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Biomedical subjects

A Schulze

Publications and source records attributed to A Schulze.

At least 73 records · Page 4Linked to original sources
PubMed2000

2-ketoglutarate dehydrogenase deficiency with intermittent 2-ketoglutaric aciduria.

2-ketoglutarate dehydrogenase (KGD) deficiency is a rare disorder of the tricarboxylic acid cycle. To date, 7 patients have been reported with clinical symptoms suggesting a neurodegenerative disease. We report a new patient in whom urinary excretion of 2-ketoglutaric acid (KGA) was intermittently found to be within normal ranges. At birth, the male patient suffered from mild perinatal asphyxia due to meconium aspiration. During the first months of life, he developed an opisthotonus, hyperexcitability and truncal hypertonia. At the present age of 14 months, these neurological symptoms became less pronounced. A cranial MRI was normal. Urinary 2-KGA excretion was found to be intermittently increased in 3 of 6 analyses between 2 weeks and 14 months of age (5-1700 mmol/mol creatinine, controls: < 340 mmol/mol creatinine). 2-KGA was not increased in plasma and CSF. Diagnosis was confirmed by measurement of decreased 2-KGD activity in cultured skin fibroblasts. This report demonstrates that the diagnosis of 2-KGD deficiency can easily be missed. In case of doubt, 2-KGD activity should be measured in fibroblasts. The clinical and long-term outcome of patients with 2-KGD deficiency is unknown. Further reports and long-term evaluation are required.

Cells, Cultured↗
PubMed2000

[Effect of repetitive prenatal corticosteroid medication on intrauterine growth and growth in early childhood].

OBJECTIVE: The evaluation of the effects of repeated antenatal corticosteriod (CS) medication on birth size and size at the age of 4 years. METHODS: 82 children exposed to CS initially between 26 and 28 weeks of gestation were matched with 82 controls of the same gestational age and sex. RESULTS: No differences were observed between the CS and control groups with regard to weight, head circumference, and length at birth and at the age of 4 years. CONCLUSIONS: Our study failed to demonstrate that repetitive antenatal medication with CS in order to induce lung maturation has a negative impact on intrauterine growth and growth in early childhood.

Betamethasone↗
PubMed2000

Dynamics of breathing during partial liquid ventilation in spontaneously breathing rabbits supported by elastic and resistive unloading.

Partial liquid ventilation (PLV) has been shown to improve gas exchange in paralyzed animals and in humans with lung disease. This study tests the hypothesis that PLV combined with respiratory mechanical unloading results in stable ventilation and gas exchange in spontaneously breathing animals. Ten adult anesthetized, intubated, and spontaneously breathing rabbits received ventilatory support by respiratory mechanical unloading (Fi(O2) 1.0). Minute ventilation, respiratory rate, esophageal pressure, heart rate, and arterial blood pressure were recorded continuously during gas ventilation for 1 h. Next, 30 mL/kg of perfluorocarbon was instilled into the endotracheal tube. Thereafter, data were recorded again for 1 h (PLV). Arterial blood gases were obtained at the end of each period. Variability of recorded data was assessed by calculating coefficients of variation using data obtained each minute. Compared with gas ventilation, minute ventilation was larger during PLV (275 +/- 93 versus 368 +/- 89 mL/kg/min.; p < 0.01). This was because of a higher respiratory rate during PLV (58 +/- 23 versus 74 +/- 18 breaths/min; p < 0.05), while tidal volume was similar. Compared with gas ventilation, Pa(O2) was lower during PLV (61.31 +/- 5.32 versus 47.35 +/- 8.38 kPa; p < 0.05). Pa(CO2), peak esophageal pressure deflections, heart rate, mean arterial blood pressure, and coefficients of variation for minute ventilation, tidal volume, respiratory rate, and peak esophageal pressure were not significantly different between modes. Compliance was decreased and resistance and work of breathing were increased during PLV. We conclude that stable ventilation and gas exchange may be achieved during PLV combined with mechanical unloading in spontaneously breathing animals without lung disease.

Animals↗
PubMed2000

Analysis of gene expression by microarrays: cell biologist's gold mine or minefield?

The development of DNA microarrays to study simultaneously the level of mRNA expressed from thousands of genes offers great promise to cell biologists. Microarrays can be used to gain detailed information about transcriptional changes involved in a specific pathway, potentially leading to the identification of novel components of the signalling system. They can also be used to obtain a fingerprint of the transcriptional status of the cell under a given condition, which may be useful for characterising the pathways used in response to novel stimuli. The use of microarrays will generate huge amounts of expression data, contributing to the transformation of biology from a data-poor to a data-rich science. Whether this leads to real advances in the understanding of cell biological problems will depend on the development of methodologies, both in experimental biology and in bioinformatics, that allow meaningful knowledge to be extracted from all this information.

Eukaryotic Cells↗
PubMed1999

Molecular diagnosis of type 1c glycogen storage disease.

Glycogen storage disease type 1 (GSD 1) results from deficiency of the microsomal multicomponent glucose-6-phosphatase system. Malfunction of the catalytic subunit characterises GSD 1a. GSD 1b and GSD 1c are characterised by defective microsomal glucose-6-phosphate or pyrophosphate/phosphate transport, respectively. Recently, a gene encoding a microsomal transporter protein has been found to be mutated in GSD 1b and 1c patients. Here, we report the genomic sequence of the transporter gene and the detection of a homozygous 2-bp deletion (1211delCT) and a homozygous donor splice site mutation (317+1G-->T) in two GSD 1c patients, confirming that GSD 1c is allelic to GSD 1b.

Antiporters↗
PubMed1999

Sensitivity of electrospray-tandem mass spectrometry using the phenylalanine/tyrosine-ratio for differential diagnosis of hyperphenylalaninemia in neonates.

The sensitivity of amino acid analysis by electrospray-tandem mass spectrometry (ESI-TMS) in differential diagnosis of the different forms of hyperphenylalaniemias (HPA) was studied in a total number of 78 dried blood samples from neonates with increased phenylalanine (Phe) concentrations (> 150 micromol/l). Simultaneous quantitative analysis of Phe and tyrosine (Tyr) were performed by ESI-TMS. By means of the Phe/Tyr-ratio it was possible to differentiate between phenylketonuria (PKU; n = 23) and nonPKU-HPA patients (n = 35; P < 0.001) with a sensitivity of 100%. Neonates with transient HPA (n = 9) showed a lower Phe/Tyr-ratio compared to the nonPKU-HPA patients (P < 0.001). Amino acid analysis by ESI-TMS represents a powerful diagnostic tool in differential diagnosis of HPA and is an appropriate technique in the setting of neonatal screening based on dried blood spots.

Diagnosis, Differential↗
PubMed1999

Proportional assist ventilation in low birth weight infants with acute respiratory disease: A comparison to assist/control and conventional mechanical ventilation.

OBJECTIVES: To compare the physiologic efficacy and safety aspects of proportional assist (PA), assist/control (A/C), and intermittent mandatory ventilation (IMV) in very low birth weight infants with acute respiratory illness and to test the hypothesis that ventilatory pressure requirements are lower and arterial oxygenation is improved during PA when compared with IMV or A/C at an equivalent inspired oxygen fraction. STUDY DESIGN: Randomized, 3-period, crossover design. METHODS: Thirty-six infants were stratified by birth weight (600 to 750, 751 to 900, and 901 to 1200 g) and exposed to consecutive 45-minute epochs of the 3 modalities in a sequence chosen at random. Tidal volumes of 4 to 6 mL/kg were targeted during A/C and IMV. The IMV rate was matched to the rate during an A/C test period. PA was adjusted to unload the resistance of the endotracheal tube and the disease-related increase in lung elastic recoil. RESULTS: Compared with A/C and IMV, PA maintained similar arterial oxygenation with lower airway and transpulmonary pressures (15% to 44% reduction depending on the index variable). The oxygenation index decreased by 28% during PA. No adverse events were observed. The number and severity of apneic episodes and periods of arterial oxygen desaturations were similar with the 3 modes. Similar results were obtained within each birth weight subgroup. CONCLUSIONS: PA safely maintains gas exchange with smaller transpulmonary pressure changes compared with A/C and IMV. It may therefore offer a way of reducing the incidence of chronic lung disease in low birth weight infants.

Acute Disease↗
PubMed1999

[Postnatal skeletal and body weight in beagles].

Growth of beagles is described on the basis of body weight and 14 bone measures. Eighteen male and 19 female dogs were investigated at 14 different ages from birth to the 13th month of life. Characteristics of the growth curves were evaluated using the modified Janoschek growth curve. For the classification into dwarfish, low, normal, big and gigantic growth, the growth curves are presented with percentiles. The arithmetic means and standard deviations for both sexes are presented in tables. Additionally, the degrees of maturity at birth (relative proportion of final weight or bone measure), the point of inflection for the growth curve, the times to grow to 50 and 95% of the final measures, and the asymptotic measures are also presented in tables. Sex differences in growth for the body weight and bone measures are discussed. Growth differences between large and small dog breeds are considered. The conclusion is drawn that the feeding of dogs has to be adapted to the growth course.

Aging↗
PubMed1999

Assisted mechanical ventilation using combined elastic and resistive unloading in cats with severe respiratory failure: effects on gas exchange and phrenic nerve activity.

This study tests the efficacy of respiratory mechanical unloading as a mode of assisted mechanical ventilation in cats with an intact breathing-control system but severe pulmonary parenchymal injury. Twelve anaesthetized, intubated cats received multiple saline lung lavages so that their total respiratory system compliance decreased from 56.1+/-10.4 to 26.8+/-6.8 ml/kPa (p < 0.001) and their PaO2 fell to 12.38+/-4.71 kPa when 100% O2 was used as inspired gas. They were then exposed to three consecutive 15-min periods of CPAP of 0.5 kPa, respiratory unloading and again CPAP of 0.5 kPa. Unloading was applied with end-expiratory pressure of 0.5 kPa, elastic assistance of 0.03 kPa/ml and resistance compensation of 2.0 kPa/l/s. Arterial blood gases for the CPAP baselines did not differ significantly before and after unloading: pH 7.14+/-0.04 vs. 7.16+/-0.06; PaCO2 8.99+/-2.07 vs. 8.33+/-2.01 kPa; PaO2 12.4+/-4.7 vs. 13.3+/-7.6 kPa. Nor did the baselines differ in terms of tidal volume, respiratory rate and phrenic nerve activity. Unloading increased tidal volume substantially by about 50% and increased respiratory rate slightly, while inspiratory time remained unchanged. PaCO2 fell to 6.63+/-1.57 kPa and pH rose to 7.25+/-0.06. Phrenic nerve activity was significantly down-regulated in terms of total number of impulses and mean impulse frequency in the phrenic nerve burst. These results suggest that combined elastic and resistive unloading may be an effective means of assisted mechanical ventilation in severe respiratory failure of pulmonary parenchymal origin.

Airway Resistance↗
PubMed1999

Activation of cyclin A gene expression by the cyclin encoded by human herpesvirus-8.

Human herpesvirus-8 (HHV-8), also known as Kaposi's sarcoma-associated herpesvirus, encodes a protein, referred to as HHV8-Vcyc, with sequence similarity to human G1 cyclins, in particular of the D type. HHV8-Vcyc is expressed in Kaposi's sarcoma and functional analysis suggests that it can activate cyclin-dependent kinases (cdk) and thereby trigger inactivation of the retinoblastoma protein (pRb), indicating that HHV8-Vcyc may contribute to the oncogenic potential of HHV-8. We show here that HHV8-Vcyc can activate transcription of the human cyclin A gene in quiescent cells, a property shared with known transforming oncogenes. Transcriptional activation by HHV8-Vcyc depends on an E2F-binding site in the cyclin A promoter, and cdk6 kinase activity is required. The ability of HHV8-Vcyc to activate cyclin A gene expression is shared by D-type cyclins and cyclin E. Unlike D-type cyclins, HHV8-Vcyc is unable to trigger phosphorylation of the pRb-related protein p107 and fails to induce dissociation of p107 from E2F. Unlike cyclin E, HHV8-Vcyc fails to interact physically with E2F complexes on the cyclin A promoter. These results provide additional evidence for the notion that the HHV-8-encoded cyclin differs in several properties from cellular G1 cyclins.

3T3 Cells↗
PubMed1999

[Congenital skull depression. Case report and review of the literature].

A 40-week gestational age infant was delivered by cesarean section because of intense contractions and pathological fetal heart rate pattern. The umbilical artery pH was 7.03, Apgar scores were 1/4/7 at 1, 5 and 10 min of age. The 3,250-gram infant had a skull depression of 5 x 7 cm in the left temporal-parietal region with a depth of 1.5 cm. There were no edemas or hematomas in this area; neurological examination was normal. A CT scan did not show a fracture, but the cortex below the depression appeared slightly compressed. At the age of 11 days, the depressed part of the parietal squama was surgically elevated. The child was discharged in good condition 8 days later and remained well at a 6-month follow-up examination.

Adult↗
PubMed1998

A rare form of spondylometaphyseal dysplasia-type A4.

We present 2 cases of a previously apparently unreported spondylo-metaphyseal dysplasia comprising dwarfism, severe metaphyseal changes, ovoid vertebrae and mild platyspondyly with anterior tonguing of the vertebral bodies. The inheritance may be autosomal recessive.

Child, Preschool↗
PubMed1998

Partial biotinidase deficiency is usually due to the D444H mutation in the biotinidase gene.

Newborn screening for biotinidase deficiency has identified children with profound biotinidase deficiency (<10% of mean normal serum activity) and those with partial biotinidase deficiency (10%-30% of mean normal serum activity). Children with partial biotinidase deficiency and who are not treated with biotin do not usually exhibit symptoms unless they are stressed (i.e., prolonged infection). We found that 18 of 19 randomly selected individuals with partial deficiency have the transversion missense mutation G1330>C, which substitutes a histidine for aspartic acid444 (D444H) in one allele of the biotinidase gene. We have previously estimated that the D444H mutation results in 48% of normal enzyme activity for that allele and occurs with an estimated frequency of 0.039 in the general population. The D444H mutation in biotinidase deficiency is similar to the Duarte variant in galactosemia. The D444H mutation in one allele in combination with a mutation for profound deficiency in the other allele is the common cause of partial biotinidase deficiency.

Alleles↗