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Biomedical subjects

P Schultz

Publications and source records attributed to P Schultz.

17 recordsLinked to original sources
PubMed1992

Modified nucleosides in human serum.

Methylated purines and pyrimidines derived from the degradation of transfer ribonucleic acid have been shown to be excreted in abnormal amounts in the urine of patients with cancer. Recent technology developed by Gehrke and Kuo has allowed the separation and quantification of modified nucleosides in serum using reversed-phase high-performance liquid chromatography with diode-array measurement. Serum levels of ten modified nucleosides were measured in 37 normal healthy adults to establish normal values and to correlate activity with age and sex. In addition, serum levels of patients with several malignancies were measured to determine activity in these diseases. Levels of modified nucleosides in normal individuals were consistently reproducible and showed no significant variation among males versus females or with age. Patients with malignant diseases showed consistent elevations and these were highest in patients with more advanced disease. The evidence of no significant differences in the mean levels of modified nucleosides in serum with age or sex in normal adults and elevations in patients with malignancies demonstrate the potential value of modified nucleosides as cancer biomarkers.

Adult↗
PubMed1992

Complementation of formyl peptide receptor-mediated signal transduction in Xenopus laevis oocytes.

Formyl-methionine-containing peptides (e.g. fMet-Leu-Phe) stimulate a variety of neutrophil functions by interacting with specific cell surface receptors which are coupled via G-proteins to stimulation of phospholipase C. Two markedly distinct cDNAs coding for formyl peptide receptors have recently been isolated from a rabbit and a human cDNA library respectively. To examine the hitherto unknown signal transduction properties of the formyl peptide receptor encoded by the human cDNA, we have used the PCR to clone this cDNA from poly(A)+ RNA of myeloid differentiated human leukaemia (HL-60) cells, and have injected the cDNA-derived receptor cRNA into Xenopus laevis oocytes. Receptor activity was determined electrophysiologically by measuring the agonist-dependent opening of intracellular Ca2+ concentration ([Ca2+]i)-independent Cl- channels. Injection of pure formyl peptide receptor cRNA did not lead to peptide-dependent changes in membrane current. In contrast, marked alterations of membrane current were observed in response to formyl peptides when the receptor cRNA was supplemented with poly(A)+ RNA isolated from undifferentiated HL-60 cells. Injection of the latter RNA did not lead to formyl-peptide-dependent alterations of membrane current. Binding studies using a radioiodinated formyl peptide revealed that injection of formyl peptide receptor cRNA alone led to expression of the formyl peptide receptor on the oocyte surface, and that co-injection of poly(A)+ RNA from undifferentiated HL-60 cells did not alter the level of receptor expression. Size fractionation of poly(A)+ RNA from undifferentiated HL-60 cells showed that the mRNA required to complement formyl-peptide-dependent signal transduction in oocytes had a size of approx. 3-3.5 kb. These results strongly suggest that the human formyl peptide receptor requires a specific cofactor(s), which is lacking in Xenopus oocytes but is present in undifferentiated HL-60 cells, to activate the second messenger pathway in oocytes. Identification of this factor will provide important information about the molecular mechanisms by which G-protein-coupled granulocyte-activating receptors stimulate phospholipase C.

Amino Acid Sequence↗
PubMed1992

Framework multipoint map of the long arm of human chromosome 4 and telomeric localization of the gene for FSHD.

Mapping the long arm of Chromosome (Chr) 4 has assumed medical relevance with the establishment of linkage of facioscapulohumeral muscular dystrophy (FSHD) to distal 4q markers. We have constructed a multipoint linkage map using DNA markers that map to the long arm of Chr 4. Segregation data were collected for 17 DNA markers on the multigenerational CEPH mapping families, and data for one marker were taken from the published CEPH database. Genotypic information for six of these markers was also collected from a set of 24 families that exhibited inheritance of FSHD. Multipoint analyses allowed us to construct a map of 12 loci, connecting two previously separate linkage groups. Significant sex-specific differences in recombination were found for some genetic intervals. Four loci from the distal region of this map showed linkage with FSHD. A map using these terminal markers gave the strongest support for FSHD in the most distal position over all other possible positions.

Chromosome Mapping↗
PubMed1992

Functional reconstitution of a receptor-activated signal transduction pathway in Xenopus laevis oocytes using the cloned human C5a receptor.

We have used the polymerase chain reaction to isolate and clone the cDNA encoding the human C5a receptor, and have injected the cDNA-derived receptor cRNA into Xenopus laevis oocytes for functional characterization of the receptor protein. Receptor activity was determined either electrophysiologically by measuring the agonist-dependent opening of [Ca2+]i-dependent Cl- channels, or by analysing the agonist-dependent efflux of 45Ca2+ from the oocytes. Using both methodologies, injection of pure C5a receptor cRNA failed to confer C5a sensitivity on the oocytes. In contrast, marked responses to C5a were observed when the receptor cRNA was supplemented with poly(A)+ RNA isolated from undifferentiated HL-60 cells, which is devoid of C5a receptor mRNA. Binding studies using radioiodinated C5a revealed that the C5a receptor polypeptide was in fact synthesized and targeted to the oocyte plasma membrane in oocytes injected with receptor cRNA alone, and that the level of receptor expression was not influenced by coinjection of poly(A)+ RNA from undifferentiated HL-60 cells. These results strongly suggest that the human C5a receptor requires a specific cofactor(s) lacking in Xenopus oocytes but present in undifferentiated HL-60 cells, to generate intracellular signals in oocytes. Identification and characterization of this factor will provide important information about the molecular mechanisms by which G-protein-coupled receptors activate phospholipase C.

Animals↗
PubMed1992

Increased urinary loss of uric acid in adults with acute respiratory failure requiring mechanical ventilation.

INTRODUCTION: The purpose of this study was to test a hypothesis of increased urinary excretion of uric acid as an indicator of adenosine triphosphate (ATP) degradation in adult patients with acute respiratory failure, and to look for a correlation to the clinical outcome. STUDY DESIGN: Prospectively 31 patients with acute respiratory failure were studied. The patients were divided into two groups according to the clinical outcome: the need for solely supplemental oxygen (group 1), death or mechanical ventilation (group 2). METHODS: Uric acid was determined by spectrophotometry. RESULTS: Mean uric acid excretion was 39 mumol/kg (range, 7 to 92 mumol/kg) body weight/per 24 h in group 1 (16 patients) compared with 65 mumol/kg/24 h (range, 8 to 253 mumol/kg/24 h) in group 2 (13 patients were mechanically ventilated, and two patients died). The difference was highly significant (p less than 0.0001). CONCLUSION: Increased amount of urinary uric acid was related to the severity of acute respiratory failure in adults.

Acute Disease↗
PubMed1992

Linkage analyses of five chromosome 4 markers localizes the facioscapulohumeral muscular dystrophy (FSHD) gene to distal 4q35.

The genetic locus for facioscapulohumeral muscular dystrophy (FSHD) has been mapped to chromosome 4. We have examined linkage to five chromosome 4q DNA markers in 22 multigenerational FSHD families. Multipoint linkage analyses of the segregation of four markers in the FSHD families and in 40 multigenerational mapping families from the Centre d'Etude du Polymorphisme Humaine enabled these loci and FSHD to be placed in the following order: cen-D4S171-factor XI-D4S163-D4S139-FSHD-qter. One interval, D4S171-FSHD, showed significant sex-specific differences in recombination. Homogeneity tests supported linkage of FSHD to these 4q DNA markers in all of the families we studied. The position of FSHD is consistent with that generated by other groups as members of an international FSHD consortium.

Chromosome Mapping↗
PubMed1991

Subhypnotic doses of thiopentone and propofol cause analgesia to experimentally induced acute pain.

Subhypnotic doses of thiopentone are considered to have a hyperalgesic effect, while propofol has a hypoalgesic effect. We investigated the effect of these drugs on the nociceptive system by measuring the pain threshold to laser stimulation and the pain evoked potential (power and latency). Nineteen patients (ASA group I) participated. Twelve patients received thiopentone 0.5 mg kg-1 and propofol 0.25 mg kg-1 in random order separated by an interval of 14 h, and seven patients received saline. Immediately after the injection of both agents, the pain threshold was increased significantly (P less than 0.001) and the amplitude of the evoked potential was reduced significantly (P less than 0.05), while the latency of the evoked potential remained constant. It is concluded that, in subhypnotic doses, both thiopentone and propofol decrease the acute pain evoked by argon laser stimulation.

Acute Disease↗
PubMed1991

Variation in spinal analgesia with plain bupivacaine 0.5% when repeated in the same patient.

The study was done to see if it was possible to predict the level of analgesia in repeated spinal blocks with our routine technique where the patient is seated during injection of plain 0.5% bupivacaine 3.5 ml at the L3-L4 interspace and placed in the lithotomy position after 0.5 min. Thirty patients with tumour of the bladder had two spinal blocks during a 13-month period. The segmental spread of sensory loss was tested with the pin-prick technique. A wide range of height of blocks was found, increasing with age. Regression analysis on maximum cephalad spread of the second spinal analgesia against the first had a slope of 0.48 (P less than 0.01 for the hypothesis that the slope is zero). A significant correlation between the time for maximal cephalad spread was found, while the correlation between duration of thoracal analgesia was non-significant.

Aged↗
PubMed1977

Giant axonal neuropathy: a childhood disorder of microfilaments.

A sural nerve biopsy was performed on an 8-year-old boy with a chronic, slowly progressive polyneuropathy. Light and electron microscopy as well as teased nerve-fiber preparations demonstrated numerous giant axons filled with closely packed neurofilaments. Both myelinated and unmyelinated fibers were involved. Segmental demyelination, remyelination, and onion-bulb formation by multiple Schwann cell processes were observed, suggesting recurrent Schwann cell dysfunction. Abundant aggregates of cytoplasmic microfilaments occurred in Schwann cells, endothelial cells, perineurial cells, endoneurial fibroblasts, and endomysial fibroblasts. These findings support the proposal that giant axonal neuropathy is a generalized disorder of cytoplasmic microfilaments and that segmental demyelination occurs concomitantly with axonal and Schwann cell disease. The pathogenesis of this rare disorder is discussed with reference to experimental toxic neuropathies.

Axons↗
PubMed1975

Adrenoleukodystrophy. Electron microscopic findings.

Ultrastructural and neurochemical studies were done on three male patients with adrenoleukodystrophy. In each case, the affected white matter contained enlarged glial cells filled with pathognomic intracytoplasmic inclusions consisting of electron-lucent spicules bounded by 25-Angstrom wide membranes. Similar inclusions were present in adrenocortical cells. These findings and a review of 47 reported cases indicate that adrenoleukodystrophy is a storage disorder caused by a sex-linked recessive error of metabolism.

Adrenal Cortex↗
PubMed1975

Nephrogenic diabetes insipidus in an Australian aboriginal kindred.

Four Australian aboriginal children were found to have nephrogenic diabetes insipidus. They are the sons of 3 sisters who were shown to have a urinary concentrating defect uncorrected by vasopressin. An extensive genealogy did not reveal any caucasian genetic influence suggesting that a new genetic mutation was responsible.

Australia↗