Skeletal manifestations in Fryns syndrome

We report on a female baby with Fryns syndrome who died soon after birth. The patient had short limbs, coarse face, hypoplastic lungs, diaphragmatic hernia, and acral hypoplasia. Literature review disclosed varying degrees of skeletal manifestations in Fryns syndrome; short limbs may be a component of Fryns syndrome. © 1995 Wiley-Liss, Inc.     

Cloning of TPA-inducible early (TIE) genes by differential hybridization using TPA-Nonresponsive variant of mouse 3T3-L1 cells

The tumor promoter 12-O -tetradecanoylphorbol-13-acetate (TPA) induces DNA synthesis in quiescent 3T3-L1 cells but not in its variant VT-1 cells. A gt10 cDNA library was constructed using poly(A)⁺ RNA from 3T3-L1 cells that were stimulated by TPA for 20 min. Radioactive cDNA probes were prepared from mRNAs of TPA-treated 3 T3-L1 and VT-1 cells and used for screening of the 3T3-L1 cDNA library by differential hybridization. Nine of 6000 phage plaques hybridized only to the 3T3-L1 cDNA probe. Analysis of the nucleotide sequence of five of these clones indicated a high degree of homology with human or mouse type I and type III collagen genes. Three other independent clones showed no homology with any known DNA sequences. These isolated clones of TPA-inducible early (TIE) genes may be useful to study the signal transduction pathway of phorbol esters.     

Genetics of cell-surface receptors for bioactive polypeptides: A variant of mouse BALBc/3T3 fibroblasts possessing altered insulin-binding ability

An insulin-nonresponsive variant was isolated from mutagenized mouse BALBc/3T3 fibroblasts. Selection was based on the insulin's mitogenic action upon quiescent cells and subsequent arrest at mitosis by vinblastine sulfate to remove insulin-responsive cells. Among four surviving colonies, one, designated IN-2, exhibited no binding for [¹²⁵I] insulin at 2× 10^–10 M and at 4° C. The binding ability, however, recovered substantially at 15° C and increased with higher temperature and at higher ligand concentrations. The binding profiles, Scatchard plot analysis, and the dissociation kinetics indicated that the receptors expressed on IN-2 cells possess lower affinity than the parental 3T3 cells. The IN-2 cells were negative for stimulating effects of insulin on 2-deoxyglucose uptake, thymidine incorporation, and cell growth. The IN-2 cells were also negative for cross-reactivity to antibodies which react with insulin receptors on 3T3 cells and for the susceptibility to a cytotoxic chimeric insulin which was cross-linked to diphtheria toxin fragment A. This negative response of IN-2 cells can be attributed to a deficiency in high-affinity receptors for insulin. The insulin bound to the low-affinity binding sites of IN-2 cells, however, undergoes internalization and intracellular degradation. Therefore, such processing by itself does not account for insulin's mitogenic action.     

Stratum-specific likelihood ratios of the general health questionnaire in the community: help-seeking and physical co-morbidity affect the test characteristics

BACKGROUND: In evidence-based medicine, stratum-specific likelihood ratios (SSLRs) are now being increasingly recognized as a more convenient and generalizable method to interpret diagnostic information than an optimal cut-off and its associated sensitivity and specificity. We previously examined the SSLRs of the General Health Questionnaire (GHQ) in primary care settings. The present paper aims to examine if these SSLRs are generalizable to the community settings. METHODS: The Composite International Diagnostic Interview (CIDI) and the GHQ were administered on a representative sample of the Australian population in the Australian National Survey of Mental Health and Well-Being. We first compared the SSLRs of GHQ in urban Australia with the estimates that we had previously obtained from the developed urban centres in the WHO Psychological Problems in General Health Care study. If the SSLRs in the community were found to differ significantly from those in the primary care, we sought for explanatory variables. RESULTS: The SSLRs in urban Australia and in the urban centres in the WHO study were significantly different for three out of the six strata. When we limited the sample to those with physical problems who visited a health professional, however, the SSLRs in the Australian study were strikingly close to those observed for primary care settings. CONCLUSIONS: Different sets of SSLRs apply to primary care and general population samples. For general population surveys in developed countries, the results of the Australian National Survey represent the currently available best estimates. For developing countries or rural areas, the results are less definitive and an investigator may wish to conduct a pilot study.     

Enhanced poliovirus replication in cytomegalovirus-infected human fibroblasts.

Replication of poliovirus in human cytomegalovirus (CMV)-infected cells is enhanced 5-to 10-fold over replication in uninfected cells. Enhanced poliovirus replication in dually infected cells was not due to a difference in adsorption on infected cells and was supported by evidence of increased synthesis of polio-specific RNA. A functional CMV genome appeared to be required for the enhancement of polio replication since enhanced replication was not seen in cells infected with uv-irradiated CMV or in cultures treated with the inhibitors of CMV replication. Enhanced polio replication in CMV-infected cells may be due to the enhanced cellular metabolism in these cells.     

Exclusion of SMAD4 mutation as an early genetic change in human pancreatic ductal tumorigenesis

Pancreatic ductal carcinoma is one of the malignant diseases with the poorest prognosis. To develop effective methods for better treatment of pancreatic cancer patients, we tried to analyze the course of multistep carcinogenesis of the pancreatic ductal cells. IPMT (intraductal papillary-mucinous tumor) is thought to be one of the premalignant lesions of the pancreas, which would transform into carcinomas. Loss of 18q at the SMAD4 locus is known to be an early genetic change in pancreatic ductal carcinomas. It is not clear, however, whether or not the target gene for inactivation is SMAD4. Using 18 IPMTs, we analyzed LOH at the SMAD4 locus and observed frequent LOH (7/14, 50%). No mutations were observed in any of the tumors. Moreover, the expression level of the SMAD4 protein did not show a reduction in IPMTs. These results suggested that (i) inactivating mutation of the SMAD4 gene is a rather late genetic change in pancreatic carcinogenesis, and (ii) there may be an unknown tumor suppressor gene in 18q, other than SMAD4, that is involved in pancreatic ductal carcinogenesis.     

Role of cytokines in autoimmune myocarditis and cardiomyopathy

Cellular as well as humoral autoimmune responses are critically associated with the pathogenesis and progression of myocarditis and cardiomyopathy. Cytokines appear to play critical roles in accentuating or regulating autoimmune mechanisms in these disorders. However, depending on the triggers of autoimmune responses against the heart, such as viral or parasitic infections and experimental immunization with cardiac myosin, the effect of each cytokine on autoimmune myocardial disease may vary. Cytokines may represent new therapeutic targets in the treatment and prevention of autoimmunity-mediated myocarditis and cardiomyopathy, though the etiology and variability in the type of autoimmune responses should be taken into account in the development of cytokine/anti-cytokine treatment of these disorders.