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Biomedical subjects

Y Takebe

Publications and source records attributed to Y Takebe.

At least 55 records · Page 3Linked to original sources
PubMed1997

In vivo sequence variability of human immunodeficiency virus type 1 envelope gp120: association of V2 extension with slow disease progression.

According to the rate of depletion of CD4 cell counts, we grouped 12 cases of human immunodeficiency virus type 1 (HIV-1) infection as 6 rapid (21.0 to 33.8 cells per microl per month) and 6 slow (0.9 to 7.9 cells per microl per month) progressors and determined the individual viral quasispecies patterns by sequencing the genome region encoding the V1, V2, and V3 loops of envelope protein. Although the quasispecies structures varied widely from one individual to another, a strong correlation was observed between a low rate of disease progression and a high degree of genetic diversity of HIV-1. Furthermore, the V2 loop extension was observed specifically in individuals with slow or no disease progression, whereas basic amino acid substitutions in V3 characteristic of a viral phenotype shift from non-syncytium inducing to syncytium inducing were observed in patients with advanced stages of disease regardless of their rate of disease progression. Studies with recombinant viruses suggested that elongation of V2 potentially restricts the capacity of HIV-1 to replicate in macrophages. Thus, our results suggest the association of distinct sequence features of both V3 and V2 with particular patterns of disease progression. Elongation of the V2 loop may be a good predictor of slow disease progression, while basic substitutions of V3 without elongation of V2 are characteristic of rapid progression.

Amino Acid Sequence↗
PubMed1997

[Localization of the pyramidal tract in the internal capsule: relationship between CT classification of thalamic hemorrhage and motor weakness].

To better understand the pyramidal tract of the internal capsule, we evaluated the relationship between the localization of thalamic hemorrhage and motor weakness. On an axial CT scan at the level of the pineal body, two lines were drawn as follows: line-a between the lateral edge of the anterior horn and the lateral edge of the trigone, line-b vertical to the sagittal line and passing the midpoint of the third ventricle. The location of the hematoma was classified into three types according to localization of the center of the hematoma and lateral extension beyond line-a as follows: type A (anterior), type P (posterior) and type PL (postero-lateral). Discrepancy of motor weakness between upper extremities and lower extremities was higher in patients with hematoma of type P and type PL (p < 0.05) than in those with hematoma of type A. Improvement of motor weakness on discharge was higher in patients with type P (p < 0.01) than in those with type A. We concluded that most of the pyramidal tract fibers were located in the third quarter of the posterior limb of the internal capsule but a small number of pyramidal tract fibers were located in the anterior two-thirds of it. A greater number of cortico-spinal fibers to the upper extremities than to the lower extremities occupy the third quarter of the posterior limb of the internal capsule.

Adult↗
PubMed1996

Establishment of human granulocyte-macrophage colony stimulating factor producing transgenic SCID mice.

Previous work has shown the usefulness of severe combined immunodeficient (SCID) mice as in vivo models for the growth of normal human haemopoietic cells and leukaemic cells. Many approaches have been made to improve the engraftment of human haemopoietic cells in SCID mice. We established transgenic mice producing human granulocyte-macrophage colony stimulating factor (hGM-CSF) with the homozygote of the scid gene. Endogenous serum hGM-CSF levels were detected by ELISA [mean 9585 pg/ml (line A, n = 4); mean 1610 pg/ml (line B, n = 4)]. Expression of hGM-CSF was observed in all organs tested including the heart, lung, liver, kidney, spleen, thymus, bone marrow and brain of hGM-CSF transgenic (hGMTg) mice. Morphological analysis of organs and peripheral blood cell counts showed no differences between hGMTg mice and their littermates. Murine Ba/F3 cells expressing functional hGM-CSF alpha beta receptor (BAF/alpha beta cells) could be successfully engrafted in hGMTg SCID mice. The cells invaded multiple organs and caused death within a few weeks of transplantation, although they infiltrated only the spleen of their littermates. These results showed that these hGM-CSF-producing SCID mice are useful as an in vivo assay system for investigating leukaemogenesis.

Animals↗
PubMed1995

Suppression of HIV replication in human monocyte-derived macrophages induced by granulocyte/macrophage colony-stimulating factor.

Susceptibility to HIV infection was examined in macrophages differentiated from human monocytes by macrophage colony-stimulating factor (M-CSF) or granulocyte/macrophage colony-stimulating factor (GM-CSF). The replication of macrophage-tropic human immunodeficiency virus type-1 (HIV-1), which was determined by reverse transcriptase (RT) activity, was significantly suppressed in macrophages induced by GM-CSF (GM-type macrophages) but not in those induced by M-CSF (M-type macrophages). Multinucleated giant cells were formed only in M-type macrophages after HIV infection. However, the expression of CD4 molecules on the surface of both types of macrophages was similar and the proviral DNA was detectable in cell lysates of both macrophages, although the amount of proviral DNA in M-type macrophages was higher than that in GM-type macrophages. Many steps have been defined in HIV infection and replication, such as adsorption of HIV to the cell surface, internalization of the viral core into the cytoplasm, uncoating of viral RNA, reverse transcription and integration of proviral DNA into cellular DNA, transcription and translation of proviral DNA, assembly of viral components, and budding of virus particles. Our findings suggested that the suppression of HIV-1 replication in macrophages induced by GM-CSF is mainly due to a disturbance at certain steps of replication after synthesis of the proviral DNA. Thus, the suppression of HIV replication in GM-type macrophages may provide a model of the latency of HIV infection in vivo.

Antigens, Surface↗
PubMed1995

Ruptured aneurysm of the distal posterior inferior cerebellar artery in a neonate--case report.

A 34-day-old male presented with a rare neonatal ruptured aneurysm of the distal posterior inferior cerebellar artery manifesting as a 10-day history of enlargement of head circumference. Magnetic resonance imaging revealed hydrocephalus and a round infratentorial enhanced lesion which compressed the medulla. Left vertebral angiography demonstrated an aneurysm on the telovelotonsillar segment of the left posterior inferior cerebellar artery. Ventriculoperitoneal shunt emplacement and proximal artery clipping were performed. The cerebrospinal fluid was bloody, suggesting aneurysm rupture had caused hydrocephalus. His postoperative course was uneventful, and neurological and developmental findings were normal 7 months later. Present neuroimaging, surgical, and neuro-anesthesiology techniques allow successful surgical intervention in cases of neonatal ruptured aneurysm.

Aneurysm, Ruptured↗
PubMed1995

[A case of successful acute revascularization using a long vein graft].

We experienced a case of successful acute revascularization using a long vein graft. A 68-year-old man was admitted to our department due to transient ischemic attack of the left hemiparesis. CT scan showed no infarction, but PAO-SPECT revealed moderate hypoperfusion in the right ACA and MCA area. Cerebral angiography demonstrated right IC occlusion at its origin and moderate collateral circulation via leptomeningeal anastomosis from the PCA area, and via the external carotid system, especially directly from STA. But the STA was very narrow. Three days after admission, left hemiparesis appeared again and deteriorated severely. This time the hemiparesis persisted. Although MRI demonstrated little infarction in the right frontal lobe, we decided to carry out revascularization on the same day. Right saphenous vein was harvested for a graft because of the narrow STA. The facial artery and angular artery was selected as a donor and a recipient respectively, to avoid a clamp of the EC and a craniotomy of the STA running area. Finally we performed a facial artery-vein graft-angular artery (M4) bypass. The patient showed no complication and the left hemiparesis improved enough to allow the patient to walk by himself. Revascularization using vein graft is dangerous for acute ischemia due to the possibility of a complication such as brain edema and hemorrhagic infarction. The usual style of vein graft bypass is an EC-vein graft-M2 or M3 bypass. Using this style, high pressure inside the EC is carried intracranially.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1994

Pharmacokinetics and safety of NM441, a new quinolone, in healthy male volunteers.

The safety and pharmacokinetics of NM441, a prodrug of a new thiazeto-quinoline carboxylic acid derivative, NM394, were evaluated in healthy male volunteers given the drug orally in single doses of 20, 50, 100, 200, and 400 mg, and multiple doses of 300 mg twice daily for 6.5 days. No remarkable abnormalities were observed in symptoms, physical tests, laboratory tests, electrocardiogram (ECG), electroencephalogram (EEG), or equilibrium test. The mean plasma concentrations of active metabolite NM394 peaked between 0.5 and 1.0 hours, and the maximum concentrations were 0.68, 1.09, and 1.88 micrograms/mL at doses of 100, 200, and 400 mg, respectively. The mean half-lives were 7.7 to 8.9 hours and were not affected by dose. The mean urinary excretion rates of NM394 were 46.0, 38.3, and 30.6% of the doses within 48 hours, respectively, and other metabolites were excreted in urine by 7% of the doses. The mean salivary concentrations of NM394 were approximately 20% of the plasma concentrations. The mean fecal excretion rates of NM394 and NM441 were 52.9 and 4.2%, respectively within 72 hours after dosing of 400 mg. The Cmax, AUC, and urinary excretion rates were not altered by food intake, whereas the Tmax was prolonged slightly. In the multiple-dose study, the steady state of plasma concentration of NM394 was achieved on day 3 or 4, and further accumulation did not occur thereafter. The mean urinary excretion rate of NM394 was 49.0% during and 48 hours after the multiple administration. The acceptable safety and tolerance and defined pharmacokinetic characteristics of NM441 support further testing.

Administration, Oral↗
PubMed1994

Genetic analysis of HIV-1 during rapid progression to AIDS in an apparently healthy man.

We encountered a case of HIV-1 infection in a previously healthy man, which was characterized by rapid progression to AIDS and death within 7 months in association with high levels of antigenemia throughout the clinical course and no humoral immune response for at least 6 months. Genetic changes of the third variable domain (V3) of the envelope gene of HIV-1 in serum samples were analyzed at four time points during his rapid clinical course. The nucleotide changes were confined to a maximum of three substitutions among 105 nucleotides of the V3 region. A major population of the viral clones in this patient showed one amino acid substitution from aspartic acid (a negatively charged amino acid) to lysine (a positively charged amino acid) at position 30 from the first cysteine of the V3 loop. This substitution was thought to be associated with phenotypic changes, and viruses with this sequence in the V3 region had a strong syncytium-inducing ability in MT-4 cells. It appears that the lack of a humoral immune response accelerated disease progression in our patient and a genetic change that appeared to produce a phenotypic change occurred at an early stage of the disease.

Acquired Immunodeficiency Syndrome↗
PubMed1994

[Sexually transmitted disease infection in HIV carriers].

Heterosexual transmission of the human immunodeficiency virus (HIV) appears to occur readily all over the world. Recent reports have suggested an association between HIV and sexually transmitted disease (STD). We conducted a case study among foreign female prostitutes who were seropositive to HIV to determine the prevalence of STD. In this study, we checked the prevalence of STD infection in 19 HIV seropositive female prostitutes. Overall, 84 percent were seropositive for Chlamydia trachomatis, 37% for HBs, 32% for Treponema pallidum (Tp) and 6% for hepatitis C virus (HCV). The high frequency of a history of STD may be associated with an increased risk of HIV infection acquired through heterosexual contact. Prevention of heterosexually transmitted HIV infection will require an extensive educational program aimed specifically at the risk associated with the number and selection of sexual partners and at promoting safer sexual practices.

Adolescent↗
PubMed1994

A naturally occurring single basic amino acid substitution in the V3 region of the human immunodeficiency virus type 1 env protein alters the cellular host range and antigenic structure of the virus.

Human immunodeficiency virus type 1 circulates in vivo as a mixture of heterologous populations (quasispecies). We previously analyzed the quasispecies of the third hypervariable region (V3) in the viral envelope glycoprotein gp120 in an infected individual and found that the species with a basic amino acid substitution (lysine for aspartic acid) at a particular position evolved and became a distinct population within a short period, followed by progression to the typical immunodeficiency stage (S. Oka et al., AIDS Res. Hum. Retroviruses 10:271-277, 1994). In the present study, we examined the biological significance of this amino acid substitution by constructing recombinant viruses with specific point mutations and comparing their replication capabilities in different cell types. The results demonstrated that the single basic amino acid substitution was sufficient to render a virus fully capable of replicating in human T-cell lines under certain conditions. With an acidic amino acid at the position, the virus grew much less fast or did not grow at all in the T-cell lines. Viral neutralization assay and peptide enzyme-linked immunosorbent assays further showed that this amino acid substitution resulted in different recognition by several of the serum specimens from human immunodeficiency virus type 1-infected individuals and thus could alter the antigenic structure. An additional finding worthy of note was that at the terminal stage, the proviral sequences of peripheral blood mononuclear cells and the viral isolates from them were without exception of the late type with the basic amino acid substitution, whereas the early sequence without the substitution was retained as a major subset in the spleen. These results support the notion that basic amino acid substitutions in V3 are a strong predictor of virus tropism and may be relevant to disease progression.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Recurrent malignant histiocytosis with cerebrospinal involvement--case report.

A 61-year-old male presented with recurrent malignant histiocytosis of the brain manifesting as nausea and headache. Malignant histiocytosis is a disorder of proliferating histiocytes characterized by a rapidly progressive and fatal course, but central nervous system involvement is relatively rare. Magnetic resonance (MR) imaging demonstrated cerebrospinal fluid (CSF) dissemination of histiocytes as a low-intensity area on the T1-weighted image with marked gadolinium-diethylenetriaminepenta-acetic acid enhancement and a high-intensity area on the T2-weighted image. CSF cytological examination revealed an increased level of atypical histiocytes. Brain and spine irradiation, and intrathecal methotrexate and prednisolone administration induced remission. MR imaging is particularly useful for the diagnosis of meningeal dissemination of malignant histiocytosis.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

[A case of early myoclonic encephalopathy accompanied with central respiratory dysfunction].

A case of unusual early myoclonic encephalopathy was reported. He showed massive and/or fragmentary myoclonic seizures soon after birth until 20 months before death. These seizures were resistant to various kinds of anti-epileptic drugs. The EEG pattern of suppression-burst was continuously seen in both waking and sleep states from 2 months to 19 months of age. He was supported with mechanical ventilator because of the central respiratory dysfunction since 4 days after birth until death. This case was electroclinically considered as that of early myoclonic encephalopathy. The central respiratory dysfunction has not been reported in early myoclonic encephalopathy.

Electroencephalography↗
PubMed1993

Importance of independence in ribozyme reactions: kinetic behavior of trimmed and of simply connected multiple ribozymes with potential activity against human immunodeficiency virus.

The kinetic behavior of ribozymes derived from two types of multiple-ribozyme expression vector were examined. In some cases, multiple ribozymes were expressed as a single RNA molecule and all the ribozymes were simply connected in tandem (connected type). In other cases, multiple ribozymes were flanked by cis-acting ribozymes at both their 5' and 3' ends so that, upon transcription, multiple ribozymes were trimmed at both their 5' and 3' ends, with resultant liberation of multiple independent ribozymes (shotgun type). When levels of ribozyme expression were examined for the shotgun-type vector, the level of the ribozyme transcript was found to be proportional to the number of units (n) connected in tandem. Accordingly, the activities of the shotgun-type ribozymes, in terms of the cleavage of HIV-1 RNA in vitro, were also found to be proportional to the number of units connected in tandem (n). By contrast, the activities of the connected-type ribozymes reached plateau values at around n = 3. These results indicate that, when the shotgun-type expression system is used, it is theoretically possible to generate various independent ribozymes, each specific for a different target site, without sacrificing the activity of any individual ribozyme.

Antiviral Agents↗
PubMed1993

Independent introduction of two major HIV-1 genotypes into distinct high-risk populations in Thailand.

To investigate the genetic heterogeneity and epidemiological distribution of human immunodeficiency virus type 1 (HIV-1) in Thailand, we determined proviral sequences for 63 HIV-1-infected patients in various risk groups from all over the country between April and July, 1991. Two distinct genotypes of HIV-1, A and B, were found to segregate by mode of transmission. Of 29 sexually infected patients, 25 (86%) had HIV-1 of genotype A and 4 (14%) had genotype B. Among 29 injecting drug users, probably parenterally infected, only 7 (24%) had genotype A and 22 (76%) had genotype B. This segregation is unlikely to have arisen by chance (p < 0.001). No patient was found to have dual infection. Nucleotide divergence averaged 3.4% among genotype-A-infected patients and 3.5% among genotype-B-infected patients, but 22.0% between the genotypes. 37 of 40 isolates (both genotypes) had the GPGQ tetrapeptide at the tip of the V3 loop, which is common in African HIV-1 strains but rare in North American and European strains, where the GPGR motif predominates. These findings suggest that the waves of HIV-1 infection in injecting drug users and in sexually infected patients in Thailand may not be epidemiologically linked. The nucleotide divergence data point to the separate introductions of the two genotypes in Thailand. Further studies in Thailand and neighbouring countries will be useful in the design and selection of candidate HIV vaccines.

Amino Acid Sequence↗