Biomedical subjects
Publications and source records attributed to S Kato.
A cell line (H2-5) producing defective doughnut-shaped particles of human immunodeficiency virus type I (HIV-1) was found to contain proviral DNA with a large deletion of 2558 bases, corresponding to the 3' half of pol gene, the vif and vpr genes, and the 5' terminal of the tat gene.
A series of human immunodeficiency virus type 1 (HIV-1) mutants in vif, vpr, vpu, and nef were constructed from an infectious plasmid (pNL 432) containing the full-length HIV-1 DNA by frameshift mutations. The capacities for replication and cell killing of these mutant viruses were examined in a clonal cell line (M 10) isolated from HTLV-I-transformed MT-4 cells. In all cases, the mutant viruses replicated, expressed HIV-1 antigens, and induced drastic cytopathic effects. However, some M 10 cells survived infection with vif, vpr, and vpu mutant viruses and became persistently HIV-1-infected, whereas no cells survived infection with the nef mutant as well as the wild-type virus. The HIV-1 particles produced from the surviving cells after infection with the vif, vpr, or vpu mutant viruses were fully replicative in M 10 cells without apparent cytopathic effects.
A total of 81 cell clones persistently infected with the LAV-1 or HTLV-IIIB strain of human immunodeficiency virus type 1 (HIV-1) was isolated from cells which were obtained by serial passage of some proliferating MT-4 cells after a drastic cytolysis of most cells by HIV-1-infection. These cell clones were classified into 8 types (I to VIII) in terms of the expression of HIV-1 antigens, syncytium formation capacity, and reverse transcriptase activity and infectivity of virus particles in the culture fluid. Type I cell clones were producers of infectious HIV-1 particles, while types II to VIII cell clones did not produce infectious HIV-1 or were producers of uninfectious defective HIV-1 particles. Immunoprecipitation followed by SDS-polyacrylamide gel electrophoresis (PAGE) showed that the gag precursor protein in L-2 cell clone (type IV) was not cleaved to mature gag proteins, while the env precursor protein on L-3 cell clone (type III) was not cleaved to mature env protein. H-7 cell clone (type VIII) did not express any HIV-1 antigen. All these cell clones after the superinfection with infectious HIV-1 synthesized intact gag and env proteins, which were, at least in part, related to the HIV-1 genome persistently present in the cell clones before the superinfection, resulting in production of infectious HIV-1. For example, it was found that L-2 cell clone contained a single copy of the LAV-1 genome per haploid cell and produced doughnut-shaped particles. On the other hand, the cell clone isolated from the L-2 cell clone superinfected with infectious HTLV-IIIB contained the integrated HTLV-IIIB genome in addition to the LAV-1 genome present before the superinfection, and produced intact HIV-1 particles in addition to doughnut-shaped particles from a single cell. These results indicate that complementation and/or genetic recombination events in the superinfected cells may account for the production of infectious intact HIV-1 virions.
To examine the synthesis of hepatic collagen in patients with alcoholic and nonalcoholic liver disease, liver biopsy specimens were incubated in vitro with 14C-proline, and the radioactivity of the newly synthesized protein-bound 14C-hydroxyproline was measured. Mean hepatic collagen synthesis was 0.82 +/- 0.19 pmole of 14C-hydroxyproline/g liver/2 h in control subjects without histological liver fibrosis. Hepatic collagen synthesis was increased in patients with alcoholic and nonalcoholic liver diseases, especially in those with alcoholic fibrosis, alcoholic cirrhosis and chronic active hepatitis. The raised collagen synthesis in alcoholic liver disease rapidly decreased after withdrawal of alcohol. When alcoholic liver disease were compared with nonalcoholic liver disease, there was no significant difference in hepatic collagen synthesis.
Thirty cases of amyotrophic lateral sclerosis (ALS) supported by respirators for more than 1 year beyond respiratory failure were followed to estimate the progression of their voluntary motor impairment. The extremities were apt to be affected within two years of the onset of the disease, but complete voluntary paralysis occurred in less than half of the cases (14/30), more frequently appearing after respiratory failure. Respiratory and bulbar paralysis were closely related, and combined complete voluntary paralysis of these muscle systems was observed in 25/30 cases. Incomplete external ophthalmoplegia also increased after respiratory failure, but complete voluntary external ophthalmoplegia was rare (5/30).
The developmental process of the testis and age-related changes in the morphology of rete testicular spermatozoa were investigated in Meishan boars at 1 to 364 days of age. Testicular weight and the diameter of seminiferous tubules increased rapidly until 150 to 180 days of age. Leptotene stage spermatocytes, round spermatids and spermatozoa were first found in the section of seminiferous tubules at 30 to 45, 60 and 75 days of age, respectively. However, after 105 to 120 days of age, most rete testicular spermatozoa were morphologically normal. These results indicate that Meishan boars reach puberty as early as 75 days of age, though the testes acquire the ability to produce morphologically normal spermatozoa at about 120 days.
The effect of neurotropin, an extract isolated from the inflamed skin of rabbits inoculated with Vaccinia virus was examined on acute experimental allergic encephalomyelitis (EAE) in Lewis rats. A dose of 40 mg per kg body weight of neurotropin was administered intraperitoneally for 7 days post-inoculation. The severity of clinical signs of acute EAE was decreased by the administration of neurotropin. Histopathologic evaluation showed that lesion severity of EAE in neurotropin-treated rats was less than that seen in untreated rats. Blood lymphocyte subset analysis revealed that in comparison to untreated EAE rats, in neurotropin-treated rats, the percentage of OX6+ (Ia antigen) cells was lower and the W3/25+ (helper T cell): OX8+ (suppressor/cytotoxic T cell) cell ratio was greater during the period of peak inflammation. Immunohistochemical examination of neurotropin-treated rats demonstrated that OX6+ and W3/25+ cells within EAE lesions were fewer and that OX8+ cells in lesions occurred in greater numbers than those in untreated rats. These findings suggest that the OX8+ cells in the inflammatory lesions may have been induced by neurotropin treatment and that the suppressive effects on the disease may have been causally related to their presence.
It has remained to be established that matching of the HLA-DP antigen plays a key role in bone marrow transplantation (BMT), mainly due to the difficulty of the primed lymphocyte test (PLT) method for DP typing. We previously reported an efficient technique for HLA class II genotyping, by digestion of polymerase chain reaction (PCR)-amplified genes with restriction fragment length polymorphisms (RFLP) endonucleases (PCR-RFLP method). DNAs from 46 recipients and corresponding donors in serologically HLA-identical sibling-BMT cases were DP typed by this PCR-RFLP method. Of the 46 cases, five (10.9%) were genetically DP mismatched (recombinant frequency between the DR-DQ and DP subregions was at least 2.7% per meiosis), providing an important opportunity to look at the effect of the disparity only seen in the DP antigen on BMT. Three of the four DP-mismatched BMT cases that could be evaluated developed severe acute graft-versus-host disease, suggesting that DP disparity played an important role in BMT.
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Full skin thickness burns covering 35 per cent of the total body surface of rabbits were followed by measurements of Na-K ATPase and arterial blood gas analyses, before and after the burn injury. Studies of the effects of intravenous fluids with different compositions showed that the active transport of the cell membrane was depressed in vivo immediately after a burn injury, mainly due to acidosis. This phenomenon was not completely corrected by the Baxter formula which uses conventional lactated Ringer's solution. However, an improvement was observed in those groups given the 'Enriched Lactate Solution' (ELS) containing large quantities of lactate as the base source. These results suggest that ELS, which positively corrected acidosis in accordance with its concentration, is very effective and more appropriate than the conventional lactated Ringer's solution for early burn resuscitation.
The uricase gene was isolated from rat genomic DNA libraries. The gene spans 40 kb and consists of eight exons. All the exon-intron junctional sequences conform to the canonical GT/AG rule. The restriction map of the isolated clones and Southern blot analysis revealed that the enzyme is encoded by a single-copy gene. Analysis of the transcription initiation site of rat uricase mRNA indicated the differential use of consecutive nucleotides; the principal repeat is located 55 nucleotides upstream from the first methionine codon. Nucleotide sequence analysis of the 5'-flanking region showed the presence of a TATA (ATAAAA) sequence at nucleotides 30 to 25 and of a CAAT (GGTCAAT) sequence at nucleotides 63 to 57 upstream of the principal transcription initiation site. The 5'-flanking region contains another possible regulatory sequence (TGTCGACA) homologous to the cAMP-regulatory element. The palindromic sequence is located 158 to 151 nucleotides upstream from the transcription initiation site, surrounded by a direct repeat (TCAGCAA).
The title compounds (19-55) with a 4-substituted 2-(aminomethyl)morpholine group were prepared and evaluated for the gastrokinetic activity by determining their effect on gastric emptying of phenol red semisolid meal in rats. Introduction of chloro, fluoro, and trifluoromethyl groups to the benzyl group of the parent compounds 1a and 1b enhanced the activity. Among compounds tested, 4-amino-5-chloro-2-ethoxy-N-[[4-(4-fluorobenzyl)-2-morpholinyl] methyl] benzamide (23b) showed the most potent gastric emptying activity (effects on phenol red semisolid meal in rats and mice, and on resin pellets solid meal in rats). The gastrokinetic activity of 23b citrate (AS-4370) compared very favorably with that of cisapride and was higher than that of metoclopramide. In contrast to metoclopramide and cisapride, AS-4370 was free from dopamine D2 receptor antagonistic activity in both in vitro ([3H]spiperone binding) and in vivo (apomorphine-induced emesis in dogs) tests.
Growth of the patients with hematological malignancies, aplastic anemia, Fanconi's anemia, and Wiscott-Aldrich syndrome who had been treated with bone marrow transplantation (BMT) was studied. Fourteen out of 21 patients showed suppression of linear growth after BMT. Recovery of the growth velocity after 1-2 years tended to occur if BMT was performed at younger age. Six of eight patients with chronic graft-versus-host-disease (CGVHD) had impaired growth after BMT, whereas eight of 13 (61%) without CGVHD did. Provocative tests for growth hormone (GH) performed 5-72 months after BMT revealed three boys who showed poor response to more than two different stimuli. Two of these three boys had prolonged suppression of growth. Neither the age at BMT, difference in disease, nor presence of posttransplant growth retardation gave significant difference in the response of GH to provocative tests. It was concluded that approximately two-thirds of marrow-grafted children experienced transient decrease in growth velocity after BMT.
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In order to study the role of CD34+ cells in hematological recovery following bone marrow transplantation (BMT), bone marrow cells stained with HPCA-1 (CD34) and MY-9 (CD33) monoclonal antibodies were analyzed by using a fluorescence-activated cell sorter on or about days 14 and 28, as well as at later times, following BMT in 6 recipients. Single cell cultures of CD34+ cells were also performed to evaluate their in vitro hematopoietic function. CD34+ cells were detectable in bone marrow cells on day 14. More than 80% of CD34+ cells co-expressed the CD33 antigen, and macrophage (Mac) colony-forming cells predominated among total colony-forming cells of CD34+ cells. In normal bone marrow cells, CD34+, CD33+ cells amounted to about 40% of CD34+ cells, and the incidences of erythroid bursts, granulocyte/macrophage (GM) colonies, and Mac colonies were similar to each other. After more than 10 weeks, CD34+, CD33- cells gradually recovered, as erythroid burst colony-forming cells increased following GM colony-forming cells. This phenomenon was well-correlated with the time course of peripheral blood cell recovery. CD34+, CD33+ cells as committed progenitors and CD34+, CD33- cells as multipotent stem cells have distinctive biological behaviors in BMT.
This report concerns the immunohistochemical demonstration of beta amyloid protein-containing neurofibrillary tangles (beta-NFTs) from patients with parkinsonism-dementia complex on Guam (PDC). Formalin-fixed paraffin-embedded tissue sections from the temporal lobe of nine PDC cases and the spinal cord of three were examined. An affinity-purified antibody to the N-terminal peptide sequence of beta amyloid protein was used. beta-NFTs were demonstrated in the temporal lobes of the three oldest individuals. Some senile plaques, probably a manifestation of ageing, were also seen. The beta-NFTs were most frequent in the entorhinal cortex. Senile plaques were invariably present in the vicinity of the beta-NFTs. Conversely, in the regions without senile plaques, even though numerous neurofibrillary tangles were identifiable with the modified Bielschowsky method, no beta-NFTs were seen. The density of beta-NFTs appeared to be proportional to that of senile plaques, none was seen in cases lacking senile plaques. No beta-NFTs were detected in the spinal cords. Our data suggest that beta-NFTs result from secondary beta amyloid deposition on certain neurofibrillary tangles.
To study age-related changes in the left bundle branch (LBB), 32 autopsied hearts were examined histopathologically using serial sections according to the method of Lev. Each division of LBB was carefully studied, i.e., the anterior and posterior radiations and the proximal, middle, and distal portions of radiations. An increase of fibrosis and fatty infiltration were observed in the LBB with aging. There was a tendency for fibrosis to be more prominent in the proximal LBB at the site of transition from bundle branch cells to Purkinje cells.
A total of 370 children who underwent upper gastrointestinal endoscopy (534 procedures) were retrospectively studied. All procedures were performed successfully. Side effects were demonstrated in only one case (0.2%), which was complicated by perioral cyanosis during the procedure. As to pre-endoscopic medication, it was thought that topical pharyngeal anesthesia alone may well be used for school-age children over 7 years of age, general anesthesia with endotracheal intubation for neonates, and intravenous sedation for infants and younger children. Of 370 patients studied, 70.8% had endoscopic diagnoses. The most common diagnosis was gastritis (136 cases), followed by peptic ulcer (75), duodenitis (29), and esophagitis (20). Several conclusions for indications were drawn from the present study. Pediatric upper gastrointestinal endoscopy is a safe and useful method for diagnostic and therapeutic approach, if adequate pre-endoscopic medication is chosen.