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Biomedical subjects

C Ray

Publications and source records attributed to C Ray.

At least 19 recordsLinked to original sources

Illness perception and symptom components in chronic fatigue syndrome.

Two-hundred and eight patients with chronic fatigue syndrome (post-viral fatigue syndrome) completed a questionnaire which dealt both with their illness in general and with the extent to which they experienced specific symptoms. A factor analysis of the symptom data yielded four components: emotional distress; fatigue; somatic symptoms; and cognitive difficulty. Emotional disturbance is a common feature of the disorder and its role has been widely debated. When the symptom components were considered independently, fatigue, somatic symptoms and cognitive difficulty were associated with questionnaire items relating to general illness severity, but emotional distress was not. Thus negative emotions did not contribute directly to patients' perception of illness severity. They were, however, correlated with the other symptom components. It is argued that this correlation reflects a reciprocal influence, with negative emotions exacerbating fatigue and other key symptoms and the debilitating nature of these symptoms enhancing emotional vulnerability.

Activities of Daily Living

Gut-specific and developmental expression of a Caenorhabditis elegans cysteine protease gene.

A Caenorhabditis elegans cysteine protease gene fragment, amplified by PCR using conserved eukaryotic protease gene sequences as primers, was used as a probe to isolate cDNA and genomic clones. The genomic clone, which had a coding sequence of 987 bp interrupted by 2 small introns, was physically mapped to the middle of linkage group V. The predicted amino acid sequence of the mature C. elegans cysteine protease was homologous to those of other eukaryotic cysteine proteases, particularly to that of the nematode parasite Haemonchus contortus (50%) and to the cathepsin B-like hemoglobinase of the trematode parasite Schistosoma mansoni (54%). The pro region of the C. elegans protease was homologous only to that of the H. contortus enzyme, implying a similar mechanism of protease activation. The C. elegans cysteine protease gene was temporally regulated: abundant 1.1-kb transcripts were detected in larvae and adults, but not in embryos. Transcription also was spatially regulated, occurring only in the intestine. Like the vitellogenin genes, which also are transcribed exclusively in the intestine, the 5' end of the C. elegans cysteine protease gene had at least one copy of each of 2 heptameric sequences which may be transcriptional regulatory elements governing gut-specific expression.

Amino Acid Sequence

Positive and negative social support in a chronic illness.

A measure of social support was developed and administered to 207 patients with chronic fatigue syndrome. Positive social support was related to anxiety, and negative social support was related to both anxiety and depression.

Activities of Daily Living

Effect of ethanol on water and chloride transport in the rat papillary collecting duct.

While it is believed that the effect of ethanol on human renal water homeostasis is indirect, amphibian membrane experiments have demonstrated direct effects albeit at high concentrations. To evaluate the direct effect of ethanol, diffusional water and chloride permeability was simultaneously measured in isolated rat papillary collecting ducts with increasing concentrations of ethanol (0, 0.12, 0.24, 0.48, 0.96 and 1.92 g%) both in the presence and absence of arginine vasopressin (AVP). Low concentration of ethanol (0.12 g%) increased basal water permeability by 9%. With increasing concentrations it then fell to control levels (0.48 g%) only to increase again with concentrations of 0.96 and 1.92 g% to a maximum increase of 26%. Similar changes in chloride permeability occurred. Water permeability in the presence of submaximal concentrations of AVP (20 microU/ml) was also significantly increased with lower concentrations of ethanol (0.12, 0.24 and 0.48 g%) but fell to control levels with higher concentrations. With the highest ethanol concentration (1.92 g%), submaximal AVP did not significantly increase water permeability. However water permeability was unaltered by increasing concentrations of ethanol in the presence of supramaximal AVP (2,000 microU/ml). These results demonstrate a direct effect of ethanol upon distal nephron water and chloride transport.

Animals

Characterization of the alpha-2C adrenergic receptor subtype in the opossum kidney and in the OK cell line.

The alpha-2 adrenergic receptors have been subdivided into two pharmacological subtypes known as alpha-2A and alpha-2B. The OK cell, a cell line derived from an opossum kidney, expresses an alpha-2 adrenergic receptor which has pharmacological characteristics different from both the alpha-2A and alpha-2B subtypes, and thus may be a third subtype. To test this hypothesis, we compared the affinities (Ki values from radioligand binding) of 49 drugs in the OK cell with their affinity for the alpha-2A (HT-29 cells) and alpha-2B (neonatal rat lung) adrenergic receptor subtypes. Eight drugs (spiroxarine, prazosin, WY 27127, L-657,743, ARC 239, akuammigine, rauwolscine and oxymetazoline) were identified whose Ki differed by 10-fold or more between the OK cells and HT29 cells. Five drugs (BAM 1303, raubasine, WB 4101, akuammigine and rauwolscine) differentiated, by at least 10-fold, between OK cells and neonatal rat lung. Correlations of pKi values between the OK cell and tissues or cell lines expressing either the alpha-2A or alpha-2B subtypes were poor, confirming that the OK cell receptor could not be classified as either alpha-2A or alpha-2B. In contradistinction, there was a good correlation between pKi values for the OK cell line and opossum kidney showing that they express the same subtype. In addition, ratios of subtype-selective drug Ki values were similar for the OK cell and opossum kidney, but different from other tissues or cell lines expressing either the alpha-2A or alpha-2B subtypes. We conclude that the OK cell line and opossum kidney express a novel subtype of alpha-2 adrenergic receptor which we term the alpha-2C subtype.

Animals

Synthetic human parathyroid hormone-related protein and rat renal electrolyte transport.

The effect of parathyroid hormone (PTH)-like peptide PTH-related protein (PTHrP)(1-34) from a human cancer cell line on renal electrolyte transport was compared with human PTH(1-34) in a thyroparathyroidectomized anesthetized rat model. Comparing submaximal, maximal and supramaximal phosphaturic concentrations of hPTH with the same PTHrP concentrations, no significant difference could be demonstrated in the urinary excretion of calcium, magnesium, inorganic phosphate or cAMP. Even the small (30.3%) and brief (45 min) reduction in fractional water excretion with the maximal (1 nM/kg/h) hPTH concentration was approximated by PTHrP. It is concluded that the structural homology between hPTH and PTHrP allows a similar action on renal electrolyte transport, including the partial agonist effect of higher concentrations of PTH on vasopressin-induced water transport.

Animals

Frequency response of the peripheral sampling sites of a clinical mass spectrometer.

Mass spectrometers are used in ICUs and ORs to measure the concentration of medical and anesthetic gases gathered from multiple sites. This investigation was designed to determine the accuracy of a clinical system, which included 12 ICU bedside stations monitored by a medical mass spectrometer (Perkin-Elmer RMS III, Pomona, CA). Each site station was connected to the analyzing unit via two Teflon tubes, one permanently installed, 30-m long, and the second disposable, 2.4-m long. A gas mixture containing 95% O2 and 5% CO2, alternating with room air, was delivered to a solenoid valve and from there to the connecting tubes. Gas flow-rate, delay time, rise time, and peak and trough concentrations were determined for each gas at solenoid cycling frequencies of 25, 50, and 100/min. After the first set of measurements, the 30-m tubes were thoroughly cleaned and all measurements repeated. In addition, the authors also measured CO2 delay and rise times when the gas was delivered to the mass spectrometer through an unused 30-m tube or a new 2.4-m tube. Gas flow-rate increased from 143 +/- 12 ml/min (mean +/- SD) to 238 +/- 9 ml/min after the tubes were cleaned. Delay time was identical for all gases at all solenoid cycling rates but decreased significantly (P less than 0.05), from 11.5 +/- 0.3 to 4.8 +/- 0.7 s after the ceiling tubes were cleaned. As solenoid valve rate increased, the difference between measured and actual gas concentration increased. The lowest accuracy was 63.6 +/- 2.1%, for CO2 at 100 cycles/min.(ABSTRACT TRUNCATED AT 250 WORDS)

Gases

The myth of the yo-yo: consistent rate of weight loss with successive dieting by VLCD.

Four subjects in a recent trial of eight weeks dieting with the 405 kcal/day, 42 g protein formula (Cambridge diet extra), had participated 18 months previously in an 8-week trial using the 330 kcal/day Cambridge diet formula. This permitted a quantitative comparison of two similar dieting episodes, but following substantial weight loss and variable weight regain after a successful experience with a very low calorie diet. Within the reasonable bounds of comparison between outpatient dieting experiences, there was no suggestion of impairment in ability to lose weight in subsequent dieting after weight loss on a VLCD. The experience of these subjects would not support the contention that lasting metabolic debilitation had occurred that could be attributed to repeated dieting experiences with VLCD.

Diet, Reducing

An automated mechanism for protection of mass spectrometry sampling tubing.

The usefulness of medical mass spectrometers in intensive care units can be limited by too frequent obstruction of the tubing that transports gases from the patients to the analyzing unit. To overcome this problem, we developed an automated system consisting of an infrared light sensor and a three-way valve. One port of the three-way valve connects to 2.4-m disposable tubing that collects gases from the patient's airway. The second port is connected to a mass spectrometer analyzing unit through 30-m permanently installed tubing. The third port is connected to a pressurized oxygen source. An infrared light sensor is placed on the shorter tubing, between the patient and the three-way valve. When increased optical density is detected, due to entrainment of respiratory secretions, the three-way valve is activated. Gas flow is closed between the patient and the mass spectrometer and opened between the pressurized oxygen source and patient tubing to flush its contents. During the six years that the protection system has been in use, the frequency with which the disposable gas collection tubing is changed has been halved. Furthermore, periodic tests of delay and response times, performed at each bedside station, indicate that permanent connection tubing only needed cleaning at 2- to 3-year intervals. The system has decreased the cost of operating our mass spectrometers while also reducing periods of unavailability due to equipment failure.

Anesthesiology

Capnography in mechanically ventilated patients.

Capnography, the science of CO2 waveforms analysis, can play a role in the management of mechanically ventilated patients. Mass spectrometers are the devices most commonly used to collect sequentially and examine CO2 waveforms from multiple patients in the ICU or operating rooms. We present here a review of some clinical and technical problems, which may be resolved efficiently and expeditiously through the use of mass spectrometry and capnography. Mechanical failures, especially those that lead to rebreathing of exhaled gases, can be readily detected. The patient's progress during weaning and the consequences of changes in mechanical assistance can be virtually and noninvasively determined. An expanded role of capnography in mechanically ventilated patients can increase the use of mass spectrometers in the ICU.

Carbon Dioxide

Suppression of ctc promoter mutations in Bacillus subtilis.

Transcription from the Bacillus subtilis ctc promoter is induced as cells enter stationary phase under conditions in which the enzymes of the tricarboxylic acid cycle are repressed. This transcription requires the presence of a secondary form of RNA polymerase, E sigma B, that is found in exponentially growing cells and in early-stationary-phase cells. Starting with a defective ctc promoter that had either a base substitution at position -15 or a base substitution at position -36, we were able to identify four independent second-site mutations within these mutated promoters that suppressed the effect of the original mutations and thereby restored function to the ctc promoter. Three of these mutated promoters had an additional base substitution(s) at positions -5, -9, or both -5 and -9 that enhanced their utilization in vivo by E sigma B, whereas one of the promoters had a single-base-pair deletion in the -15 region that placed it under a completely different form of regulation than that of the wild-type ctc promoter. In addition to mutations in the ctc promoter region, we also isolated three classes of mutants that exhibited increased ctc expression. The effects of the mutations in these strains were not allele specific, since they increased expression from both mutant and wild-type ctc promoters. One class of mutants which affected expression from the ctc promoter carried mutations that blocked the activity of the tricarboxylic acid cycle. A second class of mutations mapped near cysA and was unable to sporulate. Three-factor transformation crosses and complementation analysis indicated that one of these mutations was an allele of spo0H. The third class of mutations is closely linked to dal and may define a regulatory gene for sigB, the sigma B structural gene.

Acetyltransferases

Indirect calorimetry in the mechanically ventilated patient.

We used indirect calorimetry to measure oxygen consumption (VO2) and carbon dioxide production in 29 mechanically ventilated patients. These data were compared to VO2 measured simultaneously by a standard thermodilution technique. A good correlation was demonstrated between the methods, but VO2 measured by indirect calorimetry was 15% higher than VO2 measured by thermodilution.

Adolescent

Genetic analysis of RNA polymerase-promoter interaction during sporulation in bacillus subtilis.

The discovery of secondary sigma factors in Bacillus subtilis that enable RNA polymerase to transcribe cloned sporulation genes in vitro has led to the proposal that the appearance of new sigma factors during sporulation directs RNA polymerase to the different temporal classes of sporulation genes. One sigma factor, which appears 2 h after the initiation of sporulation, is sigma E (formerly sigma 29). Mutations that inactivate the structural gene for sigma E prevent transcription from promoter G4. To determine whether sigma E-RNA polymerase interacts with the G4 promoter in vivo, we examined the effects of six single-base-pair substitutions in the G4 promoter on its utilization in vivo and in vitro by sigma E-RNA polymerase. The mutations in the G4 promoter affected utilization of the promoter in vivo in the same way that they affected its utilization in vitro by purified sigma E-RNA polymerase; therefore, we conclude that this polymerase interacts directly with the G4 promoter in vivo. The effects of these mutations also support the model in which sigma E-RNA polymerase utilizes promoters by interacting with two distinct sets of nucleotides located 10 and 35 base pairs upstream from the start point of transcription.

Bacillus subtilis

Genetic studies of a secondary RNA polymerase sigma factor in Bacillus subtilis.

sigma B (sigma 37) is a secondary species of RNA polymerase sigma factor found in the gram-positive bacterium Bacillus subtilis. To study the function of sigma B genetically, we sought mutations that block the expression of a gene (ctc) known to be transcribed by sigma B-containing RNA polymerase in vitro. One such mutation, called crl, was found to map in or near the structural gene (sigB) for sigma B. To determine directly whether mutations in sigB would prevent transcription of ctc, we replaced sigB in the B. subtilis chromosome with insertion and deletion mutations that disrupted the sigma B coding sequence. Like crl, these in vitro-constructed mutations blocked expression of ctc, but had little or no effect on viability, sporulation, expression of the sporulation gene spoVG, or production of sporulation-associated alkaline protease. Using fusions of ctc to the reporter genes xylE and lacZ, we also identified mutations that enhanced ctc expression. One such mutation, called socB, was found to be located in an open reading frame immediately downstream of sigB.

Bacillus subtilis

Dental and social effects of malocclusion and effectiveness of orthodontic treatment: a strategy for investigation.

Study of the effectiveness of orthodontic treatment is complicated by a variety of factors, including the need for longitudinal, multidisciplinary appraisal and difficulties of randomisation, control and sample composition. This report outlines a recent initiative adopting a longitudinal, observational approach with a cohort of approximately 1000 12-yr-olds, selected by disproportionate stratified sampling in order that occlusal features of low prevalence, but high orthodontic interest, would be well represented. In the event, 4810 subjects were listed and after certain exclusions, 3420 children were screened. Using preselected screening criteria, 663 with specific occlusal features were selected and an additional 355 children with nonspecific features were randomly allocated on a pro-rata basis. This gave a final study population of 1018. Baseline dental data included the recording of caries, periodontal status and mandibular function. Study models were obtained and analysed using a new standardised technique for recording the alignment of individual teeth. Photographs of the face and dentition were collected and a rating system developed to score dental and facial attractiveness. Social-psychological data were recorded via self-rating questionnaires, interviews, parental questionnaires, teacher questionnaires and peer ratings.

Child

Regional isolated limb perfusion of melanoma intransit metastases using mechlorethamine (nitrogen mustard).

Forty-two patients with intransit metastases of melanoma in a limb were treated by isolated regional perfusion chemotherapy using mechlorethamine (nitrogen mustard). Group 1 (n = 12) underwent treatment at low dose, less than 0.35 mg/kg, or low temperature, less than 38 degrees C. Group 2 (n = 30) received higher doses, 0.35 to 0.6 mg/kg, plus heat at 38 degrees C to 41 degrees C. No patient had evidence of disease outside the limb at the time of perfusion. The median follow-up time was 48 months (range, 1 to 9 years). Of the 42 patients, 29 had measurable lesions that responded as follows: group 1, complete response (CR) in two of ten and partial response (PR) in none; group 2, CR in six of 19 and PR in six of 19. The combined CR and PR rate of 12 of 19 in group 2 was significantly higher than that of group 1 (P less than .05). CR lasted only 2 months in the two patients of group 1, but persisted in the six patients of Group 2, four of whom are still alive free of disease at 16, 21, 33, and 40 months. Relapse-free control of disease in the limb was achieved in 36% of the patients in group 2 at 24 months, compared with 0% in group 1 (P less than .05). An overall survival of 74% at 48 months was observed in group 2, significantly higher than that of 64% for group 1 (P less than .05). The status of the regional lymph nodes (RLN) and the number of metastases did not affect tumor response. However, 77% of RLN-negative patients survived 48 months, in contrast to only 38% of RLN-positive patients (P less than .05). One patient died postoperatively of myocardial infarction. No serious systemic toxicity developed. Two patients who underwent repeat salvage perfusions developed a reversible peripheral neuropathy in the limb. Limb function was good after treatment, and dramatically improved in patients who had advanced satellitosis that responded to treatment. These results suggest that heated limb perfusion using mechlorethamine at an adequate dose can offer long-term control of intransit metastases in approximately one third of these patients, with preservation of good limb function and possible prolongation of survival.

Adult