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Biomedical subjects

S Fritz

Publications and source records attributed to S Fritz.

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

A comparison of two methods of follow-up in a trial of prophylactic volume expansion in preterm babies.

The outcome at age 2 years of preterm babies recruited into a three-arm randomised controlled trial of prophylactic volume expansion was ascertained in two ways: from a neurodevelopmental assessment performed by a paediatrician and from responses on a brief questionnaire completed by the child's personal health visitor. Of 776 babies recruited into the trial, 604 survived to the age of 2 years and the findings of a paediatric assessment were available for all survivors. Questionnaires were sent to the health visitors of 601 of the survivors; 513 (85.4%) were returned. There was sufficient information on the returned questionnaires to categorise 449 of the children as normal, impaired, moderately disabled or severely disabled. We were unable to detect a response bias by severity of disability. Agreement on individual questions ranged between 86.3% and 98.4%. There was some mismatch in the reporting of vision (weighted kappa = 0.71) and hearing (weighted kappa = 0.73), with differences in perception of level of severity of sensory loss. Health visitors tended to underestimate the child's functional level compared with the paediatrician. However, of 56 children classified as severely disabled by the paediatrician, 48 were classified similarly and eight as moderately disabled on the basis of the questionnaire. The end point of the trial was death or severe disability at 2 years of age. There was close similarity in the trial results whether based on the paediatric assessment or on the questionnaire. Further refinement of the questionnaire is needed, but this methodology may be useful in ascertaining the frequency of severe disability in large cohorts of babies.

Chi-Square Distribution↗
PubMed1998

Outcome of very preterm birth: children reviewed with ease at 2 years differ from those followed up with difficulty.

AIM: To determine whether those most easily reviewed in a population prevalence study differ from those followed up only with difficulty. METHODS: All babies born before 32 weeks of gestation in the North of England in 1983, 1990, and 1991 were traced, and all the survivors assessed at two years by one of two independent clinicians. RESULTS: 818 of the 1138 live born babies survived to discharge. There was some non-significant, excess disability in the 5% of long term survivors who were difficult to trace because of social mobility, but eight times as much severe disability in the 1% (9/796) in care and in the 5% (38/796) whose parents initially failed to keep a series of home or hospital appointments for interview, and five times as much emergent disability in the 2.7% (22/818) who died after discharge but before their second birthday. Had the babies who were seen without difficulty been considered representative of all the babies surviving to discharge, the reported disability rate would have been two thirds what it really was (6.9% instead of 11.0%). CONCLUSIONS: Population prevalence studies that ignore those who seem reluctant to cooperate risk serious ascertainment bias.

Appointments and Schedules↗
PubMed1997

A 32-kDa proteolytic fragment of transcription factor Stat3 is capable of specific DNA binding.

Fragments of characteristic size retaining the ability of sequence-specific DNA binding were generated by partial proteolysis of transcription factor Stat3 with trypsin, chymotrypsin, or Staphylococcus V8 proteinase. The molecular masses of the smallest DNA-binding fragments were 75, 48, and 32 kDa after digestion with V8 proteinase, chymotrypsin, and trypsin, respectively. The fragments contained major parts of the domain controlling the sequence specificity of DNA binding (amino acids 406-514), the SH3 and SH2 domains, and the phosphorylated tyrosine residue Tyr-705, but not the C-terminal 20 amino acids. The N terminus of the 32-kDa tryptic fragment (ANCDASLIV) matched the sequence of amino acids 424-432 deduced from cDNA. The fragments were observed after proteolytic treatment of preformed complexes between DNA and native factors eluted from rat liver nuclei or recombinant, tyrosine-phosphorylated rat Stat3 from insect cells. It was possible to elute all three minimal fragments from their complexes with DNA and to obtain specific re-binding. The minimal fragments eluted from complexes with DNA still contained the phosphorylated Tyr-705 and the SH2 domain suggesting that they were probably bound to DNA as dimers. The DNA-binding domain of Stat3 identified by these experiments overlapped the domain previously identified by genetic experiments as the domain controlling the sequence specificity of DNA binding. The DNA-binding domain defined here by partial proteolysis probably represents an autonomously folding portion of Stat3.

Acute-Phase Proteins↗
PubMed1997

Characteristic T helper 2 T cell cytokine abnormalities in autoimmune lymphoproliferative syndrome, a syndrome marked by defective apoptosis and humoral autoimmunity.

Autoimmune lymphoproliferative syndrome (ALPS) is marked by massive lymphadenopathy, hepatosplenomegaly, autoimmunity and the presence of increased numbers of circulating and tissue TCR-alpha beta, CD4- CD8- T cells. The underlying defect is that of decreased T cell and B cell apoptosis, due in most, but not all, cases to heterozygous mutations of the Fas gene and corresponding defective Fas signaling function. Here we measure in vivo and in vitro cytokine secretion in ALPS to shed light on the relation of apoptosis defects to the development of autoimmunity. In in vivo studies, ALPS patients manifested greatly increased circulating levels of IL-10 (> 100-fold), compared with both healthy individuals and various disease controls; in contrast, their levels of IL-1 beta, IL-4, and IFN-gamma were normal and their levels of IL-2 and TNF-alpha were marginally increased. In parallel in vitro studies, ALPS patients CD4+ DR+ T cells stimulated either with anti-CD3/CD28 or anti-CD2/CD28 produced increased amounts of IL-4 and IL-5 (10 to 20-fold) and decreased amounts of IFN-gamma (4-fold) as compared with those of control CD4+ DR+ T cells. In contrast, ALPS patients' CD4-/CD8- T cells produced very low amounts of cytokines. Finally, ALPS patients' peripheral monocytes/macrophages produced decreased amounts of IL-12 (30-fold) and increased amounts of IL-10 (5-fold). In conclusion, ALPS is marked by the presence of DR+ T cells that exhibit a skewed Th2 cytokine response upon various forms of stimulation. This cytokine response, in the presence of increased circulating IL-10 levels, is likely to define the cytokine milieu that accounts for the humoral autoimmune features of ALPS and, perhaps, of other humoral autoimmune states.

Adolescent↗
PubMed1996

Phorbol ester-induced shedding of intercellular adhesion molecule-1 (ICAM-1) on erythroleukemic K 562 cells.

The effect of phorbol 12-myristate 13-acetate (PMA) on the expression and shedding of intercellular adhesion molecule-1 (ICAM-1) was investigated on the hematopoietic cell lines K 562 and U 937 using flow cytometry, fluorescence microscopy and ELISA technique. At low concentration of 1 nM, PMA stimulated the expression of ICAM-1 on the cell surface about 4-fold within 24 h, whereas a short-term treatment with 100 nM PMA led to the shedding of 35% of ICAM-1 from the surface of K 562 cells. The release of surface ICAM-1 was found on single cells by fluorescence microscopy to be a uniform process proceeding within 15 min. The shedding of ICAM-1 correlated with elevated levels of sICAM-1 in the supernatants of cultured cells. Also on K 562 cells stimulated by TNF-alpha, a PMA-induced release of ICAM-1 was observed in addition to the known spontaneous shedding. In contrast to the results with K 562 cells, no PMA-induced shedding of ICAM-1 was found on U 937 cells. This indicates a cell-specific process for K 562 cells. The PMA-mediated release of ICAM-1 from K 562 cells suggests that the shedding process does not only occur in parallel to the surface expression of ICAM-1, but may be controlled by particular mechanisms of down-regulation.

Blotting, Western↗
PubMed1996

Retinopathy of prematurity in a controlled trial of prophylactic surfactant treatment.

AIMS: To investigate the incidence of acute and cicatricial retinopathy of prematurity (ROP) in a cohort of premature neonates entered into a randomised, multicentre trial of prophylactic exogenous surfactant for respiratory distress syndrome (RDS) compared with controls receiving surfactant only if severe RDS developed. METHODS: The incidence of acute and cicatricial ROP was assessed in 304 neonates born at less than 30 weeks' gestation in a geographically defined population of approximately three million. RESULTS: There was a trend towards improved survival in the group receiving prophylactic surfactant with 102/151 (67.5%) surviving compared with 82/141 controls (58.2%, p = 0.12). The prophylactic surfactant group would be expected to have an increased risk of ROP due to improved survival, particularly of the most premature infants. However, there was no statistically significant difference in the incidence of acute ROP between the two groups and the incidence of cicatricial ROP was lower in the group receiving prophylactic surfactant (4/100 survivors, 4.0%) compared with neonates receiving rescue surfactant as required (6/81, 7.4%). This difference did not reach statistical significance (p = 0.35). CONCLUSION: The trend for a lower incidence of cicatricial ROP in those neonates treated with prophylactic surfactant compared with the rescue surfactant group, despite improved survival, suggests that the use of prophylactic surfactant also had a beneficial effect on the development of cicatricial ROP.

Drug Combinations↗
PubMed1996

Evaluation of soft-tissue foreign bodies: comparing conventional plain film radiography, computed radiography printed on film, and computed radiography displayed on a computer workstation.

OBJECTIVE: The study was performed to evaluate detection of soft-tissue foreign bodies using conventional radiography (film-screen radiography), computed radiography printed on films (computed radiography-hard copy), and computed radiography displayed on a computer workstation (computed radiography-soft copy). SUBJECTS AND METHODS: Fifteen foreign bodies of different size, shape, and composition were implanted at different locations in a fresh cadaveric hand, and images were obtained using three radiographic techniques. Images were evaluated by four board-certified radiologists to ascertain the conspicuity of the foreign bodies with the different techniques. A subjective grade was assigned to each image in an attempt to identify the relative conspicuity of foreign bodies when imaged with the three techniques. RESULTS: Computed radiography-soft copy is the preferred imaging technique for the detection of wood and plastic foreign bodies in soft tissue regardless of the size of the wood or the plastic. No significant differences in conspicuity among the three techniques were demonstrated with glass foreign bodies. CONCLUSION: Detection of soft-tissue foreign bodies is best done using computed radiography-soft copy instead of film-screen radiography and computed radiography-hard copy imaging.

Cadaver↗
PubMed1995

Transcription factors Stat3 and Stat5b are present in rat liver nuclei late in an acute phase response and bind interleukin-6 response elements.

Proteins binding at the interleukin-6 response element of the rat alpha 2 macroglobulin gene were purified by a combination of chromatographic procedures including binding site-specific DNA-affinity chromatography as the principal step. Three polypeptides of 92, 91, and 86 kDa were enriched approximately 6,300-fold from nuclei of rat livers excised 12 h after the induction of an experimental acute phase response. Amino acid sequence analysis identified the 86- and 91-kDa species as two forms of the transcription factor Stat3 and the 92-kDa species as the factor Stat5b. This identification was confirmed by gel mobility shift-supershift experiments using specific antisera for Stat3 and Stat5. Unexpectedly, activated Stat5 was also detected in the nuclei of untreated control rats. cDNA clones representing Stat3 and two isoforms of Stat5b were isolated from a cDNA library prepared with mRNA from rat livers excised at the peak of an experimental acute phase response. Full-length Stat5b, predicted from cDNA, consisted of 786 amino acids, while the variant Stat5b delta 40C lacked 41 amino acids at the COOH terminus. The amino acid sequence of rat Stat5b showed 26.7% overall identity with rat Stat3, 87.3% with sheep Stat5a, 92.5% with murine Stat5a, and 98.7% with murine Stat5b.

Acute-Phase Proteins↗
PubMed1995

Isolation of two interleukin-6 response element binding proteins from acute phase rat livers.

Proteins binding at the IL-6 response element of the rat alpha 2 macroglobulin gene were purified by a combination of conventional chromatographic procedures and binding-site specific DNA affinity chromatography. The proteins were purified from the nuclei of rat livers, excised at the peak of an experimentally induced acute phase response. By this procedure three polypeptides of 92, 91 and 86 kD were enriched more than 6,000-fold. Partial proteolysis with lysyl endopeptidase and aminoacid sequence analysis of proteolytic peptides identified the 86 and 91 kD species as the transcription factor Stat3 and the 92 kD species as a Stat factor distinct from Stats 1 and 3. cDNA clones for Stats 1, 3 and this 92 kD factor were isolated from a cDNA library prepared with mRNA from acute phase rat livers. Parts of their DNA sequences were determined and the sequences of the purified peptides were found in these cDNA sequences. Thus, the identity of the factors as Stat3 and a Stat factor different from Stats 1 and 3 was confirmed. These results suggest, that APRF/Stat3 and p91/Stat1 are not the only factors mediating the effects of IL-6 on class 2 acute phase genes. The 92 kD Stat factor binding at the IL-6 RE probably also functions as a transcription factor in the cytokine-induced activation of the alpha 2M gene.

Acute-Phase Reaction↗
PubMed1995

Right ventricular apical view--a new window for Doppler echocardiography of aortic valve stenosis.

We studied a new Doppler echocardiographic approach in 56 patients with valvular aortic stenosis from the right ventricular apex (AS-RV) and compared the transvalvular gradients with the results of the standard view from the left ventricular apex (AS-LV). AS-RV resulted in good or acceptable velocity curves in 59% of patients. The correlation between the two apical views for the peak/mean gradients were close (r = 0.95/0.96). Using all typical positions for Doppler investigation of aortic stenosis, highest peak gradients were best recorded in five cases by AS-RV. In one woman with a narrow left ventricular cavum and severe aortic stenosis, only AS-RV yielded a technically good spectral curve. Thus, in selected patients--probably those with a small left ventricular cavity or an enlarged right ventricle--AS-RV may be the best window or even the only possibility in Doppler investigation of aortic valve stenosis.

Adult↗
PubMed1995

Oxygraphic evaluation of mitochondrial function in digitonin-permeabilized mononuclear cells and cultured skin fibroblasts of patients with chronic progressive external ophthalmoplegia.

For quantitative elucidation of maximal mitochondrial oxidation capacities in human mononuclear cells, cultured human skin fibroblasts and human thrombocytes the optimal amount of digitonin for plasma membrane permeabilization was determined to be 5, 10, and 0.1 micrograms/10(6) cells, respectively. Using these concentrations the rate of respiration of permeabilized cells with the mitochondrial substrates succinate (+ rotenone) or glutamate + malate can be stimulated between two- and fourfold by ADP and inhibited by carboxyatractyloside. The maximal respiratory activities of well-characterized preparations of permeabilized mononuclear cells of five patients with chronic progressive external ophthalmoplegia were compared to healthy controls and a 30 to 50% decrease of the ADP-stimulated respiration rates with glutamate + malate and succinate + rotenone was detected. This is an indication for the presence of the mitochondrial defect in respiratory active blood cells. Additionally, for two of these patients the mitochondrial defects were proven to be detectable by the determination of maximal oxygen consumption rates of digitonin-permeabilized cultured skin fibroblasts. Therefore, the determination of maximal oxidation capacities of a well-defined cell population using strictly standardized conditions of digitonin permeabilization is judged as a useful and sensitive method for the elucidation of mitochondrial function in extramuscular tissue.

Adolescent↗
PubMed1995

Ocular outcome in children born before 32 weeks gestation.

Ocular outcome was assessed in a 2 year cohort of all children born before 32 weeks gestation within a geographically defined population of approximately 3 million. Five hundred and sixty-five children were born within the study period; 558 children (98.8% of the study group) were assessed at approximately 2 years old. There was a high incidence of abnormalities, particularly strabismus (70, 12.5%), cortical visual loss (7, 1.3%), sequelae of retinopathy of prematurity (16, 2.9%) and other significant refractive errors (69, 12.7%). These data provide a recent estimate of gestational age-specific prognosis and suggest that follow-up yields a significant proportion of children with visual abnormalities who could benefit from treatment.

Child, Preschool↗
PubMed1993

Increase in the adenine nucleotide translocase protein contributes to the perinatal maturation of respiration in rat liver mitochondria.

An assay based on the high-affinity binding of tritium-labelled atractyloside to the adenine nucleotide translocase (ANT) was developed for estimation of its content in samples of mitochondria, cells and tissue homogenate. The assay was used to study the developmental change of the ANT protein concentration in perinatal rat liver. Within the last 3 days before birth the content of the ANT protein per mg tissue protein increased from 29 to 45% of the maximum value found 2 days after birth. A similar developmental change of the ANT protein was found in isolated mitochondria, demonstrating that the perinatal increase in the ANT protein content was due mainly to a mitochondrial differentiation process and not the result of an increase in the number of mitochondria per cell. A close proportionality between the ANT protein and the ADP-stimulated respiration of liver homogenate was found in the perinatal period from 3 days before to 2 days after birth. This finding suggests that the developmental change in the ANT protein content plays an important role in the onset of oxidative phosphorylation after birth.

Animals↗
PubMed1993

Use of a latex cover sheath for transesophageal echocardiography (TEE) instead of regular disinfection of the echoscope?

Better visualization of cardiac structures is an advantage of transesophageal echocardiography (TEE). Because of this, the transesophageal approach is an essential window in the assessment of various cardiovascular disorders. Quick consecutive access to this instrument should not be delayed by time-consuming cleansing procedures of the probe. In this study we used a sterile latex condom in routine TEE examinations as a barrier to contamination of the echoscope, observing practical use and the incidence of perforations. Defects were detected after the procedure by visual inspection and by an airtightness test. Maneuvers or situations associated with an increased likelihood of injury were checked for. In 180 studies a total of 168 patients were consecutively examined; insertion was feasible in all but one case (99.5%). We found 8 of 181 (4.4%) sheaths defective following the procedure. Visual inspection was less sensitive (only 3 of 8) for finding defects than an airtightness test (8 times). Teeth in situ and/or a bite guard are the only sharp edges during insertion and removing the probe; these seem to be the main risk factors in latex perforation. Application of a cover sheath for each examination saves approximately two-thirds of the time otherwise necessary for a cleansing bath, and easy handling of cover sheaths for TEE make them an alternative to regular disinfection in general. For reasons of safety we recommend checking each used cover sheath after examination for holes so as not to jeopardize the following patient by the possible spread of germs from contaminated probes. Not only visual inspection but also a second method, for example, an airtightness test, is mandatory.

Disinfection↗