Biomedical subjects

K Nagashima

Publications and source records attributed to K Nagashima.

At least 19 recordsLinked to original sources

PubMed1992

Detection of human papillomavirus DNA in carcinomas of the nasal cavities and paranasal sinuses by polymerase chain reaction.

The authors retrospectively searched for human papillomavirus (HPV) types 16 and 18 in 60 cases of carcinoma arising from the nasal cavities (NC) and paranasal sinuses (PS) by using the polymerase chain reaction (PCR) on DNA extracted from formalin-fixed, paraffin-embedded tissues. In cases of SCC (n = 49), the authors also compared the clinical features of patients with HPV-positive and HPV-negative results to determine the clinical significance of HPV. HPV 16 and 18 were detected in 7 of the 49 cases (14%) of SCC. In the other histologic types of carcinoma (n = 11), neither HPV 16 nor HPV 18 was detected. No significant differences in the clinical features were observed between patients with SCC with HPV-positive and HPV-negative results. The results suggest that HPV 16 and 18 are implicated in the pathogenesis of SCC arising from the NC and PS. However, the presence of HPV is not related to local progression, occurrence of metastases, or the prognosis of the patients.

Adult↗

PubMed1992

Clinical significance of the epidermal growth factor receptor gene in squamous cell carcinomas of the nasal cavities and paranasal sinuses.

The authors retrospectively analyzed epidermal growth factor receptor (EGFR) gene amplification in 49 cases of squamous cell carcinoma (SCC) arising from the nasal cavities (NC) and paranasal sinuses (PS) by using slot-blot analysis of DNA extracted from formalin-fixed, paraffin-embedded tissues. Also, the relationship between the results of gene analysis and the clinical features of the patients was studied to investigate the clinical significance of the EGFR in SCC of the NC and PS. Amplification of the EGFR gene was detected in 5 of the 49 cases (10%). No significant difference was observed between EGFR gene amplification and the presence of lymph node metastases, local recurrence, or prognosis. This suggests that EGFR gene amplification is not related to the local progression or metastasis of the SCC in the NC and PS. In addition, it appears that amplification of the EGFR gene is not a prognostic indicator for SCC in the NC and PS.

Adult↗

PubMed1992

D-penicillamine prevents the development of hepatitis in Long-Evans Cinnamon rats with abnormal copper metabolism.

The Long-Evans Cinnamon rat is a mutant strain that contracts hereditary hepatitis and, eventually, spontaneous hepatocellular carcinoma. Because we found a corresponding gross copper accumulation in the liver of the rats, we examined whether the development of hepatitis in our rat system could be prevented by administration of D-penicillamine. D-Penicillamine is a copper-chelating agent and one of the drugs effective for human Wilson's disease, in which abnormal copper metabolism is also observed. The results show that D-penicillamine treatment inhibited the elevation of serum transaminases, suppressed abnormal histological changes in the liver and completely prevented the onset of hepatitis in the Long-Evans Cinnamon rats. We further found that the copper concentration in the liver and serum copper and ceruloplasmin levels were decreased, whereas the urinary copper level was increased in the D-penicillamine-treated Long-Evans Cinnamon rats. These findings demonstrate that the pathogenesis of hereditary hepatitis in Long-Evans Cinnamon rats is due to abnormal copper accumulation in the liver.

Alanine Transaminase↗

PubMed1992

Relationship of large and small CD3- CD56+ lymphocytes mediating NK-associated activities.

We have defined a population of CD3-, CD56+ small lymphocytes (SLs) that exhibit the same phenotype and lytic capacity as natural killer (NK) cells. NK cells characteristically express the surface markers CD16 and CD56, mediate non-major histocompatibility complex (MHC)-restricted lysis, and have been equated with CD3- large granular lymphocytes (LGLs). In the present study we extended the observation that CD3-, CD56+ SLs can mediate NK- and antibody-dependent cellular cytotoxicity activity by studying the activation signals and lytic mechanisms that might be utilized by CD3-, CD56+ SLs in comparison to CD3- CD56+ LGLs. Our results show that CD3- SLs, similar to CD3- LGLs, exhibited activated killing in response to interleukin-2 (IL-2). In addition, after IL-2 activation, the CD3- SLs exhibited morphologic changes, including increases in size and granularity, and both morphologically and phenotypically became virtually indistinguishable from CD3- LGLs. Similar to CD3- LGLs, CD3- SLs could be directly activated by IL-2 alone to secrete significant quantities of interferon-gamma (IFN-gamma) and to express IL-2 receptor (IL-2R) p55. Examination of serine esterases and pore-forming protein (PFP) demonstrated that these cells exhibited a cytoplasmic distribution of perforin, which, unlike that of CD3- LGLs, was not associated with dense cytoplasmic azurophilic granules. Serine esterase levels were similar. However, after IL-2 activation PFP was concentrated in dense cytoplasmic granules, similar or identical to the situation in CD3-, CD56+ LGLs. These CD3-, CD56+ subsets appear to represent a continuum of activated cells that might represent various states of maturation of NK cells.

Antibody-Dependent Cell Cytotoxicity↗

PubMed1992

Direct evidence for release of pore-forming protein during NK cellular lysis.

In the present study, we have examined the exocytosis model for cellular lysis. Using monoclonal antibodies reactive with human pore-forming protein (PFP), we examined the localization of PFP at the interaction site of natural killer (NK) cells and the NK tumor targets K562 and Molt-4 as well as during antibody-dependent cellular cytotoxicity. Following the interaction of effector-target cell contact, an increased frequency of PFP was detected on the effector surface, in the micro-environment, and on the target surface of the interaction site. This temporal deposition of PFP was paralleled by loss of target cell integrity and release of chromium. In addition, selective deposition of PFP was seen at the interaction site of the target cell compared to other target cell regions. Collectively, these results are consistent with the exocytosis model and further support the hypothesis that PFP is one of the secreted moieties involved in NK cellular cytotoxicity.

Antibodies, Monoclonal↗

PubMed1992

Molecular characterization of a JC virus (Sap-1) clone derived from a cerebellar form of progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease caused by polyomavirus JC (JCV). In the majority of cases of PML the cerebrum is mainly affected (cerebral PML) but on rare occasions lesions are restricted to the cerebellum and brain stem (cerebellar PML). We report a rare cerebellar PML case which occurred in a Japanese patient undergoing prolonged hemodialysis treatment. To understand the molecular basis of the viral tissue tropism, we molecularly cloned JCV DNA and compared it with those of cerebral PML. Of ten clones analyzed nine showed identical fragment patterns after digestion with various restriction endonucleases, and we designated these clones Sap-1. It could be shown that the basic structures of the regulatory regions are similar between Sap-1 and isolates from cerebral PML. Restriction endonuclease mapping analysis was used to examine the genetic relationship between Sap-1 and urine-derived isolates containing the archetypal regulatory sequence. We found that Sap-1 was genetically related to an archetypal JCV isolate in Japan.

Base Sequence↗

PubMed1992

Latent herpes simplex virus type 1 in human geniculate ganglia.

Viral infection, especially by reactivation of herpes simplex virus (HSV) has been considered to be a possible explanation for the pathogenesis of idiopathic peripheral facial nerve palsy (Bell's palsy). We investigated whether the geniculate ganglia of man contain latent HSV type 1 (HSV-1), and compared the frequency of HSV-infected ganglia and that of latently infected neurons in human geniculate ganglia and in trigeminal ganglia. From autopsy specimens of eight adults 15 geniculate ganglia and 16 trigeminal ganglia were examined by means of in situ hybridization and immunohistochemical staining. The HSV-1 genome was detected in 11 of the 15 (71%) geniculate ganglia and in 13 of the 16 (81%) trigeminal ganglia. No HSV antigen was noted in any of the ganglia. The incidence of latently infected neurons was 0.9% in the trigeminal ganglia and 5.3% in the geniculate ganglia. The difference in percentages between the two types of ganglia was significant. Our results suggest that reactivation of latent HSV in the geniculate ganglia is a probable cause of some cases of herpetic stomatitis and of idiopathic peripheral facial nerve palsy.

DNA Probes↗

PubMed1992

Non-arthritic rheumatoid valvulitis with coronary arteritis causing myocardial infarction.

Rheumatoid valvulitis occurring in an individual without arthritis has rarely been reported. A 62-year-old woman died after repeated myocardial infarction, with no articular symptoms but with a fever of unknown origin and a positive rheumatoid factor. Autopsy examination revealed granulomatous inflammatory lesions with rheumatoid nodules present in the aortic valve and the base of the left coronary artery. Wide-spread myocardial infarction was found in the septal and anterolateral walls of the left ventricle.

Aged↗

PubMed1992

Ferric(III) ions inhibits copper(II)/hydrogen peroxide-catalyzing lipid peroxidation in human erythrocyte membranes.

1. Effect of ferric ions (Fe3+) on the lipid peroxidation catalyzed by copper ions (Cu2+) and hydrogen peroxide (H2O2) was studied in human erythrocyte membranes. 2. The formation of thiobarbituric acid-reactive products elicited by CuCl2/H2O2 was inhibited by FeCl3 in a concentration-dependent manner; 0.25 mM FeCl3 were enough to cause 50% inhibition of the formation of peroxides. 3. The inhibitory effect of FeCl3 is not due to competition against Cu2+. 4. FeCl3 inhibited the initiation, but did not inhibit the propagation of Cu2+/H2O2-catalyzing lipid peroxidation. 5. In the heat- or trypsin-treated erythrocyte membranes, FeCl3 had no inhibitory effect on Cu2+/H2O2-catalyzing lipid peroxidation. 6. Sodium azide, an inhibitor of catalase, had no effect on the inhibitory effect of FeCl3. 7. These results suggest that a protein factor(s), which is not catalase, is involved in the inhibition of Cu2+/H2O2-catalyzing lipid peroxidation by Fe3+.

Copper↗

PubMed1992

Alpha-fetoprotein-producing acinar cell carcinoma of the pancreas.

A pancreatic carcinoma and liver metastases associated with marked elevation of the serum alpha-fetoprotein (AFP) level were resected from a 57-year-old man. On microscopic examination, the tumor cells showed a predominantly acinar arrangement, with tubular and trabecular structures; in some foci it had features of a medullary pattern. Alpha-fetoprotein, lipase, trypsin, chymotrypsin, and alpha 1-antitrypsin were strongly demonstrated in tumor tissue by immunohistochemical techniques. A biochemical analysis of AFP on affinity sepharose columns revealed that the AFP derived from the tumor tissues was similar to that of hepatocellular carcinoma. Ultrastructural study showed that most of the tumor cells had abundant rough endoplastic reticulum and numerous zymogen granules. No squamoid corpuscles, neuroendocrine granules, bile production, or bile canaliculi were recognized. These findings suggest that this unique tumor originated from acinar cells.

Carcinoma↗

PubMed1992

Cerebral metastasis of malignant cardiac myxoma.

A rare case of bona fide cerebral metastasis of malignant cardiac myxoma is presented. The parenchymal brain tumor of a 32-year-old woman with a history of surgical operations on cardiac myxoma and jejunal leiomyosarcoma was surgically extirpated. The initial pathological diagnosis was metastatic sarcoma. Ten months later, an occlusion of bilateral carotid arteries occurred that was due to tumor emboli. The postmortem examination revealed an unusually rapid recurrence of the cardiac tumor containing sarcomatous components that were histologically identical to the tumors of the brain and the jejunum and the emboli of the cerebral vessels. Hence it was deduced that they all originated in the primary malignant cardiac myxoma.

Adult↗

PubMed1992

Mutagenic specificity in DNA base sequence by irradiation of health lamp light (UV-B) in Escherichia coli.

A shuttle vector, pZ189, carrying a bacterial suppressor tRNA marker gene, was irradiated with health lamp (HL) light containing UV-B. Plasmid mutations were scored by transforming an indicator strain of Escherichia coli carrying a suppressive blue amber mutation in the beta-galactosidase gene. Plasmid survival was also measured by transforming activity of the indicator strain. The majority of mutations induced by HL light were GC-AT transitions (69%) and the rest were transversions (31%). Some hot-spots in the mutations were observed by sequencing the suppressor gene. Mutagenic specificity in DNA base sequences induced by HL in E. coli agrees well with previous reports about 254-nm or 313-nm light effects on mammalian cells. This agreement may depend on the substitution of the inserted base instead of a G residue at the opposite site of a damaged C residue from conformational change of DNA structure in both bacterial and mammalian cells.

Animals↗

PubMed1992

Detection of varicella-zoster virus DNA in human geniculate ganglia by polymerase chain reaction.

Latent varicella-zoster virus (VZV) has been demonstrated in the human trigeminal and thoracic ganglia by means of nucleic acid hybridization. However, the human geniculate ganglia in VZV latency have not been examined. Tissue DNA extracted from the trigeminal and geniculate ganglia of a newborn and 7 adults was examined by polymerase chain reaction with a pair of VZV-specific primers. None had symptoms of recent infection with VZV (chickenpox or shingles). VZV DNA was detected in 11 (79%) of 14 trigeminal ganglia and in 9 (69%) of 13 geniculate ganglia of the adults. VZV DNA was not detected in either type of ganglion from the newborn or from 1 adult who was seronegative for VZV antibodies. These findings indicate that VZV becomes latent in human geniculate ganglia after primary infection and suggest the possibility that reactivation of the virus from the geniculate ganglia may cause Ramsay Hunt syndrome.

Adult↗

PubMed1992

Virus-induced obesity in mice: association with a hypothalamic lesion.

In an earlier study we found that a substantial percentage of mice surviving infection with canine distemper virus (CDV) slowly developed a morbid obesity syndrome. In the present study we wished to explore the role of the virus in the development of this syndrome. The distribution of viral antigen(s) in brains of pre-obese animals shortly after intracerebral infection was mapped using immunocytochemical procedures. A distinctive pattern of cell labeling was found, extending from the anterior periventricular hypothalamus ventrally and caudally toward the posterior hypothalamus. The heaviest concentration of labeled cells was found in the arcuate-ventromedial area. Viral antigen-containing cells were not found in obese brain specimens. However, the latter revealed, by glial fibrillary acidic protein immunostaining, a gliotic lesion of the hypothalamus that approximated topographically the pattern of virus tropism. Examination of the arcuate area revealed a significant reduction in tyrosine hydroxylase immunoreactive and pro-opiomelanocortin mRNA positive perikarya. We suggest that the loss of critical populations of hypothalamic neurons as a result of an antecedent viral infection led ultimately to the development of morbid obesity.

Animals↗

PubMed1992

Triple cancers in the urogenital area of a patient with aplastic anemia.

Three epithelial neoplastic lesions, perineal Bowenoid papulosis, uterine cervical carcinoma, and bladder transitional cell carcinoma, which occurred in a mildly immunosuppressed patient who had aplastic anemia were studied for human papillomavirus (HPV) infection. In the Bowenoid papulosis, HPV type 16 DNA was identified by polymerase chain reaction (PCR) and by in situ hybridization (ISH). In contrast, in the uterine cervical carcinoma, HPV 16 was not detected, although possibly another unidentified type of HPV in the lesion was suggested by the ISH findings. In the bladder transitional cell carcinoma, neither papillomavirus genus-specific (PGS) antigen nor HPV DNA was found.

Adult↗

PubMed1992

Osteosarcoma resembling osteoblastoma and its heterotransplantation into nude mice.

We describe a case of bone tumor in the left tenth rib that was diagnosed as a low-grade osteosarcoma resembling osteoblastoma. This diagnosis was supported by clinical, radiologic, and histologic findings. Specimens of this tumor were transplanted into nude mice, and the morphology of the transplanted tumors was examined. The transplanted tumors were similar histologically to the parent tumor. Ultrastructurally, the transplanted osteoblasts showed irregular, indented nuclei, dilated endoplasmic reticulum, and varying amounts of intercellular junctional complexes. Our transplantable tumor could be valuable as an experimental model for studies on this tumor type.

Animals↗

PubMed1992

Myelin gangliosides of human peripheral nervous system: an enrichment of GM1 in the motor nerve myelin isolated from cauda equina.

Myelins of the PNS were isolated from human motor and sensory nerves of cauda equina, and their ganglioside compositions were compared. The predominant ganglioside in the human PNS myelins, both from motor and sensory nerves, was LM1 (sialosylneolactotetraosylceramide). Sialosyl-nLc6Cer and disialosyl-nLc4Cer, GD3, GM3, and GD1b were detected as common components of the two nerve myelins. Furthermore, it was revealed that the motor nerve myelin contained GM1 (about 15% of total gangliosides), whereas sensory nerve myelin contained only a trace amount of GM1 (less than 5%), by TLC analyses together with TLC immunostaining using anti-GM1 antibody. As for the disialoganglioside fraction, the content of GD1a, as well as that of GM1, differed in motor and sensory nerves. Thus, the different contents of the ganglioseries gangliosides in human motor and sensory nerve myelins were demonstrated.

Cauda Equina↗

PubMed1992

Multiple isolates and characteristics of human T-cell leukemia virus type II.

Human T-cell leukemia (or lymphotropic) virus type II (HTLV-II) was isolated from eight HTLV-seropositive patients, six of whom were also infected with human immunodeficiency virus, by cocultivation of peripheral blood mononuclear cells (PBMCs) with BJAB, a continuous B-cell line. Restriction endonuclease mapping of the proviruses demonstrated consistent differences among isolates, and two distinct physical map patterns were observed. The results suggest the existence of two closely related molecular subtypes of HTLV-II, which are tentatively designated HTLV-IIa and HTLV-IIb. This finding was supported by preliminary nucleotide sequence analysis of the env gene region encoding the transmembrane glycoprotein gp21, which showed consistent differences between the two proposed virus subtypes. Exploitation of differences in restriction endonuclease sites allowed polymerase chain reaction amplification to detect and differentiate the two subtypes in fresh PBMCs of HTLV-seropositive intravenous drug abusers (IVDAs). The results of these studies confirm that HTLV-II infection is the prominent HTLV infection in seropositive IVDAs and also show that infection with both subtypes occurs. The finding of genetic heterogeneity in the HTLV-II group of viruses may have important implications for studies on its role in human disease and will be useful in characterizing the viruses present in newly discovered endemic foci in New World indigenous populations.

Adult↗