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Biomedical subjects

O Yamada

Publications and source records attributed to O Yamada.

At least 127 records · Page 7Linked to original sources
PubMed1993

A hairpin ribozyme inhibits expression of diverse strains of human immunodeficiency virus type 1.

Ribozymes have enormous potential as antiviral agents. We have previously reported that a hairpin ribozyme expressed under the control of the beta-actin promoter that cleaves human immunodeficiency virus type 1 (HIV-1) RNA in the leader sequence can inhibit HIV-1 (pHXB2gpt) expression. For such a ribozyme in a retroviral vector delivery system to be useful in gene therapy for the treatment of HIV-1 infection, it must be able to inhibit the expression of multiple HIV-1 strains. We have now cloned this ribozyme into various regular expression vectors (including retroviral vectors) by using various gene expression control strategies. Here we show by transient transfection that inhibition of expression of diverse strains of HIV-1 can be achieved by this ribozyme expressed in the proper vectors. These data further support the potential of this hairpin ribozyme as a therapeutic agent for HIV-1.

Antiviral Agents↗
PubMed1993

[Isolation of HIV-1 and its correlation with various HIV-markers in Japan].

In Japan, the isolation rate of HIV-1 has increased in recent years, and has become as high as 36.7% in 1991. In order to evaluate the onset of AIDS, we have collected various HIV markers, which were obtained from surveillance committee of Natural History. These data include a total of 1991 specimens (actual number 556 individuals) from Japanese hemophiliacs and non-hemophiliacs since 1985. The data analysed CDC stage, leucocyte counts, lymphocyte counts, CD4+ cell counts, CD8+ cell counts, CD4/CD8 ratio and immunoglobulins (IgA, IgG, IgM). The results indicate that in HIV-isolation positive patients, leucocyte counts, lymphocyte counts, CD4+ cell counts, CD8+ cell counts and CD4/CD8 ratio were significantly lower than those of HIV-isolation negative patients in both hemophiliacs and non-hemophiliacs. IgA value of the positive patients was significantly higher than that of the negative patients, while the IgM value showed converse results to the IgA, in hemophiliacs only. In general, the difference of each HIV marker in non-hemophiliacs was more conspicuous than those in hemophiliacs.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Laboratory findings and clinical courses of 33 patients with granular lymphocyte-proliferative disorders.

The hematological and immunological findings and clinical courses of 33 patients (13 male, 20 female; median age at presentation, 60 years) with granular lymphocyte-proliferative disorders (GLPD) are presented. Based on the surface phenotypes of peripheral blood granular lymphocytes (GL), the GLPD were divided into CD3+ T cell-lineage GLPD (T-GLPD) and CD3- CD16+ natural killer (NK) cell-lineage GLPD (NK-GLPD). Twenty-one patients had T-GLPD, and 12 had NK-GLPD. One patient with T-GLPD and two patients with NK-GLPD had progressive clinical courses and died of the disease despite receiving combination chemotherapy. Twelve patients with T-GLPD were found to have severe anemia at presentation or during the course of the disease; four of them fulfilled the diagnostic criteria of pure red cell aplasia, and the others had closely related conditions. Six of these 12 patients were treated with cyclophosphamide, and all responded to the treatment. In 16 patients, the clinical course was stable, and spontaneous regression was observed in two patients. Since some of the patients with NK-GLPD had stable clinical courses while some had progressive clinical courses, clinical findings in these two groups were compared. We found, taking into consideration our cases and those reviewed in the literature, that age less than 40 years, fever, lymph node swelling, hepatosplenomegaly, and GL with CD16(Leu-11)-CD56+CD57- phenotype and low or absent antibody-dependent cellular cytotoxicity seemed to be predictors of a progressive clinical course.

Adult↗
PubMed1993

[Composite valve graft replacement for aortic root aneurysm or dissection].

Fifty four patients who had aneurysms (n = 35) or dissections (n = 19) associated with aortic regurgitation underwent the replacement of the ascending aorta and aortic valve by composite valve graft during 15-year period between September 1976 and December 1991. Of these, 49 (90.7%) patients had an annuloaortic ectasia and 26 (48.1%) had the Marfan syndrome. The methods of coronary artery reattachment to the graft were as follows: direct reattachment (original Bentall's technique) in 45 patients, aortic button technique (Carrel's patch technique) in 6, Cabrol's technique in 2 and Piehler's technique in 1 patients. Seven patients with a DeBakey type I dissection had concomitant replacement of the aortic arch with an aid of selective cerebral perfusion. The overall hospital mortality rate was 12.9%, and it has significantly decreased to 6.7% since we adopted a cold cardioplegia, preclotting the graft with albumin autoclave technique and coronary artery reattachment using conventional over-and-over and interrupted mattress sutures with pledgets during the last 10-years. The mean duration of follow-up period was 58.6 months. The actuarial survival rate at 10 years for all patients was 76.4%; for those with dissection, 78.4%; and for patients with Marfan syndrome, 70.4%. Reoperation for the prosthesis-related complications was necessary in only one patient, although operations on the remainder of aorta were required in 5 patients. Actuarial freedom from these operations at 10 years was 74.1%, but it was 69.3% for the subgroup with Marfan syndrome. The present data indicates that composite valve graft technique is an useful method for patients with aortic root aneurysms or dissections.

Adult↗
PubMed1993

Telomere reduction in hematologic cells.

The broken ends of chromosomes are unstable, and tandem fusion of telomeres has been observed in some tumors. Using Southern blot analysis, we report here telomeric DNA changes in hematologic cells. There was some variation in the length of the telomeric DNA in normal peripheral blood mononuclear cells obtained from four different individuals, ranging from 10 to 12 kilobases (kb), but there was little difference in signal strength. In two cell lines tested, HL-60 and K562, there was a telomeric sequence reduction of 2-4 kb and there was also a diminution of signal intensity. Reduction of the telomeric DNA array was also observed in two leukemic cases tested. The peak telomere length of the leukemic cells was 5 and 4 kb before and 10 and 7 kb after treatment, respectively, and in one case there was also a reduction in copy numbers of about 50%. Since no remarkable changes were detected in the Alu and alphoid sequences in either normal or leukemic cells, it appeared that the DNA change was specific to telomeric regions. Assessment of telomeric DNA changes may aid in determining the biological significance of leukemic cells.

Adult↗
PubMed1992

A deletional frameshift mutation of the beta-spectrin gene associated with elliptocytosis in spectrin Tokyo (beta 220/216).

A novel spectrin variant carrying a truncated beta-chain and designated Spectrin Tokyo (beta 220/216) is presented. It was associated with elliptocytosis and moderate uncompensated hemolysis. The dimer self-association was reduced. An increase of the alpha I 74-Kd fragment was detected upon partial trypsin digestion. Analysis of cDNA and genomic DNA showed a 1-base deletion in codon 2059 (GCC AGC-->GCA GCT; Ala-Ser-->Ala-Ala) that belongs to exon X of spectrin beta-gene. A missense sequence extended down to (new) codon 2075. Serine 2060, a potential phosphorylation site, was replaced by alanine. The shortened beta-chain failed to undergo phosphorylation in vitro. Spectrin Tokyo shared the same stop codon, overlapping normal codons 2076 and 2077 (CTG AAA), as Spectrin Nice (beta 220/216), which is caused by a dinucleotide insertion in codon 2046 and contains 2076 amino acids. However, for some reason, Spectrin Tokyo had a lower incorporation level into the membrane than Spectrin Nice.

Base Sequence↗
PubMed1992

Granular lymphocyte leukemia with pure red cell aplasia: usefulness of gene analysis in assessing therapeutic effect.

A patient with granular lymphocyte leukemia (GLL) of the CD3+, CD4-, CD8+ phenotype accompanied by pure red cell aplasia (PRCA) is described. Surface marker analysis, nonmajor histocompatibility complex (MHC)-restricted cytotoxicity assay, gene analysis, and in vitro colony assay were performed on the granular lymphocytes before and after treatment. Cyclophosphamide therapy was highly effective, and after remission clonal granular lymphocytes were no longer identified by T-cell antigen receptor (TCR) gene analysis or surface marker analysis. Lymphocytes obtained after remission did not exhibit elevated levels of non-MHC-restricted cytotoxicity, nor did they demonstrate a suppressive effect on erythroid colony formation. TCR gene analysis proved to be a sensitive parameter for evaluating the residual malignant granular lymphocytes. Gene analysis will be useful both for timing the discontinuation of treatment and for the early detection of relapse. Various factors possibly related to the development of PRCA in this patient were investigated and their significance is discussed.

Bone Marrow↗
PubMed1992

Selective cerebral perfusion during operation for aneurysms of the aortic arch: a reassessment.

Thirty-two consecutive patients with thoracic aortic aneurysms who required aortic arch reconstruction were operated on with the aid of extracorporeal circulation and selective cerebral perfusion between January 1986 and August 1990. For selective cerebral perfusion, blood was infused into both the innominate and left common carotid arteries at a rate of 10 mL.kg-1.min-1 using a single roller pump separately from the systemic circulation. In 9 patients treated before March 1987, the operations were performed without open aortic anastomosis (group 1), whereas in 23 patients treated from March 1987 onward we used open aortic anastomosis (group 2). The extracorporeal circulation and cardiac arrest times were significantly longer in group 2, but there was no significant difference in the cerebral perfusion time. Early death occurred in 1 patient in group 1 and 2 in group 2. No serious cerebrospinal neurological complications occurred in either group, and there were similar rates of postoperative hepatic and renal dysfunction in both groups. The present data suggest that selective cerebral perfusion and open aortic anastomosis are useful methods for thoracic aortic aneurysm operation requiring complex repair of the aortic arch.

Adult↗
PubMed1992

Hepatitis C virus RNA and hepatitis C virus antibody in the serum of patients with abnormal liver function.

In order to elucidate the relation between hepatitis C virus (HCV) RNA and antibody to HCV (anti-HCV) in serum, we examined samples of serum collected from 228 HBsAg-negative patients, with abnormal alanine aminotransferase (ALT) values, for HCV-RNA by nested polymerase chain reaction (PCR) assay and for anti-HCV using C100 protein as the antigen. HCV-RNA was detected in 99 (92.5%) of 107 anti-HCV-IgG-positive samples, regardless of ELISA optical density cut-off value (ELISA ratio), and in 34 (28.1%) of 121 anti-HCV-IgG-negative samples in which the frequency of the presence of HCV-RNA became higher in proportion to the ELISA ratio. Among 42 discordant cases (34 anti-HCV-IgG-negative, RNA-positive cases and eight anti-HCV-IgG-positive, RNA-negative cases), 10 were positive for anti-HCV-IgM (8/34 and 2/8, respectively) irrespective of clinical status. These findings suggest that in patients with abnormal ALT values, even if they are anti-HCV-IgG negative, HCV infection cannot be excluded. Furthermore, PCR assay for detecting HCV-RNA may be more suitable for identifying patients with infectious virus than is detection of anti-HCV-IgG. Detection of anti-HCV-IgM may also be useful.

Alanine Transaminase↗
PubMed1992

Rapid DNA diagnosis of herpes simplex virus serotypes.

The presence of nucleotide sequences specific for each of herpes simplex virus (HSV) serotypes was demonstrated. These sequences were applied for dot DNA-DNA hybridization and for PCR for rapid DNA diagnosis of HSV infections. These sequences were found by molecular cloning of HSV-DNA fragments after digestion of DNA by KpnI enzyme. The type 1-specific sequence was found around the 5' end of BamHI B-fragment in the L region of type 1 DNA (corresponds to alpha gene 27, promoter-regulatory region) and the type 2-specific sequence was around the junction region of the L and S of type 2 DNA (corresponds to a' sequence). Both simple dot blot hybridization and PCR of HSV DNA's, employing these type-specific nucleotide sequences, were proven to be much more useful than immunofluorescence in terms of type-specific diagnosis of HSV infections.

Base Sequence↗
PubMed1992

Detection of HIV-1 RNA in heparinized plasma of HIV-1 seropositive individuals.

The interference of reverse transcription by heparin was removed by heparinase. When the HIV-1 RNA in the presence of heparin was detected by a combination of reverse transcription and the polymerase chain reaction (PCR), heparinase treatment followed by removal of Ca2+ before the reverse transcription step permitted the efficient detection of HIV-1 RNA. Prior treatment with heparinase revealed HIV-1 RNA in 68% (13/19) of heparinized plasma samples from HIV-1 carriers, whereas only 26% (5/19) of the same specimens were positive without the heparinase step. Heparinase removed the inhibition of reverse transcription by heparin and is highly recommended when detecting low levels of viral RNA in heparinized plasma.

HIV Reverse Transcriptase↗
PubMed1992

A prospective study on correlation between the decrease in anti-P17 antibody level and progression to AIDS in asymptomatic carriers of HIV.

As the majority of human immunodeficiency virus (HIV) carriers are in asymptomatic stage for a long period of time, it is important to investigate the factors or surrogate markers for conversion from asymptomatic to symptomatic stage. Our study is designed to evaluate the relationship among virus isolation rate, anti-p17 antibody status and progression to AIDS. We studied anti-p17 antibody status along with virus isolation in 56 asymptomatic carriers and 46 AIDS cases. Progression to AIDS was markedly associated with high rate of virus isolation and loss of anti-p17 antibody. In order to know the meaning of loss of anti-p17 antibody during the clinical course, 15 anti-p17 antibody positive and 16 anti-p17 antibody negative cases were followed up prospectively for the development of AIDS. None of the anti-p17 antibody positive cases developed AIDS while 6 out of 16 anti-p17 negative cases developed AIDS during observation period (P < 0.05). Progression to AIDS was associated with loss of anti-p17 antibody. Identification of cases losing anti-p17 antibody in peripheral blood during asymptomatic period may help high-risk group who are in need of chemoprophylaxis. Moreover, study of anti-p17 antibody may be helpful in designing vaccine in future if it works as a neutralizing antibody to HIV in vivo.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Langerhans-cell histiocytosis in an adult patient with multiple myeloma.

A 44-year-old man who had suffered for 6 years from multiple myeloma developed multiple papules on the face and chest. Histological examination of these papules revealed the infiltration of predominantly histiocytic cells into the dermis and into parts of the epidermis. These cells were seen on electron-microscopic study to have Langerhans granules in the cytoplasm, which led to a diagnosis of Langerhans-cell histiocytosis concomitant with multiple myeloma. Possible explanations for this unusual association are discussed.

Adult↗
PubMed1992

[A case of chronic myelogenous leukemia with pulmonary aspergillosis diagnosed by the detection of circulating Aspergillus antigen].

Immunocompromised hosts usually develop invasive mycotic disease. Among many pathogenic fungi. Aspergillus spp, is the most common pathogen of respiratory infection. Early diagnosis of invasive type pulmonary aspergillosis is still difficult, and the treatment is usually difficult. Many investigations have recently suggested that detection of Aspergillus antigen from sera of the patients is useful for early diagnosis to save their lives. We have experienced a case diagnosed by the detection of circulating Aspergillus antigen by Pastorex Aspergillus, who was a 64-year-old female with the blastic crisis chronic myelogenous leukemia. After anti-leukemic chemotherapy, she suffered from pneumoniae with pleural effusions and severe hypoxia, which did not respond to antibiotics. At this point, her serum sample showed positive Aspergillus antigen by Pastorex Aspergillus. She was treated by intensive antifungal chemotherapy, and thereafter improved quickly. Titers of Pastorex Aspergillus were well correlated with her clinical course. The sensitivity of the test requires further improvement, but the specificity of the test is considered to be high enough for clinical use.

Antigens, Fungal↗
PubMed1992

[The evaluation of pre and intraoperative factors influencing the false lumen after graft replacement surgery to the extended dissecting aneurysm].

We evaluated the residual false lumen of type I and IIIb dissecting aneurysm by CT, MRI and angiography postoperatively. The 19 patients with type I dissecting aneurysm were included eleven men and eight women, the average age was 55.8 +/- 10.2 years old. The 20 patients with type IIIb dissecting aneurysm were included sixteen men and four women, the average age was 56.2 +/- 8.5 years old. The rate of distal patent false lumen was 52.6% of type I and 35% of type IIIb dissecting aneurysm after graft replacement surgery. In type I dissecting aneurysm, the rate of distal patent false lumen was 40% of acute stage vs 66.7% of chronic stage, 66.7% of ascending and partial arch replacement vs 46.2% of ascending and total arch replacement, and 90% of graft inclusion technique vs 11.1% of graft exclusion technique. The distal patent false lumen was the lowest (12.5%) with type I dissecting aneurysm of ascending and total arch replacement using graft exclusion technique. In type IIIb dissecting aneurysm, the rate of patent false lumen was 66.7% of acute stage vs 29.4% of chronic stage, 30% of graft exclusion technique vs 40% of graft inclusion technique. The size of false lumen preoperatively were larger (11.1 +/- 4.5 cm2) in patients with distal patent false lumen than that (6.7 +/- 3.2 cm2) of in patients with distal occlusive false lumen.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

[Effects of blood-diltiazem-nitroglycerin-cardioplegia in coronary artery bypass grafting].

Forty-seven patients who underwent coronary artery bypass grafting using blood cardioplegia (BCP) were studied clinically. They were divided into 3 groups based on concentration of diltiazem (DTZ) and nitroglycerin (NTG). Group I (n = 12); DTZ 5 mg plus NTG 5 mg in BCP 1,000 ml, Group II (n = 10); NTG 25 mg in BCP 1,000 ml, Group III (n = 25); DTZ 5 mg plus NTG 25 mg in BCP 1,000 ml. From the standpoint of serum enzyme analysis, there was no significant difference between 3 groups, however, the incidence of perioperative myocardial infarction (PMI) and perioperative coronary spasm (PCS) were significantly higher in Group I than that in other groups. The present data suggests that intramyocardial concentration of NTG in Group II and III were 5 times higher than Group I. Increased dose of NTG in BCP would be benefit for myocardial protection in CABG.

Adult↗