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Biomedical subjects

Y Minamishima

Publications and source records attributed to Y Minamishima.

At least 19 recordsLinked to original sources
PubMed2001

Isolation and analysis of an aciclovir-resistant murine cytomegalovirus mutant.

An aciclovir (ACV)-resistant murine cytomegalovirus (MCMV) was isolated from the Smith strain and the mutant was analysed. Attempts were also made to identify directly the mutated gene. The 50% inhibitory concentration (IC(50)) of ACV for the mutant strain was approximately 30 times higher than that for the wild-type strain. The mutant strain was equally sensitive to ganciclovir (GCV), but slightly resistant to cidofovir (CDV) and foscarnet (PFA) when compared with the wild-type. Molecular analysis of the mutant strain revealed that a single base mutation of cytosine (C) to guanine (G) occurred at the 2476th nucleotide position in the DNA polymerase gene region, resulting in an amino acid substitution of proline (Pro) with alanine (Ala) at codon 826. The marker transfer experiment confirmed that this mutation conferred ACV resistance to MCMV. This mutation at codon 826 was easily identified by means of Hae III digestion of the selected PCR product and electrophoresis.

Acyclovir↗
PubMed1999

Adenoma arising from the cystic duct and extending to the confluence of the extrahepatic biliary tract.

We describe a rare case of adenoma with a few foci of severe atypia arising from the cystic duct in a 68-year-old woman, initially diagnosed by the presence of intracholecystic tumefactive sludge on abdominal ultrasonography. Endoscopic retrograde cholangiography (ERC) disclosed a tuberous filling defect at the orifice of the cystic duct. Pathology examination of the biopsied specimen obtained from ERC disclosed not a cancerous but an adenomatous lesion. Macroscopically, the resected specimen showed a superficially spreading and shallowly elevated lesion extending from the cystic duct to the common bile duct. Although a few sporadic foci of severe atypia were observed, microscopy did not reveal any cancer findings, but confirmed the tumorous lesion as benign adenoma, showing mild-to-moderate atypia. Postoperative immunohistochemistry revealed no expression of p53 protein. We briefly refer to the rarity of adenoma in the biliary tract and discuss the difficulty of differential diagnosis of neoplastic lesions in the extrahepatic biliary tract.

Aged↗
PubMed1999

Protective effects of hochu-ekki-to, a Chinese traditional herbal medicine against murine cytomegalovirus infection.

The innate immunity against murine cytomegalovirus (MCMV) at the early phase of infection is mediated by NK cells and macrophages. We studied the effects of hochu-ekki-to (HET), a traditional Chinese herbal medicine, on the regulation of innate immunity mediated by NK cells and macrophages. We found the oral administration of HET to increase both the number of leukocytes in the spleen and liver and the splenic NK cell cytotoxicity associated with the increased induction of serum IFN-alpha/beta after an MCMV infection but it had no effect on liver NK cells. However, no differences were found in the serum IL-12, IFN-gamma, TNF-alpha and nitric oxide (NO) production in the culture of macrophages between the HET- and PBS-treated mice on day 2 after MCMV infection. In addition, HET-treated splenic and peritoneal macrophages were found to show a higher intrinsic resistance against in vitro MCMV infection than that of PBS-treated mice. Therefore, the HET-induced effects on NK cells and macrophages selectively reduced the viral load in the spleen but not in the liver at an early phase of MCMV infection. HET may thus be useful in the treatment of human cytomegalovirus infection which commonly occurs in HIV-infected AIDS patients.

3T3 Cells↗
PubMed1999

[An autopsy case of AIDS complicated with cytomegalovirus infection and multiple Kaposi's sarcoma].

Cutaneous Kaposi's sarcoma (KS) is a well-known complication of the acquired immunodeficiency syndrome. KS in the internal organs, however, is rare in Japan. We present here a 33-years-old Japanese homosexual man who had AIDS complicated with cytomegalovirus (CMV) infection and KS. He was found to be HIV-seropositive, when he was 31-years-old. He visited our hospital in June 1996 because of high fever. The peripheral blood CD4+ lymphocyte counts were 2 per cubic millimeter, and CMV antigenemia was noted (p65 antigen positive cells; 240/50,000 white blood cells). Thereafter he was successfully treated with parental ganciclovir. On admission, some brown-colored flat nodules were found on the skin, and the diagnosis of KS was made by skin biopsy. We administrated human chorionic gonadotropin (hCG) for the treatment of KS, but had no clinical response. In September 1996, he complained of severe cough, shortness of breath, and vomiting. A chest radiogram showed nodular lesions and pleural effusion in bilateral lungs. A computed tomography of his chest also revealed nodular and linear densities distributed along the bronchovascular bundles. The ultrasonic examination of his abdomen revealed a duodenal nodule. Both nodules in the lungs and duodenum were proved to be KS based on the autopsy findings. Intranuclear inclusionbodies pathognomonic for CMV infections were detected in the stomach and the colon.

AIDS-Related Complex↗
PubMed1998

Genetic analysis of a ganciclovir-resistant human cytomegalovirus mutant.

We isolated a ganciclovir (GCV)-resistant human cytomegalovirus (HCMV) from a laboratory strain, AD169, and analysed the mutant. Attempts were also made to identify directly the mutated gene. The 50% inhibitory concentration (IC50) of GCV for the mutant strain was five times higher than that of the wild-type strain. The mutant strain showed similar sensitivity to phosphonoacetic acid and cidofovir as the wild-type strain. These data suggest mutation in the UL97 gene encoding for the phosphotransferase that phosphorylates GCV. Molecular analysis of the mutant strain revealed that a single base substitution of adenine by cytosine occurred at the 1796 nucleotide position of the UL97 gene region, resulting in the substitution of lysine by threonine at codon 599 in the UL97 gene product. Marker transfer experiment confirmed that this mutation conferred HCMV resistance to GCV. The mutation at codon 599 was easily identified by means of RsaI digestion of the selected PCR product.

Antiviral Agents↗
PubMed1998

Early viral complications following CD34-selected autologous peripheral blood stem cell transplantation for non-Hodgkin's lymphoma.

A patient with non-Hodgkin's lymphoma who received a CD34-selected autologous peripheral blood stem cell transplant (PBSCT) developed cytomegalovirus retinitis, adenovirus-associated haemorrhagic cystitis (HC) and fatal herpes simplex virus pneumonia. Depletion of mature T cells from the graft and a persistent decrease in CD4+ lymphocytes following PBSCT may have predisposed this patient to such viral infections. Infusion of cryopreserved autologous PBSC (containing mature T cells) was effective for adenovirus-associated HC. Immunosuppression and resultant viral infections may affect patients receiving CD34-selected autologous transplantation.

Adenoviridae Infections↗
PubMed1998

Role of macrophages in acute murine cytomegalovirus infection.

It has been recognized that macrophages play an important role in controlling virus infection in experimental animal models. To evaluate the role of macrophages in acute murine cytomegalovirus infection, macrophages in the spleen and the liver were eliminated by an intravenous injection of liposomes containing a cytolytic agent, dichloromethylene diphosphonate. The depletion of macrophages led to a significant increase of virus titer in the spleen and lungs in both susceptible BALB/c and resistant C57BL/6 mice during the first three days after intravenous infection. In the spleen, the increase of virus titer in macrophage-depleted BALB/c mice was much greater than that in NK cell-depleted mice. These results suggest that macrophages contribute to protection mainly by the mechanisms which are independent of NK cells during the first three days after infection. The increase of virus titer in macrophage-depleted C57BL/6 mice was as great as that in NK cell-depleted mice because of the high contribution of NK cells to protection in C57BL/6 mice. In the liver in both strains of mice, the effects of macrophage depletion on virus titer were not as much as those in the spleen and lungs. Furthermore, the local depletion of peritoneal macrophages resulted in a great increase of virus titer in the spleen at three days after intraperitoneal infection. We conclude that macrophages greatly contribute to decreasing the virus load in some organs possibly through either or both intrinsic and extrinsic mechanisms in the early phase of primary infection with murine cytomegalovirus.

Acute Disease↗
PubMed1998

[Laboratory diagnosis of cytomegalovirus, HHV-6 and HHV-7 infectious diseases].

Cytomegalovirus, human herpesvirus 6 (HHV-6) and human herpesvirus 7 (HHV-7) are members of subfamily Betaherpesvirinae of family Herpesviridae. After infection, these betaherpesviruses persistent for the rest of life. Those viruses are occasionally reactivated and shed either with or without clinical symptoms. The laboratory diagnosis of the viral infections is established by the following methods: (1) isolation of the virus from specimens; (2) detection of virus antigens, and/or viral nucleic acids; and (3) detection of seroconversion or a significant rise in antibody titer. Accurate and rapid laboratory diagnosis of the viral diseases is prerequisite to effective antiviral chemotherapy. Especially, it is most important to distinguish viral diseases to be treated from mere viral infections.

Antibodies, Viral↗
PubMed1997

Genetic analysis of a clinical isolate of human cytomegalovirus exhibiting resistance against both ganciclovir and cidofovir.

Both ganciclovir-sensitive and -resistant human cytomegaloviruses (HCMV) were isolated from a patient with aplastic anemia complicated with CMV retinitis and encephalitis. Ganciclovir-resistant clinical isolate, 93-1R, also showed cross-resistance against (s)-1-(3-hydroxy-2-phosphonylmethoxypropyl) cytosine (cidofovir). Molecular analysis of plaque-cloned strains revealed that a single nucleotide substitution at 2160 (C to T) resulted in amino acid substitution at codon 501 from leucine to phenylalanine in the DNA polymerase gene. This mutation at codon 501 was easily identified by means of AluI digestion of the selected PCR product. The same mutation existed in the DNA fragment amplified from the patient's brain, suggesting that cross-resistant mutant 93-1R caused encephalitis. Furthermore, ganciclovir-resistant 93-1R-3 replicated much faster and was released more efficiently into the culture medium than ganciclovir-sensitive 91-7S-1.

Antiviral Agents↗
PubMed1997

Increased incidence of cytomegalovirus (CMV) infection and CMV-associated disease after allogeneic bone marrow transplantation from unrelated donors. The Fukuoka Bone Marrow Transplantation Group.

Cytomegalovirus (CMV) infection and CMV-associated disease were monitored using the CMV antigenemia assay in 72 patients who received allogeneic bone marrow transplantation (BMT), and their incidences were compared between related and unrelated donor transplant patients. The incidence of CMV infection after BMT was significantly higher in patients who received transplants from HLA-matched unrelated donors than from HLA-matched sibling donors (87% vs 53%, P < 0.05). CMV-associated disease developed in 73% of unrelated and in 14% of sibling donor transplant patients (P < 0.01). The peak levels of CMV antigenemia were significantly higher in unrelated donors than in sibling donor transplant patients (16 vs 1 CMV antigen-positive cells per 50000 WBCs, P < 0.01). The median number of CMV antigen-positive cells on first detection was also significantly higher in unrelated donor transplant patients (15 vs 1, P < 0.01). The detection of CMV antigen-positive cells preceded the development of CMV-associated disease in 18% of unrelated donor transplant patients, suggesting a lower predictive value of CMV antigenemia for subsequent CMV-associated disease in unrelated donor BMT. Careful monitoring and further studies are needed for the early diagnosis and prevention of CMV-associated disease in unrelated donor BMT.

Adolescent↗
PubMed1997

Comparison of cytomegalovirus (CMV) antigenemia and CMV in bronchoalveolar lavage fluid for diagnosis of CMV pulmonary infection after bone marrow transplantation.

A comparative cytomegalovirus (CMV) diagnostic study was carried out on 30 bone marrow transplant patients. Forty-three bronchoalveolar lavage fluid (BALF) samples from these patients were examined for CMV by viral culture, polymerase chain reaction (PCR), shell vial and cytology. In parallel, peripheral blood samples were subjected to CMV antigenemia assay. CMV was detected in 12 (27.9%) of the 43 BALF samples (10 samples in viral culture, 10 samples in PCR, eight samples in shell vial and three samples in cytology). The CMV antigenemia assay yielded a positive result for six samples. The rates of agreement between results of the CMV antigenemia assay and results of each of the BALF tests were as follows: 81.4% with viral culture, 76.7% with PCR, 86.0% with shell vial, and 88.4% with cytology. Although the sensitivity of the CMV antigenemia assay was inferior to the sensitive tests of BALF samples, statistically significant correlations were demonstrated between the CMV antigenemia assay, viral culture, shell vial and cytology. Although the CMV antigenemia assay was shown to be useful for detection of CMV, it may be necessary to confirm not only the sensitivity but also the specificity of this method for prevention of CMV disease after BMT.

Adolescent↗
PubMed1997

Progressive retinitis-encephalitis due to ganciclovir-resistant cytomegalovirus associated with aplastic anemia.

A 29-year-old woman with aplastic anemia who complained of visual disturbances and pain in the right eyeball was diagnosed as having cytomegalovirus (CMV) retinitis based upon the characteristic retinal changes and isolation of CMV. She received treatment with ganciclovir (GCV), and the retinitis initially responded for several months. However, the patient was found to have CMV lesions in the left eye followed by neurological symptoms. The CMV isolated just before her death was approximately 20 times more resistant to GCV than that isolated previously, suggesting that the GCV-resistant CMV had developed during the long-term treatment with GCV.

Adult↗
PubMed1997

[Foscarnet therapy for ganciclovir-refractory cytomegalovirus hepatitis in a patient who underwent bone marrow transplantation from an unrelated donor].

Cytomegalovirus (CMV) hepatitis refractory to ganciclovir treatment occurred after prolonged administration of ganciclovir in a 36-year-old woman with chronic myelogeneous leukemia who had undergone allogeneic bone marrow transplantation (BMT) from an HLA-identical unrelated donor. The number of CMV antigen-positive leukocytes in blood were well correlated with the serum levels of transaminases and the antigenemia assay was useful in monitoring CMV hepatitis. The patient was treated with foscarnet, a potent inhibitor of CMV DNA-polymerase, which led to rapid improvement of the CMV antigenemia and the transaminase concentrations. Foscarnet therapy should be considered for ganciclovir-resistant CMV disease in the setting of BMT.

Adult↗
PubMed1995

Application of in situ hybridization with a novel phenytoin-labeled probe to conventional formalin-fixed, paraffin-embedded tissue sections.

Non-isotopic in situ hybridization with a novel phenytoin (PHE)-labeled probe was developed. The mixture of cloned cytomegalovirus (CMV) DNA fragments was labeled by random primer technique using PHE-11(spacer)-dUTP, instead of dTTP. The tissue sections were treated with 0.2 N HCl and with proteinase K (1 microgram/ml), and then heated at 70 degrees C in the presence of 50 or 75% formamide. The sections were hybridized with PHE-labeled probe at 37 degrees C overnight. The hybridization signal was visualized by alkaline phosphatase-5-bromo-4-chloro-3-indolyl phosphate (BCIP)/4-nitroblue tetazolium (NBT) system. Strong hybridization signals were detected in sections of the small intestine and the placenta, even when denatured in the presence of 50% formamide. In the case of small intestine, CMV DNA was also detected in the endothelial cells of the mucosa where apparent infected cell was not observed histologically. In the sections of the submaxillary gland, the lung, the adrenal gland and the ovary, hybridization signal was not detected when denatured in the presence of 50% formamide, but detected after denaturation with 75% formamide. Thus, in situ hybridization with the novel PHE-labeled probe is applicable to conventional formalin-fixed, paraffin-embedded tissue sections.

Adrenal Glands↗
PubMed1995

Analysis of the role of CD4+ T-cells during murine cytomegalovirus infection in different strains of mice.

We examined the role of CD4+ T-cells in peritoneal exudate cells (PECs) during the course of acute murine cytomegalovirus (MCMV) infection in two strains of mice. Cell counts of PECs and cytofluorometric analysis showed that C57BL/6, a resistant strain, had more CD4+ T-cells than BALB/c, a susceptible strain, after intraperitoneal infection of 3 x 10(3) PFU of the Smith strain of MCMV, though both strains had an equivalent number of CD8+ T-cells. CD4+ T-cells of both strains expressed mRNA of IFN-gamma, IL-2, and IL-4 on days 5 and 7 after infection, with much higher expression of these cytokines in C57BL/6 than in BALB/c. At the same time point after infection, macrophages were shown to express mRNA of IL-1 alpha and TNF-alpha with higher expression of IL-1 alpha in C57BL/6 than in BALB/c. Production of nitric oxide, recently shown to be one of the antiviral effector mechanisms of macrophages, by macrophages of both strains was examined showing more production of nitric oxide on day 7 after infection in C57BL/6 than in BALB/c. From these findings, we suggest the possibility that CD4+ T-cells contribute to the protection against MCMV infection via the secretion of cytokines and the resultant activation of macrophages to produce nitric oxide.

Animals↗
PubMed1995

No relationship between HTLV-1 infection and filariasis--Serological study on patients with filariasis in Recife, Brazil.

The seroprevalence of antibodies against human T-cell leukemia virus was determined by ELISA in 68 patients with filarial infestation living in an endemic area. The total seropositivity was 2.9% and the HTLV-1-positive cases were detected in 2 microfilaremic patients 12 and 40 years old. This value is very close to that obtained for healthy individuals in the same region and age groups. This result suggests that there is no relationship between filariasis and HTLV-1 infection as previously proposed.

Adolescent↗
PubMed1995

A case of human herpesvirus-6 lymphadenitis with infectious mononucleosis-like syndrome.

The findings of a 20 year old woman with lymphadenopathy that was probably caused by an acute human herpesvirus-6 (HHV-6) infection are reported. She clinically demonstrated various signs of acute infection such as a high fever, skin rash, liver dysfunction, leukocytosis, an elevation of the erythrocyte sedimentation rate, and a positive change of C reactive protein, which mimicked the symptoms of infectious mononucleosis, but no positive titers for an Epstein-Barr virus infection were observed. HHV-6 DNA was detected using Southern blot analysis, polymerase chain reaction, and in situ hybridization in the affected node. Histologically, the lymph node showed an enlarged paracortex and infiltration of transformed lymphocytes and immunoblast-like cells with some histiocytes and eosinophils. Almost all the transformed lymphocytes and immunoblasts were positive for UCHL-1 (CD45RO), MT-1 (CD43), and OPD-4 (CD4), and some of these positive cells demonstrated HHV-6 DNA.

Adult↗