with very low-dose methotrexate (5 mg/week for 3 weeks). Hematological data showed severe pancytopenia with 0% neutrophils and bone marrow disclosed thoroughly hypocellular marrow. Shortly after the treatment with simultaneous rhG-CSF and methylprednisolone 'pulse' therapy, pancytopenia was ameliorated and bone marrow examination revealed hypercellular marrow with increasing maturation of hematopoietic components. Hematological parameters were maintained within the normal range with a low dose of prednisolone.

Aged↗
PubMed1997

Urine and plasma levels of uroguanylin and its molecular forms in renal diseases.

Uroguanylin activates the intestinal and possibly the renal guanylate cyclase C receptor, and stimulates Cl- secretion. We developed a sensitive radioimmunoassay (RIA) for human uroguanylin and measured its concentration in the urine and plasma. Twenty-four-hour urinary excretion of immunoreactive (ir-) uroguanylin for persons with a high-salt diet (10 g/day) was 137.8 +/- 14.4 pmol/day, significantly higher than that for persons with a low-salt diet (7 g/day, 95.1 +/- 16.3 pmol/day, P < 0.05). There were significantly positive correlations between the urinary excretion of ir-uroguanylin and Na+, Cl-, K+ or cyclic GMP (cGMP). We demonstrated the presence of messenger RNA of guanylate cyclase C in the medulla of human kidney. The concentration of plasma ir-uroguanylin significantly correlated with that of serum creatinine (r = 0.71, P < 0.001). Biologically active uroguanylin-16 accounted for 99% of the endogenous uroguanylin molecules in normal urine and 60% in plasma, the remainder being the 10 kDa precursor. The precursor content increased in the urine and plasma as the severity of renal impairment increased. These findings suggest that bioactive uroguanylin-16 is involved in the regulation of electrolyte homeostasis and that the kidney participates in the metabolism and excretion of uroguanylin.

Circadian Rhythm↗
PubMed1996

Cloning and characterization of a cDNA encoding a precursor for human uroguanylin.

Uroguanylin, a member of the guanylin peptide family, is an endogenous activator of intestinal guanylate cyclase (GC-C). A cDNA encoding a precursor for human uroguanylin was cloned from a human colon cDNA library and sequenced. The precursor was 112 amino acids long and included a signal peptide at the N-terminus and the human uroguanylin sequence at the C-terminus. RNA blot analysis and the reverse transcription-polymerase chain reaction (RT-PCR) showed that human uroguanylin mRNA is expressed in the stomach and intestine. Uroguanylin, as well as guanylin, may be a potent physiological regulator of intestinal fluid and electrolyte transport.

Amino Acid Sequence↗
PubMed1996

Ampullary somatostatinoma in a patient with von Recklinghausen's disease.

We report a case of somatostatinoma of the ampulla of Vater associated with von Recklinghausen's disease in a 44-year-old woman. On admission the patient was jaundiced, and percutaneous Cholangio-drainage was performed. Cholangiography revealed stenosis of the common bile duct at the lower end Duodenoscopy showed a yellowish tumor of the ampulla of Vater, and the biopsy specimens showed no malignant cells. Pylorus-preserving pancreaticoduo-denectomy was performed. Histologically, the tumor was composed of small round cells with a solid or trabecular pattern and with multiple psammoma bodies. Immunohistochemical examination showed that the tumor cells stained for somatostatin. Genomic examination showed neither K-ras nor p53 gene mutations of the resected specimen.

Adult↗
PubMed1996

Comprehensive analysis of HLA genes in Takayasu arteritis in Japan.

To identify an HLA-linked susceptibility gene to Takayasu's arteritis, comprehensive analysis of HLA genes was performed. By serologic HLA typing, positive associations of Takayasu's arteritis with HLA-B52 and B39 were observed. The DNA typing of HLA-B gene and class II genes (DRB1, DQA1, DPB1) showed positive associations of the disease with HLA-B52, B39.2, DRB1 * 1502 and DPB1 * 0901, confirming in part the serologic observations. Comparison of odds ratio for the risk of disease revealed that HLA-B52 and B39.2 were primarily involved in the susceptibility, while the associations with DRB1 * 1502 and DPB1 * 0901 were suggested to reflect a strong linkage disequilibrium of these class II alleles with HLA-B52 in the Japanese population. Sequencing analyses of HLA-B52 and B39.2 from patients confirmed that they were B 5201 and B 3902, respectively. Comparison of amino acid sequences of these disease-associated HLA-B alleles identified critical amino acid residues of the HLA-B molecule, Glu and Ser at 63rd and 67th positions, respectively, which may determine the susceptibility to Takayasu's arteritis via binding and presenting a yet unknown disease-related antigen.

Alleles↗
PubMed1996

DNA typing of the HLA-A gene: population study and identification of four new alleles in Japanese.

With the use of polymerase chain reaction (PCR) and sequence-specific oligonucleotide probe (SSOP), we established a DNA typing method of the HLA-A locus. A pair of primers to amplify the highly polymorphic region of HLA-A gene including exon 2 and exon 3 was designed and the amplified DNAs were hybridized with 91 types of 32P labeled SSOPs. This method allowed discrimination of all known HLA-A alleles except for two combinations, A*0201 or A*0209 and A*0207 or A*0215N, which have identical sequences in exon 2 and exon 3. Another pair of primers was designed for amplification of exon 4 and the PCR products were hybridized with 5 SSOPs to distinguish A*0201 and A*0207 from A*0209 and A*0215N, respectively. In this study, 81 B-lymphoblastoid cell lines (BLCL) homozygous for HLA and 553 unrelated healthy Japanese individuals were determined for their HLA-A genotypes. Based on the genotyping results, frequency of HLA-A alleles and linkage disequilibrium between HLA-A and HLA-B in the Japanese population were investigated. In addition, four new HLA-A alleles were identified and their nucleotide sequences in exon 2 and exon 3 were determined to confirm the typing results.

Alleles↗
PubMed1996

Significance of antibodies to streptococcal M protein in psoriatic arthritis and their association with HLA-A*0207.

Psoriatic arthritis (PA) is an immune disease associated with HLA-A2 in the Japanese population. To investigate mechanisms the association between HLA-A2 and PA, we examined in vivo immune responsiveness to Streptococcus pyogenes. Recombinant M proteins for the subtype specific N-terminal half (AB region) and conserved C-terminal half (C region) were produced separately. IgG antibody level against each region was measured by ELISA in 31 PA patients, 88 patients with psoriasis vulgaris, 6 patients with rheumatoid arthritis and 77 healthy controls. We found that IgG antibody levels against the C region were markedly higher in the PA patient group than in the other disease groups or controls. Further, IgG antibody levels were higher in PA patients with spondylitis and polyarticular arthritis than in PA patients with rheumatoid-like arthritis and arthritis mutilans. In contrast, no significant difference in the IgG antibody levels against the AB region was observed among the tested groups. HLA-A2 DNA typing showed that HLA-A*0207 was associated with PA (RR = 17.6; pcorr < 0.01) and the IgG antibody responses to the C region correlated well with the presence of HLA-A*0207. These results suggest that streptococcal infection may be involved in the pathogenesis of PA by participating in the HLA-linked immune responsiveness.

Antibodies, Bacterial↗
PubMed1996

Determination of total hydroxyproline and proline in human serum and urine by HPLC with fluorescence detection.

A method to measure total hydroxyproline (Hyp) and proline (Pro) in human serum and urine by HPLC was developed. Hyp and Pro in acid hydrolysates of serum and urine were derivatized with 4-(5,6-dimethoxy-2-phthalimidinyl)phenysulfonyl chloride after treatment with o-phthaladehyde and cleanup on Bond Elut C18 column. The derivatives of imino acids were separated on a reversed phase column by gradient elution with acetonitrile and phosphate buffer (1 mmol/l, pH 7) and detected by fluorescence measurement at 315 nm (excitation) and 385 nm (emission). Detection limits for both Hyp and Pro were 10 fmol per injection. The within-day and day-to-day relative standard deviations for Hyp and Pro in serum and urine were less than 3.19%. The recoveries of Hyp and Pro added to serum and urine were about 100%. The present method was applied to determine total Hyp and Pro in serum and urine from normal subjects and patients with chronic renal failure.

Adult↗
PubMed1996

Tissue distribution and plasma concentration of human guanylin.

Guanylin, a peptide homologue of the bacterial heat-stable enterotoxins, is an endogenous activator of guanylate cyclase C (GC-C). We determined the tissue content and plasma concentration of human guanylin, and its cellular source in the intestine. Human guanylin is distributed widely from the duodenum to the rectum, the highest content being in the ileum and proximal colon. The plasma concentration of immunoreactive guanylin in the normal individuals tested was 30.3 +/- 3.7 fmol/ml (mean +/- SE) and that in patients with chronic renal failure was elevated with increasing serum creatinine concentration. Guanylin immunoreactivity was detected in the villus epithelial cells in the small intestine and these guanylin-containing cells were increased in number along the cephalocaudal axis of the gut. Guanylin was also present in Paneth cells in the small intestine and superficial epithelial cells in the large intestine. Guanylin mRNA was detected in the intestine by the reverse transcription-polymerase chain reaction. Guanylin may have paracrine action on neighboring enterocytes, activating intestinal guanylate cyclase and thereby regulating intestinal fluid as well as electrolyte transport through the second messenger, cyclic GMP.

Adolescent↗
PubMed1996

[Thoracoscopic extended thymectomy in conjunction with a collar incision of the neck for cases of myasthenia gravis].

Extended thymectomy in conjunction with a collar incision of the neck was performed thoracoscopically for a 64-year-old women with myasthenia gravis. Although this patient had Osserman type II B myasthenia gravis not associated with a thymoma, the clinical symptoms were alleviated after the surgery. Although this surgical procedure has the disadvantage such as of being time-consuming, it also has various advantages such as: 1) extended thymectomy can be performed without a midsternotomy, 2) the wound is small and not prominent, 3) surgical invasiveness is slight, and 4) postoperative pain is mild. This method was considered to be an extremely useful surgical method which should be used in future for cases of myastenia gravis not associated with a thymoma.

Endoscopy↗
PubMed1995

Differences in MHC class I self peptide repertoires among HLA-A2 subtypes.

To investigate how single amino acid substitutions in MHC class I molecules affect differences in peptide repertoires, we eluted and sequenced the naturally processed peptides from three HLA-A2 subtypes (HLA-A*0204, -A*0206, and -A*0207) that differ by a single amino acid residue substitution each with HLA-A*0201 at the floor of the binding groove. Allele-specific peptide motifs for each HLA-A2 subtype substantially differed from that of HLA-A*0201 in the dominant anchor residues. The relative signal intensities for 18 self peptides, determined by mass spectrometry, precisely reflected these peptide motifs. Some overlapping peptides were isolated from both HLA-A*0201 and a single HLA-A2 variant, but no peptide was ubiquitously found across all variants. To rationalize the differences in peptide motifs, possible conformations of each allele were computer modeled by energy minimization calculations based on the reported crystal structure of HLA-A*0201. According to our models, the differences in peptide motifs could be explained by substituted-residue-driven conformational changes for each MHC-peptide complex. These results demonstrate the fine differences between HLA-A2 subtype self peptide repertoires and contribute to the prediction of antigenic peptides.

Amino Acid Sequence↗
PubMed1995

Isolation and sequence determination of 6- and 8-kDa precursors of human neutrophil peptides from bone marrow, plasma and peripheral blood neutrophils.

Human neutrophil peptides (HNPs) are 29 to 30 amino acid antimicrobial peptides localized in the azulophil granules in neutrophils. We isolated endogenous molecular forms of HNPs from normal human bone marrow, plasma and peripheral blood neutrophils and determined their primary structures to investigate their post-translational processing. HNPs initially are synthesized as 94 amino acid precursors that produce 75 amino acid pro-HNPs by cleavage of a signal peptide. The majority of pro-HNPs was processed to 56 amino acid intermediates by preaspartate proteolytic cleavage in the bone marrow then to mature HNPs in peripheral blood neutrophils. Part of pro-HNPs was released into the plasma, in which they constituted 25-30% of the HNP molecules. Pro-HNPs and their mRNAs were detected both in peripheral blood neutrophils and bone marrow. Identification of the post-translational processing products of HNPs should provide a better understanding of the biosynthesis of the peptides.

Adult↗