Biomedical subjects

K Nakata

Publications and source records attributed to K Nakata.

At least 181 records · Page 10Linked to original sources

PubMed1998

Mucin-like glycoprotein secretion is mediated by cyclic-AMP and protein kinase C signal transduction pathways in rat corneal epithelium.

Ocular surface mucin is secreted from both goblet cells in the conjunctival epithelium and corneal epithelial cells. To clarify its mechanism of secretion in corneal epithelial cells, a rat cornea organ culture system was used to evaluate the second messenger roles of cyclic-AMP (cAMP), cyclic-GMP (cGMP) and protein kinase C (PKC) in modulating mucin-like glycoprotein secretion. Rat cornea sections (3 mm diameter) were cultured in TC-199 medium, and radiolabeled with sodium sulfate for 18 hr. After washing, the corneas were treated with various second messenger modulating agents for 30 min. The culture media were reacted with Dolichos biflorus (DBA)-lectin, and mucin-like glycoprotein was isolated. Then the radioactivity of DBA-binding mucin-like glycoprotein was isolated. Then the radioactivity of DBA-binding mucin-like glycoprotein was measured. There was a time-dependent increase in mucin-like glycoprotein was measured. There was a time-dependent increase in mucin-like glycoprotein secretion, whereas after corneal epithelial debridement the secretion was markedly inhibited by 81%. Mucin-like glycoprotein secretion was stimulated in a dose-dependent manner following elevation of cAMP levels by exposure to either forskolin, dibutyryl cAMP or 3-isobutyl-1-methylxanthine. Concomitant exposure to the cAMP dependent protein kinase inhibitor, KT5720 completely inhibited their stimulatory effects. Neither exposure to dibutyryl cGMP nor nitroprusside affected mucin-like glycoprotein secretion. Stimulation by PKC, phorbol 12, 13-dibutyrate (PDBu) also increased mucin-like glycoprotein secretion in a dose-dependent fashion. The PKC inhibitor, calphostin C completely inhibited the stimulation by PDBu of mucine-like glycoprotein secretion. These results demonstrate that corneal epithelial cells secrete mucin-like glycoprotein, which is mediated by cAMP and PKC signal transduction pathways.

1-Methyl-3-isobutylxanthine↗

PubMed1998

[Microcirculation of kidney and skin during left ventricular assisted circulation--comparative studies of pulsatile and nonpulsatile assists].

We examined microcirculation of the kidney and skin over a six-hour period in an acute myocardial infarction model in pigs. The outflow cannula was placed in the ascending aorta, the inflow cannula was placed the in left atrium, and a pump was connected to each (pulsatile group, Zeon Medical pneumatic pump; nonpulsatile group, Nikkiso HPM-15). Items examined included the regional blood flow of the cortex and medulla in the kidney and skin, renal and carotid arterial flow, arterial ketone body ratio (AKBR), lactate/pyruvic acid (L/P), BUN, creatinine, and beta 2-microglobulin. After the experimental study, the major organs were removed and a pathological study was performed. The mean aortic pressure after the assist could be maintained at about 100 mmHg. There were no significant differences between the two groups in mean aortic pressure and total cardiac output. Under assisted circulation, the pulse pressure was maintained at about 15 mmHg in the nonpulsatile group and about 40 mmHg in the pulsatile group. After the assist, there were no significant differences in the carotid arterial blood flow between the two groups. However, there were significant differences between the two groups in the renal arterial, renal cortical, and regional skin blood flows. In the laboratory data, there were significant differences between the two groups in AKBR, L/P, and beta 2-microglobulin. Pathological findings on the kidney in the nonpulsatile group showed expansion of the proximal tubes, retention of red blood cells, and expansion of blood capillaries within the glomerulus. On the other hand, the pulsatile group showed almost normal formation. In the lungs, the nonpulsatile group showed edematous change in the air cells and the pulsatile group showed almost normal formation. The results of the previous and current study indicated that the pulsatile assist produced superior circulation in the kidney and peripheral organs and superior cellular metabolism in the early treatment of acute left cardiac failure. On the other hand, nonpulsatile assisted circulation was found to be ineffective in maintaining the circulation in the body, and to be potentially capable of causing irreversible damage of major organs if continuous for more than three hours. The results also indicated that pulsatility was necessary to maintain normal circulation in the peripheral organs and cellular metabolism in the early treatment of acute left cardiac failure.

Animals↗

PubMed1998

Differential in situ expression of alpha2(XI) collagen mRNA isoforms in the developing mouse.

Type XI collagen is an essential structural component of the extracellular matrix of cartilage and plays a role in collagen fibril formation and skeletal morphogenesis. The expression of all three type XI collagen genes is not restricted to cartilage. In addition, alternative exon usage seems to increase the structural diversity and functional potential of type XI collagen during development. In order to investigate type XI collagen expression during development, we have examined alpha2(XI) and alpha1(XI) collagen genes by in situ hybridization in mice. Transcripts of the alpha2(XI) collagen gene were first detected in the notochord of mouse embryos after 11.5 days of gestation. Subsequently, alpha2(XI) mRNA was mainly found in the cartilaginous tissues of the developing limbs and axial skeleton together with transcripts of the alpha1(XI) gene. The alpha2(XI) transcripts seemed to be alternatively spliced isoforms lacking exons 6-8, which code for an acidic domain. Expression of alpha2(XI) outside the cartilage was relatively restricted, whereas expression of the alpha1(XI) gene was widespread. However, expression of alpha2(XI) transcripts containing exons 6-8 was found in non-chondrogenic tissues, including the calvarium and periosteum where intramembranous ossification occurs. These results indicate that alpha2(XI) mRNA isoforms are differentially expressed in various tissues during development. In addition, alpha2(XI) mRNA isoforms containing alternative exons are present in osteogenic cells, and their expression may be closely related to the formation of bone or cartilage.

Alternative Splicing↗

PubMed1998

Ameliorative effect of SA4503, a novel cognitive enhancer, on the basal forebrain lesion-induced impairment of the spatial learning performance in rats.

We investigated the effect of successive administrations of SA4503 (1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine dihydrochloride), a novel cognitive enhancer with high affinity and selectivity for the sigma1 receptor subtype, on the cortical cholinergic dysfunction-induced impairment of the spatial learning performance in the Morris water maze (MWM) task in rats. The impairment of the spatial learning performance was produced by the ibotenic acid-induced lesion of the basal forebrain (BF) area in rats. Escape latencies to find the platform during the training trials of the MWM task were significantly prolonged in the BF-lesioned rats compared with the sham-operated rats. Daily treatment with SA4503 (0.1-0.5 mg/kg, P.O./day) for 13 days ameliorated this learning deficit. In the probe trial, BF-lesioned rats reduced the number of times each rat crossed the former platform location during the training trials (goal area) in comparison with sham-operated rats. Successive administrations of SA4503 (0.25 mg/kg, P.O./day) also significantly increased the BF lesion-induced reduction of the number of times each rat crossed the goal area. These results suggest that the successive administrations of SA4503 attenuate the impairment of the spatial learning performance in rats with cortical cholinergic dysfunction, and that SA4503 is useful as a therapeutic drug for Alzheimer's disease.

Animals↗

PubMed1998

Cytotoxic effect of endodontic bacteria on periapical fibroblasts.

This study was conducted to investigate the effects of sonicated bacterial extracts (SBEs) from anaerobic Gram-negative bacteria on periapical fibroblast obtained from the apical portion of human periodontal ligaments. Porphyromonas endodontalis, Porphyromonas gingivalis, Prevotella intermedia, and Fusobacterium nucleatum were chosen from among the endodontic bacteria isolated from root canals having a periapical lesion and compared in terms of their cytotoxicity. The purpose of this study was to examine which bacteria are involved in the development of periapical inflammation. The anaerobes were cultured under strict anaerobic conditions, and the bacterial cells were then harvested by centrifugation after incubation. The concentrated cell suspensions were sonicated and subsequently centrifuged. An SBE was made of each of the filtered supernatants. Each SBE was added to cultures of periapical fibroblasts. The cell growth and proliferation were measured by the MTT method after 3, 5, and 7 days. The SBEs from P. endodontalis, P. gingivalis, and F. nucleatum inhibited the growth of the fibroblasts, whereas the SBE from P. intermedia did not inhibit it. The SBEs from P. gingivalis and F. nucleatum inhibited the fibroblast growth more strongly than did the P. endodontalis, P. gingivalis, and F. nucleatum may participate in the development of periapical lesions.

Bacterial Proteins↗

PubMed1998

Xenopus Zic family and its role in neural and neural crest development.

We characterized two new members of the Zic family, Xenopus Zic1 and Zic2. They are very similar to mouse Zic1 and Zic2 in the protein coding region including the zinc finger domain. In early gastrula, Zic1 expression was restricted to the prospective neural plate region whereas Zic2 was expressed widely in the ectoderm. We observed enhanced neural and neural crest-derived tissue formation in the Zic1 or Zic2 overexpressed embryos and neural and neural crest marker induction in the Zic1 or Zic2 overexpressed animal cap explants. Our findings suggest that Zic1 and Zic2 have essentially the same properties as Zic3 and that the Xenopus Zic family may act cooperatively in the initial phase of neural and neural crest development.

Amino Acid Sequence↗

PubMed1998

The safety system for the rotary blood pump, combination of the valve and LVAD pulsatile mode: in vitro test.

The significant amount of regurgitation produced by a stopped rotary blood pump is one of the major considerations for its use as an implantable left ventricular assist device (LVAD), especially if the pump accidentally stops. The installation of a valve is an option for the solution of this potential problem. However, this option may lead to thrombogenic problems, particularly if the valve motion is restricted. This in vitro study analyzes the valve performance and assesses the credibility of a rotary blood pump valve. A pulsatile pump was used as the natural heart and a centrifugal pump as the LVAD. The valve was positioned into the LVAD outflow. In the low speed range (<1,000 rpm in this test condition), normal valve motion was maintained. Also, the valve model provided a higher mean bypass flow than the model without a valve due to reduced regurgitation. However, the valve motion was drastically restricted when in the high speed range (>1,600 rpm in this condition). The pulsatile mode was applied to the LVAD by periodically changing the impeller speed (40 bpm); subsequently, a constant valve motion could be provided. A possibility exists that this pulsatile mode application could eliminate thrombosis formation around the valve. A conclusion was made that the combination of a valve and an LVAD in a pulsatile mode is considered to be a unique safety system for a rotary blood pump.

Blood Pressure↗

PubMed1998

In vivo evaluation of the miniaturized Gyro centrifugal pump as an implantable ventricular assist device.

A miniaturized Gyro centrifugal pump has been developed to be incorporated into a totally implantable artificial heart. The Gyro PI (permanently implantable) model is a pivot bearing supported centrifugal pump with a priming volume of 20 ml. With the miniaturized actuator, the pump-actuator package has a height of 53 mm, a diameter of 65 mm, and a displacement volume of 145 ml. To evaluate the hemocompatibility and efficiency of the Gyro PI pump system, a plastic prototype (Gyro PI-601) was implanted into a bovine model as a left or right ventricular assist device (LVAD or RVAD), bypassing from the left ventricular apex to the descending aorta or from the right ventricular infundibulum to the main pulmonary artery. The calves were anticoagulated with heparin to maintain activated clotting times from 150 to 200 s. Four calves were supported for 23, 24, and 50 days in the LVAD studies, and 40 days in the RVAD study. The first calf died due to intrathoracic bleeding associated with sepsis. The second calf was euthanized for a low flow rate less than 2 L/min due to an obstructed inflow with growing pannus. The third and fourth calves were euthanized as scheduled. Renal and hepatic functions remained normal, and plasma free hemoglobin values were less than 8 mg/dL throughout the experiments. The fourth case showed flow rates of 4.83 +/- 0.57 L/min, input power of 6.16 +/- 0.49 W, and the inside temperature of the actuator of 43.5 +/- 0.52 degrees C. The pumps implanted in the fourth calf demonstrated no thrombus formation at the autopsy. These in vivo experiments revealed that the Gyro PI pump can provide adequate flow as an easily implantable, efficient, antithrombogenic, and nonhemolytic centrifugal LVAD or RVAD with miniaturized actuators.

Animals↗

PubMed1998

Estimation of the native cardiac output from a rotary blood pump flow: in vitro study.

The rotary blood pump will be an implantable left ventricular assist device (LVAD) in the near future. However, the best control method and the interrelationship between the rotary blood pump and native heart functions are unclear. An estimation was made of the native heart cardiac output from the change of an LVAD's outflow waveform. The mock circulation loop was composed of an aortic compliance chamber, left arterial chamber, total artificial heart as a native heart, and a rotary blood pump that was placed as an LVAD with left ventricular drainage. The fast Fourier transform (FFT) technique was utilized to analyze the LVAD's outflow waveform and calculate the pulse power index (PPI) to examine a relation between the PPI and total artificial heart (TAH) output. The PPI increased with the increase of the TAH output; there was a positive correlation, and there was an inverse correlation between the PPI and the assist ratio. From this viewpoint, an estimation of the pulsatility change of the LVAD's outflow wave may indicate the native cardiac output.

Aorta↗

PubMed1998

Clinical experiences of percutaneous cardiopulmonary support: its effectiveness and limit.

In recent years, several types of centrifugal pumps have been widely used as the main pumps for cardiopulmonary bypass (CPB) and postcardiotomy cardiac support. From April 1990 to March 1997, a percutaneous cardiopulmonary support (PCPS) system was used in 20 patients with an average age of 58 years (13 males and 7 females). They comprised 11 ischemic, 6 valvular, 2 aortic, and 1 congenital heart disease patients. Our PCPS system consists of a centrifugal pump (BioMedicus BP-80), an oxygenator, and a reservoir. The entire blood contacting surface, including that of the thin wall cannulas, is coated by heparin bonded materials. As a result of this new technology, this system can be used for the long term without systemic heparinization. No major critical thrombi were revealed inside the pumps or circuits. Of the 20 patients, 7 (35%) (Group 1) could be weaned from PCPS, and the remaining 13 (Group 2) could not. In Group 1 although 2 patients suffered from renal failure and pneumonia, respectively, both were discharged from our hospital. The long-term survival rate was 35%. In Group 2 cerebral vascular damage was recognized in 3 patients, renal failure in 4, multiple system organ failure in 4, bleeding in 2, arrhythmia in 1, and leg ischemia in 2. Pulse pressure was significantly elevated due to the recovery of the native heart in Group 1, 2 days after support. However, in Group 2, it did not elevate, and the left ventricular ejection fraction was less than 30%, associated with high left atrial pressure. In conclusion, this heparin coated PCPS system was very simple and easy to control. It demonstrated long-term biocompatibility and was very effective in recovering deteriorated cardiac function. Quicker application of this system can play an important role in preventing severe complications and obtaining better clinical results. If long-term support is necessary, a ventricular assist device (VAD), which is more powerful, durable, and biocompatible, has to be applied instead of PCPS.

Acute Kidney Injury↗

PubMed1998

Use of fructose 1,6-diphosphate aldolase to detect tumour necrosis after transcatheter arterial embolization of hepatocellular carcinoma.

Transcatheter arterial embolization (TAE) is a popular and well-established devascularization treatment modality for hepatocellular carcinoma (HCC). The persistent retention of lipiodol on follow-up computed tomography (CT) scan and time-dependent decrease in size of the lipiodol-stained area of tumour after TAE does not reveal the biological death of tumour cells. Moreover, it is difficult to clinically evaluate the effective necrosis of tumour cells by TAE in cases of HCC that do not produce alpha-fetoprotein (AFP). We therefore studied the release of a relatively tumour-specific protein by the necrotic hepatoma cells to evaluate the effectiveness of TAE. Transcatheter arterial embolization was performed in 17 patients with the imaging diagnosis of HCC; either superselective (n = 6) or non-superselective (n = 11) techniques were used. We measured serum levels of relatively tumour-specific fructose 1,6-diphosphate (FDP) aldolase and non-tumour-specific fructose 1-phosphate (F1P) aldolase by substrate-specific enzymatic methods. Enzyme activities were performed before and after TAE. The time-dependent decrease in size of the lipiodol-stained areas was studied on follow-up CT scans after TAE. Pre- and post-treatment serum AFP levels were determined by radio-immunoassay. The six cases of superselective TAE underwent marked tumour regression by CT compared with the 11 cases of non-superselective TAE. Fructase 1,6-diphosphate aldolase output correlated well with post-necrotic tumour regression after TAE (r = 0.87, P= 0.001). The elevation of serum FDP aldolase was also significantly associated with a decrease in serum AFP (r = 0.72, P < 0.01). In contrast, serum F1P aldolase output was inversely correlated with either tumour regression or serum AFP concentrations after TAE. The serum levels of the tumour-specific enzyme FDP aldolase correlated significantly with effective tumour necrosis and consequent tumour regression after TAE. We suggest that measurement of FDP aldolase activity in serum after TAE can be used clinically to detect the degree of tumour necrosis by TAE.

Adult↗

PubMed1998

Regulation of alkaline phosphatase gene expression in human hepatoma cells by bile acids.

Bile acid-dependent secretion and the translationally regulated synthesis of alkaline phosphatase (ALP) in rat liver cell culture and by bile duct ligation has already been demonstrated. With the advent of ALP cDNA cloned sequences, the mechanism of the effect of bile acids on ALP activity and the expression of the ALP gene in different hepatoma cells was investigated. The HuH7 and HepG2 cells were treated with taurine-conjugated cholic acid (CA), chenodeoxycholic acid (CDCA) and ursodeoxycholic acid (UDCA) at 0-1 mmol/L and the numbers of viable cells were counted at 24, 48 and 72 h after treatment. A [3H]-thymidine incorporation study was performed with different bile acids at a concentration of 1 mmol/L for 48 h. The cellular activity of ALP in HuH7 and HepG2 cells by bile acids was measured by a substrate-specific enzymatic assay. To elucidate the effects of bile acids on ALP gene expression, a northern blotting experiment using hybridization with mouse placental ALP cDNA was performed. Cellular ALP activity was time- and dose-dependently increased in both HuH7 and HepG2 cells treated by CA and CDCA; however, no change in ALP activity was observed following treatment with UDCA compared with controls. Induction of ALP activity was dominant in HepG2 cells and independent of cell growth and proliferation. The addition of UDCA synergistically reduced the increased activity of ALP produced by CA and CDCA in both HuH7 and HepG2 cells. By northern blot analysis, the level of ALP mRNA was elevated by CA and CDCA; however, levels of ALP mRNA were suppressed by UDCA. In conclusion, CA and CDCA cause up-regulation of ALP mRNA and UDCA leads to down-regulation of ALP mRNA by its interaction with either CA or CDCA. We assume that increased ALP synthesis in hepatoma cells after bile acid treatment results from an enhanced rate of transcription rather than translation of mRNA.

Alkaline Phosphatase↗

PubMed1998

Gefarnate increases PAS positive cell density in rabbit conjunctiva.

AIMS: The effects of three drugs for the treatment of gastritis and gastric ulcer--gefarnate, ecabet sodium, and troxipide--on periodic acid Schiff (PAS) positive cell density in rabbit conjunctiva in vivo were investigated. METHODS: Eye drops containing gefarnate (0.1%, 1%), ecabet sodium (0.1%, 1%), or troxipide (0.1%, 1%) were instilled in both eyes of rabbits, six times a day for 7 days. On the eighth day, filter paper was gently pressed on the bulbar and palpebral conjunctiva, and impression cytology was performed with PAS staining. Three points in each specimen were selected randomly, and PAS stained cells were counted. RESULTS: The instillation of gefarnate increased PAS positive cell density significantly at the concentration of 1% (p < 0.05). In contrast, instillation of ecabet sodium or troxipide failed to change PAS positive cell density. CONCLUSIONS: These results demonstrated that gefarnate stimulates PAS positive cell density in rabbit conjunctiva.

Abietanes↗

PubMed1998

Contribution of HLA genes to genetic predisposition in diffuse panbronchiolitis.

Diffuse panbronchiolitis (DPB) in East Asia is a distinctive chronic obstructive pulmonary disease of unknown etiology. We hypothesize that the disease susceptibility is due to genetic predisposition unique to Asians. Association between human leukocyte antigen (HLA)-Bw54 and the disease was previously reported. In the present study, using newly developed polymerase chain reaction (PCR)- based methods, we directly analyzed HLA class I and II alleles in 76 Japanese patients. HLA-A, -B, and -C antigens were screened by the conventional typing method, and then B22-group alleles including HLA-B54 were genotyped by single-strand conformation polymorphism analysis. Alleles of HLA-DRB1 gene were fully determined by the microtiter plate hybridization method. Thirty-seven percent of the patients possessed HLA-B*5401 allele conserved predominantly in East Asians, as compared with 15% of 110 healthy volunteers (chi2 = 12.4, p = 0.0004). In addition, 4% of the patients possessed B*5504 also unique to Asians but a rare allele which was not found in normal control subjects in this study. Typing of HLA-DRB1 class II gene did not demonstrate strong positive association with the disease. A33, B44, and DRB1*1302 showed negative association with the disease. We conclude that distinctive molecular structure of HLA-B alleles or a closely linked gene in the HLA region contributes to genetic predisposition in diffuse panbronchiolitis. This may partly explain why this disorder is found primarily in Asians.

Alleles↗

PubMed1998

Diffuse panbronchiolitis in rheumatoid arthritis.

The association of progressive obliterative bronchiolitis (OB) with rheumatoid arthritis (RA) is uncommon but has been reported previously. Diffuse panbronchiolitis (DPB) is a unique inflammation principally affecting the respiratory bronchioli and has been reported mainly in Japanese adults. Recently, DPB has also been noted in patients with RA in Japan. Therefore, there might be considerable overlap in clinical features between DPB and OB associated with RA in Japan. The aim of this study was to evaluate the clinicopathological characteristics of bronchiolitis in patients with RA. Three RA patients clinically diagnosed as having DPB were evaluated. All patients underwent chest radiographs, pulmonary function tests (PFT) and post mortem examination. Clinical features in all patients were a history of productive cough, exertional dyspnoea, wheezing and/or coarse crackles. Chest radiographs showed small nodular shadows up to 2 mm in diameter with bronchiolectasis throughout both lungs in all patients. The PFT revealed marked obstructive impairment in all patients. All patients died of progressive respiratory failure. Pathologically, two out of the three cases were confirmed as DPB, while the remaining one case was confirmed as OB, because the primary obstructive lesions were in the respiratory bronchioli in the former and in the membranous bronchioli and the proximal small bronchi in the latter. Thus, the clinical features of DPB and OB were strikingly similar, but the histopathological features revealed distinct differences. This study demonstrated that there was considerable overlap in clinical features between diffuse panbronchiolitis and obliterative bronchiolitis associated with rheumatoid arthritis, suggesting that diffuse panbronchiolitis might be a new manifestation of rheumatoid arthritis. The differentiation of these two disease entities is significant in making decisions on their therapeutic modality and is possible by analysing the precise histopathological findings of the lung.

Aged↗

PubMed1998

Distribution of uropathogenic virulence factors among Escherichia coli strains isolated from dogs and cats.

A variety of virulence factors (VFs) such as type 1 fimbriae, pilus associated with pyelonephritis, S fimbriae, afimbrial adhesin, alpha-hemolysin, aerobactin and cytotoxic necrotizing factor 1 are associated with uropathogenic Escherichia coli. In this study, 80 uropathogenic E. coli strains in 50 dogs and 30 cats suffering from UTI. In addition, 60 E. coli strains were isolated from fecal samples from 30 each of healthy dogs and cats. The distribution of VFs of uropathogenic E. coli strains isolated from dogs and cats suffering from urinary tract infections (UTI) were examined by the colony hybridization test with seven DNA probes specific for VFs, and the results were compared with those obtained in the studies on strains from humans with UTI. In uropathogenic E. coli strains isolated from dogs and cats suffering from UTI, VFs were detected as frequently as in the strains isolated from humans with UTI. Although less frequently, genes encoding these VFs especially pap, sfa, hly, and cnf 1 genes were also associated with E. coli strains isolated from feces of healthy cats, in contrast to the distribution pattern of uropathogenic E. coli observed in humans. Furthermore, all VFs except pil were significantly more frequently detected in strains isolated from urine of animals with cystitis than in those isolated from feces of healthy humans. These results indicate that VFs of E. coli contribute to the pathogenesis of UTI in dogs and cats.

Adhesins, Bacterial↗

PubMed1998

The Metal-Cancellous Cementless Lübeck total hip arthroplasty. Five-to-nine-year results.

We implanted 51 Metal-Cancellous Cementless Lübeck (MCCL) prostheses into 45 patients with dysplastic hips and followed 49 hips (96.1%) for five to nine years. One had needed revision for stem fracture and one for infection; the clinical outcome of the other 47 hips was assessed using the Merle d'Aubigné and Postel hip score. All hips were either excellent (63%) or good (37%). Three patients (6%) had mild thigh pain at six months, but this had settled within two years. Serial radiographs showed stable fixation with bone ingrowth in all hips, with increased density of the cancellous bone in contact with the implant and some trabecular ingrowth. There was early varus shift of the stem in one hip, but this stabilised in three months. Osteolysis of the femoral cortex was seen in one hip at seven years after surgery, and mild bone resorption due to stress shielding in 31 (63%). Acetabular bone grafting with autogenous bone from the femoral head gave successful support to the socket in 13 hips. The MCCL prosthesis gave satisfactory mid-term results in patients with osteoarthritis secondary to hip dysplasia.

Acetabulum↗

PubMed1998

Retrovirus-mediated gene therapy for human hepatocellular carcinoma transplanted in athymic mice.

Gene therapy using a retrovirus vector carrying herpes simplex virus thymidine kinase gene under the control of the 0.3-kb human alpha-fetoprotein (AFP) gene promoter (LNAF0.3TK virus) in combination with ganciclovir (GCV) treatment was performed in athymic mice harboring AFP-producing HuH-7 human hepatoma cells. GCV treatment resulted in pronounced growth inhibition of the virus-infected HuH-7 xenograft in mice, but did not affect growth of the parental xenograft. These results indicate that the AFP gene promoter sequence allows enough therapeutic gene expression to induce the GCV-mediated cytotoxicity in vivo in AFP-producing human hepatoma cells.

Animals↗