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Biomedical subjects

W Hauck

Publications and source records attributed to W Hauck.

At least 19 recordsLinked to original sources

Prenatal care of HIV-infected women: analysis of a large New York State cohort.

We examined the effect of methadone treatment, duration of Medicaid enrollment during pregnancy, and other maternal characteristics on receipt of prenatal care by 2,254 women infected with human immunodeficiency virus (HIV) delivering a singleton in New York state from 1985 through 1990. Data were obtained from the New York State Medicaid HIV/AIDS Research Data Base and vital statistics records. Adequacy of the number of prenatal visits reported by the mother on vital statistics records was assessed with use of the Kessner Index, which adjusts for gestational age at delivery. Too few visits were reported by 65% of the study population. Illicit drug users had higher odds of having too few visits [1.64, 95% confidence interval (CI) 1.24-2.17] than methadone-treated women but the odds were similar for non-drug users and methadone-treated women (0.79, 95% CI 0.60-1.25). Women with brief Medicaid enrollment (< or = 25% of pregnancy) had 45% higher odds of having too few visits than did longer enrollees. Treatment for drug addiction and longer Medicaid enrollment during pregnancy may offer important interventions to increase prenatal care of HIV-infected women. Approaches to increase prenatal care of HIV-infected women are especially important given trials showing a reduction in vertical transmission from zidovudine treatment during pregnancy.

Adolescent

Transcriptional regulation of the carcinoembryonic antigen gene. Identification of regulatory elements and multiple nuclear factors.

Human carcinoembryonic antigen (CEA) belongs to a family of membrane glycoproteins that are overexpressed in many carcinomas; CEA functions in vitro as a homotypic intercellular adhesion molecule and can inhibit differentiation when expressed ectopically in myoblasts. The regulation of expression of CEA is therefore of considerable interest. The CEA gene promoter region between -403 and -124 base pairs upstream of the translation initiation site directed high levels of expression in CEA-expression SW403 cells and was 3 times more active in differentiated than in undifferentiated Caco-2 cells, correlating exactly with the 3-fold increase in CEA mRNA seen in differentiated Caco-2 cells. Inclusion of additional upstream sequences between -1098 and -403 base pairs repressed all activity. By in vitro footprinting and deletion analyses, four cis-acting elements were mapped within the positive regulatory region, and one element within the silencing region. Several nuclear factors binding to these domains were identified: USF, Sp1, and an Sp1-like factor. By co-transfection, USF directly activated the CEA gene promoter in vivo in both SW403 and Caco-2 cells. In addition, the levels of factors binding to each positively acting element increased dramatically with differentiation in Caco-2 cells. Thus the transcriptional control of the CEA gene depends on the interaction of several regulatory elements that bind multiple specific factors.

Base Sequence

Transcriptional control of the human biliary glycoprotein gene, a CEA gene family member down-regulated in colorectal carcinomas.

Biliary glycoprotein (BGP) isoantigens are derived by alternative splicing from a single gene and are the human homologs of rat C-CAM and the mouse Bgp species. These glycoproteins represent a family of cell-adhesion molecules. The mouse Bgp isoforms also act as receptors for the hepatitis viral capsid-protein. BGP is a member of the carcinoembryonic antigen (CEA) gene family, which belongs to the immunoglobulin supergene family, yet it displays restricted expression patterns and unique functions. Since the loss or reduced expression of BGP is associated with human colorectal carcinomas, the elements in its upstream regulatory region were analyzed. A cluster of transcriptional initiation sites and the minimal promoter, located within 150 bp upstream of the major transcriptional start site, were active in human colon carcinoma and hepatoma cells. Unlike the CEA gene, BGP gene transcription was not modulated by a silencer region; repetitive elements in the BGP upstream region were not involved in activation or repression. Footprinting experiments identified two cis-acting elements and mobility-shift assays demonstrated that these elements bound several transcription factors, among them, USF, HNF-4 and an AP-2-like factor. In cotransfection experiments, both the USF and HNF-4 transcription factors transactivate the BGP gene promoter and compete for the same regulatory element. The Sp1 transcription factor, shown to be involved in CEA gene transcriptional regulation, does not bind to the BGP gene promoter. We, therefore, propose that the relative distributions and interactions of these transcription factors mediate distinct transcriptional regulation of the BGP gene in colon and liver; this regulation could be distorted during the oncogenic process.

Animals

Validation of virus inactivation by heat treatment in the manufacture of diaspirin crosslinked hemoglobin.

Diaspirin crosslinked hemoglobin (DCLHb), a hemoglobin based oxygen carrying solution prepared from outdated human blood, is subjected to a heat treatment step to inactivate viruses in our manufacturing process. To validate the efficacy of this inactivation, we have simulated the heat treatment procedure at a reduced scale using hemoglobin solution spiked with representative viruses. Human Immuno-deficiency Virus (HIV), Cytomegalovirus (CMV), and Duck Hepatitis B Virus (DHBV) were used in this validation. Inoculation with concentrated virus was performed just prior to the heat treatment to determine the effect of that specific process step. Samples were taken before, during, and after heat treatment and assayed for virus titer in an attempt to assess the rate as well as the extent of virus inactivation. CMV was analyzed in a plaque assay using MRC-5 indicator cells. The titer was reduced from 3.3 x 10(6) plaque forming units (PFU) per mL to less than 5 x 10(1) PFU/mL (detection limit) within 30 minutes. DHBV was analyzed by inoculation of serially diluted samples into Pekin ducklings, followed at intervals by screening sera for DHBV DNA by dot blot hybridization. The titer was reduced from 5.0 x 10(6) duck infectious units (DIU) per mL to less than 5 x 10(0) DIU/mL (detection limit) within 1 hour. HIV titers were determined through an ELISA assay for p24 antigen present in peripheral blood lymphocyte cocultivation supernatants. The titer was reduced from 2.0 x 10(4) infectious units (IU) per mL to less than 2 x 10(0) IU/mL (detection limit) within 1 hour. These data indicate that high titers of these blood borne viruses are rapidly inactivated by this heat treatment process.

Aspirin

Control of carcinoembryonic antigen gene family expression in a differentiating colon carcinoma cell line, Caco-2.

The levels of control involved in the regulation of expression of the carcinoembryonic antigen (CEA) gene family members were investigated using cultured Caco-2 cells that differentiated after confluence as characterized by the production of polarized monolayers and the subsequent appearance of domes. Three transcripts representing CEA (3.0 and 3.5 kilobases) and nonspecific cross-reacting antigen (NCA) (2.6 kilobases) were detected in Northern analyses of mRNA preparations of such cells when probed with human CEA cDNA, albeit at different levels. The major CEA 3.0-kilobase transcript increased 3-fold over an 11-day culture period after confluence, whereas the NCA transcript increased 25-fold over the same time period. gamma-interferon treatment enhanced CEA mRNA levels 32-fold and NCA mRNA levels 53-fold in Caco-2 monolayers 11 days after confluence. The NCA gene thus appears to be regulated by a mechanism different from that of CEA. During gamma-interferon treatment, the normal increase in Caco-2 dome formation with time in culture was increased further by a factor of 2. Over the 13-day time span for Caco-2 cultures, CEA protein levels increased 7-fold, NCA (Mr 48,000) protein 5-fold, while gamma-interferon treatment augmented CEA 18.5-fold further and NCA 20-fold. In 2 other colon carcinoma cell lines, SW1222 and T84, which are differentiated in culture to varying degrees, little if any changes were seen in CEA and NCA mRNA and protein levels in pre- versus postconfluent cultures. Both cell lines, however, responded to gamma-interferon treatment by increases in CEA and NCA mRNA levels and, in some cases, disproportionate increases in the corresponding proteins. The lack of direct proportionality between mRNA and protein expression suggests that, as observed in human colon carcinoma and adjacent normal tissue, both transcriptional and post-transcriptional control mechanisms regulate CEA gene family member expression in colon carcinoma cells.

Antigens, Neoplasm

Comparison of blood biocompatibility during haemodialysis with cuprophane and polyacrylonitrile membranes.

Clotting within the dialyser is one of the most significant clinical parameters of biocompatibility. A study was designed to evaluate the biocompatibility of two different dialysis membranes (cuprophane and polyacrylonitrile) during therapy with conventional heparin. Transient leukopenia during cuprophane but not during polyacrylonitrile haemodialysis was observed, and elastase release using polyacryonitrile membranes was reduced (P less than 0.001). An elevation in F VIII:C activity during cuprophane haemodialysis has to be taken as an indication of endothelial disturbances. There was a significant (P less than 0.001) platelet activation (beta-thromboglobulin) and combined thrombin/plasmin generation using cuprophane membranes. This new synthetic polyacrylonitrile membrane inactivates the clotting in an extracorporeal system to a sufficient degree and allows a reduction in dosages of heparin. Platelet activation, platelet turnover, disturbances of endothelium, fibrinolysis activation, and granulocyte activation are reproducible parameters of a described interaction model. They also permit a comparison of different haemodialysis membranes.

Acrylic Resins

Contributions to biorheology during hemodialysis.

Thrombogenicity is the property of a foreign surface to induce clotting processes or formation of aggregates after contact with blood. Beside the sort of anticoagulation patient's prethrombotic state, rheological factors as well as physicochemical properties of foreign membranes decisively influence thrombogenicity. We examined the influence of chronic renal failure and different hemodialyzers and blood transfusion therapy during hemodialysis on hemorheological parameters. Different membranes cannot be discriminated by the used hemorheological parameters. We clearly could demonstrate the close relationship between the hemofiltration rate and an increase of viscosity. Blood transfusion therapy or elevated hematocrit in combination with increased hemofiltration rate have influence on the flow behaviour of blood, especially in disturbed microcirculation.

Biocompatible Materials

Oral mucosal lesions found in smokeless tobacco users.

The risk for oral mucosal lesions associated with use of smokeless tobacco among 1,109 professional baseball players during spring training in 1988 was investigated. Leukoplakia was very strongly associated with use of smokeless tobacco in this population of healthy young men. Of the 423 current smokeless tobacco users, 196 had leukoplakia compared to seven of the 493 nonusers (OR = 60.0, 95% CI = 40.5-88.8). The amount of smokeless tobacco used (in hours per day that smokeless tobacco was held in the mouth), recency of smokeless tobacco use (hours since last use), type (snuff versus chewing tobacco), and brand of snuff used were significantly associated with risk for leukoplakic lesions among smokeless tobacco users. Ninety-eight leukoplakic areas in 92 subjects were biopsied and examined microscopically. All lesions were benign, but one specimen had mild epithelial dysplasia. The long-term significance of leukoplakia in smokeless tobacco users and their relation to oral cancer is not clear.

Adult

Periodontal effects associated with the use of smokeless tobacco.

This report describes periodontal findings from a comprehensive study of smokeless tobacco use in professional baseball players. Subjects consisted of 1,094 players, coaches, and training staff of seven major league and their associated minor league teams. Before being examined, subjects completed questionnaires on patterns of smokeless tobacco use (validated by blood chemistry studies), rinsed their mouths under supervision, and were cautioned not to discuss their use of tobacco with the dental examiners. They then received a complete oral examination that included recording of all mucosal abnormalities, missing teeth, caries, extrinsic stain, attrition, Plaque Index, Gingival Index, pocket depth, attachment loss, and gingival recession. More than 50% of team members reported using smokeless tobacco, and 39% reported use during the current week. Among current week users, 46% had oral mucosal lesions, located primarily in the mandible at sites where the smokeless tobacco quid was placed. The use of smokeless tobacco was not necessarily associated with severe forms of periodontal disease, and the presence of poor oral hygiene and gingivitis in these users was not related to the development of oral lesions. However, sites adjacent to mucosal lesions in smokeless tobacco users showed significantly greater recession and attachment loss than in sites not adjacent to lesions in users or comparable sites in non-users.

Adult

Platelet-tumor cell interaction.

Several reports have appeared with regard to the potential role of platelets in tumor cells metastasis. Our in vitro studies with colon tumor cells in normals and in patients give some evidence against platelet aggregation as the determinant factor in tumor cell invasion and metastasis. Dimethylhydrazine induced colon tumors in Wistar rats demonstrate characteristic features of tumor cell dissociation in the invasion line and changes in intercellular adhesion.

Actin Cytoskeleton

Estimation of a common odds ratio in paired-cluster randomization designs.

We develop two estimators of a common odds ratio psi for designs in which the investigator randomly assigns each of two clusters to interventions within strata. The estimators rely on an empirical adjustment for clustering to provide improved estimators of psi relative to the standard Woolf and Mantel-Haenszel estimators, respectively. The results of a simulation study show that the suggested adjustment improves the accuracy of both of these well-known estimators under conditions likely to arise in practice. We find the clustered Woolf estimator as particularly effective in terms of mean squared error reduction. We also discuss interval estimation.

Humans

Organic anions and the diarrhea of inflammatory bowel disease.

To determine if organic anions contribute to the diarrhea of inflammatory bowel disease, we measured osmolality, electrolytes, short-chain fatty acids, lactic acid, and some Krebs cycle anions in 24-hr fecal collections from 18 patients with chronic ulcerative colitis, 20 with Crohn's disease of the colon, and 16 normals. Mean lactic acid concentration was significantly elevated in ulcerative and Crohn's colitis, but values correlated with fecal weight only in the former syndrome. In ulcerative colitis, concentrations of each short-chain fatty acid, especially butyrate, were decreased compared with those from normals or Crohn's disease. Lactate and short-chain fatty acids accounted for nearly half the variability in fecal weight in ulcerative colitis. Crohn's patients had elevated mean fecal water osmolality and osmotic gap not observed in ulcerative colitis. Increased lactic acid and/or deficient short-chain fatty acids may modulate the diarrhea of ulcerative colitis. This mechanism seems less important in Crohn's colitis where an additional osmotic component may be significant.

Anions

Estimation of a common odds ratio in case-control studies of familial aggregation.

A new estimator of a common odds ratio is proposed for case-control studies of familial aggregation. The proposed estimator is a modification to the usual Mantel-Haenszel estimator that relies on an empirical adjustment for the within-family clustering which is typical of such designs. A simulation study shows that the estimator tends to have smaller mean squared error than the unmodified Mantel-Haenszel estimator under conditions likely to arise in practice. The construction of confidence intervals is also discussed.

Biometry

Oculoauriculovertebral dysplasia and variants: phenotypic characteristics of 294 patients.

Here we describe the phenotypic characteristics of a single craniofacial clinic population of 294 individuals affected with oculoauriculovertebral dysplasia (OAV) and variants. To our knowledge, this is the largest population so described in the literature. The study population was divided into five subgroups based on the presence of combinations of minimal diagnostic criteria: microtia, mandibular hypoplasia, anomalies of the cervical spine and/or epibulbar or lipodermoids. The following data were recorded: sex (M:F 191:103); race (78% Caucasian); the presence of unilateral or bilateral microtia (193 unilateral, 98 bilateral); the presence of symmetric microtia in bilateral cases (34/98); the presence of mandibular hypoplasia ipsilateral or contralateral to the microtic ear or most severely microtic ear in bilateral cases (135/137 were ipsilateral in unilateral cases, 55/62 were ipsilateral in bilateral cases); the number of individuals with no other congenital anomaly in addition to the minimal diagnostic criteria (154/294), with only one other congenital anomaly (51/294), and with two or more other congenital anomalies (89/294); and the type of other congenital anomalies. Finally, we compared our results with other studies. Findings from our study include: mandibular asymmetry should be expected in patients with unilateral or bilateral microtia; bilateral involvement is frequent in patients with microtia; other malformations are seen frequently in all subgroups; anomalies of the cervical spine are more likely to be associated with other anomalies; and other malformations are seen in all systems and should be searched for to provide optimal management.

Adolescent

Multiple forms of the sigma 3 protein of reovirus: occurrence and binding properties.

The sigma 3 protein of reovirus serotype 3 is present in different forms differing in isoelectric point, as already described by other authors. Proteolytic digestion of each of these forms generates similar peptides. The different forms are present in the mature virus and have affinity for double-stranded RNA and for ribosomes. The observations that the different forms have the same functional properties and are absent in reovirus serotype 1 suggest that the presence of multiple forms is dispensable. The different forms can be synthesized by in vitro translation of mRNA extracted from infected cells. However, only one form is clearly made when mRNA synthesized in vitro, using the cloned S4 gene encoding sigma 3 as a template, is translated in vitro. Similarly the cloned S4 gene expressed in vivo produces only one form of the protein. These results indicate that the other forms are not derived by post-translational modification. The different forms are possibly due to the presence of mutant viruses.

Genes, Viral

Estramustine affects bone mineral metabolism in metastatic prostate cancer.

A patient with metastatic prostate cancer is described where treatment with Adriamycin (doxorubicin) and estramustine produced severe hypophosphatemia (serum phosphate level, 1.2 mg/dl), which was reversible when treatment was discontinued. Previous studies have shown no effect of Adriamycin on serum phosphate levels. A retrospective study of serial serum chemistry values was done in 15 patients treated with estramustine. A significant fall in the serum phosphate level (mean, 0.8 +/- 0.3 mg/dl) was observed during the first 6 weeks of treatment. When compared with similar patients treated with bilateral orchiectomy, estramustine-treated patients had lower levels of serum calcium, fractional excretion of calcium, serum phosphate, and renal tubular threshold for phosphate reabsorption (TmPO4/GFR). Qualitatively similar but quantitatively smaller effects were also seen in a group of patients treated with diethylstilbestrol (DES) in a dose of 1 to 3 mg daily. Estramustine appears to have significant effects on bone mineral metabolism, particularly on renal phosphate handling resulting in significant hypophosphatemia. This is probably due to an estrogenic effect.

Adenocarcinoma