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Biomedical subjects

T Kawano

Publications and source records attributed to T Kawano.

At least 217 records · Page 12Linked to original sources

Molecular cloning of a cDNA for the glutamate transporter of the nematode Caenorhabditis elegans.

We cloned a cDNA for the glutamate transporter of the nematode Caenorhabditis elegans. The nucleotide sequence and Northern blotting indicated that the glutamate transporter gene is transcribed as a polycistronic mRNA in C. elegans and that subsequent trans-splicing yields two distinct monocistronic mRNAs for the glutamate transporter and the ATP synthase c subunit, respectively. The yields of these monocistronic mRNAs were quite different, suggesting that glutamate transport in C. elegans is regulated in the post-transcriptional phase. The glutamate transporter of C. elegans shows about 50-60% sequence similarity with those of mammals. This is the first description of invertebrate glutamate transporters.

ATP-Binding Cassette Transporters↗

Essential requirement of an invariant V alpha 14 T cell antigen receptor expression in the development of natural killer T cells.

NK1.1+ T [natural killer (NK) T] cells express an invariant T cell antigen receptor alpha chain (TCR alpha) encoded by V alpha 14 and J alpha 281 segments in association with a limited number of V betas, predominantly V beta 8.2. Expression of the invariant V alpha 14/J alpha 281, but not V alpha 1, TCR in transgenic mice lacking endogenous TCR alpha expression blocks the development of conventional T alpha beta cells and leads to the preferential development of V alpha 14 NK T cells, suggesting a prerequisite role of invariant V alpha 14 TCR in NK T cell development. In V beta 8.2 but not B beta 3 transgenic mice, two NK T cells with different CD3 epsilon expressions, CD3 epsilon(dim) and CD3 epsilon(high), can be identified. CD3 epsilon(high) NK T cells express surface V alpha 14/V beta 8 TCR, indicating a mature cell type, whereas CD3 epsilon(dim) NK T cells express V beta 8 without V alpha 14 TCR and no significant CD3 epsilon expression (CD3 epsilon(dim)) on the cell surface. However, the latter are positive for recombination activating gene (RAG-1 and RAG-2) mRNA, which are only expressed in the precursor or immature T cell lineage, and also possess CD3 epsilon mRNA in their cytoplasm, suggesting that CD3 epsilon(dim) NK T cells are the precursor of V alpha 14 NK T cells.

Animals↗

Selective reduction of V alpha 14+ NK T cells associated with disease development in autoimmune-prone mice.

A novel peripheral T cell subset characterized by the expression of a NK marker and invariant TCR encoded by V alpha 14 J alpha 281 gene segments with a 1-base N-region was investigated in relation to autoimmune disease development. First, we observed that invariant V alpha 14+ NK T cells are specifically reduced with aging in C57BL/6 lpr/lpr or MRL lpr/lpr mice, whereas no change was observed in age-matched control C57BL/6 or MRL +/+ mice as determined by FACS analysis and RNase protection assay. This reduction precedes the disease development and could also be detected in other autoimmune disease-prone mice, such as C3H gld/gld and (NZB x NZW)F1 mice. These results suggest that the specific decrease in invariant V alpha 14+ NK T cells correlates strongly with the development of autoimmunity. Second, injection of MRL lpr/lpr mice with anti-V alpha 14 mAb resulted in the early onset and exacerbation of lymphosplenomegaly due to the accumulation of abnormal CD3+ B220+ CD4-CD8- T cells as well as an increase in the titers of anti-dsDNA autoantibodies. These results indicate that V alpha 14+ NK T cells regulate autoimmune responses and play a crucial role in controlling the development of autoimmune diseases.

Age Factors↗

A naturally occurring 46-amino acid deletion of cytidine monophospho-N-acetylneuraminic acid hydroxylase leads to a change in the intracellular distribution of the protein.

Cytidine monophospho-N-acetylneuraminic acid (CMP-NeuAc) hydroxylase is a key enzyme for the expression of N-glycolylneuraminic acid. The molecular cloning of this enzyme from mouse liver has been described in our previous report (Kawano T, Koyama S, Takematsu H, Kozutsumi Y, Kawasaki H, Kawashima S, Kawasaki T, Suzuki A (1995) J Biol Chem 270: 16458-63). During the cDNA cloning, a cDNA containing a truncated open reading frame (ORF) was isolated. This clone encodes a protein of 531 amino acids which lacks 46 amino acids in the middle of the normal full-length protein. The percentage of this mRNA containing the truncated ORF out of the total population of CMP-NeuAc hydroxylase mRNA in various mouse tissues was about 10-25%. The truncated protein was expressed in COS-1 cells, but did not show any enzymatic activity. The truncated protein was localized to the region which appeared to be the endoplasmic reticulum, whereas the full-length protein with normal enzymatic activity was detected in the cytosol. These data suggest that this naturally occurring 46-amino acid deletion leads to a change in the intracellular distribution of CMP-NeuAc hydroxylase, and a loss in the activity of this enzyme.

Amino Acid Sequence↗

Liver cell adenoma in a young man with elevated serum PIVKA-II level.

A 21-year-old man was referred to our hospital because of a liver mass lesion detected by abdominal ultrasonography. He had received no hormonal treatment. Physical examinations revealed no abnormalities, and laboratory data, including hepatic function test results, were within normal ranges, with the exception of elevated levels of serum protein induced by vitamin K absence or antagonist (PIVKA)-II (2.2 AU/ml). Abdominal ultrasonography revealed a hyperechoic mass lesion measuring 10 x 10 cm, with hypoechoic areas located in the right posterior segment of the liver. A low-density area and a hypervascular area were detected in the right posterior segment of the liver by computed tomography and celiac angiography, respectively. As hepatocellular carcinoma could not be completely excluded, the tumor was resected. The tissue consisted of sheets of tumor cells with eosinophilic cytoplasm and round nuclei showing a thin trabecular pattern, and these histological findings indicated liver cell adenoma. After resection of the tumor, serum PIVKA-II returned to the normal level.

Adenoma, Liver Cell↗

Giant epiphrenic diverticulum with achalasia occurring 20 years after Heller's operation.

We report a case of giant epiphrenic diverticulum in a 43-year-old woman who underwent Heller's myotomy because of achalasia 20 years earlier. She complained of heartburn and dysphagia from March of 1991 and was hospitalized in our institution. An upper gastrointestinal X-ray examination with contrast medium revealed a large hemispheric lesion (7.8 x 4.8 cm) occupying the right posterior wall of the lower thoracic and abdominal esophagus. Manometry revealed a motility disorder and high pressure of the lower esophageal sphincter due to achalasia. Therefore she was diagnosed as having a giant diverticulum with achalasia after Heller's operation. She underwent transhiatal esophagectomy and reconstruction with placement of a gastric tube on June 4, 1992. Pathology results on the resected specimen revealed a false diverticulum. She has been doing well for 4 years since the operation. It has been said that a complication of incomplete long myotomy causes pulsion diverticulum, but we could not find a case of epiphrenic diverticulum after myotomy for achalasia reported in the literature in the last 10 years.

Diverticulum, Esophageal↗

Delayed post-neonatal intensive care unit hearing disturbance.

Ten children, who developed hearing disturbance after discharge from the neonatal intensive care unit (NICU), are reported. All were born at full term, between November 1988 and November 1992, weighed at least 2500 g and had normal auditory brainstem response (ABR) at discharge from the NICU. All ten underwent thorough evaluation to determine the cause of the subsequent hearing loss. All had severe cardiovascular and/or pulmonary disorders at birth, and persistent pulmonary hypertension of the newborn (PPHN) was diagnosed in eight. A total of 25 PPHN cases were treated at our facility during the 1988-1992 period, the rate of hearing disturbance in PPHN patients being 32%. The 10 infants in this study were mechanically ventilated for, on average, 30 days. High frequency oxygenation (HFO) was required in five cases, extra corporeal membrane oxygenation (ECMO) in six. During this period, only eight ECMO-treated infants survived. The rate of hearing loss in surviving cases was therefore very high, 75% (6 8). All 10 of our cases were treated with an aminoglycoside, furosemide and a muscle relaxant. We recommend follow-up at 6 and 12 months of age, as these children are at very high risk of developing hearing disturbance.

Age of Onset↗

Palliative steroid therapy and serum interleukin-6 levels in a patient with lung cancer.

We report a patient with metastatic adenocarcinoma of the lung who had a detectable serum interleukin-6 (IL-6) level. Despite systemic chemotherapy, the tumor progressed, with elevation of serum IL-6 level. Palliative steroid therapy with 20 mg/day of prednisolone resulted in the decline of serum IL-6 level and, simultaneously, improved anorexia and oral intake. Although there was no weight gain or improvement in hypoalbuminemia, these results suggest that steroids may suppress the abnormal production of IL-6 in cancer patients and that this action affects symptoms. Further study is warranted to clarify the role of IL-6 in tumor-related symptoms and the effect of steroid therapy in relation to IL-6 production in cancer patients.

Aged↗

Band neutrophil count and the presence and severity of coronary atherosclerosis.

It has been consistently shown that the total blood leukocyte count is an independent risk factor for coronary artery disease. Few studies, however, have addressed the relation between differential leukocyte counts and coronary artery disease. We investigated the relation of total and differential leukocyte counts to angiographically determined coronary atherosclerosis. The study included 486 subjects (335 men, 151 women) who underwent coronary angiography for suspected coronary artery disease. Band neutrophil count was significantly positively related to coronary atherosclerosis (p = 0.004) after adjustments for age, sex, body mass index, cigarettes per day, serum total cholesterol, and hypertension. Although sex and age-adjusted total blood leukocyte count was significantly positively related to coronary atherosclerosis (p = 0.04), this relation did not reach significant levels (p = 0.08) after adjusting for other risk factors. The positive association with band neutrophil counts was at least as strong as that with serum total cholesterol concentrations. This study indicates that band neutrophil counts serve as an independent risk factor for coronary atherosclerosis.

Adult↗

Endoscopic ultrasonography of superficial esophageal cancers using a thin ultrasound probe system equipped with switchable radial and linear scanning modes.

BACKGROUND: Detailed information on the depth of invasion of superficial esophageal cancer is required for endoscopic mucosal resection. As a pretherapeutic diagnostic procedure, endoscopic ultrasonography using conventional 7.5 MHz systems has been ineffective at providing sufficient details. A newly developed, thin ultrasound probe system provides both radial and linear scanning for evaluation of superficial esophageal cancer. METHODS: Endoscopic ultrasonography was performed in 16 patients using a switchable probe driven at 20 MHz. Seventeen lesions of superficial esophageal cancer were evaluated for depth of invasion to discriminate mucosal from submucosal penetration. RESULTS: The overall accuracy of staging was 64.7%. In all six errors, mucosal cancers were overstaged as submucosal invasion. The diagnostic accuracy was 80% when the muscularis mucosae was visualized. CONCLUSION: A 20 MHz linear-radial switchable probe is a useful new method in the staging of superficial esophageal cancer.

Aged↗

V alpha 14+ NK T cells: a novel lymphoid cell lineage with regulatory function.

A novel lymphoid lineage, NK T cells, was recently found. The NK T cells are the major population in the periphery comprising 5% of splenic T cells and 40% of bone marrow T cells. They express a unique TCR composed of invariant V alpha 14J alpha 281 and V beta 8.2 together with NK receptor (NKRPI). Surprisingly, the invariant V alpha 14+ TCR is exclusively expressed on NK T cells but not on conventional T cells. As the selective decrease in V alpha 14+ NK T cell population in the periphery is tightly correlated with autoimmune disease development, V alpha 14+ NK T cells control development of autoimmune diseases. We also found that V alpha 14 TCR gene rearrangement and transcripts were detected at an early embryogenesis (d9.5) before the thymus formation. Therefore NK T cells are in the distinct category from conventional T cells. The target of NK T cells is found to be CD1 (class 1b, monomorphic class I MHC-like molecule) present on bone marrow-derived cells and is killed by Fas-FasL interaction or perforin-mediated mechanisms. These results indicate that NK T cells consist of an immunoregulatory system different from defense system in terms of homogeneous repertoire, extrathymic development in early stage of gestation, and their regulatory functional role.

Animals↗

Mutations in the TRKA/NGF receptor gene in patients with congenital insensitivity to pain with anhidrosis.

Congenital insensitivity to pain with anhidrosis (CIPA; MIM 256800) is an autosomal-recessive disorder characterized by recurrent episodes of unexplained fever, anhidrosis (absence of sweating) and absence of reaction to noxious stimuli, self-mutilating behaviour and mental retardation. The genetic basis for CIPA is unknown. Nerve growth factor (NGF) induces neurite outgrowth and promotes survival of embryonic sensory and sympathetic neurons. Mice lacking the gene for TrkA, a receptor tyrosine kinase for NGF, share dramatic phenotypic features of CIPA, including loss of responses to painful stimuli, although anhidrosis is not apparent in these animals. We therefore considered the human TRKA homologue as a candidate for the CIPA gene. The mRNA and genomic DNA encoding TRKA were analysed in three unrelated CIPA patients who had consanguineous parents. We detected a deletion-, splice- and missense-mutation in the tyrosine kinase domain in these three patients. Our findings strongly suggest that defects in TRKA cause CIPA and that the NGF-TRKA system has a crucial role in the development and function of the nociceptive reception as well as establishment of thermoregulation via sweating in humans. These results also implicate genes encoding other TRK and neurotrophin family members as candidates for developmental defect(s) of the nervous system.

Amino Acid Sequence↗

p53 mutations in two patients with intraductal papillary adenoma of the pancreas.

There has been no report on p53 gene mutation in benign human pancreatic intraductal tumors. We examined pancreatic juice and tissue specimens from two patients with intraductal papillary adenoma of the pancreas by polymerase chain reaction-single-strand conformation polymorphism analysis and direct sequencing and found point mutations of p53 gene resulting in amino acid substitutions in exons 6 and 8. Thus, p53 gene mutation may be an early event in the neoplastic process of some pancreatic intraductal tumors and may play an important role in tumorigenesis.

Adenoma↗

Enhancing effects of epidermal growth factor on human squamous cell carcinoma motility and matrix degradation but not growth.

In order to ascertain the effects of epidermal growth factor (EGF) on human cancer invasion abilities, three cell lines of human oral squamous cell carcinoma were studied using a phagokinetic track assay and zymography. EGF (1-100 ng/ml) was found to inhibit the growth but enhance the random motility of all three cell lines in a concentration-dependent fashion. Exposure to EGF, dose-dependently, led to an increased production of urokinase-type plasminogen activator and M(r) 92 kD matrix metalloproteinase by the same cells. These results strongly suggest that EGF may promote human squamous cell carcinoma invasion and metastasis.

Carcinoma, Squamous Cell↗

Retinal complications during interferon therapy for chronic hepatitis C.

OBJECTIVES: Various side effects of interferon (IFN) therapy have been reported. In this study, we examined retinal change during IFN therapy. METHODS: We performed ophthalmological examinations before, during, and after therapy on 63 patients with chronic hepatitis C who were receiving either natural IFA-alpha or recombinant IFN-alpha 2a or 2b. RESULTS: No retinal lesion was detected before IFN therapy, but, during therapy, retinal abnormality or retinopathy developed in 36 (57.1%) of 63 patients, including retinal hemorrhage in 25 patients and cotton-wool spots in 28 patients. They were noted early in the course of IFN therapy, within the first 4 wk in 67% (24/36) and within 8 wk in 86% (31/36). The incidence was not influenced by the type of IFN but was higher among diabetic (11/12, 92%, p < 0.05) or hypertensive patients (4/5, 80%, not significant) than among patients without either diabetes or hypertension (24/49, 49%). There was no relation between the incidence of retinopathy and the level of ALT activity or white blood cell or platelet counts. However, retinopathy occurred in most patients receiving IFN therapy after white blood cell count and platelet count reached a nadir. The levels of LDL-cholesterol and the atherosclerotic index in patients with retinopathy were slightly higher than those in the patients without retinopathy. CONCLUSIONS: These results suggest that retinopathy often occurs in patients with chronic hepatitis C who are receiving IFN and that we should closely monitor patients for retinal complications during IFN therapy.

Adult↗

[Neonatal brain injury and evoked potentials].

Marked abnormalities in ABR at discharge from NICU can predict overall prognosis in patients with neonatal asphyxia. However, in patients with neonatal asphyxia as a single risk factor, the incidence of ABR abnormalities was low and ABR was not indicative of their long-term prognosis. Over the past 10 years, we encountered 13 patients with deterioration of ABR and progressive hearing impairment after discharge from NICU. All patients showed severe cardiorespiratory symptoms in the neonatal period. Nine of thirteen patients were diagnosed as persistent neonatal pulmonary hypertension. Multimodal evoked potential studies could predict life expectancy and functional state in patients with severe motor and intellectual impairment. These kind of neurophysiological test can show the patients' functional state at the time of the examination. Discrepancies in evoked potentials and clinical symptoms provide important information regarding the pathophysiology of the patients.

Asphyxia Neonatorum↗