[Inflammatory bronchial polyp].
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Biomedical subjects
Publications and source records attributed to T Tsuda.
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A locus for Machado-Joseph disease (MJD) has recently been mapped to a 30-cM region of chromosome 14q in five pedigrees of Japanese descent. MJD is a clinically pleomorphic neurodegenerative disease that was originally described in subjects of Azorean descent. In light of the nonallelic heterogeneity in other inherited spinocerebellar ataxias, we were interested to determine if the MJD phenotype in Japanese and Azorean pedigrees arose from mutations at the same locus. We provide evidence that MJD in five pedigrees of Azorean descent is also linked to chromosome 14q in an 18-cM region between the markers D14S67 and AACT (multipoint lod score +7.00 near D14S81). We also report molecular evidence for homozygosity at the MJD locus in an MJD-affected subject with severe, early-onset symptoms. These observations confirm the initial report of linkage of MJD to chromosome 14; suggest that MJD in Japanese and Azorean subjects may represent allelic or identical mutations at the same locus; and provide one possible explanation (MJD gene dosage) for the observed phenotypic heterogeneity in this disease.
A 50-year-old woman was admitted to our hospital on April 4, 1992, because of progressive worsening of dry cough and exertional dyspnea. Moderate hypoxemia and obstructive ventilatory impairment were present. Her chest roentgenogram and CT films showed thickened bronchovascular bundles in the absence of significant parenchymal fibrosis. Transbronchial lung biopsy revealed the formation of noncaseous epithelioid cell granulomas. Pulmonary perfusion scintigraphy showed multiple perfusion defects predominantly in the upper lung fields. Pulmonary ventilation scintigraphy showed a normal pattern. After administration of prednisolone for 3 months, her chest roentgenogram and CT films demonstrated marked decrease of infiltrates, but there was no improvement of hypoxemia and perfusion defects on pulmonary perfusion scintigraphy. Pulmonary angiography revealed multiple stenoses and occlusions of segmental and subsegmental branches of pulmonary arteries. Long-term steroid treatment will be necessary for this rare form of pulmonary sarcoidosis to prevent the development of pulmonary hypertension.
Immunohistochemical study of sarcoid granulomatous lesions. In first we studied the distribution of each functionally distinct T lymphocyte subsets in sarcoid lesions by use of a single and double stain methods with monoclonal antibodies for T cell markers including CD4, CD8, CD45RA, and CD45RO. The results showed that CD4(+)+CD45RA- T cells "Helper/helper inducer" distributed diffusely though the lesions and CD8(+)+CD45RA- T cells "Cytotoxic" distributed at edge of the granulomas. And CD4(+)+CD45RA+ T cells "Suppressor inducer" and CD8(+)+CD45RA+ T cells "Suppressor" also distributed near the granulomas. In second we studied populations of T cells expressed with each antigen including CD26, 28, 29, 11a, 54, 43, 58, 69, 45RA, 45RO, and CD25. The results showed that T cells expressed with each antigen as described above were more numerously in granulomas than out of granulomas. In third we studied T cells designated as T helper 1 (Th-1) and T helper 2 (Th-2) by use of ant-IFN gamma for Th-1 and anti-IL4 and IL6 for Th-2. The results showed that IFN gamma producing cells were scantily demonstrated out of granulomas and conversely IL4 and IL6 producing cells were demonstrated more numerously in granulomas than out of granulomas. From above results we concluded that Immunologic event in sarcoidosis might be Th-2 biased response.
We performed extended aortic arch anastomosis, which was so called EAA procedure, for Coarctation of the Aorta (CoA) with hypoplastic aortic arch (HAA) and interruption of the aortic arch (IAA) in 17 infants under three months of age. The proximal anastomosis site was extended into ascending aorta in order that we could make non-obstructive pathway of systemic flow. During anastomosis, we employed mild systemic hypothermia and topical cooling of head and lumber lesion. Satisfactory anastomoses were performed without any neurological and renal complications except one case. Postoperative Doppler echographic evaluation revealed that the mean peak flow velocities at anastomotic site were under 2.0 m/sec at 1 and 2 years after surgery. We concluded that EAA procedure was useful for CoA with HAA and IAA in early infancy.
Reversible myocardial perfusion abnormality was quantified by bull's eye and unfolded surface mapping methods in exercise thallium SPECT before and after coronary revascularization in 47 patients with angina pectoris, including 34 patients with previous myocardial infarction (PMI) and 13 with effort angina (AP). There was no difference in the incidence or extent of myocardial ischemia between the 2 groups before revascularization. However, the ischemic scores were significantly smaller in PMI group preoperatively than the reductions of the ischemic scores after revascularization. The ischemic scores, preoperatively estimated reversible perfusion abnormality was 32%, 69% and 48% of the improvement of the ischemic score (extent score, severity score, and ischemic area, respectively). Using the 3 ischemic scores, the improvement of perfusion abnormality was well predicted in 70-89% of AP patients but 35-57% of PMI patients. Thus, quantitative analysis in stress thallium SPECT is useful for detecting myocardial ischemia and evaluating the effect of coronary revascularization. However, about a half of myocardial viability was underestimated in one third of PMI patients by the conventional exercise-stress thallium SPECT study.
Postoperative pulmonary vein stenosis is a major complication after the correction of the total anomalous pulmonary venous connection. Six patients developed this complication 2 to 3 months after surgery. Five underwent reoperation (3 had the third operations) with only one survivor. Risk factors for developing the stenosis were 1. small common pulmonary vein with small branches occurring in the patients with the ages at the operation below 2 days and accordingly with the infradiaphragmatic connection and 2. Y-shaped common pulmonary vein with the confluence situated far below the left atrium. Turbulence seemed the major cause of the intimal thickening occurring in the common pulmonary vein shortly distant from the orifices of the branches. Typically the anastomotic orifice was not narrowed. Relief of the stenosis was done by the excision of the hypertrophied intimal tissue frequently cutting into the branches. Severe stenosis recurred in 4 patients necessitating another operation in 3 patients which was fatal in two. Prevention is important. Creation of a large anastomosis with the incision not extending into the branches and the use of the absorbable suture materials were effective. In the infradiaphragmatic connection incorporation of the divided stump of the descending vein into the anastomosis and a T-shaped incision of the left atrium were also important.
In cultured vascular smooth muscle cells, interferon gamma (IFN-gamma) induced the accumulation of nitrite, a stable metabolite of nitric oxide, in a dose- and time-dependent manner. In parallel with this reaction, this cytokine increased the mRNA and protein levels of an inducible macrophage-type of nitric oxide synthase (iNOS). Forskolin, a direct activator of adenylate cyclase, or dibutyryl cAMP alone caused small increases in nitrite accumulation and iNOS mRNA and protein levels and synergistically enhanced the IFN-gamma-stimulated reactions. 8-Bromo-cGMP neither increased by itself nor synergized with IFN-gamma to increase the same reactions. Prostaglandin E1 and beraprost, a stable analogue of prostaglandin I2, which by themselves showed only marginal effects on these reactions, also synergized with IFN-gamma to stimulate the reactions. Interleukin 1 beta or tumor necrosis factor alpha stimulated the same reactions which were similarly enhanced by forskolin. These results indicate that an elevation of intracellular cAMP, particularly in combination with inflammatory cytokines, positively regulates nitric oxide production at the level of iNOS mRNA expression in vascular smooth muscle cells.
The purpose of this study was to isolate airway mucin cDNAs for use in studies of mucin biosynthesis in rat models of human airway disease. To this end, we screened a rat airway cDNA library with the human intestinal mucin cDNA SMUC 41 and obtained 7 positive clones. Preliminary characterization of each of these led us to focus on the clone expressing the 390 bp cDNA RAM 7s. Evidence indicating that RAM 7s encodes part of a rat airway mucin gene is that RAM 7s: (a) hybridizes in plaque lifts to SMUC 41, (b) hybridizes in Northern blots to large, polydisperse transcripts, (c) has a sequence encoding threonine-rich tandem repeats and (d) shows appropriate tissue-specific expression of cognate mRNA. The repetitive peptide encoded by RAM 7s includes five copies of the consensus sequence TTTTIITI. Because this sequence is different from those reported for two cDNAs previously isolated from rat intestinal libraries, we tentatively conclude that RAM 7s encodes part of a previously unidentified rat mucin gene.
Recent genetic linkage studies have implicated a gene on chromosome 14 in the pathogenesis of FAD. The identity of this gene remains unknown but it has been speculated that it may be involved in the cellular processing of the amyloid precursor protein (APP). We have analyzed the nucleotide sequence of the entire open reading frame of the cathepsin G gene located on chromosome 14q. No mutations were observed, suggesting that defects in this lysosomal protease are not responsible for aberrant accumulation of proteolytic products of APP in FAD brain tissue.
In unstimulated cultured vascular smooth muscle cells (VSMC), mRNA of an inducible macrophage-type of nitric oxide synthase (iNOS) was barely detectable. Interferon gamma (IFN gamma) and tumor necrosis factor alpha (TNF alpha) markedly increased iNOS mRNA levels in time- and dose-dependent manners. The induction of iNOS mRNA paralleled the cytokine-induced nitrite production. Actinomycin D abolished the IFN gamma- and TNF alpha-induced increases in iNOS mRNA and nitrite production. Cycloheximide, which abolished both the IFN gamma- and TNF alpha-induced increases in nitrite production, had no effect on the IFN gamma-induced increase in iNOS mRNA but markedly inhibited the TNF alpha-induced one. These results suggest that IFN gamma directly induces the expression of the iNOS gene whereas TNF alpha mainly induces it via the induction of an intermediary protein in cultured VSMC.
There have been few reports investigating the depressive states in workers using computers. We describe the depressive states observed in workers using computers and discuss the sources of their occupational stresses. The first subject is a 34-year-old male manager of a manufacturing company who had customarily worked until 9 PM. In 1985, it become necessary for him to work until midnight; symptoms of depression began to appear during this period, exacerbated after trouble with a computer. In 1986, he visited a psychiatrist and his condition was diagnosed as Major Depression according to DSM-III. The second subject is a 26-year-old male VDT (visual display terminal) operator in a general hospital. Before the onset, he had had to work until 8 PM and, at the end of each month, until midnight. Two months later, he became depressed and his condition was diagnosed as Major Depression according to DSM-III. The third subject is a 32-year-old male chief in the computer programming section of a bank. He had had to work until 8 PM, became depressed, and visited a psychiatrist who diagnosed his condition as Major Depression according to DSM-III. The authors discuss these cases from the standpoint of occupational stresses, as they are associated with work overload, and the important role these stresses played in the onset of the workers' depressive states.
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A solitary pedunculated gastric polyp in the gastric fundus was removed from an asymptomatic 36-year-old woman with normal gastric acid secretion and a normal serum gastrin level. This lesion exhibited distinctive histological features including prominent proliferation of pseudopyloric glands, fundic glands, foveolar epithelium and a fibromuscular stroma. Moreover, its surface was entirely covered by a layer of normal gastric epithelium. Biopsies of the background mucosa taken from the gastric fundus revealed only mild superficial gastritis. A gastric gland heterotopia was diagnosed because of its unique morphology.
The calcium channel blockers, diltiazem and verapamil, and the beta agonist orciprenaline sulfate all demonstrated significant protection against methacholine-induced bronchoconstriction in 11 stable asthmatics (5 males and 6 females). Ten and 20 mg of inhaled diltiazem, 5 mg of verapamil or 30 mg of orciprenaline administered 15 min before stepwise increasing doses of methacholine hydrochloride produced significant reduction in respiratory resistance (Rrs), minimum dose of methacholine hydrochloride required for Rrs increase (Dmin) and bronchial reactivity measured with an Astograph. The mechanism of action of the calcium channel blockers is presumably at the level of the smooth muscle cells themselves. The combination of positive influence and lack of any adverse effect on blood pressure or heart rate with any of the agents tested indicates that their clinical application for alleviation of acute asthma can be recommended.
The primary follicle (PF) emerges as a globular nest of follicular dendritic cells (FDC) and lymphocytes in the lymph node anlage in the 16th gestational week. It increases in size with age but no germinal center is found until several months later, after birth. Using a panel of monoclonal antibodies, the authors have defined phenotypes of component cells of the PF. The PF contains a B-cell population including IgM+, CD20+, CD21+, and CD24+ cells, together with a T-cell population including CD3+, CD4+, CD5+, and CD8+ but no IgG+ cells. It also contains many CD5+ B cells and several IgD+ and alkaline phosphatase-positive cells but few CD15+, CD25+, CD30+, CD38+, and Ki-67+ cells. CD24+ and dendritic reticulum (DRC)-1+ cells show an irregular meshwork pattern in the PF. CD5+ B cells appear even before the formation of the PF and increase after formation of the PF. The lymphocytic phenotype of the PF is similar to that of the mantle zone of the secondary follicle. The phenotypic characteristics indicate that the PF appears as an aggregation of CD5+ B cells and plays an important role as the ancestor of the secondary follicle as well as helper T cells and FDC.