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Biomedical subjects

C Conrad

Publications and source records attributed to C Conrad.

At least 37 records · Page 2Linked to original sources
PubMed1998

CD4+ T lymphocytes migrating in three-dimensional collagen lattices lack focal adhesions and utilize beta1 integrin-independent strategies for polarization, interaction with collagen fibers and locomotion.

Cell migration may depend on integrin-mediated adhesion to and deadhesion from extracellular matrix ligands. This concept, however, has not yet been confirmed for T lymphocytes migrating in three-dimensional extracellular matrices. We investigated receptor involvement in T cell migration combining a three-dimensional collagen matrix model with time-lapse videomicroscopy, computer-assisted cell tracking and confocal microscopy. In collagen lattices, the migration of CD4+ T cells (1) involved interactions with collagen fibers at the leading edge and uropod likewise, (2) occurred independently of the co-clustering of beta1, beta2, or beta3 integrins with F-actin, focal adhesion kinase, and phosphotyrosine at interactions with collagen fibers, (3) was counteracted by high-affinity beta1 integrin binding induced by antibody TS2/16; however, (4) the migration could not be blocked by a combination of adhesion-perturbing anti-beta1, -beta2, -beta3, and alpha v integrin antibodies. Integrin blocking neither affected cell polarization, interaction with fibers, beta1 integrin distribution, migration velocity, path structure, nor the number of locomoting cells in spontaneously migrating or concanavalin A-activated cells. Hence, T lymphocytes migrating in three-dimensional collagen matrices may utilize highly transient interactions with collagen fibers of low adhesivity, thereby differing from focal adhesion-dependent migration strategies employed by other cells.

Antibodies, Monoclonal↗
PubMed1998

[Comparison between steam and gas sterilized optics. Costs, availability, maintenance].

METHODS: In a 300-bed acute-care hospital we compared optical instruments employed, for orthopedic, urological and gynecological operations during their use in practice. The comparison between 33 ethylene oxide(EO)-sterilized optical instruments and 14 steam-sterilized optical instruments took into account the following criteria: frequency of use; availability; sterilization cycles; kind, cost and number of repairs. RESULTS: The 33 EO-sterilized optical instruments were handled 1043 times and were repaired 10 times (at a cost of up to 2000 SFR). The 14 steam-sterilized optical instruments were treated 1101 times and were repaired 8 times (2000 SFR). The total costs were 77,000 SFR for the 14 steam-sterilized instruments and 132,000 SFR for the 33 EO-sterilized instruments. INTERPRETATION: Steam-sterilization is a reasonable, safe and fast method of sterilizing optical instruments. We prefer this method, given its advantages (less toxicity, personal care and pollution control).

Cost-Benefit Analysis↗
PubMed1998

Use of amoxicillin-clavulanate and resistance in Escherichia coli over a 4-year period.

OBJECTIVE: To reduce the use of amoxicillin-clavulanate after high-resistance rates in Escherichia coli were detected. DESIGN: Intervention study; the interventions were introduced successively over a 4-year period while closely monitoring the resistance patterns. SETTING: A 260-bed acute-care hospital in Switzerland. INTERVENTIONS: Introduction of therapeutic guidelines for specific departments or indications, which proposed alternative antibiotics to amoxicillin-clavulanate. The perioperative prophylactic use of amoxicillin-clavulanate was eliminated completely. RESULTS: The absolute amount of amoxicillin-clavulanate consumed decreased by 23%, from 24.8 g per 100 patient days in 1992 to 18.5 g per 100 patient days in 1995. The number of courses, a parameter that takes the prophylactic use into account, decreased by 62% from 2.3 per 100 patient days in 1992 to 0.9 per 100 patient days in 1995. The percentage of sensitive strains increased from 54.9% (n=512) in 1992 and 54.0% (n=506) in 1993 to 72.1% (n=546) in 1994 and 83.1% (n=668) in 1995. No major changes were detected for other antimicrobials, such as cotrimoxazole, tetracycline, or cefuroxime, used in this 4-year period. CONCLUSIONS: A decrease in the use of amoxicillin-clavulanate was followed by an increase in susceptibility of E coli to it. It was not possible to prove a causative relationship. Only a temporal association was discovered. The reduction of the use of amoxicillin-clavulanate was achieved through the implementation of treatment guidelines, facilitated through a close collaboration among the clinical pharmacists, the infection control practitioner, the microbiology laboratory, and the physicians in charge of the respective departments.

Amoxicillin-Potassium Clavulanate Combination↗
PubMed1997

Neuropsychological profiles in schizophrenia: paranoid versus undifferentiated distinctions.

Research on schizophrenia has searched for subtype-specific cognitive dysfunction to elucidate the neurodevelopmental underpinnings of the disorder. The neuropsychological distinctions between 21 paranoid and 15 undifferentiated schizophrenics were studied. The paranoid group had significantly better Verbal IQ, executive functioning on the Wisconsin Card Sorting Test, and memory for spoken language on the Sentence Repetition Test compared to undifferentiated schizophrenics. While the paranoid subtype showed trends toward better performance on a wide variety of tasks, both subtypes showed impairments on tasks requiring continuous auditory attention and fine motor speed and coordination. Despite the paranoid subjects' more intact verbal skills, both groups showed significant deficits in verbal learning on the Rey Auditory Verbal Learning Test. This suggests that temporal-hippocampal system dysfunction may be a common denominator in both schizophrenic subtypes. These findings were not accounted for by subtype differences in the level of education, depression or severity of illness.

Adult↗
PubMed1997

Genetic evidence for the involvement of tau in progressive supranuclear palsy.

A dinucleotide repeat polymorphism in a tau intron was identified and used in a case-control study to analyze the genetic association of tau with several neurodegenerative diseases with tau pathology. Subjects with the homozygous tau AO alleles were excessively represented in the progressive supranuclear palsy (PSP) group, compared with the age-matched healthy control group. Consequently, this allele is more frequently found in PSP than in a group of healthy subjects. This trend was not found in Alzheimer's disease or parkinsonism-dementia complex of Guam, both of which are accompanied by major tau pathology. The result suggests a possible involvement of tau in the pathogenesis of PSP.

Base Sequence↗
PubMed1997

The treatment of recurrent cerebral gliomas with all-trans-retinoic acid (tretinoin).

Malignant gliomas continue to be a significant source of mortality in young and middle aged adults. The introduction of new treatment strategies and multidisciplinary approaches has improved the outcome of patients with these tumors only slightly. Because retinoic acid has growth inhibitory activity against glioma and neuroblastoma cells in cultures, we assessed the efficacy of all-trans-retinoic acid in the treatment of recurrent cerebral gliomas. Thirty-six patients with recurrent cerebral gliomas were entered in the study and treated with 120 or 150 mg/ m2/day of all-trans-retinoic acid as a single agent. The drug was given for 3 weeks followed with one week of rest. Two blocks of 4 weeks constituted one course of treatment. One (3%) of 34 evaluable patients had a minor response and 14 (41%) had stable disease. In the rest of the patients (56%), tumors continued to progress despite treatment. The median time to progression of all evaluable patients was 8 weeks, and for the responders was 17 weeks. The higher dose level (150 mg/m2) was associated with high incidence of headache, which responded to dose reduction. The lower dose level was very well tolerated, with mild, mainly dermatological toxicity. All-trans-retinoic acid as a single agent has no significant activity against recurrent cerebral gliomas.

Adolescent↗
PubMed1996

Identification and analysis of the rnc gene for RNase III in Rhodobacter capsulatus.

The large subunit ribosomal RNA of the purple bacterium Rhodobacter capsulatus shows fragmentation into pieces of 14 and 16S, both fragments forming the functional equivalent of intact 23S rRNA. An RNA-processing step removes an extra stem-loop structure from the 23S rRNA [Kordes, E., Jock, S., Fritsch, J., Bosch, F. and Klug, G. (1994) J. Bacteriol., 176, 1121-1127]. Taking advantage of the fragmentation deficient mutant strain Fm65, we used genetic complementation to find the mutated gene responsible for this aberration. It was identified as the Rhodobacter homologue to mc from Escherichia coli encoding endoribonuclease III (RNase III). The predicted protein has 226 amino acids with a molecular weight of 25.5 kDa. It shares high homology with other known RNase III enzymes over the full length. In particular it shows the double-stranded RNA-binding domain (dsRBD) motif essential for binding of dsRNA substrates. The Fm65 mutant has a frame shift mutation resulting in complete loss of the dsRBD rendering the enzyme inactive. The cloned Rhodobacter enzyme can substitute RNase III activity in an RNase III deficient E. coli strain. Contrary to E. coli, the Rhodobacter mc is in one operon together with the lep gene encoding the leader peptidase.

Amino Acid Sequence↗
PubMed1996

High-resolution fluorescence in situ hybridization of RBM- and TSPY-related cosmids on released Y chromatin in humans and pygmy chimpanzees.

Applying two-colour fluorescence in situ hybridization (FISH) we simultaneously hybridized RBM- and TSPY-related cosmids to Y chromosomes in prophase and to released Y chromatin in interphase nuclei of man and pygmy chimpanzee. Whereas, even on prophasic Y chromosomes, no resolution of the overlapping RBM and TSPY signal clusters could be achieved, the RBM and TSPY signals are completely separated from each other in our maximum released Y chromatin stretches in interphase nuclei. These results unequivocally lend support to the view that the RBM and TSPY families have an interspersed organization on the Y chromosomes of man and higher apes. Thus, the distribution of RBM and TSPY signals might well go back to a common organization of these genes next to each other on an ancient Y chromosome.

Animals↗
PubMed1996

Intensive care unit stay is prolonged in chronic alcoholic men following tumor resection of the upper digestive tract.

BACKGROUND: The prevalence of chronic alcohol misuse in patients with oral, pharyngeal, laryngeal or esophageal carcinomas exceeds 60%. No data is available, to our knowledge, on the morbidity and mortality of chronic alcoholics in surgical intensive care units (ICU) following tumor resection. We investigated whether the subsequent ICU stay in chronic alcoholics following tumor resection was prolonged and whether the incidence of pneumonia and sepsis was increased. METHODS: 213 patients with carcinomas of the upper digestive tract were evaluated regarding their drinking habits. Chronic alcoholics met either the DSM-III-R criteria for alcohol abuse or dependence. Conventional laboratory markers and serum carbohydrate-deficient transferrin were determined preoperatively. Major intercurrent complications during ICU stay such as an alcohol withdrawal syndrome, pneumonia and sepsis as well as the frequency of death were documented. RESULTS: Patients did not differ significantly between groups regarding age or APACHE score on admission to the ICU.121 patients were diagnosed as being chronic alcoholics, 39 as being social drinkers and 61 as being non-alcoholics. In chronic alcoholics the frequency of death was significantly increased. Due to the increased incidence of pneumonia and sepsis the ICU stay was significantly prolonged in chronic alcoholics by approximately 8 days. CONCLUSIONS: The increased mortality and morbidity rate demonstrates that chronic alcoholics undergoing major tumor surgery have to be considered as high-risk patients during their postoperative ICU stay. Further studies are required with respect to the immuno-competence of chronic alcoholics and the prevention of alcohol withdrawal syndrome, pneumonia and sepsis in these patients.

APACHE↗
PubMed1995

Cigarette smoking and breast cancer.

OBJECTIVE: To investigate cigarette smoking in relation to the risk of breast cancer. DESIGN: Interviews with women referred for mammography. SETTING: Hjørring District Hospital, a public, population based hospital in Denmark. SUBJECTS: 3240 women aged 15-92 years referred for mammography during 1 June 1989 to 1 November 1991. MAIN OUTCOME MEASURES: Smoking, parity, age, reason for referral, breast cancer. RESULTS: In a multiple logistic regression analysis adjusted for six variables a pronounced increased risk of breast cancer was found in women who had smoked for over 20 years, and this was significant in women who had smoked for over 30 years (odds ratio 1.6, 95% confidence interval 1.1 to 2.3). The median age of women with breast cancer was 59 (range 31-81) years for smokers and 67 (38-92) years for nonsmokers. The difference of eight years between the median ages was significant (P < 0.01). CONCLUSION: Smoking may increase the risk of breast cancer after 30 years of smoking.

Adolescent↗
PubMed1995

Beta-carbolines in chronic alcoholics undergoing elective tumor resection.

The prevalence of chronic alcoholism in patients with carcinomas of the upper digestive tract exceeds 60%. The patient's history and laboratory markers, preoperatively, are often not sensitive or specific enough to detect alcohol-dependent patients, preoperatively, who are at risk of developing alcohol withdrawal syndrome (AWS) during their postoperative intensive care unit (ICU) stay. Previously, it was found that plasma norharman was elevated in chronic alcoholics, suggesting marker characteristics for chronic ethanol misuse and possibly alcohol dependence. We investigated whether beta-carbolines (i.e., harman and norharman) were different between chronic alcoholics and nonalcoholics with carcinoma, and how the levels change in alcohol-dependent patients during their hospital stay. Ninety-seven patients with oral, pharyngeal, laryngeal, or esophageal carcinomas were evaluated regarding their drinking habits. Sixty patients were transferred to the ICU following tumor resection. Chronic alcoholics met the DSM-III-R and ICD-10 criteria for alcohol dependence or chronic alcohol abuse/harmful use. The daily ethanol intake in chronic alcoholics was > or = 60 g. Blood samples were collected on admission to the hospital, preoperatively, on admission to the ICU and on days 2, 4, and 7 in the ICU. Harman and norharman were determined by HPLC. Elevated norharman was found in chronic alcoholics on admission to the hospital, whereas harman did not differ between groups. On admission, the area under the receiver operating characteristics curve was significantly larger for carbohydrate-deficient transferrin and preoperatively for norharman. The preoperative norharman levels were significantly correlated with the period of mechanical ventilation and the length of ICU stay. Postoperatively, norharman decreased in all patients, except a group of 11 alcohol-dependent patients who developed AWS during their ICU stay. The finding that elevated norharman levels were found in chronic alcoholics on admission to the hospital and preoperatively supports the view of a specific marker for alcoholism. Preoperative norharman was superior to carbohydrate-deficient transferrin and was associated with a prolonged ICU stay and a prolonged period of mechanical ventilation. Further studies are required to determine whether norharman aids in the preoperative diagnosis of chronic alcohol misuse with respect to the prevention of postoperative complications.

Adult↗
PubMed1995

Alveolar stem cell transduction by an adeno-associated viral vector.

In inherited disorders such as surfactant protein deficiencies or cystic fibrosis (CF), where lung damage develops progressively after birth, gene replacement is best accomplished in the neonatal period. We use the adeno-associated virus (AAV) as a vector for gene transfer in the newborn rabbit lung where stem cells are activated for lung growth and differentiation. AAV-mediated gene transfer as assayed by lacZ gene expression occurred preferentially in alveoli in the alveolar epithelial progenitor cell, the type II cell, and in the large airway tracheobronchial basal and ciliated cells. Cell proliferation was confirmed by 5-bromo-deoxyuridine (BRDU) labeling in regions undergoing alveolarization and airway branch points. Regions of cell proliferation coincided with areas of significant lacZ expression. Thus, dividing and differentiating cells can be targeted by AAVlacZ delivery to newborn lung.

Animals↗
PubMed1993

Stable in vivo expression of the cystic fibrosis transmembrane conductance regulator with an adeno-associated virus vector.

Adeno-associated virus (AAV) vectors expressing the normal cystic fibrosis transmembrane conductance regulator (CFTR) cDNA complement the cystic fibrosis (CF) defect in vitro. Unlike other DNA virus vectors, AAV is a stably integrating virus, which could make possible long-term in vivo complementation of the CF defect in the airway epithelium. We report AAV-CFTR gene transfer and expression after infection of primary CF nasal polyp cells and after in vivo delivery of AAV-CFTR vector to one lobe of the rabbit lung through a fiberoptic bronchoscope. In the rabbit, vector DNA could be detected in the infected lobe up to 6 months after administration. A 26-amino acid polypeptide sequence unique to the recombinant AAV-CFTR protein was used to generate both oligonucleotide probes and a polyclonal antibody which allowed the unambiguous identification of vector RNA and CFTR protein expression. With these reagents, CFTR RNA and protein were detected in the airway epithelium of the infected lobe for up to 6 months after vector administration. AAV vectors do, therefore, efficiently promote in vivo gene transfer to the airway epithelium which is stable over several months. These findings indicate that AAV-CFTR vectors could potentially be very useful for gene therapy.

Amino Acid Sequence↗