No abstract available.
Genetic Therapy*

No abstract available.
Hyperparathyroidism*

BACKGROUND: Herpes simplex virus thymidine kinase (HSVtk) phosphorylates the prodrug ganciclovir to a nucleoside analog that inhibits DNA synthesis, causing cell death. Neighbouring nontransfected cells may be affected through a 'bystander effect', thereby amplifying the antiproliferative actions. This study was carried out to determine whether retrovirus-mediated HSVtk gene therapy could reduce intimal hyperplasia and prevent stenosis following balloon injury of the rat carotid artery. METHODS: A replication-defective recombinant retroviral vector containing HSVtk cDNA (LtkSN) was constructed. Cultured primary rat smooth muscle cells (SMCs) infected with this vector (SMC/LtkSN) were transplanted to the balloon injured rat right carotid artery. One week after transplantation, HSVtk gene therapy group was administered a 2-week treatment of ganciclovir (30 mg/kg/d). Three weeks after balloon injury and SMC/LtkSN transplantation, carotid arteriography was performed and carotid arteries were perfusion-fixed for histologic examination. RESULTS: Carotid arteriographic evaluation comparing with the uninjured left carotid artery showed that the mean luminal diameter of HSVtk gene therapy group (n=5, 85+/-3%) was significantly larger than that of balloon injury only group (n=5, 65+/-5%). The neointimal mass of HSVtk gene therapy group was less than that of balloon injury only group. SMC/LtkSN transplantation without ganciclovir treatment group (n=3) showed asymmetric intimal proliferation probably because of gravitational pooling of seeding. There were inflammatory cell infiltrations at the gravity dependent portion of HSVtk gene therapy group. CONCLUSION: Retrovirus-mediated HSVtk gene therapy following balloon injury of the rat carotid artery reduced neointimal expansion and arteriographic stenosis.
Angiography ; Animals ; Carotid Arteries* ; Carotid Artery Injuries* ; Cell Death ; Constriction, Pathologic* ; DNA ; DNA, Complementary ; Ganciclovir ; Genetic Therapy* ; Gravitation ; Herpes Simplex* ; Hyperplasia ; Myocytes, Smooth Muscle ; Phenobarbital ; Phosphotransferases* ; Rats* ; Simplexvirus* ; Thymidine Kinase ; Zidovudine

152 curative gastrectomy specimens from patients with gastric carcinoma were examined in an attempt to assess the prognostic value of c-erbB-2 and mutant p53 protein expressions. The labeled streptavidin-biotin method was applied to routinely fixed and paraffin-embedded tissue sections, using the polyclonal and monoclonal antibodies against the c-erbB-2 protein and the mutant form p53 protein, respectively. In this examination, staining of c-erbB-2 protein was found in 9.2% of these carcinomas. The c-erbB-2 stained tumors were significantly associated with the tumors whose diameters were smaller than 5cm, and were more likely to be associated with serosal invasion and nodal involvement than the unstained ones. However, there was little association between staining of c-erbB-2 protein and clinicopathologic findings such as age, sex, location, histology, gross type, lymph node status, depth of invasion, and stage. The survival analysis of 104 patients with stage III gastric carcinoma revealed no significant association between c-erbB-2 staining status and survival duration. The 5-year survival rates of the c-erbB-2 positive group and its negative group were 21% and 28%, respectively. Positive p53 protein expression was observed in 46% of 152 carcinomas. There was no significant association between p53 expression and parameters such as age, sex, location, histology, gross type, and size. The p53 stained tumors were more likely to be associated with lymph node metastasis, serosal invasion than p53 unstained ones; but this did not reach significance. The 5-year survival rates of the p53 positive group and counter part group were 27% and 31%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult ; Aged ; Female ; Human ; Male ; Middle Age ; Multivariate Analysis ; Prognosis ; Protein p53/*analysis ; Receptor, erbB-2/*analysis ; Stomach Neoplasms/*chemistry/mortality ; Survival Rate

No abstract availble.
Adenoma/diagnosis/epidemiology/*etiology ; Anticipation, Genetic ; Colonic Neoplasms/diagnosis/epidemiology/*etiology ; Humans ; *Insulin Resistance ; Obesity/*complications/epidemiology ; Risk Factors

In the metastatic CNS lymphoma, parenchymal involvement, especially in both temporal lobes, is rare. A 54-year-old man complained of memory impairment and personality changes that began two weeks prior. He had ulcerated skin lesions and multiple subcutaneous nodules. Brain MRI revealed a diffuse low in T1WI, high in T2WI, and contrast-enhancement in both temporal lobes. Treatment was done with acyclovir and dexamethasone, and symptoms were improved. One week later, symptoms were aggravated and a brain biopsy was performed. The result was a peripheral T-cell lymphoma. (J Korean Neurol Assoc 19(4):417~422, 2001)
Acyclovir ; Biopsy ; Brain ; Dexamethasone ; Humans ; Lymphoma ; Lymphoma, T-Cell* ; Lymphoma, T-Cell, Peripheral ; Magnetic Resonance Imaging ; Memory ; Middle Aged ; Skin ; T-Lymphocytes* ; Temporal Lobe* ; Ulcer

No abstract available.
Adrenal Rest Tumor* ; Liver*

BACKGROUND: The granulocyte colony-stimulating factor (G-CSF) is crucial in neutrophil regulation. Since recombinant G-CSF became clinically available, it has been widely used in the treatment of neutropenia. Ex vivo therapy of recombinant G-CSF, however, requires large dose and frequent administration, which brings financial burden on the patients. To overcome disadvantages of ex vivo therapy, we have tried to make an in vivo G-CSF delivery system in rat using gene therapy technique. METHODS: We have tried to make an in vivo G-CSF delivery system using transduced vascular smooth muscle cells with G-CSF gene in a rat model. Retroviral vector plasmid containing rat G-CSF gene was made employing LXSN and LNFX plasmid. Recombinant retrovirus was produced from PA317 packaging cells. Infection of the vascular smooth muscle cells with the virus and selection with G418 was done in vitro. These transduced cells were transplanted to the balloon-injured carotid arteries of Fisher 344 rats, and complete blood count as well as differentials were measured in sequence. RESULTS: The virus titer was three times greater in case of LNFG than LGSN, whereas G-CSF production from infected vascular smooth muscle cell was lower in LNFG vector (0.1ng/106cells/day) than in LGSN vector (0.4ng/106cells/day). The increment of WBC count was observed until 25 days after transplantation, being 9,600 +/- 1,000/uL on seventh day after transplantation, which was significantly higher than that of controls, 7,300 +/- 540/uL. The levels of neutrophil increased gradually after transplantation, reached to the peak after 1 week (3,250 +/- 1,099/uL in case of neutrophil count and 30 +/- 10% in case of differentials). The duration of increment, however, was relatively short, neutrophil count being decreased to the basal level within 4 weeks. CONCLUSION: The effective increase of neutrophil count with low dose of G-CSF produced from vascular smooth muscle cells could make this gene therapy feasible in the clinical settings only if the problem of short duration of effect could be solved.
Animals ; Blood Cell Count ; Carotid Arteries ; Genetic Therapy ; Granulocyte Colony-Stimulating Factor* ; Granulocytes* ; Humans ; Leukocytes* ; Models, Animal ; Muscle, Smooth, Vascular* ; Neutropenia ; Neutrophils ; Plasmids ; Product Packaging ; Rats* ; Retroviridae ; Viral Load ; Zidovudine*

BACKGROUND: Diabetic nephropathy develops in 20-30% of patients with non-insulin dependent diabetes mellitus (NIDDM). Poor glycemic control, hypertension and duration of diabetes are known as risk factors for the development of diabetic nephropathy and there is high prevalence of diabetic nephropathy in the patients who have familial history of diabetic nephropathy, so it has been assumed that genetic factor is associated with the background of its occurences. Recently it has been observed that a cytosine to thymidine substitution of the methylenetetrahydrofolate reductase (MTHFR) gene at nucleotide 677 (C677T) was related to diabetic nephropathy in patients with NIDDM and MTHFR gene polymorphism was also known to predispose to vascular disease. This study was performed to investigate whether MTHFR gene polymorphism is associated with the development of diabetic nephropathy and macrovascular disease in NIDDM patients. METHODS: The study population consisted of 243 NIDDM patients (duration> OR = 10 years). Nephropathy was defined by 24 hour urinary protein excretion of more than 500 mg. The MTHFR gene fragment was extracted using the polymerase chain reaction. The presence of the mutation was identified by HinfI digestion, which cuts at the mutation site, followed by 2.5% metaphore agarose electrophoresis and ethidium bromide staining. Statistical differences in genotype distribution and allele frequencies among the groups were assessed by the chi-square test. RESULTS: There was no difference in clinical characteristics except the prevalence of hypertension and diabetic retinopathy between nephropathy group and non-nephropathy group. The data do not show any difference of genotype distribution or allele frequencies between patients with or without diabetic nephropathy and macrovascular disease CONCLUSION: With the above results, it is assumed that there are no significant relationships among MTHFR gene polymorphism, diabetic nephropathy, and macrovascular disease.
Cytosine ; Diabetes Mellitus ; Diabetes Mellitus, Type 2* ; Diabetic Nephropathies* ; Diabetic Retinopathy ; Digestion ; Electrophoresis ; Ethidium ; Fibrinogen ; Gene Frequency ; Genotype ; Humans ; Hypertension ; Metaphor ; Methylenetetrahydrofolate Reductase (NADPH2) ; Polymerase Chain Reaction ; Prevalence ; Risk Factors* ; Sepharose ; Thymidine ; Vascular Diseases

PURPOSE: Chronic rejection accounts for the majority of late renal graft losses and there is good evidence that both immunologic and non-immunologic factors are important in late graft loss. The hyperfiltration hypothesis postulates that kidneys with reduced renal mass will progress toward failure due to hypertrophy of the remaining nephron to meet the excess metabolic demand, eventually leading to nephron exhaustion. The impact of metabolic demand and renal mass supply on the early graft function, especially hyperfiltration phenomenon, remains uncertain. METHODS: In this study, we analyzed age, gender, body weight, height, body surface area (BSA), lean body weight (LBW), and serum creatinine (SCr) of both donors and recipients. We weighed the donated kidney and measured the recipient's SCr and LBW for six months postoperatively. Modified Cockcroft-Gault Equation standardized for BSA was used to calculate renal glomerular filtration rate (CrCl, mL/min/1.73 m2). The variables and the CrCl of the 3rd day and 6th month were analyzed with accordance to donor/recipient LBW ratio(D/R LBW) and graft weight/recipient LBW (GW/RLBW) by independent sample t-test and paired t-test using SPSS, and P<.05 was considered significant. RESULTS: The means of the 3rd day and 6th month CrCl were 76.90+/-24.35 and 73.41+/-10.80, respectively and there were no statistical differences (P=0.340). In D group (D/R LBW>1), the 3rd day and 6th month CrCl were 80.82+/-28.74 and 71.66+/-12.12, respectively. In R group (D/R LBW< or =1), the 3rd day and 6th month CrCl were 69.94+/-12.06 and 75.80+/-7.24, respectively. D group CrCl was decreased (P=0.093) and R group CrCl was increased slightly (P=0.169) during the study period, but there was no statistical significance. In H group (GW/RLBW>3), the 3rd day CrCl was 86.08+/-25.13, which was significantly decreased to 73.48+/-11.64 at the 6th month (P=0.023). In L group (GW/RLBW< or =3), the 3rd day and 6th month CrCl were 66.95+/-19.94 and 73.34+/-10.60 (P=0.158), respectively. the 3rd day CrCl of H group was higher than that of L group significantly (P=0.047), but 6th month CrCl showed no difference between the two groups (P=0.975). CONCLUSIONS: The 3rd day CrCl represents early graft function well. GW/RLBW has a strong correlation with early graft function. In L group with low early graft function, CrCl was tended to be increased to meet the metabolic demand for following the 6 months. Conversely, in H group with high early graft function, CrCl was decreased to reduce the excess graft function. So the 6th month CrCl represents adapted graft function. In this study, therefore, we postulate that the hyperfiltration or hypofiltration develops according to metabolic demand and renal mass supply.
Body Height ; Body Weight ; Creatinine ; Glomerular Filtration Rate ; Humans ; Hypertrophy ; Kidney ; Kidney Transplantation* ; Living Donors* ; Nephrons ; Tissue Donors ; Transplants*