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Biomedical subjects

J Wells

Publications and source records attributed to J Wells.

At least 73 records · Page 4Linked to original sources
PubMed1996

An outbreak of cholera from food served on an international aircraft.

In February 1992, an outbreak of cholera occurred among persons who had flown on a commercial airline flight from South America to Los Angeles. This study was conducted to determine the magnitude and the cause of the outbreak. Passengers were interviewed and laboratory specimens were collected to determine the magnitude of the outbreak. A case-control study was performed to determine the vehicle of infection. Seventy-five of the 336 passengers in the United States had cholera; 10 were hospitalized and one died. Cold seafood salad, served between Lima, Peru and Los Angeles, California was the vehicle of infection (odds ratio, 11.6; 95% confidence interval, 3.3-44.5). This was the largest airline-associated outbreak of cholera ever reported and demonstrates the potential for airline-associated spread of cholera from epidemic areas to other parts of the world. Physicians should obtain a travel history and consider cholera in patients with diarrhoea who have travelled from cholera-affected countries. This outbreak also highlights the risks associated with eating cold foods prepared in cholera-affected countries.

Adolescent↗
PubMed1996

Indirect argon laser drainage of subretinal fluid.

We report on a new method of subretinal fluid drainage which uses the indirect ophthalmoscopic delivery of argon laser energy to perforate the choroid. This carries all the theoretical advantages of drainage with the endolaser probe but is simpler and less expensive. We present a prospective series of 31 patients in whom this method was applied. Satisfactory drainage was obtained in 28. There were 4 cases of limited subretinal haemorrhage attributable to the laser, and 1 case of subfoveal haemorrhage. No cases of retinal perforation or incarceration were observed.

Adult↗
PubMed1996

Dosage-sensitive maternal modifiers of the drosophila segmentation gene runt.

The protein encoded by the pair-rule gene runt functions as a transcriptional regulator during anterior-posterior patterning of the Drosophila embryo. Results of over-expression experiments as well as parallels drawn from the recent characterization of vertebrate homologues indicate that interactions with other proteins are likely to be central to the function of the Runt protein. To identify factors important for runt activity, we took advantage of an adult visible phenotype observed in animals heterozygous for runt mutations. Using a set of 126 different deficiency chromosomes we screened approximately 65% of the genome for genes that act as dose-sensitive maternal modifiers of runt. Eighteen deficiencies representing 12 putative loci were identified as maternally acting enhancers of runt haplo-insufficiency. Further characterization of two of these regions led to the identification of the interacting loci. Both of these loci affect the spatial regulation of runt transcription and appear genetically complex. Furthermore, the effects of one of these loci, M(1)1B, is indirect and mediated through effects on the transcriptional regulation of posterior gap genes.

Animals↗
PubMed1996

Protein-DNA interactions at the major and minor promoters of the divergently transcribed dhfr and rep3 genes during the Chinese hamster ovary cell cycle.

In mammals, two TATA-less bidirectional promoters regulate expression of the divergently transcribed dihydrofolate reductase (dhfr) and rep3 genes. In CHOC 400 cells, dhfr mRNA levels increase about fourfold during the G1-to-S phase transition of the cell cycle, whereas the levels of rep3 transcripts vary less than twofold during this time. To assess the role of DNA-binding proteins in transcriptional regulation of the dhfr and rep3 genes, the major and minor dhfr-rep3 promoter regions were analyzed by high-resolution genomic footprinting during the cell cycle. At the major dhfr promoter, prominent DNase I footprints over four upstream Sp1 binding sites did not vary throughout G1 and entry into the S phase. Genomic footprinting revealed that a protein is constitutively bound to the overlapping E2F sites throughout the G1-to-S phase transition, an interaction that is most evident on the transcribed template strand. On the nontranscribed strand, multiple changes in the DNase I cleavage pattern are observed during transit through G1 and entry into the S phase. By using gel mobility shift assays and a series of sequence-specific probes, two different species of E2F were shown to interact with the dhfr promoter during the cell cycle. The DNA binding activity of one E2F species, which preferentially recognizes the sequence TTTGGCGC, did not vary significantly during the cell cycle. The DNA binding activity of the second E2F species, which preferentially recognizes the sequence TTTCGCGC, increased during the G1-to-S phase transition. Together, these results indicate that Sp1 and the species of E2F that binds TTTGGCGC participate in the formation of a basal transcription complex, while the species of E2F that binds TTTCGCGC regulates dhfr gene expression during the G1-to-S phase transition. At the minor promoter, DNase I footprints at a consensus c-Myc binding site and three Sp1 binding sites showed little variation during the G1-to-S phase transition. In addition to protein binding at sequences known to be involved in the regulation of transcription, genomic footprinting of the entire promoter region also showed that a protein factor is constitutively bound to the first intron of the rep3 gene.

Animals↗
PubMed1996

Confocal microscopy analysis of living Xenopus eggs and the mechanism of cortical rotation.

The dorsoventral body axis in amphibian embryos is established by a rotation of the outer cortex relative to the inner cytoplasmic core. This cortical rotation depends on microtubules and is correlated with a parallel array of microtubules just inside the vegetal cortex. Since the parallel array moves with the inner cytoplasm and most of its microtubules are oriented with their plus ends facing the direction of cortical movement, it has been suggested that plus end-directed motor molecules attached to the cortex drive the rotation by moving along microtubules of the parallel array. Using an inverted confocal microscope to examine living eggs, however, we found that rotation movements precede the formation of a detectable parallel array at the vegetal pole, that the parallel array consists of multiple layers of microtubules at depths ranging from 4 to 8 microns inside the plasma membrane and that the velocity of rotation is immobilized eggs increases with depth in this region. These findings suggest that (1) early cytoplasmic movements are due to something other than the fully formed parallel array and (2) the motor molecules responsible for the bulk of the rotation movement are not restricted to a monolayer at the subcortical interface but may be distributed throughout the parallel array, perhaps causing microtubules to slide along other microtubules by a mechanism similar to that seen in cilia and eukaryotic flagella.

Animals↗
PubMed1996

Cutaneous respiration in Octopus vulgaris

The skin of Octopus vulgaris consumes considerable quantities of oxygen in vitro, averaging 4.55x10(-5)±1.80x10(-5) ml mm-2 h-1 (mean ± s.d.), if a flow is maintained over the skin sample (N=32). The consumption is higher still in vivo, 11.36x10(-5)±2.73x10(-5) ml mm-2 h-1 (N=8), suggesting an additional net import of oxygen through the skin when the blood system is intact. If a substantial boundary layer is allowed to develop, oxygen uptake in vitro falls to 2.09x10(-5)±0.56x10(-5) ml mm-2 h-1 (N=15). The proportion of the animals' total oxygen consumption that cutaneous uptake will represent must thus depend on how much of the skin is exposed and how well it is ventilated. Estimates indicate that some 41 % of the total oxygen requirement of an animal at rest might be satisfied in this manner. During exercise, with water flowing over the entire surface of the animal, cutaneous uptake will increase but is nevertheless likely to form a smaller proportion (about 33 %) of the total uptake. In an animal curled up in its den and digesting a substantial meal, cutaneous uptake could shrink to as little as 3 % of the total. Similar results were obtained in a small number of pilot experiments with a range of octopod, sepioid and teuthoid species.

Journal Article↗
PubMed1996

Micronucleus induction in human lymphocytes: comparative effects of X rays, alpha particles, beta particles and neutrons and implications for biological dosimetry.

The cytokinesis-block micronucleus assay in peripheral blood lymphocytes has the potential for being a simple and rapid method of biological dosimetry. This technique has been used to study the induction of micronuclei in the blood from 12 donors after exposure to a range of radiations with track-averaged LET values ranging from 0.26 to 44 keV microns -1. Data based on the average response of the 12 individuals for 250 kVp X rays were found to agree well with results published previously from other laboratories using similar techniques. Low dose-limiting RBE values relative to 250 kVp X rays for the radiations studied were found to be 0.50 for strontium/yttrium-90 beta particles, 6.9 for 20-23 keV microns -1 alpha particles and 17 for 24 keV neutrons. The pattern of the variation of individual radiosensitivity was found to be complex and dependent on dose, and the evaluation of individual radiosensitivity based on the response at one dose only can be misleading. It is concluded that, although the cytokinesis-block micronucleus assay in blood lymphocytes is a radiobiologically appropriate technique to use for biological dosimetry, its practical implementation may be limited by a need to perform individual pre-exposure calibrations.

Adult↗
PubMed1996

Evidence for major gene inheritance of Alzheimer disease in families of patients with and without apolipoprotein E epsilon 4.

Apolipoprotein E (APOE) genotype is the single most important determinant to the common form of Alzheimer disease (AD) yet identified. Several studies show that family history of AD is not entirely accounted for by APOE genotype. Also, there is evidence for an interaction between APOE genotype and gender. We carried out a complex segregation analysis in 636 nuclear families of consecutively ascertained and rigorously diagnosed probands in the Multi-Institutional Research in Alzheimer Genetic Epidemiology study in order to derive models of disease transmission which account for the influences of APOE genotype of the proband and gender. In the total group of families, models postulating sporadic occurrence, no major gene effect, random environmental transmission, and Mendelian inheritance were rejected. Transmission of AD in families of probands with at least one epsilon 4 allele best fit a dominant model. Moreover, single gene inheritance best explained clustering of the disorder in families of probands lacking epsilon 4, but a more complex genetic model or multiple genetic models may ultimately account for risk in this group of families. Our results also suggest that susceptibility to AD differs between men and women regardless of the proband's APOE status. Assuming a dominant model, AD appears to be completely penetrant in women, whereas only 62%-65% of men with predisposing genotypes develop AD. However, parameter estimates from the arbitrary major gene model suggests that AD is expressed dominantly in women and additively in men. These observations, taken together with epidemiologic data, are consistent with the hypothesis of an interaction between genes and other biological factors affecting disease susceptibility.

Adult↗
PubMed1995

A mitochondrial elongation factor-like protein is over-expressed in tumours and differentially expressed in normal tissues.

The tissue-specific expression of an antigen (P43) ubiquitously expressed at high levels in a variety of tumours of human and animal origin was investigated using a monoclonal antibody to P43. Whereas low amounts of P43 are expressed in the spleen, skeletal muscle and pancreas, P43 is abundantly produced in the liver and in other tissues such as the kidney, heart and brain which have levels of oxidative metabolism. Interestingly, a related protein of higher molecular weight is abundantly expressed in the lung and in amounts which were higher than those observed with other tissues. The human cDNA for P43 was isolated from a human liver cDNA library and mapped to chromosome 16 between p11.2 and 12 and also to a position near the centromere on the long arm of chromosome 17. The deduced amino acid sequence of P43 is remarkably similar to that of E. coli EF-Tu and the mitochondrial EF-Tu of S. cerevisiae with the structurally and functionally important amino acids of EF-Tu being completely conserved in P43. A comparison of the distribution of P43 and a mitochondrial protein Hsp 60 among different cellular fractions indicated a likely mitochondrial localisation for P43. Taken together these results suggest that P43 is a human mitochondrial elongation factor.

Amino Acid Sequence↗
PubMed1995

The role of somatosensory information in a constrained locomotor task.

The purpose of this project was to study the role of somatosensory information in the performance of a constrained locomotor task by rats and to further examine the influence of structural recovery in the somatosensory thalamus, specifically the ventral posterolateral nucleus (VPL). Groups of rats were trained to traverse an elevated, one inch bar for a reward. The time taken to run across the bar (run time) was used as a measure of the success of the goal-directed behavior. The movement pattern of the hindlimb during the swing phase of the locomotor task was quantified from videotape on Preoperative (PRE) Day 15 and during the 46-day postoperative period. The movement pattern was characterized using six different parameters: the area, the X and Y values of the centroid under the normalized curve of the hindlimb trajectory, the vertical displacement of the hindlimb in the flexion and extension phases of the swing cycle, the maximum instantaneous hindlimb velocity, and the proportion of time spent in the acceleration versus deceleration phases of the swing cycle. In order to disrupt the central pathways for somatosensory information, lesions were made in (i) the right gracile nucleus (GN) (n = 18), (ii) bilateral GN (n = 7), (iii) the right GN and the left VPL (n = 6), and (iv) bilateral VPL (n = 8), and (v) sham-operated animals (n = 5). The run time and the pattern of the hindlimb swing cycle were used as measures of loss and recovery of function. Only the bilateral VPL group showed an impairment in run time and they recovered by Postoperative (POST) Week 4. All groups demonstrated an impairment in initial flexion of the hindlimb during the swing cycle that recovered in the right GN group only. On POST Day 49, the right GN, bilateral GN, and the sham groups received injections of 5% WGA-HRP into both CN to determine the location of these projections in VPL. The CN projections were not redistributed into the gracile area of VPL after GN lesions. Since our previous study (24) had shown the number of synapses in VPL returned to normal after dorsal column nuclei (DCN) lesions by POST Day 50, the recovery of the number of synapses alone was not sufficient to restore the normal gait pattern, while the recovery of the run time preceded the complete recovery of the number of synapses.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1995

The "revolution" in outpatient care.

Although the concept of outpatient care is not a new one, the growth in ambulatory facilities has revolutionized medical care in the United States. The growth in ambulatory surgery centers, imaging centers, and cancer centers in Florida is explored in detail. With the many changes forthcoming in health care, ambulatory care will play an increasing role in delivering good health care at a reasonable cost.

Ambulatory Care↗
PubMed1995

The control of ventilatory and cardiac responses to changes in ambient oxygen tension and oxygen demand in octopus

Octopus vulgaris can regulate its oxygen uptake down to a PO2 of around 6.7 kPa. As the tension falls from 18.6 to 6.7 kPa (140 to 50 mmHg), Pv (the pressure pulse driving the ventilatory flow, measured inside the mantle cavity) can more than double while fv (the ventilation frequency) increases by a few per cent at most. Both changes are reversed when the ambient oxygen tension is returned to normal. Cutting the visceral nerves linking the hearts and gills to the brain prevents these adaptive changes in Pv and fv, as does section of the branchial nerves linking the cardiac ganglia to the gills. Responses to changes in ambient oxygen tension are very fast, beginning within two or three ventilation cycles. It is concluded that changes to Pv and fv depend upon receptors in the gills and on the integrity of a nervous pathway to the brain. Changes in oxygen tension also affect the hearts, where aortic pulse amplitude (Pa) and, to a lesser extent, heartbeat frequency (fh) fall and rise with the ambient PO2. In this case, section of the visceral or branchial nerves has no effect. Responses are again very rapid. It is concluded that the observed fall and return to normoxic values of Pa and fh are local responses to a fall and rise in the oxygen tension of blood coming from the gills into the systemic heart. Changes to ventilation and heartbeat can also occur in normoxic water when oxygen demand rises after feeding. These responses are not prevented by section of the visceral or branchial nerves. Possible control of ventilation and heartbeat through the neurosecretory system in the anterior vena cava is discussed.

Journal Article↗
PubMed1994

Elevated levels of shed type II IL-1 receptor in sepsis. Potential role for type II receptor in regulation of IL-1 responses.

Two types of cellular IL-1Rs have been characterized and cloned from both human and murine sources. The type II IL-1R has a very short cytoplasmic domain and does not seem to participate in IL-1 signaling. We demonstrate that type II IL-1Rs are released from the surface of neutrophils in response to treatment with TNF or endotoxin. In addition, serum from patients with sepsis syndrome contains elevated levels of soluble type II IL-1Rs. Neutrophils isolated from patients with sepsis have greatly enhanced expression of type II IL-1R mRNA and cell surface receptors and are therefore a likely source for the shed receptors in serum. Of the three forms of IL-1, soluble type II IL-1R binds IL-1 beta with highest affinity and also selectively inhibits IL-1 beta activity. We propose that increased cell surface expression and rapid release of preformed type II IL-1R from neutrophils, as a soluble IL-1 beta binding protein, represents a mechanism that has evolved for regulating IL-1 activity in sepsis.

Blotting, Northern↗
PubMed1994

The purification, cloning, and expression of a novel luteinizing hormone-induced mitochondrial protein in MA-10 mouse Leydig tumor cells. Characterization of the steroidogenic acute regulatory protein (StAR).

The acute response of steroidogenic cells to trophic hormone stimulation is the mobilization of cholesterol from cellular stores to the mitochondrial outer membrane and the transfer of this cholesterol to the mitochondrial inner membrane where the first enzymatic step in steroidogenesis occurs. The transfer of cholesterol across the mitochondrial membranes is dependent upon de novo protein synthesis, and this is the regulated step in the process. Although the newly synthesized regulatory protein(s) have yet to be identified, we previously have proposed a candidate protein which we identified in MA-10 cells that is synthesized in response to luteinizing hormone stimulation and that is localized to the mitochondria. In the present study, we report the isolation of a cDNA that encodes this luteinizing hormone-induced protein. Analysis of the cDNA and protein sequences reveals this is a novel protein. Importantly, we demonstrate for the first time that expression of the protein in MA-10 cells in the absence of hormone stimulation is sufficient to induce steroid production. We conclude that this protein is required in the acute regulation of steroidogenesis and propose to call this protein the Steroidogenic Acute Regulatory protein (StAR).

Amino Acid Sequence↗
PubMed1994

Thrombin generation in patients undergoing carotid endarterectomy: implications in acute vessel wall closure and antithrombotic therapy.

We determined the extent and duration of activation of coagulation during the first 24 hours after carotid endarterectomy. Serial blood samples were collected before, during and after surgery from 10 patients with severe stenosis (> 70%) undergoing carotid endarterectomy with heparinization. Platelet poor plasmas prepared from these samples, were analysed for activated prothrombin fragment F1 + 2 and thrombin-antithrombin III (TAT) levels, using commercially available ELISA kits. F1 + 2 and TATs were measured as indices of thrombin generation and inhibition respectively. Baseline F1 + 2 and TAT levels were 1.19 +/- 0.27 nMol/ml and 17 +/- 10 pMol/ml, respectively. Neither the F1 + 2 nor TAT level increased during surgery at a time when the patients were heparinized. However, both the F1 + 2 and TAT levels increased significantly within 3 hours after surgery and after the heparin had been neutralized with protamine, (p < 0.01). Moreover, both the F1 + 2 and TAT levels remained elevated in 75% of the patients for at least 24 hours, p < 0.01. We conclude that i) thrombin generation is significant post surgery in patients undergoing carotid endarterectomy despite their receiving heparin during surgery; ii) heparin may not be the ideal anticoagulant for carotid endarterectomy; and iii) persistent thrombin generation may contribute to early post-endarterectomy ischemic events.

Acute Disease↗
PubMed1994

The differentiation of dentate granule cells following transplantation.

Immature cells transplanted into an adult host must adapt to their new environment. In the present study we have shown the dendritic development of dentate granule cells following transplantation. The adult host granule cells were lesioned by a fluid injection into the infragranular cleavage plane of the dentate gyrus. Few, if any, granule cells survived the lesion and the molecular layer (ML) shrank. When allogeneic neonatal granule cells were included in the fluid, the host granule cells were simultaneously killed and replaced. In order to visualize the dendrites, the granule cells were filled with Lucifer yellow (LY) in fixed sections and subsequently immunoreacted with an antibody to LY. The granule cell dendrites in the transplant were shorter in length, had a greater cross-sectional area, had more spines, and were more coiled and bent than control granule cell dendrites. The dendrites in the transplant formed functional synapses as indicated by cytochrome oxidase histochemistry and the transplant prevented xc03some of the ML shrinkage. Acetylcholinesterase (ACHE) xkreaction product increased both in lesioned and in transplant groups. The laminar pattern of ACHE in the control ML was not seen after the lesion and did not return in animals with successful transplants. We conclude that (i) the dendrites of neurons in the transplant adapted to the adult host environment and a shrinking ML with remarkable structural plasticity; (ii) the transplant prevented some of the shrinkage of the ML; (iii) the transplant could not reverse some of the lesion-induced changes in host organization, such as the organization of ACHE inputs to the ML; and (iv) a phenotypically specific population of transplanted neurons can replace traumatically lesioned neurons of the same type even if the host conditions continue to change.

Acetylcholinesterase↗