A case of neonatal diabetes mellitus is described. The child presented with low birth weight but was normal in appearance. She was acidotic and ketonuria was observed. The HLA typing was DR1 and 3, and insulin autoantibodies were negative. Genetic analysis with polymorphic DNA markers for chromosome 6 indicated biparental inheritance. She required insulin therapy for the control of hyperglycemia, and insulin dependence continues after 8 months of age.
Autoantibodies ; Child ; Chromosomes, Human, Pair 6 ; Diabetes Mellitus* ; Genetic Markers ; Histocompatibility Testing ; Humans ; Hyperglycemia ; Infant, Low Birth Weight ; Infant, Newborn ; Insulin ; Ketosis ; Wills

PURPOSE: Ataxia Telangiectasia (AT) is a hereditary multi-systemic disease resulting from mutations of AT gene and is characterized by progressive neurodegeneration, cancer, immune system defects, and hypersensitivity to ionizing radiation. AT gene has a homologue sequence of PI3-kinase. The activity and cellular function of PI3-kinase in AT gene remains unclear. This study was undertaken to evaluate the function of AT gene through the effect on cell survival and differentiation by the inhibition of AT gene expression. MATERIALS AND METHODS: NH2-terminal portion of AT gene was isolated from MCF-7 cells by RT-PCR. The isolated DNA fragment was ligated in reverse orientation in pcDNA3. This antisense ATM expression vector was transfected to PC-12 cells by calcium phosphate method, and the transformed cells were selected using G418 and immunohisto- chemistry. To analyze the cell survival and differentiation, cells were cultured in serum free medium supplemented with/without NGF. We performed the immunoprecipitation for the p53 induction of cells after ionizing radiation, and the FACS for the apoptosis of cells after the exposure of wortmanin. RESULTS: PC-12 cells which down-regulated AT gene (like ATM, AT mutated) showed decreased survival and ceased differentiation with NGF. Also, PC-12 (ATM) cells showed increased apoptosis with wortmanin and reduced or delayed p53 induction after ionizingradiation. CONCLUSION: Results obtained from these studies suggest that AT gene regulates survival and differentiation of PC-12 cells through PI3-kinase activity. It seems that apoptosis is induced by the inhibition of AT gene expression.
Apoptosis ; Ataxia Telangiectasia ; Calcium ; Cell Survival ; Chemistry ; DNA ; Gene Expression ; Hypersensitivity ; Immune System ; Immunoprecipitation ; MCF-7 Cells ; Nerve Growth Factor ; Phenotype* ; Phosphatidylinositol 3-Kinases ; Radiation, Ionizing

BACKGROUNDS: The molecular genetic characteristcs of cis-AB blood group have shown that its allele had C, G, C and C at nucleotide positions (nps) 526, 703, 796 and 803, respectively. And all cis-AB analysed and reported molecular genetically in Korea and Japan had T at np 467 (leucine at amino acid position 156). We report a first case of cis-AB with C at np 467 (proline at amino acid position 156). METHODS: Genomic DNA was extracted from peripheral blood of cis-AB patient and amplified by DS1/DS2 and DS3/DS4 allele-specific primers. After PCR, we analysed nps 261, 467, 526, 646, 703, 796, and 803 by restriction digestion, autoradiography and automatic sequencing. RESULTS: PCR-RFLP with DS1/DS2 primers and restriction enzyme KpnI showed that cis-AB had an 0 allele. The results of genomic sequencing, autoradiography and restriction digestion showed that cis-AB allele at nps 467, 526, 646, 703, 796 and 803 had C, C, T, G, C and C, respectively. CONCLUSION: This cis-AB showed characteristic molecular genetic features at nps 526, 703, 796, and 803. And this is a first case of A(Pro) cis-AB with C at np 467. (Korean J Blood Transfusion 10(1): 13-19, 1999)
Alleles ; Autoradiography ; Blood Transfusion ; Cytosine* ; Digestion ; DNA ; Humans ; Japan ; Korea ; Molecular Biology* ; Polymerase Chain Reaction

Deep skin and soft tissue defects with exposed bone and tendon is difficult to treat, because skin graft rarely survives and flap surgery is sacrifice of donor site. Since "Stage I" membrane was developed by Yannas and Bruke in 1980, numerous kinds of artificial skin have been developed. The adaptability of "Terudermis", developed by the Terumo Co., as an artificial skin composed of sponge made of a fibrillar atelocollagen and a heat-denatured atelocollagen, was clinically evaluated on application to 13 cases presenting deep skin and soft tissue defect with exposed bones and tendons from October 1997 to march 1998. Terudermis has the advantage of allowing early incorporation of fibroblasts and capillaries into its collagen sponge due to very weak dehydrothermal cross-linking. Before Terudermis graft, several days of wet dressing and debridement were required to prepare healthy well-vascularized bed because Terudermis was weak on unsanitary wounds. After bed preparation, Terudermis was grafted like usual skin graft. Tie-over bolster dressing or compressive dressing was used case by case. The dressing was opened 2~3 days after Terudermis grafting. Wet dressing was done daily until the skin graft was done. Autologous skin graft was done 2-3 weeks after Terudermis graft. Our clinical results indicated that Terudermis was beneficial in treating 77% of our patients. Through the use of this new method, treatment of severe skin and soft tissue defects that are usually treated by musculocutaneous or other conventional skin flaps can be replaced by Terudermis as an new artificial dermis.
Bandages ; Capillaries ; Collagen ; Debridement ; Dermis ; Fibroblasts ; Humans ; Membranes ; Porifera ; Skin ; Skin, Artificial ; Tendons ; Tissue Donors ; Transplants ; Wounds and Injuries*

No abstract available.
Genetic Therapy*

The authors regret that two co-authors were missing in the article.

PURPOSE: PTEN/MMAC1, a novel tumor suppressor gene, is mutated in a variety of advanced and metastatic cancers. It acts as a phosphatase, and thereby, regulates the PI-3 kinase/Akt pathway. In this study, we examined to evaluate the new function of anti-tumor effects of PTEN/MMAC1 through the regulation of the IGFs-IGFBPs in gastric cancer cells. METHODS: PTEN/MMAC1 was expressed in an adenovirus-mediated gene delivery system and introduced into gastric cancer cells(SNU-484 & SNU-668) in vitro. The effect of cell growth and the expression of IGFs and IGFBPs after Ad/PTEN infection was analyzed by MTT assay, RT-PCR and Western immunoblot. RESULTS: Ad/PTEN infected cells were inhibited in cell growth compared with moak cells and Ad/ LacZ infected cells. Overexpression of PTEN/MMAC1 induced decrease in expression of IGF-I, -II and IGF-I receptors which are known as growth prompt molecules in a variety of cancers. Of the six IGFBPs, the expressions of IGFBP-4 and IGFBP-6 were decreased in Ad/PTEN infected cells. In contrast, IGFBP-3 expression was markedly increased by up to 3-fold in Ad/PTEN infected cells. Overexpression of PTEN/MMAC1 inhibited the activation of Akt/PKB pathway, but had no effect on the MAPK pathway. CONCLUSION: These findings suggest that the tumor suppressor function of PTEN/MMAC1 is, at least in part, mediated through the down-regulation of IGF-I abd IGF-II, and up-regulation of IGFBP-3 in gastric cancer cells by the inhibition of PI-3 kinase pathway.
Blotting, Western ; Down-Regulation ; Gene Transfer Techniques ; Genes, Tumor Suppressor ; Insulin-Like Growth Factor Binding Protein 3 ; Insulin-Like Growth Factor Binding Protein 4 ; Insulin-Like Growth Factor Binding Protein 6 ; Insulin-Like Growth Factor Binding Proteins* ; Insulin-Like Growth Factor I ; Insulin-Like Growth Factor II ; Phosphatidylinositol 3-Kinase ; Phosphatidylinositol 3-Kinases ; Receptor, IGF Type 1 ; Stomach Neoplasms ; Up-Regulation

PURPOSE: Gap junction intercellular communication(GJIC) is an important mechanism of the bystander effect in herpes simplex thymidine kinase/ganciclovir(HSVtk/GCV) gene therapy Therefore, we attempted to enhance the bystander effect in vitro by exogenous overexpressing connexin 37(Cx37) in cells to increase GJIC. METHODS: NIH3T3 cells were transfected with the Cx37 and HSVtk gene or the HSVtk gene alone by the calcium phosphate method, and we detected their expression from these cells by RT-PCR. GCV-mediated cytotoxicity and the bystander effect of each transfectant was then assessed and compared. RESULTS: Cells transfected with HSVtk became sensitive to low concentration of GCV. We found significantly increased cytotoxicity in HSVtk/GCV gene therapy after introduction of the HSVtk and Cx37 genes together compared with the cytotoxicity seen after introduction of the HSVtk gene in vitro. Co-expression of the HSVtk and Cx37 genes potentiates HSVtk/GCV gene therapy through the bystander effect. CONCLUSION: These results indicated that the increase of GJIC using Cx37 have potentiated the by stander effect of HSVtk/GCV therapy, and may be a new approach to improve response in suicidal cancer gene therapy.
Bystander Effect* ; Calcium ; Gap Junctions* ; Genes, Neoplasm ; Genetic Therapy* ; Herpes Simplex ; Thymidine

This article summarizes the era from when Paul Broca had first introduced his aphasia case study and theory in 1861 to clinical-neuroanatomical approach which was widely known until early twentieth century. The article also comprises the cognitive-neuropsychological approach which appeared after the cognitive revolution in 1956. It investigated and compared the definition, classification method and the primary research object of aphasia in the perspectives of clinical-neuroanatomical approach and cognitive-neuropsychological approach. Each approach has its own advantages and disadvantages. Therefore, it is inappropriate to only support for a certain approach but better if two approaches are incorporated together and used effectively in certain situations. In order for the best research and treatment for the aphasic patients, clinical practitioners who prefer clinical-neuroanotomical approach and researchers who prefer cognitive-neuropsychological approach should participate together to incorporate the two approaches.

No abstract available.
Adenocarcinoma, Papillary* ; Thyroid Gland*