Biomedical subjects

M Hashimoto

Publications and source records attributed to M Hashimoto.

At least 19 recordsLinked to original sources

PubMed1997

Direct measurement of doxorubicin concentration in the intact, living single cancer cell during hyperthermia.

BACKGROUND: It is well known that the effect of doxorubicin on cancer cells is enhanced by hyperthermia. The mechanism of this phenomenon is not fully understood. METHODS: Two esophageal squamous cell carcinoma cell lines, TE-2 and TE-6, were used; these cell lines have different sensitivities for doxorubicin. The cells were exposed to 1 microgram/mL of doxorubicin for 30 minutes. With a confocal laser scanning microscope and a transparent warming plate, doxorubicin concentration was measured continuously in the intact, living single cancer cells, and the two-dimensional distribution of the drug during hyperthermia (43 degrees C) was analyzed. RESULTS: A doxorubicin sensitivity difference was confirmed between TE-2 and TE-6 cells by colonogenic assay (P < 0.05). Hyperthermia increased the sensitivity of both cell lines to the drug (P < 0.05) and eliminated the sensitivity difference. Doxorubicin accumulated in the nuclei in both cell lines 30 minutes after exposure to the drug in a time-dependent manner (P < 0.05). Without hyperthermia, the doxorubicin concentration in the nuclei of the TE-2 cells (4.8 +/- 0.3 micrograms/mL) was higher than in the nuclei of the TE-6 cells (2.3 +/- 0.5 micrograms/mL) (P < 0.05). With hyperthermia, there was no significant difference in doxorubicin concentration between the nuclei of the TE-2 cells (20.8 +/- 1.3 micrograms/mL) and the nuclei of the TE-6 cells (16.5 +/- 3.9 micrograms/mL). CONCLUSIONS: Hyperthermia increased the uptake of doxorubicin in the nuclei of cancer cells. Thus, the authors concluded that hyperthermia increases the cells' sensitivity to the drug.

Antibiotics, Antineoplastic↗

PubMed1997

Epstein-Barr virus in lymphoproliferative diseases in the sino-nasal region: close association with CD56+ immunophenotype and polymorphic-reticulosis morphology.

Association between Epstein-Barr virus (EBV) and nasal T-cell lymphoma (NTL) has been demonstrated. NTL has 2 types of histologic figures: one is ordinary non-Hodgkin's lymphoma (NHL) with monomorphous proliferation, and the other is polymorphic-reticulosis (PR) morphology. The presence of the EBV genome and its sub-types (A and B) were examined on paraffin-embedded specimens from 36 cases of sino-nasal lymphomas (SNL) collected from Seoul, Republic of Korea, where the frequency of NTL is high. Patients' ages ranged from 2 to 74 years (median 54 years) with a male-to-female ratio of 2.5:1. Immunophenotypically, 8 cases were B-cell type, 11 were T-cell type with CD56-, 14 were CD56+ type, and 3 were null-cell type. Five of 11 cases with ordinary NHL of T-cell type and 9 of 14 cases with PR were CD56+. The EBV genome was found by polymerase chain reaction (PCR) and in the tumor cells by in situ hybridization (ISH) in 1 of 4 B-cell type (25%), 5 of 10 T-cell type (50%), 11 of 13 CD56+ type (85%), and in both of null-cell type (100%). Of 16 cases with PR morphology, 15 (94%) were positive for the EBV genome. All of the 5 NTLs of ordinary NHL with CD56- were negative for EBV. Concerning the sub-type of EBV, 16 cases had type A, while none had type-B EBV. These findings suggest that NTL comprises 2 groups: EBV-positive NTLs are CD56+ and/or histologically PR, and EBV-negative NTLs are CD56- and histologically ordinary NHL. The current results on Korean patients, together with earlier studies on Japanese and Malaysian patients, have shown the predominance of type-A EBV in sino-nasal lymphoma in Asia.

Adolescent↗

PubMed1997

Stomach-partitioning gastrojejunostomy for unresectable gastric carcinoma.

OBJECTIVES: To analyze the results of a new type of bypass procedure, stomach-partitioning gastrojejunostomy (SPGJ), for unresectable gastric carcinoma and to compare these results with those of conventional gastrojejunostomy (GJ). DESIGN: Retrospective review. SETTING: A university hospital in Japan. PATIENTS: Eight patients underwent SPGJ in 1 group, and 13 underwent conventional GJ in the other group. Staging was determined using preoperative diagnostic imagings and intraoperative findings. MAIN OUTCOME MEASURES: Assessment of food intake and mean survival rates. RESULTS: There were no significant differences between the 2 groups regarding male-female ratio, mean age, and histological type of carcinoma. All patients had stage IV cancers according to the classification of the Union Internationale Contre le Cancer. The rates of taking a regular meal at 2 weeks after an operation were 88% in the SPGJ group and 31% in the GJ group (P < .05). The mean 1-year survival rates for SPGJ and GJ groups were 42.9% and 7.7%, respectively (P < .05). The mean survival times were 13.4 months in the SPGJ group and 5.8 months in the GJ group (P < .05). CONCLUSIONS: Stomach-partitioning gastrojejunostomy achieved an improved quality of life and a better prognosis for patients, and it is the preferred bypass procedure for unresectable gastric carcinoma.

Aged↗

PubMed1997

Pretreatment virus load and multiple amino acid substitutions in the interferon sensitivity-determining region predict the outcome of interferon treatment in patients with chronic genotype 1b hepatitis C virus infection.

Hepatitis C virus (HCV) genotype 1b and high pretreatment virus load are predictive factors of poor response to interferon therapy in patients with chronic hepatitis C. To further examine the factors predicting the response to interferon in patients with genotype 1b infection, we analyzed 110 consecutive patients with HCV who were treated with a total of 624 million units of lymphoblastoid interferon alfa. Thirty-six patients (33%) were responders, while the remaining 74 patients (67%) were nonresponders. Multivariate analysis showed that a high virus titer (assessed by serum core protein level, P = .0021) and the presence of more than two amino acid substitutions in the interferon sensitivity-determining region (ISDR) (P = .0036) correlated significantly with the response to interferon therapy. Because mutations analyzed by direct sequencing of polymerase chain reaction (PCR) products may reflect artifacts of direct sequencing, we further analyzed quasispecies of HCV in this region by cloning and sequencing. Although PCR-based analysis of responders with multiple amino acid substitutions in the ISDR showed the presence of a small amount of wild-type strain in their serum, the results obtained by direct sequencing and cloning were essentially the same. A longitudinal study of quasispecies in 2 patients who showed a dramatic change in the virus titer showed no conversion from wild type to mutant or vice versa. Our results indicate that amino acid substitutions and virus load are independent predictors of the response to interferon therapy. The ability of some patients with no mutation in the ISDR or high virus load to eliminate the virus suggests the presence of other unidentified factors, host or viral, that influence the response to interferon therapy.

Adult↗

PubMed1997

The effects of transmural pressure on prostacyclin release from porcine endocardial endothelial cells--comparison with vascular endothelial cells.

We assessed the effect of pressure on the release of prostacyclin (PGI2) from cultured endocardial endothelial cells (EECs) and vascular endothelial cells (VECs). EECs were harvested from the right ventricle (RV) and left ventricle (LV) of porcine hearts, and VECs from pulmonary artery (PA), aorta (Ao) and coronary artery (CA). Confluent EECs and VECs were incubated for 30 min under various pressures (0, 50, 100, 150 mmHg) and PGI2 release from each cell was measured. Pressure-induced PGI2 release from LV-EECs was larger than that from RV-EECs. Pressure also increased PGI2 release from both PA- and Ao-VECs, but not from CA-VECs. These findings suggest that endocardium can produce PGI2 in response to pressure and PGI2 released into the coronary blood from the ventricle may play an important role in the prevention of myocardial ischemia.

Animals↗

PubMed1997

Haplotypic diversity of DQA103 and 05 subtypes differing at amino acid residue 160 encoded in the third exon in 2215 Japanese individuals.

We analyzed the frequencies and haplotypes of DQA1*03 and *05 subtypes, DQA1*03011 or DQA1*0302 and DQA1*0501 or DQA1*0503, respectively, differing only at codon 160 in the non-polymorphic third exon of the DQA1 gene. Of these, 1,862 and 337 individuals selected as DQA1*03- and DQA1*05-positive samples, respectively among 2,215 unrelated Japanese were typed for their nucleotide variation at residue 160 using PCR-SSP. As observed in other populations, all the samples carrying DQA1*03011 (Gene Frequency, GF: 7.8%) were found to share DQB1*0302, whereas those carrying DQA1*0302 (GF: 44.3%) were associated with a variety of DQB1 alleles including DQB1*0302. Both of the DQA1-DQB1 haplotypes with DQA1*03011 and DQA1*0302 carrying DRB1*0406, DQA1*03011-DQB1*0302 and DQA1*0302-DQB1*0302, showed a strong linkage disequilibrium with B62 (p < 0.001, p < 0.05). These results suggested that DQA1*03011 was generated from a single amino acid change at residue 160 in the DQA1*0302-DQB1*0302 haplotype. However, none of the haplotypes with two different DQA1*03 subtypes carrying DRB1*0403,*0405,*0802 and *0901 showed a linkage disequilibrium with any common B-locus antigens, revealing extensive haplotypic diversity of the DQA1*03 group. For example, DRB1*0802 haplotypes showed linkage disequilibria with two different B-locus antigens, B35 and B61 depending on the presence of DQA1*03011 and DQA1*0302, respectively. The GFs of DQA1*0501 and *0503 were 5.1% and 2.7%, respectively. The DQA1*05 associated haplotypes in the DR52-antigen group with DQB1*0301 were divided into two groups, depending on the bimorphism at residue 160. Such a high degree of haplotypic diversity in association with DRB1 and B alleles observed in the DQA1*03 and *05 groups related to amino acid variation at residue 160, which may affect biological function such as the interaction between CD4 and HLA-DQ molecules, seems to reflect selective pressure in the evolutionary process of HLA antigens.

Alleles↗

PubMed1997

Responses of monkeys with pollinosis to two major allergens of Japanese cedar pollen.

We examined the responses of two Japanese monkeys with pollinosis to two major allergens (Cry j 1 and Cry j 2) of Japanese cedar pollen. The two monkeys (A and B) had specific IgE antibodies to the allergens and showed a strong positive reaction to both of them in the intradermal test. In the histamine release test with peripheral blood mononuclear cells (PBMC), monkey A showed a typical pattern similar to that seen in human patients, while monkey B released a low level of histamine. The proliferative response of PBMC to both allergens in monkey A was weak, but was typical in monkey B. From clinical as well as immunological points of view, these monkeys may be a suitable animal model for Japanese cedar pollinosis in humans.

Allergens↗

PubMed1997

Production of the immunosuppressive cytokine interleukin-10 by Epstein-Barr-virus-expressing pyothorax-associated lymphoma: possible role in the development of overt lymphoma in immunocompetent hosts.

Malignant lymphomas frequently develop in the pleural cavity of patients with long-standing pyothorax. Thus, the term pyothorax-associated lymphoma (PAL) has been proposed for this type of tumor. Most PALs are diffuse lymphomas of B cell type and contain Epstein-Barr virus (EBV) DNA. We have established two lymphoma cell lines from the biopsy specimens of PAL cases, OPL-1 and OPL-2. Both cell lines contain EBV DNA, but only OPL-1 expresses EBV nuclear antigen 2, which works as a target molecule for the cell-mediated immune response. As systemic immunodeficiency is unlikely to be present in PAL patients, PAL from which OPL-1 derived was not expected to be fully developed. In this study, we examined the expression of immunosuppressive factors in OPLs. Only OPL-1, not OPL-2, expressed interleukin-10 (IL-10) mRNA and secreted IL-10 into culture supernatant. Both OPL-1 and OPL-2 expressed transforming growth factor (TGF)-beta 1 mRNA; however, neither expressed latent TGF-beta-binding protein mRNA at a detectable level by Northern blot analysis. Because TGF-beta expresses its functions in cooperation with latent TGF-beta-binding protein, the biological functions of TGF-beta 1 could be negligible. Neither cell line expressed at a detectable level EBV BCRF-1 mRNA, a viral gene product that is partly homologous to human IL-10 and shares biological activities of IL-10. Although IL-10 is reported to promote the growth of activated or neoplastic B cells, OPL-1 did not respond to human recombinant IL-10 by growing faster. As OPL-1 expresses a target antigen for the host cytotoxic T-cell response, the production of an immuno-suppressive cytokine, IL-10, might contribute to the development of overt lymphoma by inducing locally immunosuppressive circumstances. The present study suggests that an immunosuppressive cytokine plays a role in lymphomagenesis of immunocompetent patients.

Animals↗

PubMed1996

New form of platyspondylic lethal chondrodysplasia.

We report on a sporadic case of hitherto unknown lethal skeletal dysplasia. The cardinal clinical manifestations consisted of frontal bossing, cloudy corneae, low nasal ridge, and micrognathia, hypoplastic thorax, and rhizomelic micromelia. Laryngoscopy and neck CT disclosed laryngeal stenosis, and brain CT demonstrated hypoplasia of the corpus callosum. Skeletal survey demonstrated hypoplasia of facial bones and short skull base, extremely severe platyspondyly, hypoplastic ilia, and delayed epiphyseal ossification and rhizomelic shortness of tubular bones. The long bones appeared overtubulated with exaggerated metaphyseal flaring. The humeri were particularly short and bowed. Bowing of the radii and ulnae with subluxation of radial heads presented as a Madelung-like deformity. Unlike the long bones, the short tubular bones were not short and normally modeled. The skeletal changes were superficially similar to those in a group of lethal platyspondylic chondrodysplasias, but were inconsistent with any known subtypes of this group or other lethal skeletal dysplasias.

Abnormalities, Multiple↗

PubMed1996

Synthesis and characterization of a carbene-generating biotinylated N-acetylglucosamine for photoaffinity labeling of beta-(1-->4)-galactosyltransferase.

A photoreactive N-acetylglucosamine derivative, N-[2-[2-[2-(2-biotinylaminoethoxy)-ethoxy]ethoxy]-4-[3-(trifluo rom ethyl)-3-H-diazirin-3-yl]benzoyl]-N4-[2-(acetylamino)-deoxy-beta-D -glucopyranosyl]-L-aspartamide (BDGA), was synthesized as a carbene-generating biotinylated probe for UDP-galactose:N-acetylglucosamine beta-(1-->4)-galactosyltransferase (GalT). The photoaffinity labeling experiments of bovine GalT with BDGA under various condition were examined based on the quantitative chemiluminescent detection of the biotinyl residue which was photochemically introduced into in GalT protein. A progressive decrease in the yield of specific photolabeling was observed upon lowering the incubation temperature from 37 degrees C to 20 degrees C or 4 degree C. The amount of photoincorporation was also decreased when UMP was not included in the incubation mixture. Using a crude protein mixture of recombinant human GalT, a band corresponding to the glutathione S-transferase fusion GalT protein was also specifically visualized. Furthermore, combine use of BDGA photolabeling with an immobilized avidin was found to be effective for the selective retrieval of photolabeled GalT from a reaction mixture containing a large amount of unlabeled GalT protein. The results obtained clearly demonstrate that the covalent biotinylation using the carbene-generating photoaffinity reagent BDGA would be useful for the analysis of acceptor substrate binding sites within the GalT protein.

Acetylglucosamine↗

PubMed1996

The role of a hydroxyl radical scavenger (nicaraven) in recovery of cardiac function following preservation and reperfusion.

We investigated the efficacy in reducing myocardial preservation and reperfusion (P/R) injury of direct hydroxyl radical scavenging by nicaraven as compared with scavenging of both superoxide radicals and hydrogen peroxides by superoxide dismutase (SOD) and catalase (CAT), respectively. Isolated rat hearts were mounted on a Langendorff (L) apparatus to estimate the baseline aortic flow (AF), coronary flow (CF), cardiac output (CO), systolic pressure (SP), aortic mean pressure (MP), rate pressure product, and LV dp/dt. They were divided into 3 groups: group 1, 12 hr storage in HTK solution; group 2, 12 hr storage in HTK solution containing 2.5x10(5) U/L SOD and 2x10(5) U/L mg/L CAT; and Group 3, 12 hr storage in HTK solution containing 10(-3) M nicaraven. SOD, CAT, and nicaraven were administered intraperitoneally before harvesting. Hearts were stored in each preservation solution at 4, and then reperfused. Postpreservative function and concentrations of leaked enzymes were measured. The hearts were switched back to the L-mode and paced at 330 beats/min. CF following perfusion with Krebs-Henseleit bicarbonate buffer (KHB) solution containing 10(-6) M 5-hydroxytryptamine (5-HT) or 10(-5) M nitroglycerin (NTG) then evaluated. The myocardial water content also was measured. The recovery of CF, CO, SP, MP, and LV dp/dt was significantly greater in group 3 than in group 1. The recovery of CF was superior to that in group 2 (P<0.05). There were no significant differences in the recovery of cardiac function between groups 1 and 2. 5-HT caused a decrease in CF in each group, however, CF in group 3 was higher than that in group 1 (P<0.05). NTG caused no significant differences among the groups. There were no significant differences in leaked enzymes and myocardial water content among the three groups. These results suggest that nicaraven protects against myocardial P/R injury through its hydroxyl radical scavenging activity, and that therapy with oxygen-free radical scavengers should be directed toward inactivation of hydroxyl radicals rather than superoxide radicals and/or hydrogen peroxides.

Animals↗

PubMed1996

Silver-stained nucleolar organizer regions in the uterine myomatous tumors.

The numbers of silver-stained nucleolar organizer regions (AgNORs) were counted in uterine myomatous tumors, and compared with those in corresponding normal myometria. The mean number of AgNORs in myomatous tumors tended to increase according to the neoplastic changes. The mean number of AgNORs in leiomyosarcoma (6.4 +/- 0.9) was significantly higher than that in cellular leiomyoma (4.5 +/- 0.7, P < 0.01). or leiomyoma (3.0 +/- 0.5, P < 0.001). In the normal myometria, the mean number of AgNORs (3.3 +/- 0.4) in the premenopausal women showed a higher tendency than that in the post-menopausal women (2.4 +/- 0.5). These results therefore suggest that AgNOR counts may be useful for diagnosis of cellular activity in uterine myomatous tumors.

Female↗

PubMed1996

Lowering extracellular Na+ concentration causes NMDA receptor-mediated neuronal death in cultured rat hippocampal slices.

Reduction of the transmembrane Na+ gradient is expected to induce neurotoxic glutamate release via reversed uptake. We describe neuronal death induced by lowering extracellular Na+ concentration in cultured rat hippocampal slices. When slices were exposed to 3.6 mM Na+ for 30 min, almost all the neurons in the CA1 region were degenerated within 20-24 h. The marginal concentration of external Na+ for induction of neurotoxicity was 6.6 mM. N-methyl-D-aspartate (NMDA) receptor antagonists, MK-801 at 1-3 microM and (+/-)-CPP at 30 microM, significantly decreased these neurotoxic effects. A non-NMDA receptor antagonist, DNQX at 30-100 microM, had no protective effect against neurotoxicity. Removal of external Ca2+ completely eliminated neuronal death, but replacing external Cl- with SO4(2-) had no protective effect against neurotoxicity. A drastic 40-fold increase in glutamate release was produced by 30 min exposure to 3.6 mM Na+, and this release was partially independent of external Ca2+. These findings suggest that the low-Na(+)-induced neurotoxicity we observed is mediated by excessive release of glutamate via reversed uptake and subsequent Ca(2+)-influx through NMDA receptors. The model reported here may be useful for investigation of the mechanism of neuronal injury mediated by endogenous glutamate.

Animals↗

PubMed1996

The effects of omega-3 polyunsaturated (correction of polyunsatulated) fatty acids on the recovery of cardiac function following cold preservation and reperfusion in hyperlipidemic rats.

We examined the effects of supplementation with eiosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), major components of omega-3 polyunsaturated (correction of polyunsatulated) fatty acids (PUFAs), on basal cardiac function and recovery of cardiac function of "donor hearts" from adults (30 week) rats following cold preservation and reperfusion (P/R). In groups 1, 2, 3, and 4, respectively, 30-week-old rats were fed a soybean oil diet, a high-cholesterol oil (HC) diet, an HC diet with EPA, or an HC diet with DHA for 5 weeks. After collecting blood to analyze plasma levels of fatty acids among each group, the heart was excised and perfused on a Langendorff apparatus. Following evaluation of each rat's cardiac function, each heart was stored in HTK solution for 8 hr at 4 degrees C. The heart was then reperfused and the coronary perfusate was collected to evaluate enzyme that had leaked. After cardiac functional recovery was estimated, myocardial fatty acids were measured. EPA supplementation significantly increases the plasma and cardiac levels of EPA as well as the ratio of EPA to arachidonic acid (AA). EPA supplementation also led to improved recovery of cardiac function following P/P, compared with that of rats who received soybean oil, high-cholesterol oil, and DHA. DHA supplementation significantly increased the plasma and cardiac levels of DHA as well as the ratio of DHA to AA--however, the cardiac functional recovery was almost identical to that of the rats who received high-cholesterol oil and was higher only than that of the rats who received soybean oil. There were no significant differences in enzyme that had leaked and myocardial water content among each group. These results suggest that alterations in the myocardial phospholipid composition by EPA supplementation may be profoundly responsible for attenuating myocardial I/R injuries. In contrast, DHA supplementation may not exert a cardioprotective effect following cold P/R. DHA supplementation alone may not increase the myocardial level of EPA enough to cause a protective effect against P/R injury. EPA supplementation to hyperlipidemic patients may be clinically warranted for increasing the potential number of donors.

Animals↗

PubMed1996

Different carcinogenesis in the gastric remnant after gastrectomy for gastric cancer.

BACKGROUND: The incidence of gastric remnant cancer after surgery for gastric malignancies has been increasing. The interval between previous operations and the diagnosis of gastric remnant cancer, location of cancer development, and histologic type were different from those after surgery for benign diseases. However, very little is known about the reasons for these differences. Patients with gastric cancer already have cancer-related gastric mucosal changes at gastrectomy, and they undergo a wide range of dissection of nerve distribution to the stomach due to lymph node dissection. Therefore, the effects of preliminary administration of a carcinogenic agent and denervation of the gastric mucosa on tumorigenesis in the gastric remnant were investigated. METHODS: Using male Wistar rats, N-methyl-N'-nitro-N-nitroguanidine (MNNG; 50 mg/L) was given in drinking water for 10 weeks. The animals were then assigned into four groups of those undergoing Billroth I (B-I) gastrectomy or Billroth II (B-II) gastrectomy, with and without denervation. Subdiaphragmatic truncal vagotomy was performed in the denervated group. Thirty weeks after gastrectomy, the following investigations were performed: histologic examination and periodic acid-Schiff-Alcian blue (PAS-AB) staining of the gastric mucosa by immunohistochemistry of proliferating cell nuclear antigen (PCNA). RESULTS: In macroscopic findings, the groups undergoing nitrosoguanide (NG) gastrectomy with denervation showed a significant increase in the development of whitish, nodular changes in the gastric body. These changes mainly consisted of intestinal metaplasia in microscopic findings. In the NG gastrectomy group, the cancer developed at a lower rate of incidence at the anastomotic site and in the gastric body (1 of 11 rats and 1 of 11 rats, respectively). Conversely, a higher incidence of cancer development (5 of 13 rats) in the gastric body was observed in the group that underwent NG gastrectomy with denervation. Furthermore, the denervation group showed a significant increase in the PCNA labeling index and a distinct increase in the staining of Alcian blue positive mucin in the mucosa of the gastric body. The cancers that developed in the gastric body showed horizontal growth and were accompanied by intestinal metaplasia. In contrast, the cancers that developed in the gastric stumps showed downward growth, and were always accompanied by adenocystic proliferation, but not intestinal metaplasia. CONCLUSIONS: Different processes of carcinogenesis in the gastric remnant are postulated after the surgery for gastric malignancies. The developed cancer is defined by its location and the gastric mucosal changes that developed at the time of gastrectomy.

Animals↗

PubMed1996

A neural cell-type-specific expression system using recombinant adenovirus vectors.

We demonstrated neural cell-type-specific gene expression using an adenovirus vector, which is useful for delivering foreign genes into quiescent neural cells. We produced eight recombinant replication-defective adenoviruses carrying the lacZ reporter gene driven by various promoters, including those of the L7/PCP2 gene (highly restricted expression in cerebellar Purkinje cells), and the myelin basic protein (in oligodendrocytes) gene. We demonstrated in vitro and in vivo promoter-driven, neural cell-type-specific gene expression by recombinant adenoviruses. The genes were transferred into these recombinant adenoviruses and expressed with high levels of efficiency in vitro and in vivo. In primary culture, the recombinant adenoviruses AdexL7-NL-LacZ and AdexMBP-NL-LacZ appeared to be expressed in a Purkinje cell and oligodendrocyte-specific manner. Introduction of 10(8) pfu of these viruses into the adult rat cerebellum by stereotactic injection yielded neural cell-type-specific expression without apparent toxicity to the animals. Thus, adenovirus vectors are useful for cell-type-specific therapeutic uses and in studies requiring neural cell-type-specific gene expression.

Adenoviruses, Human↗

PubMed1996

Epstein-Barr virus in Hodgkin's disease patients in Japan.

BACKGROUND: The association of Epstein-Barr virus (EBV) and Hodgkin's disease (HD) has been suggested by serologic, epidemiologic, and molecular biologic studies. The high level of EBV association with HD in the developing countries was discussed in relation to the high HD incidence in these areas. Japanese HD shows a distinct peak incidence in older adults. In contrast, Western HD shows a bimodal pattern, the first peak in young adulthood and a second peak in older patients. In the present study, the EBV association with HD in Japan was investigated, and the results were compared with those reported from industrialized and developing countries. METHODS: Fifty-seven patients with HD were studied for the presence or absence of the EBV genome by the polymerase chain reaction and in situ hybridization methods. Seven cases were excluded from the analysis for EBV because of poor preservation of nucleotides in the specimens. RESULTS: EBV genomes were detected in the Reed-Sternberg (R-S) cells of 32 of the 50 patients examined (64%). The EBV association was independently affected by histologic subtype (84% in mixed cellularity and 44% in others), sex (76% in males and 31% in females), and age (76% in patients aged 40 years and older and 38% in patients younger than 40 years of age; P < 0.01). High EBV association is found at the peak in older adults predominantly with mixed cellularity type. Previous studies revealed that the high EBV was associated with the older peak of the bimodal peaks in Western HD, and a unimodal peak in childhood in developing countries. The EBV subtype was predominantly type A, which is identical to the immunocompetent type of HD reported previously. CONCLUSIONS: The results of the current study, together with those reported previously, showed that the presence of the Epstein-Barr virus correlated with mixed cellularity type, age older than 40 years, and male sex.

Adolescent↗

PubMed1996

Effect of fentanyl citrate analgesia on glucose production following trauma in rats.

The postoperative hormonal milieu enhances glucose production. The objectives of this study were to determine whether fentanyl plus pentobarbital anesthesia reduced the excretion of stress hormones and whether this resulted in decreased glucose production following trauma. Male Sprague-Dawley rats were assigned into control and trauma. The trauma group was further subdivided into three groups according to the methods of anesthesia: T-1, pentobarbital (PB) alone; T-2, pentobarbital plus fentanyl (FE); and T-3, given PB during surgery and FE at the end of surgery. Glucose production was measured by a primed constant infusion of 3-3H-glucose. Fentanyl plus pentobarbital anesthesia prevented an increase in corticosterone levels in the plasma compared with in T-1 and T-3, 0.5 hr after the surgery. Fentanyl plus pentobarbital, anesthesia caused reductions of insulin and glucagon levels in the plasma and a decrease in catecholamines excretion in the urine. Glucose production was lower with FE+PB anesthesia than with PB alone (PB: 4.6 +/- 0.1 mg/kg/min vs PB+FE: 3.6 +/- 0.2 mg/kg/min, P < 0.05). However, fentanyl given at the end of surgery did not alter hormonal milieu and glucose production compared with pentobarbital alone. Blocking afferent neural stimuli from the wound and injury during the surgery is one approach to prevent an enhancement of postoperative glucose production.

Analgesia↗