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Biomedical subjects

K Nakata

Publications and source records attributed to K Nakata.

At least 19 recordsLinked to original sources
PubMed1995

Gene therapy for hepatoma cells using a retrovirus vector carrying herpes simplex virus thymidine kinase gene under the control of human alpha-fetoprotein gene promoter.

The alpha-fetoprotein (AFP) gene is normally expressed in fetal liver and is transcriptionally silent in adult liver but is reactivated in hepatocellular carcinoma. It has been shown that the positive and negative transcriptionally regulatory elements of the human AFP gene, which play an important role in its developmental regulation, exist over the quite extended region (4 kb). We constructed a hybrid gene consisting of herpes simplex virus thymidine kinase (HSV-tk) gene under the control of the 0.3-kb human AFP gene promoter and inserted it into a retroviral vector. When AFP-producing hepatoma cells were infected with this recombinant retrovirus (LNAF0.3TK virus), the cells expressed HSV-tk gene and exhibited increased sensitivity to ganciclovir parallel with the ability of AFP production. On the other hand, the retroviral infection had little effect on ganciclovir-mediated cytotoxicity in AFP-nonproducing hepatoma or non-hepatoma cells. Moreover, the addition of dexamethasone increased the cytotoxicity of aciclovir to the virus-infected, AFP-producing cells through a glucocorticoid-responsive element in the AFP promoter, although aciclovir, by itself, had little cytotoxicity. These results demonstrate that the AFP promoter sequence alone can provide enough tumor-specific activity for therapeutic gene expression and induce selective growth inhibition by ganciclovir in the virus-infected, AFP-producing human hepatoma cells. In addition, it is possible that expression of the therapeutic gene is modulated by administration of dexamethasone or other agents that alter AFP promoter activity after gene transduction.

3T3 Cells↗
PubMed1995

Expansion of circulating gamma delta T cells in active sarcoidosis closely correlates with defects in cellular immunity.

The relationship between the level of gamma delta T cells and cellular immunity of T lymphocytes was assessed in the peripheral blood of active sarcoidosis patients and healthy controls. We divided the active sarcoidosis patients into two groups: a group of patients with a normal distribution of circulating gamma delta T cells (group A; n = 11, less than 8.2% lymphocytes) and another group with increased gamma delta T cell levels (group B; n = 11, greater than 8.2% lymphocytes). The proportion and absolute count of CD4+ lymphocytes in group B (28.6 +/- 11.2%, 374.1 +/- 193.8/microliters) were remarkably smaller than control subjects (45.7 +/- 6.8%, 818.3 +/- 290.2/microliters, P < 0.001, P < 0.002, respectively). Group A, however, showed a moderate reduction in CD4+ lymphocytes when compared with controls. Serial measurements of T cell subtypes were performed on five patients in group B. gamma delta T cells and CD4+ lymphocytes were inversely correlated over the observation period which ranged from 2 to 18 months. When peripheral blood T cells were stimulated with PHA or PPD in vitro, the responses were weaker in group B compared with both group A and control subjects. These results suggest that the increase in circulating gamma delta T cells in sarcoidosis closely relates to a defect in cellular immunity which progresses during the disease process.

Adult↗
PubMed1995

The immune reaction to heterologous serum causes osteonecrosis in rabbits.

Osteonecrosis (ON) was produced experimentally in rabbits by intravenous injection of horse serum. Eighty adult rabbits were used: 16 were injected twice with isotonic saline (Group A), 24 were injected once with saline and once with horse serum (Group B), and 40 were injected twice with horse serum (Group C). Both femurs of each rabbit were obtained from 2 h to 7 weeks after the final injection an were subjected to histological examination. No pathological changes were seen in Groups A and B. In Group C, 5 of 15 rabbits (33%) showed ON (necrosis of trabecula and bone marrow) in the femoral metaphysis. In Group C, the early major pathological findings in bone marrow are extravasation of erythrocytes in sinusoidal spaces and microthrombi in small arteries and arterioles near the lesion of extravasation. Immune complexes were demonstrated in the kidney within 24 h of the final injection of horse serum. The present study suggests that immunological reaction associated with serum sickness may play an important role in inducible ON and this model will contribute toward clarifying the pathogenesis of ON.

Animals↗
PubMed1995

Effect of ethanol on nitrite oxidation in the perfused rat liver.

The effect of ethanol on nitrite oxidation was investigated in the perfused rat liver. Real-time spectral changes in catalase were obtained using a reflectance scanning spectrophotometer in rat liver perfused with Krebs-Henseleit bicarbonate buffer in a non-recirculating system. The nitrite oxidation rate and nitrate production rate were calculated from the differences in concentrations between the influx and efflux perfusates and from the flow rate/g liver weight. Nitrite infusion caused an increase in absorbance difference delta A (640-660 nm), indicating decomposition of catalase compound I to the free form. Administration of ethanol during the nitrite infusion caused a further increase in delta A (640-660 nm) and significant decreases in both the nitrite oxidation rate and the nitrate production rate. Both the nitrite oxidation rate and nitrate production rate decreased, depending on the concentration of ethanol administered. At 10 mM ethanol, they reached about half the rates before the ethanol infusion. In conclusion, ethanol inhibits nitrite oxidation by catalase in the perfused rat liver at relatively low concentrations that can be realized in blood by daily alcohol consumption.

Animals↗
PubMed1995

Effects of lipopolysaccharides on human dental pulp cells.

Human dental pulp cells were treated with 1, 10, and 100 micrograms/ml of lipopolysaccharide (LPS). The effects of treatment were examined by measurement of the DNA content, protein content, and alkaline phosphatase activity of the cells. LPS samples were purified from Porphyromonas gingivalis, Porphyromonas endodontalis, and Fusobacterium nucleatum isolated from root canals, and Escherichia coli 0111:B4 LPS was used as a positive control. At a concentration of 1 microgram/ml, none of the LPSs caused any change in the production of DNA or protein, whereas the amount of DNA was increased at 10 micrograms/ml and inhibited at 100 micrograms/ml. Protein synthesis was decreased by LPSs at both 10 and 100 micrograms/ml. Alkaline phosphatase activity was not changed at any concentration of LPS tested.

Alkaline Phosphatase↗
PubMed1995

Effects of simultaneous administration of ethanol on styrene metabolism under fed and fasted conditions in the perfused rat liver.

The purpose of this study was to clarify the simultaneous administration of ethanol on styrene metabolism in the perfused rat liver under fed and fasted conditions. Styrene uptake rate, production rate of styrene glycol, oxygen consumption rate, and changes in reduced pyridine nucleotide fluorescence were monitored in the perfused rat liver. The effects of ethanol on parameters of styrene metabolism were observed in rat livers under fed and fasted conditions: fed (group I), fasted (group II), and fasted with xylitol in the perfusate (group III). The simultaneous administration of ethanol and styrene significantly decreased styrene uptake rate, production rate of styrene glycol, and oxygen consumption rate, and produced significant reduction of pyridine nucleotide fluorescence as compared with the single administration of styrene in groups I and III. In contrast, the simultaneous administration of ethanol and styrene significantly increased the production of styrene glycol and oxygen consumption as compared with the single administration of styrene in group II. Significant effects on the styrene uptake rate and the reduced pyridine nucleotide fluorescence were observed with regard to factors of both nutritional status and the interaction between ethanol and nutritional status by two-way analysis of variance. These findings showed that the effects of ethanol on styrene metabolism in the liver were dependent upon the nutritional status of the animal. The fed and fasted conditions affected the effect of ethanol on styrene metabolism by changing the supply of NADPH to the mixed-function oxidase system. In conclusion, ethanol suppressed styrene metabolism in the fed condition, but enhanced it in the fasted condition. This phenomenon should be considered in the prevention of occupational hazard of styrene exposure in industrial workers with alcohol drinking habits and nutritional problems.

Animals↗
PubMed1995

Prediction of zinc finger DNA binding protein.

Using the neural network algorithm with back-propagation training procedure, we analysed the zinc finger DNA binding protein sequences. We incorporated the characteristic patterns around the zinc finger motifs TFIIIA type (Cys-X2-5-Cys-X12-13-His-X2-5-His) and the steroid hormone receptor type (Cys-X2-5-Cys-X12-15-Cys-X2-5-Cys-X15-16-Cys-X4-5-Cys-X8-10- Cys-X2-3-Cys) in the neural network algorithm. The patterns used in the neural network were the amino acid pattern, the electric charge and polarity pattern, the side-chain chemical property and subproperty patterns, the hydrophobicity and hydrophilicity patterns and the secondary structure propensity pattern. Two consecutive patterns were also considered. Each pattern was incorporated in the single layer perceptron algorithm and the combinations of patterns were considered in the two-layer perceptron algorithm. As for the TFIIIA type zinc finger DNA binding motifs, the prediction results of the two-layer perceptron algorithm reached up to 96.9% discrimination, and the prediction results of the discriminant analysis using the combination of several characters reached up to 97.0%. As for the steroid hormone receptor type zinc finger, the prediction results of neural network algorithm and the discriminant analyses reached up to 96.0%.

Algorithms↗
PubMed1995

Use of standardized protease enzymes for antibody screening of blood donor samples with the microplate system AutoAnalyzer.

Papain, bromelin and ficin can be standardized by the casein method for use in red blood cell antibody screening tests. The minimal and optimal enzyme activity for detecting blood group antibodies in donors, using the new Automated Pre-Transfusion Blood Testing System Olympus PK7200 by the two-stage method for all three enzymes, is one casein unit. One casein unit of proteinase activity changed the red blood cell surface charge to a low plateau value as measured by electrophoretic mobility and sialic acid content, and removed sterically inhibiting structures of surface protein as detected by SDS-PAGE.

Autoanalysis↗
PubMed1995

Mycobacterium tuberculosis enhances human immunodeficiency virus-1 replication by transcriptional activation at the long terminal repeat.

Tuberculosis has emerged as an epidemic fueled by the large number of individuals infected with the human immunodeficiency virus, especially those who are injecting drug users. We found a striking increase from 4- to 208-fold in p24 levels in bronchoalveolar lavage fluid from involved sites of Mycobacterium tuberculosis infection vs uninvolved sites in three HIV+ patients. We used an in vitro cell culture model to determine if tuberculosis could activate replication of HIV-1. Mononuclear phagocyte cell lines U937 and THP-1 infected with HIV-1JR-CSF, in vitro and stimulated with live M. tuberculosis H37Ra, had a threefold increase in p24 in culture supernatants. Using the HIV-1 long terminal repeat with a chloramphenicol acetyltransferase (CAT) reporter construct, live M. tuberculosis increased transcription 20-fold in THP-1 cells, and cell wall components stimulated CAT expression to a lesser extent. The nuclear factor-kappa B enhancer element was responsible for the majority of the increased CAT activity although two upstream nuclear factor-IL6 sites may also contribute to enhanced transcription. Antibodies to TNF-alpha and IL-1 inhibited the increase in CAT activity of the HIV-1 long terminal repeat by M. tuberculosis from 21-fold to 8-fold. Stimulation of HIV-1 replication by M. tuberculosis may exacerbate dysfunction of the host immune response in dually infected individuals.

AIDS-Related Opportunistic Infections↗
PubMed1995

Attenuation of postmenopausal high turnover bone loss in patients with hypoparathyroidism.

To elucidate the role of PTH in postmenopausal bone loss, we studied 33 postmenopausal patients who received total thyroidectomy due to thyroid carcinoma. Among these patients, 13 were patients with hypoparathyroid function (HPf), and 20 retained normal parathyroid function (NPf) after thyroidectomy. Bone mineral density (BMD), the rate of BMD loss, and incidence of spinal deformity as well as varying bone metabolic markers were analyzed in all patients. The age-matched BMD was clearly higher, and the incidence of spinal deformity was significantly lower in HPf than in NPf. The rate of BMD loss in HPf was significantly lower than in NPf during the early postmenopausal period (within 5 yr after menopause; mean +/- SD, -0.567 +/- 3.05% vs. -2.49 +/- 1.86%/yr, P < 0.05). In contrast, the rates were similar between the two groups during the late postmenopausal period (> 5 yr after menopause). Bone metabolic markers indicated that an accelerated bone turnover occurred during the early postmenopausal period in NPf, but not in HPf. These results suggest that the hypoparathyroid condition provides protection against age-related bone loss. This is due in part to attenuation of the high turnover bone loss that occurs early in menopause.

Adult↗
PubMed1995

Regulation of proliferation and osteochondrogenic differentiation of periosteum-derived cells by transforming growth factor-beta and basic fibroblast growth factor.

We studied the effects of transforming growth factor-beta and basic fibroblast growth factor on the regulation of proliferation and osteochondrogenic differentiation of periosteum-derived cells, which have the potential to differentiate into bone and hypertrophic cartilage in vitro. Histological observation revealed that transforming growth factor-beta stimulated chondrogenesis of periosteum-derived cells while basic fibroblast growth factor stimulated proliferation of fibroblast-like cells and inhibited osteochondrogenic differentiation. Immunohistochemical studies revealed that basic fibroblast growth factor inhibited the expression of osteocalcin. Transforming growth factor-beta enhanced uronic acid content but decreased DNA content, alkaline phosphatase activity, and calcium content. In contrast, basic fibroblast growth factor enhanced DNA content but decreased alkaline phosphatase activity, calcium content, and uronic acid content. In addition, transforming growth factor-beta shortened the time-course of gene expression of type-X collagen whereas basic fibroblast growth factor inhibited the gene expression. These results indicate that transforming growth factor-beta stimulates osteochondrogenic differentiation of periosteum-derived cells but inhibits proliferation. They also indicate that basic fibroblast growth factor stimulates proliferation of periosteum-derived cells but inhibits osteochondrogenic differentiation.

Alkaline Phosphatase↗
PubMed1995

Conservative treatment of isolated injuries to the posterior cruciate ligament in athletes.

We assessed arthroscopically 22 young athletes with an isolated acute posterior cruciate ligament (PCL) injury. Four had significant damage to the articular cartilage of the medial femorotibial compartment and were advised not to resume sports. Three underwent PCL reconstruction because of a reparable meniscal tear or instability. The other 15 were treated conservatively and resumed sport. At an average follow-up of 51 months, one had developed arthritic symptoms due to newly-developed severe chondral damage to the medial femoral condyle, but none of the other 14 had developed arthritic symptoms and most remained athletically active. Severe chondral damage should be seen at an early arthroscopy. Knees with an isolated injury to the PCL with concomitant articular damage may be successfully managed by conservative treatment.

Activities of Daily Living↗
PubMed1995

Polyethylene sockets and alumina ceramic heads in cemented total hip arthroplasty. A ten-year study.

From 1981 to 1983, we implanted Bioceram type-4 and type-5 prostheses in 61 hips in 54 patients with osteoarthritis secondary to acetabular dysplasia, congenital subluxation, or congenital dislocation of the hip. Fifty-seven hips in 50 patients were followed for a mean of 11.1 years (10 to 13). The mean age of the patients at operation was 53 years (31 to 70). Functional evaluation using the Merle d'Aubigné and Postel hip score showed a 77% success rate. Radiological loosening occurred in three femoral (5%) and 16 acetabular components (28%). Autologous femoral head grafts were used in 18 hips and became incorporated, giving mechanical support to the socket except for one which occupied a large weight-bearing area and eventually collapsed. The mean polyethylene wear was 1.1 mm (0 to 3.6) and the mean wear rate was 0.10 mm/year (0 to 0.31). A high rate of wear correlated with calcar resorption (p > 0.002) but not with acetabular loosening. There was no breakage of a ceramic head. Study of the ceramic heads and polyethylene sockets retrieved after ten years showed excellent surface roughness, sphericity, and bending strength for the heads but scratches and voids were seen on the sockets.

Bone Cements↗
PubMed1995

Second-look arthroscopy after meniscal repair. Review of 132 menisci repaired by an arthroscopic inside-out technique.

From 1986 to 1993, we repaired 278 torn menisci in 264 patients using an arthroscopically assisted inside-out technique. A total of 132 meniscal repairs in 122 patients were evaluated by second-look arthroscopy. At review, only nine patients had meniscal symptoms, such as locking, swelling or pain. Ninety-seven menisci (73%) had healed completely at the repair site, but there were new tears in different areas of 21 menisci, some of which had complete healing at the repair site. Incomplete healing, seen in 23 menisci (17%), was frequently near the popliteus tendon, most commonly where there had been an associated anterior-cruciate-ligament injury. Arthroscopically-assisted meniscal repair seems to be a reliable procedure, but some clinically successful cases had incomplete healing at the repair site or a newly-formed tear in the meniscal body or both. These lesions may cause meniscal symptoms to appear at a later date.

Adolescent↗
PubMed1995

[Successful treatment of acute myelomonocytic leukemia developed from MDS with cytarabine ocfosfate (SPAC)].

A 65-year-old female with acute myelomonocytic leukemia (AMMoL) developed from myelodysplastic syndrome (MDS), successfully treated with cytarabine ocfosfate (SPAC) is reported. Ubenimex, calcitriol and corticosteroid had a minor effect on her MDS. Since she had severe anemia and congestive heart failure on developing leukemia, she was treated with oral administration of SPAC, a cytidine deaminase resistant derivative of Ara-C. After the second course of SPAC (200 mg/day, for 14-28 days), marked erythroid bursts were found and she entered complete remission. The samplings of SPAC and its metabolites of SPAC were investigated in 2 cases including this case, but there seemed to be no relation between their content and effects. In AML patients, especially in cases developed from MDS, SPAC might be useful because it can be given orally even in an outpatient.

Aged↗
PubMed1994

Risk of hepatocellular carcinoma in patients with cirrhosis in Japan. Analysis of infectious hepatitis viruses.

BACKGROUND: The development of hepatocellular carcinoma (HCC) is associated closely with cirrhosis. In the present study, the cumulative risk of HCC in patients with cirrhosis was investigated. METHODS: A total of 401 patients were registered from April 1977 and followed for a mean of 4.4 years. Of 401 patients, 255 (64%) were tested for hepatitis B surface antigen (HBsAg) and antibody (anti-) to the hepatitis C virus (HCV); 87 (34%) patients were positive for HBsAg but were negative for anti-HCV (hepatitis B virus [HBV] group), 126 (49%) were negative for HBsAg but were positive for anti-HCV (HCV group), 10 (4%) were positive for both and 32 (13%) were negative for both (non-B non-C group). RESULTS: By the end of March 1993, HCC was diagnosed in 127 (31.6%) patients. The cumulative risk of HCC in the HCV group was slightly higher than that in HBV group (P = 0.3, 5-year risk: 36.9 versus 21.2%). In contrast, the rate was significantly lower in the non-B non-C group than in the HBV or HCV groups (P < 0.05 and P < 0.01, respectively, 5 year risk: 12.4%). CONCLUSIONS: These results suggest that not only HBV infection but also HCV infection increase the risk for HCC in patients with cirrhosis.

Adult↗