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Biomedical subjects

K Nakata

Publications and source records attributed to K Nakata.

At least 235 records · Page 13Linked to original sources
PubMed1996

The effect of thalidomide on the pathogenesis of human immunodeficiency virus type 1 and M. tuberculosis infection.

Tumor necrosis factor alpha (TNF-alpha), a cytokine produced during the host defense against infection, is associated with fevers, weakness, and progressive weight loss. Thalidomide inhibits the synthesis of TNF-alpha both in vitro and in vivo and may have clinical usefulness. We therefore initiated a pilot study of thalidomide treatment in patients with human immunodeficiency virus type 1 (HIV-1)-associated wasting with or without concomitant infection with tuberculosis. Thirty-nine patients were randomly allocated to treatment with either thalidomide or placebo in a double-blind manner for 21 days. Thirty-two patients completed the study. In patients with concomitant HIV-1 and tuberculosis infections, thalidomide therapy was associated with a reduction in both plasma TNF-alpha levels and HIV-1 levels. No significant reduction in either TNF-alpha or HIV- 1 levels was observed in patients with HIV-1 infection only. During the study period, patients receiving thalidomide treatment (n=16) showed a significant weight gain (mean +/- SEM: 6.5 +/- 1.2%; p<0.02) relative to placebo-treated patients (n=16). Patients with simultaneous HIV-1 and tuberculosis infections experienced a higher mean weight gain during thalidomide treatment than the group of patients with HIV-1 infection only. The results of this pilot study suggest that thalidomide may have a clinical role in enhancing weight gain and possibly reducing TNF-alpha and HIV-1 levels in patients with HIV-1 and concomitant mycobacterial infections.

Adult↗
PubMed1996

Identification of a minimum enhancer sequence for the type II collagen gene reveals several core sequence motifs in common with the link protein gene.

The type II collagen gene (Col2a1) is expressed primarily in chondrocytes. Transcription of Col2a1 is mediated by cell-specific regulatory elements located within the promoter and first intron. Here, we map a minimal enhancer and identify elements that determine cartilage-specific Col2a1 expression by analyzing the activity of a series of chimeric genes consisting of rat Col2a1 first intron deletion mutants ligated to the chloramphenicol acetyltransferase reporter gene. We show that a 100-base pair (bp) segment within the first intron is the minimum size necessary for high level, cell type-specific expression of Col2a1. Sequence analysis of this 100-bp Col2a1 enhancer revealed several sequence motifs similar to motifs present within the regulatory region of the link protein gene, another cartilage gene. These motifs include an AT-rich element, a C1 motif and a C3 motif. Deletion of any of these elements reduced Col2a1 enhancer activity in chick embryo chondrocytes. We also tested enhancer-mediated activity in CFK2 cells which differentiate to a chondrogenic phenotype and begin to express type II collagen mRNA after extended culture. In stably transfected CFK2 cells, constructs containing the 100-bp enhancer were activated during the transition from prechondrogenic to chondrogenic cell populations and deletions within the enhancer strongly down-regulated activity. Chondrocyte-specific DNA-protein complexes were identified using nuclear extracts prepared from chick embryo chondrocytes and 32P-labeled oligonucleotides from these regions of the first intron. These results suggest that interaction of chondrocyte specific nuclear factors with multiple core elements from a small region within the first intron are important for cell-type specific Col2a1 enhancer activity.

Animals↗
PubMed1996

The remodelling process of allogeneic and autogenous patellar tendon grafts in rats: a radiochemical study.

In order to study the remodelling of collagen fibres of transplanted tendons, one-half of the patellar tendon of the knee in 54 rats was replaced with a radioisotope (3H-proline)-labelled patellar tendon procured from a donor rat. Three transplantation models were used in this study: fresh-frozen allograft, fresh-frozen autograft (fresh-frozen isograft), and fresh autograft (fresh isograft). The percentage of old collagen was calculated as an indicator of collagen turnover from the amount of hydroxyproline and the radioactivity level of 3H-hydroxyproline in the transplanted tendons at 4, 12 and 24 weeks postoperatively. Histological evaluation was also performed at 2, 4, 12 and 24 weeks. At 4 weeks, the percentage of old collagen in the grafts from the fresh-frozen allograft group was significantly lower than in the autograft groups (20% vs. 48%). Although the percentage of old collagen in the fresh-frozen autograft group had decreased to the same level as in the fresh-frozen allograft group by 12 weeks (approximately 10%), the value was still high in the fresh autograft group at 12 weeks and remained higher (38%). Histologically, at 2 weeks, the cellularity in the fresh-frozen allograft was higher than in the fresh-frozen autograft. After 4 weeks, however, no significant difference was found between these two groups. In the fresh autograft group, the cellularity was lower than in the fresh-frozen groups at all times. In conclusion, the collagen turnover rate in the fresh-frozen allograft was the most rapid of the three transplantation models based on hydroxyproline turnover.

Animals↗
PubMed1996

Seasonality of mortality in Sri Lanka: biometeorological considerations.

The seasonal variation of mortality in Sri Lanka was studied in relation to meteorological variables. Time series data of the total monthly number of deaths in men and women from 1976 to 1980 were analyzed by power spectrum analysis of the fast Fourier transformation method in the areas of Colombo (lowland area, altitude 7 m) and Nuwara-Eliya (highland area, altitude 1890 m), respectively. In the Colombo area, where the mean temperature was always high (mean, 27.5 degrees C), a seasonal variation in mortality of 6 months was validated by power spectrum analysis with peak times in June and November. These mortality peaks corresponded to those of the amounts of rainfall which also showed an identical predominant period of 6 months. In the Nuwara Eliya area, where the mean temperature was always low at about 15-16 degrees C, a seasonal variation of approximately 3 months was found in addition to the 6 months' periodicity. The comparison of the power spectrum pattern of mortality with those of meteorological variables suggested that the amount of rainfall was associated with the seasonal variation of mortality in the Nuwara-Eliya area. In conclusion, the seasonality of mortality in Sri Lanka, a typical tropical zone country, was related to seasonal variation in the amount of rainfall, or a humidity factor, but not to mean temperature.

Female↗
PubMed1996

Extensive polymorphism of ABO blood group gene: three major lineages of the alleles for the common ABO phenotypes.

Polymorphism of the ABO blood group gene was investigated in 262 healthy Japanese donors by a polymerase chain reactions-single-strand conformation polymorphism (PCR-SSCP) method, and 13 different alleles were identified. The number of alleles identified in each group was 4 for A1 (provisionally called ABO*A101, *A102, *A103 and *A104 according to the guidelines for human gene nomenclature), 3 for B (ABO*B101, *B102 and *B103), and 6 for O (ABO*O101, *O102, *O103, *O201, *O202 and *O203). Nucleotide sequences of the amplified fragments with different SSCP patterns were determined by direct sequencing. Phylogenetic network analysis revealed that these alleles could be classified into three major lineages, *A/*O1, *B and *O2. In Japanese, *A102 and *B101 were the predominant alleles with frequencies of 83% and 97% in each group, respectively, whereas in group O, two common alleles, *O101 (43%) and *O201 (53%), were observed. These results may be useful for the establishment of ABO genotyping, and these newly described ABO alleles would be advantageous indicators for population studies.

ABO Blood-Group System↗
PubMed1996

Progressive degeneration of articular cartilage and intervertebral discs. An experimental study in transgenic mice bearing a type IX collagen mutation.

Transgenic mice expressing mutant alpha 1(IX) collagen were produced and found to develop progressive joint degeneration with age, as well as accelerated intervertebral disc degeneration. Radiological and histological studies showed that cervical and lumbar disc degeneration was more advanced in the transgenic mice than in control litter-mates. The changes included shrinkage or disappearance of the nucleus pulposus, and fissures in the annulus fibrosus which sometimes lead to herniation of disc material and slight osteophyte formation. These findings suggest that mutations of the type IX collagen may cause certain forms of degenerative disease in the spine as well as in joints.

Animals↗
PubMed1996

Inducible osteonecrosis in a rabbit serum sickness model: deposition of immune complexes in bone marrow.

We established inducible osteonecrosis in a rabbit serum sickness model. Osteonecrosis with marrow necrosis could be induced by the intravenous injection of horse serum in two doses separated in time by a period of three weeks. In this model, osteonecrosis could be successfully produced in rabbit femoral metaphysis. The incidence of marrow necrosis was 45% (9 of 20 rabbits) and trabecular necrosis occurred in 6 of 20 rabbits (30%) at 7 days after the second injection of the horse serum. In bone marrow of the femoral metaphysis, extravasation of erythrocytes and the formation of micro-thrombi in arterioles were often observed in an early stage of the present model and both findings correlate well each other (p = 0.0001). Immune complexes could be demonstrated using immunohistochemistry in bone marrow of the femoral metaphysis as well as in glomeruli of the kidney. Extravasation of erythrocytes in bone marrow of the femoral metaphysis was observed in 8 of 12 (67%) cases with immune complex deposition in the sinusoidal space of the femoral metaphysis and in 12 of 21 (57%) cases with immune complex deposition in glomeruli of the kidney. Immune complex deposition both in the sinusoidal space of femoral bone marrow (p = 0.0385) and in glomeruli of the kidney (p = 0.0209) closely related to extravasation of erythrocytes and microthrombi in arterioles in the early stage of this model. Early microcirculatory injury (extravasation of erythrocytes and microthrombi in arterioles) adjacent to osteonecrosis could be induced by immune complex deposition in femoral bone marrow and might be predictable characteristics for the inducible osteonecrosis in the present serum sickness model. The important findings in this study were that early microcirculatory injury was closely related to the deposition of immune complexes in femoral bone marrow, and that early microcirculatory injury associated with immune complex deposition was located close to osteonecrotic regions.

Animals↗
PubMed1996

Prevalence of hepatitis B or C virus infection in patients with fulminant viral hepatitis. An analysis using polymerase chain reaction.

BACKGROUND/METHODS: The cause of fulminant hepatitis is still not fully understood. We studied 23 patients with fulminant hepatitis, using polymerase chain reaction to detect hepatitis virus genomes. Tests for HBsAg and IgM anti-HAV and IgM anti-HBc were performed in all patients. Serum samples were stored at -70 degrees C for later analysis of anti-HCV and hepatitis virus genomes such as hepatitis B virus, hepatitis C virus and hepatitis D virus. RESULTS: Of 23 patients, 17 (74%) had HBV-DNA and two (9%) had HCV-RNA. No patient was positive for both viruses or positive for HDV-RNA. Serological tests indicated that two patients, negative for HBV-DNA and HCV-RNA, were positive for IgM anti-HAV. In contrast, 8 of 17 (47%) HBV-DNA positive patients were negative for both IgM anti-HBc and HBsAg in conjunction with low levels of viremia. Four patients were positive for anti-HCV, but only one was positive for HCV-RNA. One patient, positive for HCV-RNA, was negative for anti-HCV. CONCLUSIONS: Our results indicate that analysis of hepatitis virus genomes using polymerase chain reaction allows accurate identification of the virus causing fulminant hepatitis.

Adolescent↗
PubMed1996

Separable cis-regulatory elements that contribute to tissue- and site-specific alpha 2(XI) collagen gene expression in the embryonic mouse cartilage.

Type XI collagen is a structural component of the cartilage extracellular matrix and plays an important role in skeletal morphogenesis. As a step toward defining the molecular mechanisms responsible for the regulation of type XI collagen expression, we characterized the promoter region of the mouse alpha 2(XI) collagen gene (Coll1a2). We also generated transgenic mice harboring various fragments of the promoter and the first intron of Coll1a2 linked to the Escherichia coli beta-galactosidase gene to identify the cis-acting elements responsible for tissue- and site-specific expression during development. Cloning and sequence analysis of the 5' flanking region of Coll1a2 showed that the putative 3' end of the retinoid X receptor beta gene was located 742 bp upstream of the Coll1a2 start site. This suggested that the promoter region of Coll1a2 was localized within this 742-bp sequence, which contained multiple consensus regulatory elements. Examination of the transgenic mice revealed that the longest DNA construct (containing the entire promoter and first intron sequences) directed lacZ expression in the notochord as well as in the primordial cartilage throughout the body, with the pattern of expression mimicking that of endogenous Coll1a2 transcripts. On the other hand, deletion of the upstream approximately 290 bp resulted in the elimination of lacZ expression in the primordial cartilage of the carpals, tarsals, and vertebral bodies, whereas lacZ expression in the notochord and in the other primordial cartilage elsewhere was not affected. Deletion of the first intron sequence also resulted in the loss of lacZ expression in the primordial cartilage of the carpals, tarsals, and vertebral bodies, as well as in the notochord. These results demonstrate that the upstream 742-bp and first intron segments of the mouse Coll1a2 gene contain the necessary information to confer high level tissue-specific expression in mouse embryos. In addition, our observations suggest the presence of site-specific cis-acting elements that control Coll11a2 gene expression in different cartilaginous components of the skeleton.

Animals↗
PubMed1996

Assessment of the significance of virulence factors of uropathogenic Escherichia coli in experimental urinary tract infection in mice.

Four Escherichia coli strains, isolated from cystitis patients, belonging to serotype 02:H- and possessing different combinations of urovirulence factors were examined in an experimental pyelonephritis mouse model to assess the relative importance of virulence factors in causation of urinary tract infections (UTI). The results suggest not only that the each virulence factor has a role in causation of UTI but also that the presence of P fimbriae and production of hemolysin significantly reduced the LD50 and ID50 of the strains in the mouse model. The results also demonstrate that the presence of additional virulence factors acts in an additive or synergetic fashion enhancing the cumulative impact of the strain.

Agglutination Tests↗
PubMed1996

Reservoir competence of the vole, Clethrionomys rufocanus bedfordiae, for Borrelia garinii or Borrelia afzelii.

In autumn of 1994 and spring of 1995, we examined Borrelia infection among Microtinae voles, Clethrionomys rufocanus bedfordiae, in Hokkaido, Japan. In BSK culturing of the earlobe tissues of 45 C. rufocanus bedfordiae captured, twelve rodents were positive for Borrelia. Eight isolates were used for the polymerase chain reaction (PCR) and the restriction fragment length polymorphism (RFLP) analysis. According to the results, these isolates were classified into B. garinii or B. afzelii. It is considered that a common vole, C. rufocanus bedfordiae, plays a significant role in the transmission and maintenance of B. garinii and B. afzelii, similar to the role of Apodemus speciosus mice.

Animals↗
PubMed1996

Comparison studies of major organ microcirculations under pulsatile- and nonpulsatile-assisted circulations.

In these comparison studies, we examined changes in major organ microcirculations during circulatory support using pulsatile and nonpulsatile pumps. Acute myocardial infarction was created by left anterior descending (LAD) branch ligation. After the animals in these studies fell into cardiogenic shock, they were supported by mechanical assist devices: a pulsatile ventricular assist device (VAD) in 4 pigs, a nonpulsatile VAD in 4 pigs, and an intraaortic balloon pumping (IABP) plus nonpulsatile VAD in 4 pigs. Each group was supported for 3 h with an identical mean aortic pressure being maintained. As for parameters, the stomach mucosa, liver regional blood flow, stomach mucosal pH, and arterial blood keton body ratio (AKBR) were measured. Both regional blood flow and AKBR increased in the pulsatile group as compared with the nonpulsatile group. There were no differences in the stomach mucosal pH among the 3 groups. These results suggest that pulsatile assist rather than the nonpulsatile assist plays a significant role in the recovery of deteriorated splanchnic organs due to cardiogenic shock.

Animals↗
PubMed1996

Pathogenesis of focal and random hepatocellular necrosis in endotoxemia: microscopic observation in vivo.

The present study was undertaken in rats to clarify the role of sinusoidal circulatory disturbances due to fibrin thrombi in the development of focal and random hepatocellular necrosis in endotoxemia. Sinusoidal circulation was examined microscopically in vivo in rats injected with endotoxin or heparin, or both. The sinusoids in places were occluded by adherent fibrin and neutrophils soon after endotoxin injection, and subsequently the sinusoidal blood flow stagnated, reversed, or detoured. Most of these sinusoidal circulatory disturbances recovered in a few hours. However, when the sinusoidal occlusion developed simultaneously in clusters of adjacent sinusoids, the sinusoidal circulatory disturbance persisted and induced ischemic foci and then hepatocellular coagulative necrosis. Pretreatment with heparin definitely prevented the adherence of fibrin and neutrophils to the sinusoidal walls, and focal hepatocellular necrosis did not appear. These results suggest that focal and random hepatocellular necrosis in endotoxemia is caused by circulatory disturbances due to fibrin thrombi in clusters of adjacent sinusoids.

Animals↗
PubMed1996

Ocular complication in congenital erythropoietic porphyria.

Congenital erythropoietic porphyria (CEP), classically known as "Günther disease', is an extremely rare autosomal recessively inherited disorder characterized by mutilating cutaneous photosensitivity and abnormal porphyrin heam biosynthesis in the bone marrow. So far there is no effective therapy for CEP. Because of severe cutaneous photosensitivity, treatment of CEP has mainly been focused upon the avoidance of sunlight and trauma of the skin to minimize skin symptoms. Recently we have encountered ocular complications, especially scleral involvement, in 5 CEP patients. From this point of view, we should pay attention not only to cutaneous symptoms but also to scleral involvement and ophthalmological examination is required to assess the quality of life of CEP patients.

Adult↗
PubMed1996

Toward understanding the function of amelogenin using transgenic mice.

The purpose of this study was to establish transgenic mouse lines as a tool to investigate the function of amelogenin during mineralization by causing ectopic production of amelogenin and studying its effect. The mouse amelogenin (mAme) was cloned from a 16-day-old whole mouse embryo cDNA library and was determined to be "full-length" mouse amelogenin (with a complete coding region) by comparison with the mouse amelogenin reported previously by Snead et al. (1985) and Lau et al. (1992). The overexpression construct contained: (1) the rat osteocalcin (OC) promoter (1.8 kb); (2) the adenovirus splicing casettes, including introgenic (Int) sequence (0.3 kb); (3) the full-length mAme cDNA (0.8 kb); and (4) the polyadenylation signal sequence from the pSG5 mammalian expression vector. Both Southern blotting and polymerase chain-reaction (PCR) analyses were performed, by means of a specific probe and a pair of oligodeoxynucleotides to OcIntmAme(A)+, respectively. The animals which showed transgene-positive in both analyses were further used to establish F1 animals. Heterozygocity was confirmed with F1 animals by PCR analysis of DNA from the F0 x FVB/N pups. Three independent transgenic F1 heterozygous lines (640t, 706t, and 708t) have now been established. The generation of F2 homozygous lines is under way. The heterozygous transgenic animals are currently being analyzed for alterations in the morphology and structure of various bone tissues.

Amelogenin↗
PubMed1996

Cloning of stress tolerance gene in Torulaspora delbrueckii No. 3110.

A cryptic plasmid (pSRY1) was found in Torulaspora delbrueckii No. 3110. A plasmid vector (pSRY21) was constructed by ligating it to pPR1-RIM-C ORF with a cycloheximide resistance gene (RIM-C). The transformation efficiency of the strain No. 3110 with pSRY21 by the protoplast-PEG method was increased by 3000-fold by treatment of the protoplasts with polylysine [poly(epsilon-L-lysine)]. Previously we have reported a mutant No. 3110, T1, which can neither assimilate nor accumulate trehalose. The mutant was salt- and temperature-sensitive. We cloned a DNA fragment from No. 3110, which, when introduced, complemented these mutant characters of T1. These results suggested an important role of metabolism of trehalose for the stress tolerance.

Cloning, Molecular↗
PubMed1996

Chain conformation of deacetylated beijeran calcium salt.

A well-defined X-ray fiber diffraction pattern was obtained from a stretched film of the calcium salt of a new uronic acid containing polysaccharide designated as beijeran in the deacetylated form, poly[-->3)-alpha-D-GalUA-(1-->3)-beta-L-Rham-(1-->3)-alpha-D -Glc-(1-->]. The oriented film showed no diffraction spots, indicating it to be amorphous. However, when annealed at high temperature, the film exhibited high crystallinity. All the visible reflections could be indexed in terms of a monoclinic unit cell with the following dimensions: a = 1.297; b = 1.676; c (fiber axis) = 2.509 nm; and gamma = 106.50 degrees. The length of the fiber axis and the absence of meridional reflections at any odd layer line indicate that an extended two-fold helical conformation was made up of two trisaccharide residues.

Acylation↗