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Biomedical subjects

S Iida

Publications and source records attributed to S Iida.

At least 145 records · Page 8Linked to original sources

Functional analysis of vif genes derived from various primate immunodeficiency viruses.

Replication property in cells of human and simian immunodeficiency viruses (HIVs and SIVs) lacking intact vif gene was evaluated. Of 10 vif mutants constructed in vitro of the major four HIV/SIV groups, only those derived from HIV-1 and HIV-2/SIVmac displayed replication defect. The cell lines non-permissive for the vif mutants of HIV-1 and SIVmac were found to be different. To determine whether Vif is exchangeable between HIV-1 and SIVmac, chimeric virus clones with respect to the vi gene were constructed and virus replication in the cells non-permissive for the vif mutant viruses was monitored. Productive infection in these cells of chimeric viruses clearly indicated that Vif is functionally exchangeable, and that Vifs of different virus origin act through a similar mechanism.

Animals↗

Deregulation of MUM1/IRF4 by chromosomal translocation in multiple myeloma.

The pathogenesis of multiple myeloma (MM), an incurable tumour causing the deregulated proliferation of terminally differentiated B cells, is unknown. Chromosomal translocations (14q1) affecting band 14q32 and unidentified partner chromosomes are common in this tumour, suggesting that they may cause the activation of novel oncogenes. By cloning the chromosomal breakpoints in an MM cell line, we show that the 14q+ translocation represents a t(6;14)x(p25;q32) and that this aberration is recurrent in MM, as it was found in two of eleven MM cell lines. The translocation juxtaposes the immunoglobulin heavy-chain (IgH) locus to MUM1 (multiple myeloma oncogene 1)/IRF4 gene, a member of the interferon regulatory factor (IRF) family known to be active in the control of B-cell proliferation and differentiation. As a result, the MUM1/IRF4 gene is overexpressed--an event that may contribute to tumorigenesis, a MUM1/IRF4 has oncogenic activity in vitro. These findings identify a novel genetic alteration associated with MM, with implications for the pathogenesis and diagnostics of this tumour.

Animals↗

Complete cytogenetic response with host-derived hematopoiesis induced by cyclosporin A discontinuation in a patient with relapsed chronic myelogenous leukemia after bone marrow transplantation.

A 46-year-old woman with Ph-positive CML received an unmanipulated BMT from an HLA-identical brother, conditioned with busulfan-cyclophosphamide. Five months after BMT, cytogenetic relapse occurred, and CsA was decreased and then discontinued. Mild acute GVHD occurred, but gradually improved with no immunosuppression. Forty days after CsA discontinuation, both cytogenetic and fluorescence in situ hybridization analyses showed a host-derived normal karyotype, 46,XX, and no evidence of leukemic cells or donor graft. The sustained host-derived hematopoiesis lasted for 2 years until sudden recurrence of CML. In this case, the discontinuation of CsA led to GVHD and also suppression of the relapsed leukemia, presumably by a 'specific' GVL effect. There was also graft failure. The observation that subsequent hematologic recovery was of host origin implies that, at least in this case, the GVL effect was not directed against normal host-type hematopoiesis.

Bone Marrow Transplantation↗

Analysis of glycosaminoglycans in human prostate by high-performance liquid chromatography.

OBJECTIVE: To investigate changes in glycosaminoglycan (GAG) profiles in human prostatic tissue. MATERIALS AND METHODS: Seventeen human prostatic samples were examined; five were normal, six hyperplastic and six were cancerous. Prostatic proteoglycans were extracted with 4 mol/L guanidine-HCl containing protease inhibitors. After digestion of the freeze-dried proteoglycan extract with papain, the prostatic GAGs were purified. Total GAGs were measured by a modified dimethylmethylene blue (DMB) method. High-performance liquid chromatography (HPLC) was used to quantify the extracted GAGs. RESULTS: Six types of GAGs, i.e. chondroitin 4-sulphate (Ch-4S), chondroitin 6-sulphate (Ch-6S), dermatan sulphate (DS), chondroitin, heparan sulphate and hyaluronic acid, were analysed qualitatively and quantitatively. The total amount of GAGs was increased in hyperplastic and cancerous prostates, with the predominant components being DS and Ch-6S in these specimens. The Ch-S:DS ratio in cancerous prostate was significantly higher than that in normal and BPH tissue (P < 0.05). Moreover, chondroitin was increased in hyperplastic prostatic tissue (P < 0.01). CONCLUSIONS: These results suggest that an increase in chondroitin levels may be associated with hyperplastic change and an increase in the Ch-S:DS ratio may be related to the development of malignancy.

Adult↗

Identification of new chalcone synthase genes for flower pigmentation in the Japanese and common morning glories.

New cDNA sequences for chalcone synthase (CHS), a key enzyme in the flavonoid biosynthesis, were obtained from the Japanese and common morning glories; they are more closely related to other CHS sequences than the six previously described CHS genes from the same plants. The newly isolated CHS-D gene is abundantly expressed in the pigmented flower buds, while its expression is drastically reduced in the white flower buds. Thus CHS-D appears to produce major CHS transcripts for flower pigmentation.

Acyltransferases↗

The gene encoding flavanone 3-hydroxylase is expressed normally in the pale yellow flowers of the Japanese morning glory carrying the speckled mutation which produce neither flavonol nor anthocyanin but accumulate chalcone, aurone and flavanone.

The Japanese morning glory carrying the recessive mutable speckled allele with the dominant speckled-activator bears colorless flowers with fine and round colored spots distributed over the corolla whereas the plant without the speckled-activator produces pale yellow flowers. Previous chemical analysis has indicated that a mutation in the gene for flavanone 3-hydroxylase (F3H) is a likely candidate for the speckled allele. However, the F3H mRNA without sequence alteration accumulates normally in the pale yellow flowers, indicating that the speckled allele is neither the F3H gene nor a regulatory gene acting on the F3H gene expression.

Amino Acid Sequence↗

Inhibition of the hepatic uptake of paracetamol sulphate by anionic compounds.

The effect of anionic compounds on the hepatic uptake of paracetamol sulphate, a conjugative metabolite of paracetamol, has been studied. Hepatic uptake of paracetamol sulphate by isolated hepatocytes was inhibited by bromosulphophthalein, dibromosulphophthalein and p-nitrophenyl sulphate, but not by probenecid or cholic acid. Bromosulphophthalein and dibromosulphophthalein also inhibited the uptake of paracetamol sulphate in the rat isolated perfused liver. Saturable uptake of paracetamol sulphate was also observed in the absence of inorganic sulphate. The uptake of paracetamol sulphate was reduced by 1 and 10 mM inorganic sulphate. Bromosulphophthalein and p-nitrophenyl sulphate inhibited the uptake of paracetamol sulphate in the absence of inorganic sulphate. These results indicate that paracetamol sulphate shares a transporter with bromosulphophthalein, dibromosulphophthalein and p-nitrophenyl sulphate, all of which contain the sulphate or sulphonate group. Therefore, the sulphate or sulphonate moiety might be crucial for interaction with the transporter, and mutual inhibition of hepatic uptake among these compounds is likely.

Acetaminophen↗

Measurement of velopharyngeal movements induced by isolated stimulation of levator veli palatini and pharyngeal constrictor muscles.

The levator veli palatini (LVP) and superior pharyngeal constrictor muscles (PC) close the velopharynx. However, for the velopharyngeal movements to be understood in detail, each muscle contraction must be analyzed precisely. This study was performed to clarify the velopharyngeal movement which was induced by a single muscle contraction, LVP or PC. Using a nasopharyngeal fiberscope, we analyzed the velopharyngeal movement associated with the contraction of the LVP and PC muscles in mongrel dogs. To elicit the maximal contraction of each muscle, we applied repetitive electrical stimulation to each peripheral nerve efferent to the LVP or PC muscle. Stimulation with a frequency of 77 Hz and 83 Hz induced maximal tension in the LVP and PC muscles, respectively, in isometric contraction. In a second series of experiments, fiberscopic views of the velopharyngeal movements associated with each muscle's maximal contraction were recorded. The degree of closure was calculated at several sections. The LVP muscle pulled the caudal fourth of the soft palate, while the PC projected the posterior wall at the level of the caudal end of the soft palate. The PC muscle also projected the lateral wall of the velopharynx. The effect of LVP contraction on the lateral wall was very small. These results show that the velopharyngeal movement associated with LVP contraction is very different from that with PC contraction.

Animals↗

Sex difference in the metabolism of pirmenol in rats.

The in vitro metabolism of pirmenol (cis-alpha-[3-(2,6-dimethyl-1-piperidinyl)propyl]-alpha-phenyl-2-pyri dinemethanol) and glucuronidation of its metabolites, a 4-hydroxylated derivative of pirmenol (M3) and 3-methylether of M3 (M5), were investigated using a hepatic 9000 x g supernatant and microsomes, respectively, of female and male rats in order to elucidate the higher urinary excretion of M3G and M5G (glucuronides of M3 and M5, respectively) in females previously observed in in vivo metabolism. Pirmenol delta1' iminium ion (M2) and M3 were formed by the oxidation of pirmenol in both sexes; however, M2 was the main metabolite in males, while M2 and M3 were formed at nearly the same level in females. On glucuronidation of M3 and M5, the Vmax values of both compounds were higher in female rats, consistent with the results in vivo. In addition, the sex difference in the urinary excretion ratio of M5G to M3G (1.1 in female, 2.5 in male) might reflect the lower availability of M3 for glucuronidation in male rats in vivo. The chromatographic separation of diastereomers of M5G was also described.

Animals↗

Osteonecrosis of the femoral head: a prospective study with MRI.

We performed a prospective study using MRI to evaluate early necrosis of the femoral head in 48 patients receiving high-dose corticosteroids for the treatment of various autoimmune-related disorders. The mean interval from the initiation of corticosteroid therapy to the first MRI examination was 2 months (0.5 to 6). MRI was repeated, and the mean period of follow-up was 31 months (24 to 69). Abnormalities were found on MRI in 31 hips (32%). The initial changes showed well-demarcated, band-like zones which were seen at a mean of 3.6 months after initiation of treatment with steroids. In 14 of these hips (45%) there was a spontaneous reduction in the size of the lesions about one year after treatment had started, but there was no further change in size with a longer follow-up.

Adolescent↗

Activities of superior pharyngeal constrictor and levator veli palatini muscles related to respiration in dogs.

OBJECTIVE: This study, using mongrel dogs, attempted to delineate the respiratory activity of two closure muscles of the velopharynx, the levator veli palatini (LVP) and superior pharyngeal constrictor (PC) muscles. METHOD: Fifteen mongrel dogs were given tracheotomies, with intratracheal tubes being connected to their respiratory circuits. Activities of the PC and LVP muscles were recorded electromyographically, and the effects of PaO2 and PaCO2 were analyzed along with the effects of lung inflation intratracheally with O2 and N2. RESULTS: Under hypoxic conditions, expiratory LVP activity was observed while PC activity diminished. The effects of lung inflation on both LVP and PC activities were also studied. The activities of both muscles were enhanced by lung inflation. CONCLUSION: It was thus suggested that the roles of both muscles during velopharyngeal closing movements are not the same.

Administration, Inhalation↗

Breast feeding for cleft lip and palate patients, using the Hotz-type plate.

OBJECTIVE: Oral-cavity feeding movements were analyzed during sucking and used to modify a Hotz-type plate to facilitate sucking in infants with cleft lip and palate. DESIGN: Sucking movements were analyzed using lateral view cine radiography as three adults fed from a bottle. A Hotz-type plate was then modified to better isolate the oral cavity and to occlude the oral airway. The plate was then utilized in direct breast feeding by 10 babies. OUTCOME MEASURES: Sucking rate, amount of milk taken, and duration of use of the plate were assessed. RESULTS: Wearing this plate, four babies with cleft lip and palate could suck their mother's breast, drinking about 22 g/trial. CONCLUSIONS: Although supplemental bottle feeding was required to provide enough nourishment, this is the first step to reaching ideal breast feeding situation for these patients.

Adult↗

A flow cytometric analysis of cytotoxic effects of nitrobenzene on rat spermatogenesis.

Cytotoxic effects of nitrobenzene (NB) on spermatogenesis of mature Sprague-Dawley (Crj:CD) rats were analyzed by measuring the DNA content distribution and testicular weight at 1, 2, and 3 weeks of daily oral dose of NB (60 mg/kg/day). Rats at the age of 9 weeks were used because the ratios of 1C, 2C, S, 4C to total testicular cells were stabilized after the age of 52 days. Within a week of administration, a large number of 1C cells were lost but 2C cells proliferated, resulting in little change of testicular weight. In another week that followed, the number of 1C cells and testicular weight were decreased, but the ratio of S-4C cells was increased, indicating that an appreciable number of 2C cells could progress to the 4C compartment. The data indicated that (1) 1C cells were destroyed, and (2) meiosis of secondary spermatocytes was suppressed, but (3) NB had little effect on the spermatocytes prior to the early pachytene stage. This interpretation was reinforced by the observation that (4) the ratio of 1C cells returned to a nearly normal level during a recovery period of 2 weeks. In conclusion, flow cytometry could offer an efficient method for the quantitative analysis of male reproductive toxicity.

Animals↗

[Factors on motives for rehabilitation of post-CVA clients at homes].

Qualitative studies have been made on the motives for rehabilitation of post-CVA 14 clients at homes by semi-constitutional questions. As a result, rehabilitating motives were classified into 8 influential factors such as prospects for future, sense of satisfaction for living, change in sense of self personality, change in personal relations, change in family-relation, attitude towards the post-CVA symptom, emotional mainstay, sense of health, and composing factors as with positiveness, voluntariness and subjective individuality. The contents of the influential factors and number or the manners of connections were characteristic of individuals. Among them, 4 factors such as change in family-relation, change in personal relations, change in sense of self-personality, sense of satisfaction for living have constituted the attitudes towards relation between oneself and the other after falling into the sickness. In order to elevate the motives for rehabilitation of clients at homes, it is necessary to enhance the affirmative influential factors by making assessment of influential factors and constituting factors of individual motives in a sense of individual subjects, and also, the assistance is necessary to make negative influential factors on the motives related affirmatively.

Aged↗

Transposon tagging in rice.

To develop an efficient gene isolation method for rice we introduced the maize Ac/Ds system into rice. Extensive analysis of their behavior in rice for several generations indicated that Ac and Ds in the presence of Ac transposase gene actively transpose in rice. A wide spectrum of mutations affecting growth, morphogenesis, flowering time and disease resistance have been obtained in the population carrying Ac/Ds and some of them were genetically analyzed. Main efforts are currently being made to isolate genes responsible these mutations. In addition, a number of Ac/Ds were mapped on chromosomes and mapped elements will be used in the future for directed tagging of genes with known chromosomal positions.

Cloning, Molecular↗

Hepatic uptake of p-nitrophenyl sulfate by transporter that acetaminophen sulfate shares for uptake: sulfate moiety as a vector for metabolite transport.

Hepatic uptake of the sulfate conjugate of p-nitrophenol (p-NPsul) has been studied. Uptake clearance of p-NPsul by isolated rat hepatocytes was dependent on p-NPsul concentration, suggesting carrier-mediated transport. The uptake of p-NPsul by isolated rat hepatocytes was inhibited by acetaminophen sulfate (APAPsul), the uptake of which had been previously reported to be inhibited by p-NPsul. The hepatic uptake of p-NPsul was also inhibited by bromosulfophthalein (BSP) or dibromosulfophthalein (DBSP), which had been reported to inhibit hepatic uptake of APAPsul in the previous study. These inhibitory effects were observed in isolated perfused liver experiments as well as in isolated hepatocyte experiments. Therefore, it was concluded that hepatic uptake of p-NPsul was mediated by a transporter, which mediates hepatic uptake of APAPsul as well as BSP or DBSP. It is suggested that sulfate moiety may have a key role as a vector for the hepatic transport of sulfate conjugate metabolites. Interaction between sulfate conjugate metabolites in hepatic uptake may also be expected.

Acetaminophen↗

The t(9;14)(p13;q32) chromosomal translocation associated with lymphoplasmacytoid lymphoma involves the PAX-5 gene.

The t(9;14)(p13;q32) translocation is associated with approximately 50% of lymphoplasmacytoid lymphoma (LPL), a subtype of B-cell non-Hodgkin's lymphoma (NHL). We cloned the chromosomal breakpoint of der (14) from an LPL case (1052) and showed that it involved a junction between 9p13 and the switch micro region of the Ig heavy chain locus (IgH) on 14q32. Using a YAC contig spanning 1.5 megabase (Mb), we determined that the 9p13 breakpoint in one case (1052) mapped within a 270-kb restriction fragment containing two previously reported 9p breakpoints associated with a alpha-heavy chain disease case (MAL) and KI-1 positive diffuse large cell lymphoma (DLCL) cell line (KIS-1). The same fragment also contained the PAX-5 gene which encodes a B-cell specific transcription factor involved in the control of B-cell proliferation and differentiation. The breakpoints of KIS-1 and 1052 were mapped within the 5' noncoding region of PAX-5, while the 9p13 breakpoint of MAL mapped 230 to 270 kb upstream to PAX-5. In all three cases, the translocation caused the juxtaposition of the PAX-5 gene to the IgH locus in the opposite direction of transcription. When compared with six other DLCL cell lines lacking t(9;14)(p13;q32), the KIS-1 cell line showed an 11-fold overexpression of PAX-5 mRNA and a significantly reduced expression of the p53 gene, which is normally regulated by PAX-5. Moreover, metaphase and interphase fluorescence in situ hybridization (FISH) analysis using a YAC clone spanning 1 Mb including the PAX-5 as a probe identified chromosomal translocations in 5 of 7 cases carrying 9p13 translocations. These findings suggest that the PAX-5 gene is the target of the t(9;14) in LPL whereby its expression may be deregulated by juxtaposition to IgH regulatory elements, thus contributing to lymphomagenesis.

Aged↗