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Biomedical subjects

M Nakazato

Publications and source records attributed to M Nakazato.

At least 127 records · Page 7Linked to original sources
PubMed1995

Change in variant transthyretin levels in patients with familial amyloidotic polyneuropathy type I following liver transplantation.

Three patients with familial amyloidotic polyneuropathy (FAP) type I underwent liver transplantation from heart-beating cadaveric donors. Since 2 patients underwent blood transfusion during the operation, variant transthyretin (TTR) levels in the plasma did not decrease time dependently. However, in 1 patient without blood transfusion variant TTR levels decreased in a time dependent manner and plasma half life of variant TTR was calculated to be 2.1 days. Total protein, normal, and variant TTR levels in cerebrospinal fluid (CSF) remained unchanged after liver transplantation.

Adult↗
PubMed1995

[A study of defensins in bronchoalveolar lavage fluid in patients with diffuse panbronchiolitis].

We estimated defensins, antimicrobial and cytotoxic peptides localized in azurophil granules of neutrophils, in bronchoalveolar lavage fluid (BALF) in patients with diffuse panbronchiolitis (DPB). BALF from DPB patients contained a higher concentration of defensins than those from patients with idiopathic pulmonary fibrosis and healthy volunteers. A significant correlation was observed between the concentration of defensins and the number of neutrophils, the concentration of interleukin-8 or neutrophil elastase in BALF of DPB patients. An immunohistochemical defensins in neutrophils and mucinous exudates in the airways and in the surface of bronchiolar epithelial cells. After treatment with macrolide antibiotics, significant reductions in the concentrations of defensins, IL-8 and neutrophil numbers in BALF of DPB patients were observed. These findings suggest that the lung injury in DPB could be caused by defensins released by neutrophils accumulated in the airways.

Adult↗
PubMed1995

Familial hypocalciuric hypercalcemia associated with mutation in the human Ca(2+)-sensing receptor gene.

Familial hypocalciuric hypercalcemia (FHH) is generally characterized by lifelong hypercalcemia without hypercalciuria and is inherited in an autosomal dominant manner. Affected individuals show abnormal parathyroid and renal responses to changes in the extracellular calcium concentration. A Japanese FHH family was screened for mutations in the Ca(2+)-sensing receptor gene by the polymerase chain reaction and single strand conformation polymorphism. The proband with hypercalcemia showed an abnormal pattern in exon 1 of the gene, whereas her two sisters with normocalcemia showed a normal pattern. The consanguineous parents with borderline serum calcium concentrations showed both patterns. Nucleotide sequence analysis identified a G-->C point mutation at nucleotide 118 that resulted in the conversion of the normal codon for proline into a codon for alanine at amino acid 40 (numbered according to the bovine complementary DNA). The proband was homozygous for the mutation, and the parents were heterozygous. These results imply that this mutation in the human Ca(2+)-sensing receptor gene causes FHH and that the dosage of the gene defect determines disease phenotype.

Adult↗
PubMed1995

[Influence of aging on electrogustometric threshold].

Electrogustometric testing was carried out, with one researcher examining the electrogustometric threshold at three sites, in 461 normal cases, by TR-06 (Rion Co.), over a wide range. A multiple comparison procedure (Tukey-Kramer) was applied to age groups, revealing a significant increase in the threshold with advancing age; high threshold values were observed in the "60s and older" group for the chorda tympani nerve area (tongue tip) and the glossopharyngeal nerve area (tongue base), and in the "70s and older" group for the superficial greater petrosal nerve area (soft palate). As to the gender difference in women, a significant drop was observed in the late teens whereas a low tendency in all sites tested was not statistically, significant in other age groups. Differences between the right and the left sides were seen in most cases but were within 6dB. As to site differences, the soft palate threshold was higher than those of the tongue tip and the tongue base in all age groups. A significant decrease in the threshold of the tongue tip, as compared to the tongue base, was observed for those in their late teens, whereas minimal differences were noted in the other age groups and at other sites. The soft palate threshold was significantly reduced in smokers in their 30s and 40s as compared with non-smokers.

Adolescent↗
PubMed1995

[Protein and DNA sequencing analyses of transthyretin in familial amyloidotic polyneuropathy].

Recent advances in protein chemistry and the molecular biology of amyloid proteins have led to knowledge of the primary etiology of FAP. The protein product of the gene in question was identified, then the chromosomal location and point mutations in the gene were determined. Diagnosis of the disorder now can be made at the protein and DNA levels. Recombinant techniques for producing variant proteins have been established and a transgenic mouse that carries the mutated gene have been produced. Liver transplantation, a curative therapy for FAP, has been used for some patients. Procedures for the diagnosis of TTR-related FAP and the elucidation of TTR abnormality are summarized as follows: TTR-related FAP should be considered when biopsies of abdominal fat, the gingiva, stomach, rectum and sural nerves demonstrate amyloid deposits that are specifically stained by anti-TTR antiserum. Analysis of the TTR gene based on RFLP and single strand conformational polymorphism is useful for detecting the genetic mutations identified so far. Even when no known mutations have been detected, protein sequence analysis of serum TTR and nucleotide sequence analysis of the TTR gene have shown new variant TTRs. These advances in FAP research herald a new era in our investigation of the molecular biology of inherited neuropathy.

Amyloid Neuropathies↗
PubMed1994

Identification of 10-kDa proguanylin as a major guanylin molecule in human intestine and plasma and its increase in renal insufficiency.

Guanylin is a 15-amino acid peptide that acts on intestinal guanylate cyclase, thereby regulating intestinal fluid and electrolyte transport through the second messenger, cyclic GMP. Using synthetic rat guanylin, we prepared an antiserum that recognizes human and rat guanylin equally on a molar basis and developed a sensitive radioimmunoassay (RIA). The major endogenous guanylin molecule in human intestine and plasma is 10-kDa proguanylin, 15-amino acid guanylin being a minor component. Human guanylin is distributed widely from the duodenum to colon, the highest contents being in the ileum and proximal colon. The plasma concentration of immunoreactive guanylin in the normal individuals tested was 31.2 +/- 3.0 fmol/ml (mean +/- SE) and that in patients with chronic renal failure who were undergoing hemodialysis 7,924 +/- 2,140 fmol/ml. The RIA we established is a promising tool for clarifying the physiological functions and pathophysiological significance of guanylin in water and electrolyte homeostasis.

Aged↗
PubMed1994

Structure of the rat thyroid transcription factor-1 (TTF-1) gene.

TTF-1 is a homeodomain-containing thyroid transcription factor which activates the genes of thyroid specific protein, thyroglobulin, thyroid peroxidase and thyrotropin receptor. We have cloned the TTF-1 gene from rat liver genomic library, and the exon/intron organization and the structure of the 5' flanking region were determined. The clone contained the 5.2 kbp upstream sequence from translation initiation site, and we found that the gene has a single intron in the coding sequence. We found in the 5' flanking region the TTF-1 binding consensus sequence, CTCAAGC, at -175 to -169, which overlaps the consensus sequence of CAAT box, DNase I foot print analysis has revealed that the region is protected by nuclear extract from thyroid cells but not by the extract from the liver, suggesting that expression of the TTF-1 gene is autoregulated by TTF-1.

Animals↗
PubMed1994

Isolation and sequence determination of two N-terminal fragments of islet amyloid polypeptide in rat pancreas.

Using a highly sensitive and specific radioimmunoassay (RIA) for the N-terminal hexadecapeptide of islet amyloid polypeptide (IAPP), we isolated two N-terminal fragments of IAPP from rat pancreas. They were identified as IAPP(1-16) and IAPP(1-17) by amino acid sequencing. The two fragments were also found in rat plasma. IAPP(1-37) was the major molecular form of rat IAPP, IAPP(1-16) and IAPP(1-17) accounting for 6.0% and 32.3% of the immunoreactivity for the N-terminal region of the peptide in pancreata of normally fed rats. In human pancreas, the N-terminal fragments of IAPP were not present, indicating that the processing of IAPP in the pancreas differs between human and rat. Food deprivation increased the molar ratios of IAPP(1-16) and IAPP(1-17) to IAPP(1-37) in comparison to values for fed rats. Identification of novel fragments of IAPP, in addition to IAPP(1-37), offers a promise for the elucidation of the physiological function of IAPP and the identification of factors that regulate the biosynthesis and catabolism of the peptide.

Amino Acid Sequence↗
PubMed1994

Familial amyloid polyneuropathy in Taiwan: identification of transthyretin variant (Leu55-->Pro).

We report a family with familial amyloid polyneuropathy (FAP), showing an early-onset and a fatal outcome before age 30. Transthyretin (TTR) gene analysis showed one point mutation (T-->C change) in the second base of codon 55, and the corresponding amino acid substitution of proline (Pro) for leucine (Leu) was confirmed at the protein level. This is the first FAP family of Taiwanese origin demonstrating a causative gene abnormality, and FAP with TTR-Pro55 was considered to be more serious compared with other forms of FAP.

Adolescent↗
PubMed1994

Localization of human neutrophil peptide (HNP) and its messenger RNA in neutrophil series.

Human neutrophil peptides (HNPs) 1,2 and 3, also called defensins, have high antimicrobial activity and are cytotoxic to both normal and transformed human cells. The localization of HNPs 1-3 and their mRNAs in cells of normal human bone marrow and peripheral blood was investigated. Immunoreactivity for HNPs 1-3 appeared in the promyelocyte stage and increased with the maturation of the neutrophil series. HNPs 1-3 were absent from such mononuclear phagocyte systems as peripheral monocytes, alveolar macrophages, and Kupffer cells in the liver. HNP 1-3 mRNAs were detected in bone marrow cells by Northern blot analysis and in peripheral leukocytes by the reverse transcription-polymerase chain reaction (RT-PCR). HNPs 1-3 are restricted to cells of neutrophil lineage and seem to function as microbicidal agents in the neutrophil-mediated defense system.

Adolescent↗
PubMed1994

Familial amyloidotic polyneuropathy with late-onset and well-preserved autonomic function: a Japanese kindred with novel mutant transthyretin (Ala97 to Gly).

We report the characteristics of one patient and two asymptomatic carriers from a Japanese family with familial amyloidotic polyneuropathy (FAP). The clinical features were somatic sensory and motor neuropathy with well-preserved autonomic function and late onset with slow insidious progression. These symptoms and signs are different from those of type 1 FAP. There were massive amyloid deposits with transthyretin (TTR) in the myocardium and the sural nerve. DNA sequencing of the TTR gene and amino acid sequence analysis of serum TTR revealed a new mutation in which Gly97 was substituted for Ala. We suggest that patients with somatic sensory and motor neuropathy of unknown origin without apparent autonomic dysfunction should be further studied for TTR mutation.

Age of Onset↗
PubMed1994

Prostalase: basic clinical research and preliminary clinical results with laser thermotherapy for symptomatic benign prostatic hyperplasia.

Prostalase¿ has a probe that emits a laser beam at 360 degrees . Targeted obstructive prostatic adenoma tissue was heated to above the cytotoxic threshold temperature of 45 degrees C. After successful canine prostate study, from September 1992 to April 1993, 45 patients were treated. This paper reports the 9 months results of this initial cohort of patients. Prostatic and periprostatic temperature mapping showed the mean temperature within the adenoma zone was 49 degrees C, while the periprostatic tissue remained within the safety level of less than 42.5 degrees C. The mean prostate volume reductions at 3, 6, and 9 months were 36, 33, and 38%, respectively. Those patients whose surgery was unsuccessful had prostatic tissue removed by TURP at 2 to 3 months. This tissue revealed a definite zone of coagulative necrosis. For the clinical assessment, patients were divided into urine retention (UR) and nonretention (NR) subgroups. At 9 months, 20 of the 32 UR subgroup and 10 of the 13 NR subgroup patients were available for assessment. Due to poor response or complications, 6 of the 26 UR patients (23%) required ancillary treatment. Hence, 20 of the 26 cases (77%) remained catheter free and their mean maximum uroflow +/- SE was 9.6 +/- 0.7 ml/sec. Based on a Siroky normogram only 7 of these 26 patients (27%) became unobstructed. Two of the 12 NR subgroup patients (17%) required ancillary treatment. The mean maximum uroflow +/- SE was 10.7 +/- 1.2 ml/sec.(ABSTRACT TRUNCATED AT 250 WORDS)

Equipment Design↗
PubMed1994

Endoscopic and ultrasonographic observation of the canine prostate after transurethral balloon laser therapy (PROSTALASE).

We investigated the healing process and changes in the canine prostate after transurethral balloon-equipped laser (PROSTALASE) prostatectomy using both endoscopy and transrectal ultrasonography (TRUS). On TRUS, the prostate volume was significantly increased (123%) just after irradiation, decreasing to 106% at 1 week. Cavity formation was observed in the prostate 1 week after irradiation, and the median volume was 1.5 cm3 at 4 weeks. A TRUS study performed immediately after irradiation revealed a 1- to 2-mm deep hyperechoic lesion around the urethra. Urethrocystoscopy disclosed red and markedly edematous mucosa of the prostatic urethra, but no hemorrhage. The hyperechoic mass was also observed in the cavity on TRUS images 1 week later. Urethrocystoscopy disclosed abundant necrotic tissue within the cavity, and reddish granulomatous sections were observed on a portion of the cavity surface. At 4 weeks, the hyperechoic mass in the cavity was no longer observed on TRUS images. The prostate parenchyma was thin but uniformly isoechoic. At urethrocystoscopy, a smooth surface without redness and with the small craters, which were histologically identified as the duct openings of the prostate gland, were observed.

Angioplasty, Balloon, Laser-Assisted↗
PubMed1994

Human prostate acid phosphatase is carrier protein for ABH blood group antigens of semen.

Prostate acid phosphatase (PAcP) was characterized as one of carrier proteins for ABH blood group antigens in semen. The diluted semen was sensitized with anti-PAcP. The resulting immunocomplex was subjected to SDS-PAGE after being washed with saline. SDS-PAGE patterns of the immunocomplex consisted of four bands. After electroblotting from gel to nitrocellulose filter, immunostaining using anti-PAcP or monoclonal anti-blood group antibodies was performed. The result showed that the protein of 50 kD was the subunit of PAcP and the band of 94 kD was identified with blood group antigens respectively. Other two bands were rabbit IgG against PAcP and its fragment. When semen was treated with the chemicals such as papain, SDS, 2-mercaptoethanol and dithiothreitol, the ABH of antigen which was captured by anti-PAcP were considerably reduced. The reduction of ABH activity by these treatments indicated that ABH antigens were located on PAcP in semen which was inactivated by the treatment. Therefore, PAcP was one of proteins carrying ABH epitopes in semen in addition to alpha 2-seminoglycoprotein.

ABO Blood-Group System↗
PubMed1994

Treatment of a Japanese patient with familial amyloidotic polyneuropathy with orthotopic liver transplantation.

A 28-year-old male patient with familial amyloidotic polyneuropathy (FAP) underwent a liver transplantation from a heart-beating cadaveric donor in Sweden. He had suffered from the disease for 2.5 years. It took 5.5 hours to carry out the operation without blood transfusion. After the liver transplantation, serum amyloidgenic variant transthyretin (TTR) levels became extremely low and diarrhea stopped after the 7th day. On day 13, the patient was discharged from the hospital and one month after the transplantation, his general condition remained quite good. This is the first case of a Japanese patient with congenital metabolic disorders as well as FAP to receive a liver transplantation from a heart-beating cadaveric donor.

Adult↗
PubMed1994

[Three siblings homozygous for the transthyretin-Met30 gene in familial amyloidotic polyneuropathy--evaluation of their clinical pictures with reference to those of other 10 cases reported].

We reported clinical pictures of three siblings homozygous for a transthyretin-Met30 (TTR-Met30) gene in a family with familial amyloidotic polyneuropathy (FAP) type I residing in Kanazawa city, and evaluated their clinical pictures with reference to those of other 10 cases previously reported. Ages at onset of two homozygous patients with FAP were 58 and 68 years. They showed sensory-dominant polyneuropathy and mild autonomic dysfunctions. One of them showed vitreous opacities and the other showed multifocal white sheaths along the retinal blood vessels and obstruction of the vessels. A morphometric study of the sural nerve in one patient showed a marked reduction in both myelinated and unmyelinated nerve fiber densities. The third subject was an asymptomatic carrier aged 59 years. The studies of our cases and those in the literature have shown the clinical features of homozygotes for the TTR-Met30 gene as follows: (1) all the homozygous subjects belong to families with incomplete penetrance of the disorder; (2) the clinical features common to 10 symptomatic homozygotes are late onset, mild autonomic dysfunctions, and high frequency of ocular amyloidosis; (3) there are three asymptomatic cases. In addition to TTR-Met30 abnormality, some unknown mechanisms that control its deposition into the tissues are presumed to be involved for the onset of FAP.

Aged↗