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Biomedical subjects

M Nakazato

Publications and source records attributed to M Nakazato.

At least 109 records · Page 6Linked to original sources
PubMed1996

Uroguanylin gene expression in the alimentary tract and extra-gastrointestinal tissues.

Uroguanylin, a member of the guanylin peptide family, is a novel peptide regulator for intestinal salt and water transport. A cDNA encoding a precursor for rat uroguanylin was cloned from a rat jejunum cDNA library and sequenced. The precursor was 106 amino acids long and included a 21 residue putative signal peptide at the N-terminus. Rat uroguanylin consisted of 15 amino acids similar to, but distinct from human uroguanylin; the C-terminal leucine residue was deleted and 3 residues were substituted compared to those in the human peptide. Synthetic rat uroguanylin-15 dose-dependently increased the cyclic GMP level in cultured T84 cells. RNA blot analysis showed that rat uroguanylin mRNA is expressed not only in the gastrointestinal tract but also in the lung, pancreas and kidney. Evidence for uroguanylin expression in extra-gastrointestinal tissues indicates the possible existence of a novel system for water and electrolyte homeostasis, and a more global effect of uroguanylin on epithelial cell function.

Amino Acid Sequence↗
PubMed1996

Autoantibody against thyroid iodide transporter in the sera from patients with Hashimoto's thyroiditis possesses iodide transport inhibitory activity.

Recently we have newly identified an autoantibody against thyroid iodide transporter (TIT) in the sera from patients with autoimmune thyroid disease. In order to study the function of these autoantibodies, we established CHO-KI cells stably expressing recombinant rat TIT (CHO-TIT cells), and the effect of IgGs from the patients with Hashimoto's thyroiditis on iodide uptake activity of CHO-TIT cells was investigated. We found that 4 out of 34 sera from patients with Hashimoto's thyroiditis strongly recognized TIT by Western blot analysis. These 4 IgGs, purified by protein A column chromatography, caused 14 to 62% inhibition of I- accumulation in CHO-TIT cells. Next, using synthetic peptides, we determined the recognition site of the autoantibody on the TIT molecule. The autoantibody reacted with the synthetic peptide corresponding to the 6th extracellular loop of the TIT molecule. These results suggest that autoantibody against TIT in the sera from patients with Hashimoto's thyroiditis binds to the 6th extracellular loop of TIT protein and inhibits I- transport into the thyrocytes. Anti-TIT autoantibody might participate in the pathogenesis of Hashimoto's thyroiditis and modulate thyroid function of patients with the disease.

Animals↗
PubMed1996

Autoantibody against Na+/I- symporter in the sera of patients with autoimmune thyroid disease.

Using recombinant rat Na+/I- symporter (NaIS) protein, we have immunochemically searched for the autoantibody in the sera from patients with autoimmune thyroid disease. We found that 22 out of 26 sera (84%) from patients with Graves' disease and 3 out of 20 sera (15%) from patients with Hashimoto's thyroiditis recognized it. By Western blot, these IgGs reacted with 80 kDa protein in FRTL-5 cell membrane, which co-migrated with the band stained by rabbit antibody toward NaIS. These results indicate that autoantibody against NaIS, newly identified antibody, frequently exists in patients with autoimmune thyroid disease, especially in Graves' disease.

Animals↗
PubMed1996

Identification of biologically active and inactive human uroguanylins in plasma and urine and their increases in renal insufficiency.

Uroguanylin, a 16-amino acid peptide, is an endogenous activator of intestinal and possibly renal guanylate cyclase C (GC-C). Using two synthetic topological isoforms of human uroguanylin, one bioactive, the other inactive, we prepared two antisera specific for the individual isoforms and developed sensitive radioimmunoassay (RIAs). The respective plasma concentrations of the bioactive and inactive uroguanylins in the normal individuals tested were 5.0 +/- 0.3 fmol/ml (mean +/- SE) and 1.6 +/- 0.1 fmol/ml. These concentrations increased in chronic renal failure (CRF). The major endogenous uroguanylin molecule in normal human urine was 16 amino acids long, whereas in the plasma and urine of CRF patients the major molecule was 10-kDa prouroguanylin. The RlAs established are promising tools for clarifying the physiological functions and pathophysiological implications of uroguanylin in water and electrolyte homeostasis.

Biomarkers↗
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

Experimental and clinical studies on balloon laserthermia using Nd: YAG laser for uterine endometrial cancer.

BACKGROUND AND OBJECTIVE: No conservative therapy for endometrial cancer exists. We therefore evaluated the new balloon laserthermia for such cases. STUDY DESIGN/MATERIAL AND METHODS: Experimental and clinical study. We examined experimentally porcine kidney and stomach, human resected uterus and clinically on 12 patients with endometrial cancer and two patients with hyperplasia. RESULTS: Temperatures were safely kept at the balloon surface. Laser irradiation should be performed for at least 10-15 min, 65-70 degrees C to produce a suitable degeneration, experimentally. Clinically, necrosis and degeneration to a depth of 4-6 mm was histologically observed. Eight patients with carcinoma and hyperplasia for which laserthermia was effective showed that the surface of cancer was smooth and the depth of invasion was in most cases up to 1/4 of muscle layer. CONCLUSION: Balloon laserthermia may be effective in early endometrial cancer or precancerous lesions. Its clinical usefulness should be investigated further.

Adult↗
PubMed1996

A case of small cell carcinoma of the uterine cervix presenting Cushing's syndrome.

A proportion of small cell carcinoma of the uterine cervix is known to secrete a neuroendocrine substance. However, cases presenting Cushing's syndrome due to ACTH secreted from a cervical small cell carcinoma are extremely rare. Here, we report a case of small cell carcinoma of the uterine cervix that ectopically secreted ACTH and presented Cushing's syndrome. A 42-year-old woman was initially admitted to the endocrine unit for investigation of ectopic ACTH syndrome. Serum cortisol and plasma ACTH levels were elevated with no diurnal variation. After gynecologic examination, her original disease was found to be a stage IIb cervical small cell carcinoma. She underwent a radical hysterectomy and pelvic lymphadenectomy. The entire tumor was excised and post-TNM classification was T2bN1M0. Immunohistochemically, tumor cells stained strongly for ACTH and chromogranin. Electronmicroscopic pictures showed typical neurosecretory granules. Although plasma ACTH returned to normal after surgery, liver metastasis appeared during the course of postoperative irradiation. She died 9 months after operation in spite of vigorous systemic chemotherapy.

Adrenocorticotropic Hormone↗
PubMed1996

Lattice corneal dystrophy type II associated with familial amyloid polyneuropathy type IV.

BACKGROUND: Finnish-type familial amyloidosis (FAP-IV) is an autosomal, dominantly inherited disorder characterized by progressive polyneuropathy and lattice corneal dystrophy type II. The vast majority of families with this disorder originated from Finland. Only two families, in neighboring districts, have been reported in Japan previously. METHODS: The authors report two additional Japanese patients with FAF-IV. The proband, a 70-year-old man, had decreased perspiration and abnormal facial muscle movement. Results of neurologic examination showed bilateral facial and hypoglossal nerve palsies, and an autonomic disturbance, including orthostatic hypotension and dysfunction of perspiration. Histochemical, immunohistological, and DNA studies confirmed the diagnosis of FAP-IV. RESULTS: Results of ophthalmologic examination showed asymptomatic lattice corneal dystrophy of both eyes, but the appearance of the cornea was different from that described in the patients from Finland. Lattice lines in the authors' patient were very fine, short, and glassy and could be observed with indirect retroillumination, but might be missed with direct illumination by the slit-lamp microscope. The proband's younger half-sister, a 68-year-old woman, showed clinical findings and laboratory data similar to those of the proband. CONCLUSION: The authors report two Japanese patients with lattice corneal dystrophy type II related to FAP-IV. This is the third Japanese family with this disorder, and there is no familial relationship to the two previously reported families in Japan.

Aged↗
PubMed1996

Neutrophil-related cytokines and neutrophil products in bronchoalveolar lavage fluid of a patient with ANCA negative Wegener's granulomatosis.

We report a case of Wegener's granulomatosis (WG), with neutrophil accumulation in bronchoalveolar lavage fluid (BALF). Peripheral blood neutrophilia was present but the anti-neutrophil cytoplasmic antibody (ANCA) was negative. The serum and BALF levels of neutrophil-related cytokines, including interleukin (IL)-8, granulocyte colony-stimulating factor (G-CSF) and IL-1 beta, were increased, particularly in BALF. Plasma and BALF levels of neutrophil elastase and defensins, which are released by neutrophils and are potentially toxic to cells, were also elevated. Our findings suggest that neutrophils and neutrophil-related cytokines may play an important role in the pathogenesis of anti-neutrophil cytoplasmic antibody negative as well as anti-neutrophil cytoplasmic antibody positive Wegener's granulomatosis.

Antibodies, Antineutrophil Cytoplasmic↗
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

[Surgical experiences of fenestrated total cavopulmonary connection in patients under four year of age].

The fenestrated Fontan operation is an interim steps for patients who considered to be at high risk for one step Fontan procedure. We performed total cavopulmonary connection with baffle fenestration in five patients under four year of age (33 month of mean age at operation). All patients previously underwent palliative surgery (Blalock shunt in 3, PA banding in 2). Three patients weighed less than 10 kg. Pulmonary vascular resistance index (PARI) were 2.03 +/- 0.18 U/BSA and exceeded 2 U/SQm in 3 patients. Nakata's indice were ranged from 282 to 644 (mean 394) mm2/BSA. Bidirectional cavopulmonary shunt was considered to be alternative pathway for three patients in staged Fontan strategy. Postoperative hemodynamics were relatively stable in all patients and weaned from mechanical ventilation within 5 days with various arterial oxygen saturation. There was no pleural effusion lasting longer than 1 week. One patient died of ileus caused from congenital malrotation. Follow up catheter examination at 1 year showed 83 to 96% of SaO2 and survived patients were doing well. Fenestrated TCPC can be applied safely in younger patients who are considered to need surgical treatments in staged Fontan strategy. Whether fenestration should be closed has to be wait further studies.

Age Factors↗
PubMed1996

[Familial amyloidosis, Finnish type with marked anhidrosis].

Familial amyloidosis, Finnish type (FAF), is a gelsolin-related systemic amyloidosis that has an autosomal-dominant inheritance pattern and is clinically characterized by progressive cranial neuropathy, corneal lattice dystrophy and skin changes such as cutis laxa, blepharochalasis, and lichen amyloidosis. A 70-year-old Japanese male proband, who was believed to be originally from Fukuoka Prefecture, showed signs and symptoms characteristic of FAF. In addition, he complained of progressive anhidrosis and heat intolerance during the daytime in summer. On examination, perspiration was absent on the almost entire body surface. Molecular genetic studies showed a G-to-A transversion that resulted in the substitution of asparagine for aspartic acid 187 in the gelsolin gene, a mutation found in most patients with FAF. Skin biopsy revealed marked deposition of amyloid, which was positive with anti-gelsolin antibody staining, around eccrine sweat glands and ducts, and around sebaceous glands, outside the basal lamina; slight to mild deposition around small vessels and small nerve fascicles; and very slight deposition in the perineurium and endoneurium. Morphometric evaluation of the nerve terminals and axons of eccrine sweat glands revealed a significant decrease in the number of nerve terminals per transverse profile of the sweat gland. Compared with controls, nerve terminals were further from the secretory epithelial cell owing to deposition of amyloid outside its basal lamina. The proband's sister had almost identical, although much less severe, clinical signs and symptoms with the same mutation of the gelsolin gene. Autonomic signs and symptoms in FAF are reported to be less frequent and less severe than those in familial amyloid polyneuropathy of Andrade type. Findings in our proband suggest that perspiration may be markedly decreased in FAF owing to marked deposition of amyloid around the eccrine sweat gland which causes degeneration of the nerve terminals and disturbs access of the neurotransmitter to the secretory epithelial cell.

Aged↗
PubMed1996

[Familial amyloidotic polyneuropathy with a transthyretin variant (Val30-->Leu)].

We report a Japanese woman with familial amyloidotic polyneuropathy (FAP) with a transthyretin variant that substituted leucine for valine at position 30. Family history was not informative. She had initially suffered from repeated petechiae in the eyelids at the age of 51. Two years later, dysesthesia in the lower extremities appeared. Distal muscle weakness and sensory disturbance gradually developed. Autonomic dysfunction emerged and vomiting and orthostatic hypotension were marked in the late stage of her illness. Because of renal failure, she died at the age of 54. At autopsy, amyloid deposits were prominent in peripheral nerves including autonomic nerves, heart, blood vessels, gastrointestinal tract, kidneys, and bladder. In the nervous system, we found amyloid deposits in anterior roots, posterior roots, posterior root ganglions, peripheral nerves, and sympathetic ganglions. Cardiac weight was increased (595 g) with conspicuous amyloid deposits in the myocardium. The kidneys showed massive deposition of amyloid in the glomeruli and vascular walls. Amyloid accumulated moderately in tongue, submandibular gland, gallbladder, spleen, and pancreas, and slightly in the thyroid gland, lung, liver, and adrenal gland. No amyloid deposits were seen in the CNS with the exception of perivascular deposits in the choroid plexus.

Amyloid↗
PubMed1996

[A late onset familial amyloidotic polyneuropathy (FAP) with a novel variant transthyretin characterized by a basic-for-acidic amino acid substitution (Glu61-->Lys)].

A 64-year-old man has suffered from intractable diarrhea since January 1990. He noticed numbness and weakness in the distal portion of four extremities in the following several months. His symptoms were gradually progressive. In June 1992, neurological examination revealed mild muscular atrophy and weakness in the proximal and distal portions of four extremities. There were paresthesia and severe impairment of superficial sensations in the lower limbs, lower half of the trunk and upper limbs. All deep tendon reflexes were reduced or absent. Autonomic dysfunctions such as orthostatic hypotension, impotence and diarrhea were evident. On sural nerve biopsy, myelinated fibers showing axonal degeneration were predominantly seen, and densities of both myelinated and unmyelinated fibers were markedly decreased. No amyloid deposits were found in the endoneurium. Amyloid deposition was identified in the gastric mucosa by Congo red staining and immunostaining with anti-transthyretin (TTR) antibody. Edman degradation showed one amino acid substitution of Lys for Glu at position 61 in the TTR-peptides from the serum. Direct DNA sequencing revealed a new point mutation in the 61st codon of TTR gene. The same point mutation of TTR gene was identified in the DNAs from his 67-year-old brother and 63-year-old sister and one of the paternal cousins, a 64-year-old woman, although their clinical symptoms and signs were negative. Clinical features such as late onset of the symptoms and signs and presence of carriers in their sixties in this family are unique and atypical as compared with those of more frequent Val30-->Met FAP families. A variant TTR, characterized by a Glu61-->Lys substitution (a basic-for-acidic amino acid substitution) found in this family, has not been reported in the literature. In the case of the examination of the patients with autonomic and sensory symptoms and signs of unknown etiology, amyloidotic polyneuropathies, including FAP even in the absence of the family history, should be differentiated. When FAP is highly suspected, the combination of family study and DNA analysis of a possible variant TTR is indispensable for the establishment of the diagnosis.

Age of Onset↗
PubMed1996

[Defensin in plasma and in bronchoalveolar lavage fluid from patients with acute respiratory distress syndrome].

We measured the levels of defensins, antimicrobial peptides, and cytotoxic peptides in azurophil granules of neutrophils in plasma, and in bronchoalveolar lavage fluid (BALF) from patients with the acute respiratory distress syndrome (ARDS). High levels of plasma defensins were observed in samples from patients with ARDS. Samples of BALF from patients with ARDS also had more neutrophils and higher concentrations of defensins than did samples from healthy volunteers and from patients with idiopathic pulmonary fibrosis or diffuse panbronchiolitis. In addition, the concentration of interleukin (IL)-8 in BALF was higher in patients with ARDS than in other subjects. A significant correlation was found between the concentration of defensins and that of IL-8 in BALF from patients with ARDS. These findings suggest that the lung injury in ARDS is caused by defensins released by neutrophils that accumulate in the lungs.

Aged↗
PubMed1995

Two novel rat guanylin molecules, guanylin-94 and guanylin-16, do not increase cyclic GMP production in T84 cells.

Guanylin, a 15-amino acid peptide homologue of bacterial heat-stable enterotoxins, is an endogenous activator of guanylate cyclase C (GC-C). We isolated two novel guanylin molecules from rat intestinal mucosa. They contained guanylin-15 at their C-termini and were identified as guanylin-94 and guanylin-16 by amino acid sequencing and mass spectrometry. Guanylin-94 and guanylin-16 in total account for 85% of guanylin molecules in both the small and large intestine, guanylin-15 being a minor component. Rat guanylin-94 and guanylin-16 did not increase cyclic GMP production in T84 cells. Identification of the post-translational processing products of guanylin should provide a better understanding of the biosynthesis of the peptide.

1-Methyl-3-isobutylxanthine↗
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↗