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Biomedical subjects

K Nishida

Publications and source records attributed to K Nishida.

At least 235 records · Page 13Linked to original sources

Isolation and chromosomal localization of the human cone cGMP phosphodiesterase gamma cDNA (PDE6H).

By comparing lists of 3'-directed partial cDNA sequences (gene signatures) randomly collected from various tissues, genes unique to each tissue can be identified. A full-size cDNA clone, corresponding to one such tissue-specific gene signature that recurred only in a retina library, was isolated and analyzed. This clone encoded 83 amino acids highly homologous to the bovine blue cone cGMP phosphodiesterase gamma subunit. The retina-specific expression of this gene was confirmed by multiple tissue Northern blotting, and its cone specificity was confirmed by in situ hybridization to a human retina specimen. From these results, we concluded that this clone (HGMW-approved symbol PDE6H) encodes for the gamma subunit of human cone-specific cGMP phosphodiesterase, and it was assigned to chromosome 12p13 by fluorescence in situ hybridization.

3',5'-Cyclic-GMP Phosphodiesterases↗

Polymerase chain reaction detection of herpes simplex virus in tear fluid from atypical herpetic epithelial keratitis after penetrating keratoplasty.

PURPOSE: We investigated the efficacy of polymerase chain reaction (PCR) in diagnosing atypical epithelial keratitis after a penetrating keratoplasty (PKP) for herpetic corneal scarring. METHODS: We examined three eyes of three patients with keratitis after a PKP for herpetic corneal scarring. The clinical presentation of the keratitis was atypical. DNA extracted from the tears was subjected to PCR and Southern blot hybridization. RESULTS: Herpes simplex virus DNA was identified in all cases of presumptive recurrent herpetic keratitis. CONCLUSION: Polymerase chain reaction is rapid and effective for diagnosing atypical recurrent herpetic keratitis.

Aged↗

Corneal endothelial changes in schizophrenic patients with long-term administration of major tranquilizers.

PURPOSE: To examine corneal endothelial changes in schizophrenic patients who underwent long-term administration of major tranquilizers. METHODS: We performed slit-lamp examination and endothelial specular microscopy on 100 eyes of 50 schizophrenic patients (range, 31 to 68 years old; mean, 54 years) who underwent long-term (12 to 44 years) treatment with major tranquilizers. We also studied 50 eyes of 25 patients (range, 31 to 65 years old; mean, 53 years) with no history of corneal disease, as a control group of similar age. Mean cell density, coefficient of variation, and percentage of hexagonal cells were calculated and statistically compared between patients and controls using an unpaired t-test. RESULTS: Slit-lamp examination disclosed pigmentation of the cornea in nine eyes of five patients and pigmentation of the lens in 25 eyes (25%) of 35 patients. Corneal pigmentary changes were seen only in patients with lenticular changes. No eyes showed corneal edema. In contrast, no corneal abnormalities were seen in any control eye. Specular microscopic analysis showed mean cell density of 3,484.4 +/- 462.6 cells/mm2, coefficient of variation of 0.31 +/- 0.06 and percentage of hexagonal cells to be 60.2% +/- 7.5% in the patient group, and 3,291.3 +/- 384.4 cells/mm2, 0.32 +/- 0.07, and 60.6% +/- 7.0%, respectively, in the control subjects. There were no statistically significant differences between patient and control eyes in these three factors. The nine eyes with corneal pigmentation showed no significant differences in these three factors as compared with the control subjects. CONCLUSIONS: These results indicate that long-term treatment with major tranquilizers is not associated with morphometric abnormalities of the corneal endothelium.

Adult↗

Histopathology of Kienböck's disease. Correlation with magnetic resonance and other imaging techniques.

Histopathological studies of extracted whole lunate bones obtained from 10 patients with Stage 3 Kienböck's disease at surgery for tendon-ball replacement were correlated with magnetic resonance imaging (MRI), computed tomography (CT) and tomography images made prior to surgery. A reforming zone, or a reactive interface between the reactive new bone and granulation tissue formation, and new vascularization were observed surrounding the bone necrosis area showing empty lacunae, fatty necrosis, and disappearance of osteoid. Findings of CT, tomography and microradiography of slices of extracted lunate bone confirmed that fractures of the articular cartilage and the subchondral bone occurred secondarily by overloading, and showed the extent of the collapsed area of the lunate. MRI showed complete loss of signal intensity in T1 images of the lesion of the lunate in advanced Stage 3 Kienböck's disease. MRI is at present unable to distinguish bone necrosis, the histological reactive interface or surrounding hyperaemia in detail. However, the low-intensity arc, or the reactive interface present on MRI in early Stage 3, sometimes correlates with the histological findings of osteoid and granulation zones.

Adult↗

Dorsally displaced epiphyseal fracture of the phalangeal base.

A dorsally displaced epiphyseal fracture of the middle phalanx (Salter-Harris Type I) is described. The epiphyseal fragments were attached to the central slip of the extensor tendon and collateral ligaments. The articular surface of the PIP joint was intact and smooth. The epiphysis was reduced and fixed without cutting the central slip or the collateral ligaments 8 months after injury. This kind of fracture can occur in the PIP and DIP joints, and presents special diagnostic difficulties. Open reduction is evidently necessary to correct the displacement.

Child↗

The Galeazzi-equivalent lesion in children revisited.

A fracture at the medial end of the distal third of the radius with an epiphyseal separation of the distal ulna in a 16-year-old boy is described. This injury, known as the Galeazzi-equivalent lesion in children, is characterized by complete distal ulnar epiphyseal separation without rupture of the distal ligamentous stabilizing system between the radius and ulna, which includes the triangular fibrocartilage complex, interosseous ligaments and periosteal tube of the ulnar. The Galeazzi fracture-dislocation and the Galeazzi-equivalent lesion appear to be completely dissimilar in their pathological anatomy. We suggest calling the latter a "pseudo-Galeazzi injury".

Adolescent↗

In situ ocular absorption of tilisolol through ocular membranes in albino rabbits.

The purpose of this study is to characterize the in situ absorption properties of ocular membranes using a cylindrical cell. Drug disappearance in the cell was determined as in situ absorption after an application of drug solution into the cell on the comea, sclera (bulbar conjunctiva and sclera layer), or palpebral conjunctiva. Tilisolol was used as a model of an ophthalmic beta-blocker. Tilisolol disappeared from the conjunctival and scleral surfaces although hardly any disappearance of tilisolol from the corneal surface was observed. Depletion of drug from the precorneal space was much faster in situ than extrapolated from permeability measurements (in vitro) of the separate tissues. This may arise from an influence of blood flow. The in situ apparent permeability coefficient of tilisolol through the conjunctiva was almost constant at various concentrations of drug (5-100 mM), suggesting a passive diffusion of tilisolol that was affected by medium pH. A high concentration of tilisolol in the aqueous humor was observed in the corneal application although the scleral and conjunctival applications showed a slight concentration of tilisolol. The corneal route was a dominant route of access to the aqueous humor. Access to the vitreous body for tilisolol was 4 times more effective through the sclera than through the cornea. On the other hand, the corneal application showed an extremely low concentration of tilisolol in plasma compared to the scleral and conjunctival applications. Thus, the in situ method using a cylindrical cell is a useful method for investigation of the ocular absorption of ophthalmic drugs.

Absorption↗

Increased brain levels of platelet-activating factor in a murine acquired immune deficiency syndrome are NMDA receptor-mediated.

Mice infected with the LP-BM5 murine leukemia virus (MuLV) develop an immunodeficiency syndrome (murine AIDS) and an encephalopathy characterized by impaired spatial learning and memory. Because platelet-activating factor (PAF) has been implicated in the pathogenesis of HIV-associated dementia complex, brain PAF levels were measured in LP-BM5 MuLV-infected mice. PAF levels in cerebral cortex and hippocampus were significantly increased at 6 and 12 weeks after LP-BM5 MuLV inoculation, whereas significant increases in striatal and cerebellar PAF levels were observed only at 12 weeks after inoculation. Administration of the NMDA antagonist MK-801 significantly reduced the increased PAF levels in the cerebral cortex and hippocampus of LP-BM5 MuLV-infected mice. These results indicate that the LP-BM5 MuLV-induced increases in brain PAF levels are the results of NMDA receptor activation and are consistent with the hypothesis that elevated CNS PAF levels contribute to the behavioral deficits observed in LP-BM5 MuLV-infected mice.

AIDS Dementia Complex↗

Modification of chemo-radiosensitivity of a human lung cancer cell line by introduction of the glutathione S-transferase pi gene.

Recent studies have suggested that glutathione S-transferase pi (GST-pi) may play a role in determining tumor sensitivities to cytotoxic drugs. In order to better understand the role of this enzyme in chemo- and/or radioresistance of lung cancer cells, we examined whether introduction of GST-pi cDNA into a chemo- and radiosensitive lung cancer cell line altered its sensitivities to various chemotherapeutic agents and/or ionizing radiation, which are often used in the management of lung cancers. Modestly increased resistance of the GST-pi transfectants preferentially to sublethal damage caused by ionizing radiation as well as to adriamycin (ADM) was observed. In contrast, resistances to cisplatin (CDDP), etoposide (VP-16), irinotecan hydrochloride (CPT-11) and paclitaxel were virtually unaltered. These results suggest that GST-pi may not play a major role in chemo- and radioresistance of lung cancers, although it could afford selective and limited protection against ADM- and ionizing radiation-induced damage.

Antineoplastic Agents↗

Nitric oxide synthase inhibition during experimental sepsis improves renal excretory function in the presence of chronically increased atrial natriuretic peptide.

OBJECTIVE: To test whether renal excretory function decreases after nitric oxide synthase inhibition during experimental hyperdynamic sepsis. DESIGN: Prospective, randomized, controlled animal trial. SETTING: Research laboratory at a large university medical center. SUBJECTS: Chronically instrumented Merino breed ewes (n = 18). INTERVENTIONS: Continuous infusion of Escherichia coli endotoxin (10 ng/kg/min) for the experimental period of 32 hrs. One group received a bolus of the nitric oxide synthase inhibitor, N omega-nitro-L-arginine methyl ester (25 mg/kg), after 24 hrs, and the remaining sheep were given the carrier, sodium chloride 0.9%. MEASUREMENTS AND MAIN RESULTS: The sheep developed a hyperdynamic cardiovascular response characterized by a decrease in systemic vascular resistance index (p < .05), and an increased cardiac index (p < .05) by 24 hrs. The sheep retained fluid, with creatinine clearance decreasing in the presence of chronically increased atrial natriuretic peptide. After the administration of N omega-nitro-L-arginine methyl ester, systemic vascular resistance index and cardiac index returned to baseline values, fluid balance normalized, and glomerular filtration rate increased (p < .05), while the control animals continued to retain fluid and their creatinine clearance continued to decrease. The concentrations of atrial natriuretic peptide did not differ significantly between groups after N omega-nitro-L-arginine methyl ester administration. CONCLUSIONS: In this ovine model of experimental hyperdynamic sepsis, renal excretory function decreases in the presence of chronically increased concentrations of atrial natriuretic peptide. Administration of the nitric oxide synthase inhibitor, N omega-nitro-L-arginine methyl ester, reverses the vasodilatory state, thereby improving fluid balance and glomerular filtration.

Animals↗

Interleukin-1 beta and tumor necrosis factor-alpha stimulate synergistically the expression of monocyte chemoattractant protein-1 in fibroblastic cells derived from human periodontal ligament.

The present study demonstrates that interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) induce and synergistically stimulate monocyte chemoattractant protein-1 (MCP-1) expression in fibroblasts from human periodontal ligament. IL-1 beta and TNF-alpha induced in a dose-dependent manner the expression of the MCP-1 gene in the fibroblasts from the human periodontal ligament. However, such an inducing effect was not observed with IL-6 and interferon-gamma. The peak expression of the MCP-1 gene by IL-1 beta or TNF-alpha was observed at 3 h after initiation of their treatment. Furthermore, IL-1 beta in combination with TNF-alpha synergistically stimulated the MCP-1 gene expression in the cells. We also observed significant chemotactic activity for human monocytes in conditioned medium of fibroblasts from the human periodontal ligament treated with both cytokines. The stimulated chemotactic activity induced by these cytokines depended on both dose and treatment time. The chemotactic activity in conditioned medium of IL-1 beta-treated fibroblasts from the human periodontal ligament was neutralized by antiserum specific for MCP-1 protein. The MCP-1 gene product in conditioned medium of IL-1 beta-treated fibroblasts from the human periodontal ligament was shown to have a molecular mass of 11,000 Da by immunoprecipitation with the specific antiserum, and IL-1 beta also stimulated synergistically MCP-1 protein expression in combination with TNF-alpha. These results suggest that IL-1 beta and TNF-alpha may contribute to the infiltration of monocytes into inflammatory sites of periodontal ligament tissues via the MCP-1 gene product produced by fibroblasts from the human periodontal ligament.

Chemokine CCL2↗

Detecting herpesvirus DNA in uveitis using the polymerase chain reaction.

BACKGROUND: Herpesviruses are involved in the pathogenesis of many ocular diseases including keratitis, iridocyclitis, and acute retinal necrosis syndrome. The rapid and accurate diagnosis of herpetic infections has become increasingly important with the rising incidence of immunosuppressive diseases. The purpose of this study was to evaluate the use of the polymerase chain reaction (PCR) to detect herpesvirus DNA in uveitis patients. METHODS: Aqueous samples were aspirated from 11 patients with active uveitis of suspected viral origin. Using PCR, masked samples were assayed for herpes simplex virus (HSV), varicella zoster virus (VZV), and cytomegalovirus (CMV) to assist in supporting the clinical diagnosis of viral aetiology. Masked controls included 10 aqueous humour specimens from normal patients undergoing cataract surgery and specimens from seven patients diagnosed with active non-viral uveitis--Behçet's disease, sarcoidosis, Fuchs' heterochromic iridocyclitis, or Harada's disease. RESULTS: Ten of 11 cases clinically diagnosed as being of possible viral aetiology yielded aqueous PCR positive for a herpesvirus. Eight patients were PCR positive for amplified HSV DNA, of whom two had acute retinal necrosis, one had corneal endotheliitis, and five had recurrent iridocyclitis. VZV DNA was detected in one case of iridocyclitis, and CMV DNA in one case of chorioretinitis. Successful therapy was based on the PCR results. Ten normal aqueous specimens and the seven uveitis samples from cases not suspected of a viral aetiology were PCR negative for HSV, VZV, and CMV. CONCLUSION: These results demonstrate that detecting herpesvirus DNA in the aqueous humour is useful to support a clinical diagnosis of viral uveitis.

Adolescent↗

Platelet-activating factor in brain regions after transient ischemia in gerbils.

BACKGROUND AND PURPOSE: Platelet-activating factor (PAF) has been reported to be an active mediator in ischemic brain damage on the basis of indirect pharmacological data from PAF antagonists. The direct measurement of PAF in neuronal tissues has not been reported previously in analogous animal models. We have examined regional brain PAF concentration changes during the reperfusion period after ischemia in gerbils to obtain direct evidence for the involvement of PAF with ischemic brain damage and reported gas chromatography/mass spectrometry (GC/MS) methods of PAF quantitative analysis in brain tissues. METHODS: After transient (10 minutes) ischemia followed by controlled periods (0 to 96 hours) of reperfusion and recovery, regional PAF concentrations were determined in gerbil brain tissue. Quantitative analysis of PAF in brain regions is performed using an electron-capture negative chemical ionization GC/MS method, modified for brain tissue. RESULTS: The level of PAF was increased significantly and maximally in hippocampus (211%), cortex (168%), and thalamus (169%) after 1 hour of reperfusion. In contrast, there were no significant changes of PAF in any brain region from 6 hours to 96 hours after reperfusion. CONCLUSIONS: PAF is increased in gerbil brain in response to ischemia at early stages of reperfusion. PAF increases could contribute to the onset and progress of ischemic neuropathology.

Animals↗

High total TGF-beta 2 levels in normal human tears.

Mature and total TGF-beta 2 levels were determined in normal human tears, from 37 volunteers, using a quantitative "sandwich' enzyme immunoassay technique. Since this ELISA method recognizes only mature TGF-beta 2, total TGF-beta 2 levels in tears were measured after acid activation. Aqueous humor samples from 9 patients with cataract were also tested as controls. Mature and total TGF-beta 2 in aqueous humor (AH) averaged 182 pg/ml and 737 pg/ml, respectively. The levels of mature TGF-beta 2 in normal human tears ranged from 36 to 71 pg/ml (mean: 55 pg/ml). And the levels of total TGF-beta 2 ranged from 3446 to 14910 pg/ml (mean: 7854 Pg/ml), a very high level. Percentage of mature TGF-beta 2 ranged 0.4 to 1.3% (mean: 0.9%). It is reported for the first time that there are very high levels of total TGF-beta 2 in normal human tears.

Adult↗

Non-random chromosomal rearrangements and their implications in clinical features and outcome of multiple myeloma and plasma cell leukemia.

Rearrangements of bands 14q32.3 and 19p13.3 and preferential deletion of the short arm of chromosome 1 were nonrandom chromosomal abnormalities in MM and PCL, warranting further investigation at the molecular level. From the viewpoint of clinical relevance, chromosome 14q32 translocation seems to be associated with leukemic manifestation, level of LDH, and shorter survival period from the time of chromosomal analysis. However, these results were obtained from patients with advanced disease, most of whom had already been treated with alkylating agents prior to cytogenetic analysis. To investigate the karyotypes of MM in the early stage and to determine correlations with clinical features, non-dividing cells should be analyzed. For this purpose, interphase FISH and/or comparative genomic hybridization are promising procedures to detect genomic alterations in early multiple myeloma.

Adult↗