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Biomedical subjects

T Yazaki

Publications and source records attributed to T Yazaki.

At least 19 recordsLinked to original sources
PubMed1995

Treatment of human malignant meningiomas by G207, a replication-competent multimutated herpes simplex virus 1.

We have demonstrated that replication-competent attenuated mutants of herpes simplex virus type 1 (HSV-1) have therapeutic potential for malignant gliomas. Moreover, a recently described multiple mutant HSV (termed G207) has properties which may allow human clinical trials. G207 is able to replicate within and kill cells from three human malignant meningiomas in cell culture. In nude mice harboring s.c. human malignant meningioma (F5), G207 can inhibit growth in a dose-dependent fashion. In nude mice harboring intracranial subdural human malignant meningioma (F5), one injection of G207 caused significantly decreased tumor growth and one apparent cure with neither neurological dysfunction nor pathological changes in the surrounding brain. These results suggest that G207 should be considered for therapeutic trials in the treatment of malignant meningioma refractory to currently available therapies.

Animals↗
PubMed1995

Decrease of NCAM expression and astrocyte-neurone interaction in long-term cultured astrocytes.

In order to assess the characteristics of the older astrocyte, we obtained long-term cultured rat astrocytes (20 months) and examined the features of protein expression in relation to neuronal interaction. In short-term cultured astrocytes, NCAM expressed strongly in contrast to weak expression of laminin by both immunocytochemical and ELISA assay. On the contrary, in long-term cultured astrocytes, a marked decrease of NCAM expression was observed along with increased laminin expression compared with short-term cultured astrocytes. The long-term cultured astrocytes remained positive to anti-GFAP antibody and showed a much lower ability to interact with neurones than the short-term cultured astrocytes. NCAM may be one of the responsible molecules related to the astrocyte-neurone interaction in the developing and ageing nervous system.

Animals↗
PubMed1995

Detection of human herpesvirus 6 DNAs in samples from several body sites of patients with exanthem subitum and their mothers by polymerase chain reaction assay.

Polymerase chain reaction amplification was used to detect human herpesvirus 6 (HHV-6) DNAs in peripheral blood mononuclear cells (MNCs), plasma, saliva, stool, and urine from three patients with exanthem subitum and in peripheral blood MNCs, plasma, and saliva from their mothers. HHV-6 DNAs were detected in MNCs during and after the disease and were found in plasma only in the acute phase. The virus DNAs were also detected in saliva after recovery from the illness and were found persistently or intermittently in stool but not in urine samples after the onset of the disease. In contrast, one of the three mothers excreted HHV-6 DNAs persistently in saliva. None of the mothers had the virus DNAs in peripheral blood MNCs and plasma nor a significant increase in antibody titers to HHV-6 after possible exposure from their children. These findings suggest systemic replication of HHV-6 during the acute phase in patients with exanthem subitum and persistent infection of the virus in several organs after recovery from the disease.

Adult↗
PubMed1995

Inhibition of angiogenesis and growth of human non-malignant and malignant meningiomas by TNP-470.

Meningiomas are relatively common (22%) vascular brain tumors. 3-11% of meningiomas are malignant, and defy currently available therapy. Inhibition of neovascularization is one potential strategy for treating these hypervascular tumors. Inhibition of tumor-induced angiogenesis by TNP-470 (previously termed AGM-1470), a synthetic analogue of fumagillin, was tested on the growth of human non-malignant and malignant meningiomas in nude mice. TNP-470 significantly inhibited tumor neovascularization and tumor growth of both non-malignant and malignant meningiomas. TNP-470 is now in human trial and should be tested for efficacy in treating malignant or recurrent aggressive meningiomas.

Animals↗
PubMed1995

Attenuated multi-mutated herpes simplex virus-1 for the treatment of malignant gliomas.

We have created a double mutant of the herpes simplex virus (HSV) type 1 (termed G207) with favourable properties for treating human malignant brain tumours: replication-competence in glioblastoma cells (and other dividing cells), attenuated neurovirulence, temperature sensitivity, ganciclovir hypersensitivity, and the presence of an easily detectable histochemical marker. G207 has deletions at both gamma 34.5 (RL1) loci and a lacZ gene insertion inactivating the ICP6 gene (UL39). G207 kills human glioma cells in monolayer cultures. In nude mice harbouring subcutaneous or intracerebral U-87MG gliomas, intraneoplastic inoculation with G207 causes decreased tumour growth and/or prolonged survival. G207 is avirulent upon intracerebral inoculation of mice and HSV-sensitive non-human primates. These results suggest that G207 should be considered for clinical evaluation in the treatment of glioblastomas.

Animals↗
PubMed1995

Clinical features and viral excretion in an infant with primary human herpesvirus 7 infection.

OBJECTIVE: To find clinical features of a virologically-confirmed patient with primary human herpesvirus 7 (HHV-7) infection and a relationship of the excretion of viruses between HHV-7 and human herpes-virus 6 (HHV-6). PATIENT AND METHODS: A 13-month-old boy who had a known prior history of exanthem subitum at 6 months of age developed fever for 3 days and a skin rash appeared as the fever was resolving. The course was accompanying with nonspecific signs and symptoms such as anorexia, irritability, mild diarrhea, palpebral edema, mild inflammation of pharynx, and mild occipital and cervical lymphadenopathy. Heparinized blood samples were used for isolation of HHV-6 and HHV-7 and detection of both virus DNA sequences by a nested polymerase chain reaction (PCR) amplification. Samples from other body sites were also tested for their DNA sequences using the PCR. Both virus antibody activity was measured by an indirect immunofluorescent assay or a neutralization test. RESULTS: Cultured mononuclear cells from the patient at the acute stage of the disease produced morphologic changes, which reacted only with the monoclonal antibody to HHV-7 but not with the antibody to HHV-6. Both viruses were not isolated from blood obtained at the convalescent stage. An antibody response of the patient indicated a seroconversion to HHV-7 but not to other microbial agents including HHV-6 and Mycoplasma pneumoniae. Both virus DNA sequences were detected in peripheral blood mononuclear cells at acute and convalescent stages. HHV-7 DNA was excreted into saliva and transiently into stool at an early convalescent stage followed by HHV-6 excretion into saliva. No HHV-7 and HHV-6 was excreted into urine. CONCLUSIONS: Clinical features of a virologically confirmed patient with primary HHV-7 infection were comparable with those of primary HHV-6 infection and HHV-7 infection may reactivate HHV-6.

Antibodies, Viral↗
PubMed1994

Peripheral myelin P0 protein mediates neurite outgrowth of cortical neurons in vitro and axonal regeneration in vivo.

Peripheral myelin P0 protein is a homophilic adhesion molecule of immunoglobulin superfamily to compact myelin structure. In addition to its roles in formation and maintenance of myelin, P0 shows neurite-outgrowth promotion activity of dorsal root ganglions. In this paper, we examined biological activity of P0 in central nervous system (CNS). Neurite outgrowth of cortical neurons of rat embryo was markedly promoted in the co-culture on C6 transformants expressing P0 protein. The neurite outgrowth was not inhibited by the P0-glycopeptide but specifically inhibited by the anti-P0 monoclonal antibody recognizing the extracellular peptide of P0. In in vivo studies, we observed significant axonal regeneration into grafts only in animals implanted with P0-expressing transformants after spinal one-third transection. These results suggest that P0 protein has promoting activity on the neurite elongation in CNS as well as in peripheral nervous system.

Animals↗
PubMed1994

The effect of some proteinase inhibitors on liquefaction of human semen.

This study examined the effect of some proteinase inhibitors on liquefaction of human semen. It revealed that a strong plasmin inhibitor, 6-amidino-2-naphthyl-6-guanidinobenzoate dihydrochloride (Fusan) showed a significant inhibition of liquefaction, while t-amino caproic acid (t-ACA) showed a weak retardation effect. In terms of sperm quality after liquefaction, Fusan (10 mM), ethyl diamine tetra-acetic acid (EDTA) and Urinastatin completely inhibited sperm motility. Fusan (1 mM) and Lima bean trypsin inhibitor (LBTI) decreased sperm motility significantly, while leupeptin and t-ACA had little effect. Leupeptin, LBTI, t-ACA and Fusan (1 mM) did not affect sperm speed. 50% inhibition of sperm motility was calculated to be approximately 1.7 mM of Fusan concentration. In addition, two inhibitors, Chymostatin and Phosphoramidon were also tested with each experiment and had no effect on liquefaction or on sperm motility and speed. These results strongly suggest that plasmin may play an important role in the liquefaction process of human semen.

Adult↗
PubMed1994

[Inferior vena caval tumor thrombus in a patient with renal angiomyolipoma associated with tuberous sclerosis].

A 34-year-old woman with tuberous sclerosis presented with an increase of an abdominal mass and intermittent left flank pain on May 20, 1991. Computed tomography showed multiple bilateral renal masses with fatty density areas and a fatty density thrombus in the inferior vena cava, which extended through the right renal vein of the right kidney on ultrasonography. The inferior vena caval thrombus was also demonstrated by magnetic resonance imaging. Since marked deterioration of the right renal function was found on renography, right radical nephrectomy with thrombectomy was performed on July 2. Microscopically all tumors were identical with angiomyolipoma. She was discharged on Jury 20 and had been followed with good renal function at the outpatient clinic for more than 2 years. Follow up CT revealed no interval changes in the left renal masses.

Adult↗
PubMed1993

Seroepidemiology of human herpesvirus 7 in healthy children and adults in Japan.

The isolation of human herpesvirus 7 (HHV-7) from saliva and blood, and the prevalence of antibodies to the virus in healthy individuals were investigated in Japan. By cocultivating samples with phytohemagglutinin-P-stimulated cord blood mononuclear cells, HHV-7 was isolated from the saliva of 1 of 20 children and from 4 of 38 adults but not from their blood. The isolates were confirmed as closely related to RK strain of HHV-7, but not to U1102 (human herpesvirus 6, HHV-6 type A) or Z29 (HHV-6 type B) strains by restriction cleavage patterns of the DNA. The virus antibody of 330 healthy children and adults was measured with an indirect immunofluorescence assay, using one of our isolates (FG7-6). The positivity rate of antibody was 40% in the first 2 months of life, declined during the first 6 months, then gradually increased and was 45% at 1-4 years of age. It reached the highest level (60%) at 11-13 years of age and was maintained until the end of the third decade, then decreased thereafter. Additionally, no simultaneous rise in the antibody titers was observed in 7 virologically confirmed exanthem subitum patients.

Adolescent↗
PubMed1993

Two forms of acidic arginine amidases in human kidney.

Two forms of acidic arginine amidases were separated from human kidney extract using the techniques of basic ion exchange adsorption and elution as well as lima bean trypsin inhibitor (LBTI) and aprotinin affinity adsorptions and elutions. The enzymes were tentatively named acidic human renal arginine amidase-L (AHRAA-L, with affinity to an LBTI column) and -A (AHRAA-A, with affinity to an aprotinin column). Both enzymes showed a similar molecular mass of approximately 3.0 x 10(4) daltons, differing from that of human renal kallikrein (HRK, molecular mass of 4.8 x 10(4) daltons). The specific activity of AHRAA-L and -A were 106 and 680 nmol/min/A280 of Val-Leu-Arg-pNA amidolysis, respectively, and they were strongly inhibited by LBTI and human urinary trypsin inhibitor (UTI), while ethylenglycol-bis(beta-amino ethylether)-N,N,N',N'-tetraacetic acid (EGTA) showed a weak or no effect on both enzymes.

Esterases↗
PubMed1993

Clinical features of primary human herpesvirus-6 infection in an infant with acute lymphoblastic leukemia.

PURPOSE: The primary infection with human herpesvirus-6 developed concurrently with diagnosis of acute lymphoblastic leukemia and initiation of intensive chemotherapy for the disease in a 4-month-old girl. RESULTS: Prolonged viremia persisted for 7 days in the presence of neutralizing antibodies, and clinical features such as prolonged febrile and diarrheal period, no appearance of skin rash, and marked bulging fontanelle for 7 days in the absence of the virus DNA in spinal fluid may suggest an atypical clinical course of exanthem subitum and an unusual viral replication in immunocompromised condition.

DNA, Viral↗
PubMed1992

Glycopeptide of P0 protein inhibits homophilic cell adhesion. Competition assay with transformants and peptides.

Expression of major myelin glycoprotein P0 by P0 cDNA transfection into C6 glioma cells promoted homophilic cell adhesion of the cells. After the dissociated cells were incubated for various times, the number of particles at each time point was measured. The total number of particles decreased to 24% in 60 min for transformant (C6P0) cells, in contrast to only 68% for control (C6P0') cells. To confirm the homophilic mechanism of adhesion, mixed-cell aggregation experiments were performed. Among the four synthetic peptides corresponding to a part of the P0 sequence used, only peptide 3 (residues 90-96), which contained a carbohydrate attaching site, caused considerable inhibition of cell aggregation (approximately 50%). In addition, the glycopeptide (residues 91-95) obtained from bovine P0 markedly inhibited cell aggregation (by approximately 85%).

Amino Acid Sequence↗
PubMed1992

Endonuclease analyses of DNA of human herpesvirus-6 isolated from blood before and after bone marrow transplantation.

Three strains of human herpesvirus-6 (HHV-6) were isolated from peripheral blood mononuclear cells of a leukemic child with the antibody of HHV-6 before and after bone marrow transplantation (BMT); two strains were obtained before BMT and one after BMT. The DNA extracted from the three isolates was analyzed by six different restriction endonucleases. The cleavage profiles of two strains obtained before BMT were different, but the third strain isolated after BMT was identical with one of the two, which suggest reactivation of HHV-6 from the recipient's own body after BMT and possible mutation or super-infection of the virus in an immunocompromised patient.

Bone Marrow Transplantation↗
PubMed1992

Activation of human herpesvirus-6 in children with acute measles.

Virological and serological studies were carried out prospectively to evaluate the possible activation of human herpesvirus-6 (HHV-6) in 50 infants and children with acute measles by isolation of HHV-6 from peripheral blood and by determining neutralizing antibodies to the virus. All but 5 patients (90%) were seropositive to HHV-6 in the acute stage of measles and 18 (40%) had a significant increase in HHV-6 antibody titers thereafter, whereas only 2 of 27 patients who were initially seropositive to Epstein-Barr virus (EBV) viral capsid antigen (VCA) had a significant rise in antibody titers to EBV VCA. Among 18 patients with a significant increase in HHV-6 titers, the virus was isolated from the peripheral blood mononuclear cells of three patients in the early convalescent stage of measles. These results indicate that activation of HHV-6 may occur frequently a few weeks after primary infection with the measles virus.

Acute Disease↗