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Biomedical subjects

S Harada

Publications and source records attributed to S Harada.

At least 433 records · Page 24Linked to original sources

Comparison of atrophic and goitrous auto-immune thyroiditis in children: clinical, laboratory and TSH-receptor antibody studies.

We studied the clinical features, laboratory and thyroid functions and thyrotropin (TSH)-receptor and thyroid-stimulation antibodies in 21 patients with atrophic auto-immune thyroiditis (AAT) and 48 patients with goitrous auto-immune thyroiditis (GAT) of childhood onset. The clinical features of patient with AAT were cessation of growth and obesity, while asymptomatic enlargement of the thyroid gland was the sole symptom in most patients with GAT. Although the ages at diagnosis were comparable in both groups, the estimated ages at onset were much lower in patients with AAT than in those with GAT. Patients with AAT exhibited more severe hypothyroidism when evaluated by serum thyroxine (T4), tri-iodothyronine (T3), TSH, cholesterol levels and basal metabolic rates. The 24 h 123I-thyroidal uptake was significantly lower in patients with AAT than in those with GAT. None of the 19 patients with AAT possessed TSH-binding inhibitor immunoglobulins (TBII). On the other hand, 3 of the 32 GAT patients tested, possessed weak to potent TBII activities. Three TBII-positive patients with GAT also possessed thyroid-stimulation blocking antibodies. These findings suggest that: 1. Pathogenesis of AAT in children whose onset of hypothyroidism was before puberty is not due to TSH-receptor blocking antibodies, which are often found in patients with AAT of postpubertal onset. 2. AAT in children is considered not to be due to the later stage of GAT. 3. Some patients with GAT possessed TSH-receptor blocking antibodies. The aetiology and pathogenesis of AAT in children have yet to be elucidated.

Adult↗

Unintegrated DNA in cells infected in vitro with human immunodeficiency virus (HIV): a new approach to suppression of virus release.

Retroviral RNA is copied into DNA by reverse transcriptase when the viral genome enters into its life cycle. In the case of human immunodeficiency virus (HIV), massive amounts of unintegrated viral DNA reportedly appear in the early phase of primary infection. However, the relationship between the accumulation of this DNA and the cytopathic effect (CPE) remains obscure. In an attempt to delineate this association, we examined the appearance of the unintegrated viral DNA by means of two experimental systems: (1) primary infection of highly susceptible MOLT-4#8 cells and (2) induction of CPE by cell-fusion of persistently infected MOLT-4#8 cells. A correlation was observed between the accumulation of unintegrated viral DNA and the appearance of CPE, both when MOLT-4#8 cells were infected with cell-free virus and when persistently infected MOLT-4#8 cells were co-cultured with uninfected cells. Persistently infected cells did not fuse spontaneously in culture, because they lack the CD4-molecule on their surfaces. However, when treated with polyethylene glycol (PEG), the cells fused, exhibited ballooning degeneration, and released fewer viruses. After PEG treatment, unintegrated viral DNA also appeared. Since such DNA is generally not detected in persistently infected cells, it is possible that some cellular mechanism exists to suppress the synthesis of viral DNA and that the fusion induced by PEG treatment cancels the suppression. Treatment of persistently infected cells with Ca2+ ionophore and Ca2+ antagonist also resulted in the accumulation of unintegrated viral DNA and inhibited virus release. These findings suggest that the induction of unintegrated HIV DNA may be an effective strategy for reducing the release of the virus.

Animals↗

2,3 Dimercapto-1-propanol inhibits HIV-1 tat activity, viral production, and infectivity in vitro.

We have examined the effect of 2,3 dimercapto-1-propanol (DMP), which is known as an anti-heavy metal-poisoning drug, against human immunodeficiency virus type 1 (HIV-1). We demonstrate that DMP inhibited transactivation directed by tat protein, which is a metal containing transcriptional transactivating factor and also interfered with viral production. Furthermore, treatment and pretreatment of cells with DMP strongly reduced their sensitivity for HIV-1 infection through unknown mechanisms. These results indicate that DMP reveals pleuripotent effects on HIV-1 infection and production in vitro and thus may provide an exploitable hypothesis for designing new drugs against AIDS.

Amino Acid Sequence↗

Synergistic infectivity of highly and minimally infectious clones of human immunodeficiency virus in vitro.

To explore the biologic significance of the presence of a heterogeneous human immunodeficiency virus (HIV) population within infected individuals with regard to ultimate disease progression, the effect of coinfection of more than one variant of HIV on infectivity and cytopathogenicity in CD4-positive cells was examined. Using the lowest and highest infectious clones of HIV obtained by the plaque-cloning method, a clear consistent synergism of infectivity and cytopathic effects was detected when different cell lines were coinfected with a mixture of the two clones. These data suggest that the emergence of a highly infectious variant of HIV due to mutation may modify the infectivity of a minimally infectious latent variant with the final progression of HIV infection to overt AIDS.

Cell Line↗

Interaction between two distinct plaque-cloned human immunodeficiency viruses (HIVs): the possible existence of heterozygous virus.

To know the biological significance of the HIV variation, we investigated the interaction between two different HIV clones. Two distinct clones were mixed and propagated by infecting MT-4 cells. After passaging the mixture viruses 8 times, and cloning by the plaque method, we obtained not only viruses of homogeneous type like each parental clone but also heterogeneous-type viruses which showed a mixture of two parental viruses with regard to phenotype and genotype. To further segregate a single virus from the mixture, we recloned the heterogeneous viruses using the plaque method. We found that about 40% of recloned viruses from heterogeneous-type viruses were still heterogeneous.

Animals↗

[Epidemiologic analysis of DNA's of herpes simplex virus, type 1 and type 2 isolates obtained from family members and from different lesions of individuals].

We analyzed herpes simplex virus type 1 (HSV-1) or type 2 (HSV-2) infections in 6 families, to see whether or not a single strain had infected members of each family, analyzing DNA's of viral isolates with restriction endonucleases. We also analyzed 29 isolates from 13 patients to examine if herpetic lesions on different sites of each patient's body had been caused by a single strain. In 4 cases of family infection and 10 cases of individual infection with multiple site manifestations, electrophoretic profiles of digested DNAs of the epidemiologically closely related HSV-1 or HSV-2 isolates were exactly the same. In the other 2 family infections and the other 3 individual infections, there were some differences in size of certain DNA fragments among the isolates which were epidemiologically related to one another. But, these differences did not necessarily indicate that they were distinct strains. Thus, it has been suggested that a single strain spreads among members of a family, and herpetic lesions on different sites of an individual body are caused by the same viral strain in most cases of HSV-1 or HSV-2 infections.

Adult↗

Interference with human immunodeficiency virus (HIV) replication by CD8+ T cells in peripheral blood leukocytes of asymptomatic HIV carriers in vitro.

A long asymptomatic period is one of the characteristics of human immunodeficiency virus (HIV) infection, despite its fatal consequences. Antiviral defense in HIV-infected individuals controls viral replication during this period. In the present study, we demonstrate that peripheral blood leukocytes (PBL) of asymptomatic HIV-1 carriers, following exogenous HIV-1 infection in vitro, do not support viral replication. These cells do not produce detectable amounts of reverse transcriptase or accumulate unintegrated proviral DNA. This is a striking contrast to the behavior of HIV-1-infected PBL of seronegative individuals, which produce large amounts of RT and unintegrated DNA. Such resistance to HIV-1 replication is not seen in PBL of patients with advanced disease. Since the binding of HIV-1 to CD4 molecule is not impaired in PBL of asymptomatic carriers, the interference with HIV replication must occur after the stage of virus binding. PBL lose their resistance when CD8+ lymphocytes are removed. In addition, these PBL are not resistant to an exogenous infection with HIV-2. These observations suggest that certain populations of CD8+ lymphocytes of asymptomatic HIV-1 carriers operate on the target cells in PBL to block viral replication in an HIV-1-specific manner. Such CD8+ lymphocyte-mediated interference with HIV replication could play an important role in the maintenance of the period of disease latency.

AIDS-Related Complex↗

Increased gamma-aminobutyrate aminotransferase activity in brain of patients with Alzheimer's disease.

In order to search for more proximal factors in the pathogenesis of Alzheimer's disease, we studied the activities of various enzyme in the brains of patients, as well as control cases, by postmortem autopsy. In addition to the findings already known, such as the increase in prolyl endopeptidase (post-proline cleaving enzyme, PPCE) activity and the decrease in kallikrein activity, we found, anew, an increase in aminobutyrate aminotransferase (GABA-T) activity in the Alzheimer brain. This may be an important impetus for the reduction of gamma-aminobutyric acid (GABA) in the brain, one of the neurotransmitters. It has to be determined whether the former two abnormalities offer a background for such an abnormality of the neurotransmitter.

4-Aminobutyrate Transaminase↗

Increase in aminobutyrate aminotransferase and cholineacetyltransferase in cerebrum of aged rats.

We previously reported an increase in aminobutyrate aminotransferase (GABA-T) activity in the cerebrum of Alzheimer patients. In the present study, we investigated whether such findings are common in the usual aging process as well. We examined the activity of various enzymes, which were examined in the previous study, in the cerebrum of Wistar-Kyoto rats and spontaneously hypertensive rats. In the two strains, we compared the enzyme activities between the two groups of animals, 5 weeks and 13 weeks of age. In both strains, the older animals had significantly higher activities of GABA-T and choline acetyltransferase (ChAc-T). In spite of other enzymatic changes coexisting, the above two enzymes were suggested by discriminant function analysis to be playing a major role in the multiple enzymatic changes in the cerebrum of the animals.

4-Aminobutyrate Transaminase↗

Fosfadecin and fosfocytocin, new nucleotide antibiotics produced by bacteria.

Two new nucleotide antibiotics, fosfadecin and fosfocytocin, have been isolated from the culture filtrates of Pseudomonas viridiflava PK-5 and Pseudomonas fluorescens PK-52, respectively. These antibiotics were purified by column chromatographies using adsorption, gel filtration and ion exchange resins. On the basis of the spectroscopic and degradation studies, the chemical structures of fosfadecin and fosfocytocin were determined. These antibiotics were either enzymatically or chemically hydrolyzed to generate fosfomycin and a new antibiotic, fosfoxacin, which are also produced in the culture filtrates. They showed antibacterial activity against Gram-positive and Gram-negative bacteria. The antibacterial activity of these nucleotide antibiotics was weaker than that of fosfomycin and fosfoxacin.

Adenosine Diphosphate↗

[Tuberculosis sequelae: clinical aspects].

We studied the pulmonary diseases which had developed as consequent deformities after healing of tuberculosis, which we called tuberculosis sequelae. Results are described as follows. 1. The frequency of tuberculosis sequelae was about 6% in the patients with pulmonary diseases admitted to our hospital. 2. 93 cases of them consisted of 4 groups, which were 39 of repeated bacterial infection of lower respiratory tract, 23 of pulmonary aspergilloma, 13 of atypical mycobacteriosis and 28 of chronic respiratory failure. 3. Patients with tuberculosis sequelae were distributed more in the younger age group than others with resembled pulmonary diseases. The men to women ratio was about 2:1. Patients with pulmonary aspergilloma were younger than those with atypical mycobacteriosis. 4. Death rate in tuberculosis sequelae was about 5% per year. 46% of patients with atypical mycobacteriosis and 44% with chronic respiratory failure died within 4 years. 5. In chest X-ray findings, fibrosis and shrinkage of the lung, compensatory pulmonary emphysema, deformity or dilatation of bronchi, bulla formation and residual tuberculous cavities were recognized in 40 to 65% of the cases. Severe pleural thickness or past thoracoplasty were frequently recognized in the patients with chronic respiratory failure. All the patients with pulmonary aspergilloma had one or more residual cavities. 6. The frequency of systemic complications was not more than in the control population matched by age. Comparatively, serum IgG and IgA were elevated and PHA-induced lymphocyte activation was not lowered in the patients with pulmonary aspergilloma and atypical mycobacteriosis. From these results, the main factor in the development of tuberculosis sequelae seemed to be local defects of the chest.

Adult↗

The influence of materials difference on stress distribution and bone remodeling around alumina and titanium dental implants.

The long-term complications of dental implants are associated with loosening of the implant-bone interface, due to bone resorption and subsequent connective tissue interposing at the implant-bone interface. Mechanical stresses, which are induced in the surrounding bone, play a key role in the interface bone remodeling. In the present study, it is investigated how local stress patterns are associated with local bone structure. For identical geometry alumina, and titanium implants, the stress patterns, determined in the finite element models with boundary conditions, are compared with the local bone structure found in animal experiments. The results indicate that there appears to be relationship between the stress patterns and the bone remodeling at the implant-bone interface independently on the materials properties in alumina and titanium.

Aluminum Oxide↗

Three main components in plasma proteases and their relation to the renin-angiotensin system.

The relation of plasma renin activity (PRA) and plasma levels of angiotensin I (AI) and II (AII) to those of various proteases, including eight endopeptidases and four aminopeptidases, was investigated in 51 normal control subjects. The multivariate study using factor analysis showed that the plasma proteases can be classified into three main components: the aminopeptidase, the plasmin, and the kinin-kallikrein. PRA and AI were related almost exclusively to the aminopeptidase component, while the AII level was related not only to the same component but also to the kallikrein-kinin component. This kind of multivariate study may help in the elucidation of the role of proteases and bioactive peptides, such as angiotensin derivatives, in essential hypertension through a comparison of multivariate relationships in controls and patients.

Amino Acid Sequence↗

[Serological diagnosis of pulmonary aspergillosis--measurement of IgG-, IgM- and IgA- antibodies against Aspergillus fumigatus by means of ELISA].

Serological diagnosis plays an important role in the diagnosis of pulmonary aspergillosis, however, precipitation-in-gel test is neither sensitive nor quantitative. Recently, several investigators have used the ELISA technique for the detection of antibodies against Aspergillus fumigatus and reported the usefulness of this method. In this report, we measured IgG-, IgM-, and IgA- antibody titers against Aspergillus fumigatus by means of ELISA in sera from patients with several different lung diseases including pulmonary aspergillosis. The results obtained were as follows: 1) Measurement of IgG-antibody titers was most useful for the diagnosis of pulmonary aspergillosis. 2) Measurement of IgG-antibody titers was more sensitive than precipitation-in-gel test. 3) IgG-antibody titer was quantitative and reflected the clinical course of pulmonary aspergillosis.

Antibodies, Fungal↗

[Anesthetic experience of a patient with blue rubber bleb nevus syndrome].

We report an anesthetic experience of a 63-year-old female patient with blue rubber bleb nevus syndrome who underwent an open reduction of the fracture of the right femur. The syndrome is characterized by bluish nevus scattered throughout the skin of the whole body and angiomas of the gastrointestional tract causing serious bleeding. Anesthesia was induced with thiopental followed by intravenous injection of succinylcholine chloride and maintained with neuroleptanesthesia in nitorous oxide and oxygen. The course of anesthesia and emergence from anesthesia were uneventful. Anesthetic management of patients with blue rubber bleb nevus syndrome was also discussed.

Female↗