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Biomedical subjects

T M Williams

Publications and source records attributed to T M Williams.

At least 109 records · Page 6Linked to original sources
PubMed1993

Effects of insulin-dependent diabetes on learning and memory efficiency in adults.

Previous work with elderly adults with maturity-onset non-insulin-dependent diabetes has demonstrated the presence of significant learning and memory deficits which are correlated with the degree of chronic hyperglycemia. This study was conducted to examine learning and memory processes in a group of 82 younger adults (mean age = 33.4 years) with a long history (mean duration = 26.2 years) of childhood-onset insulin-dependent diabetes. Contrary to expectation, diabetic subjects performed as well as a group of 82 age- and SES-matched nondiabetic control subjects on all measures of learning and memory. On the other hand, they performed significantly worse on measures of psychomotor efficiency, with degree of chronic hyperglycemia being the best predictor of psychomotor slowing. These findings, together with earlier studies of elderly diabetic patients, suggest that specific neural systems within the aging brain may be differentially sensitive to the "toxic" effects of chronic hyperglycemia.

Adult↗
PubMed1993

The physiology of bottlenose dolphins (Tursiops truncatus): heart rate, metabolic rate and plasma lactate concentration during exercise.

Despite speculation about the swimming efficiency of cetaceans, few studies have investigated the exercise physiology of these mammals. In view of this, we examined the physiological responses and locomotor energetics of two exercising adult Tursiops truncatus. Oxygen consumption, heart rate, respiratory rate and post-exercise blood lactate concentration were determined for animals either pushing against a load cell or swimming next to a boat. Many of the energetic and cardiorespiratory responses of exercising dolphins were similar to those of terrestrial mammals. Average heart rate, respiratory rate and oxygen consumption for dolphins pushing against a load cell increased linearly with exercise levels up to 58 kg for a female dolphin and 85 kg for a male. Oxygen consumption did not increase with higher loads. Maximum rate of oxygen consumption (VO2max) ranged from 19.8 to 29.4 ml O2 kg-1 min-1, which was 7-11 times the calculated standard metabolic rate (VO2std) of the dolphins. Blood lactate concentration increased with exercise loads that exceeded VO2max. The maximum lactate concentration was 101.4 mg dl-1 (11.3 mmol l-1) for the male, and 120.6 mg dl-1 (13.6 mmol l-1) for the female. When swimming at 2.1 m s-1, heart rate, respiratory rate and post-exercise blood lactate concentration of the dolphins were not significantly different from values at rest. The cost of transport at this speed was 1.29 +/- 0.05 J kg-1 min-1. The energetic profile of the exercising bottlenose dolphin resembles that of a relatively sedentary mammal if the exercise variables defined for terrestrial mammals are used. However, the energetic cost of swimming for this cetacean is low in comparison to that of other aquatic and semi-aquatic mammals.

Animals↗
PubMed1992

Suppression of interleukin-2 and interleukin-2 receptor expression in Jurkat cells stably expressing the human immunodeficiency virus Tat protein.

The Jurkat T cell line was stably transfected with an Epstein-Barr virus-based episomal replicon designed to express high levels of the HIV-1 Tat protein. After selection in hygromycin B, high-level Tat activity was detected in 3 of 18 transfected cell lines. After stimulation with phytohemagglutinin (PHA) and phorbol myristate acetate (PMA), Tat transfectants with high Tat expression showed diminished expression of interleukin-2 (IL-2) and the interleukin-2 receptor alpha chain (IL-2R) when compared to untransfected Jurkat cells or Jurkat cell lines transfected with the parent control plasmid. Sublines derived from the high-level Tat transfectants with reduced Tat activity showed normalization of PHA/PMA-induced IL-2 expression. Northern analysis showed diminished expression of IL-2 and IL-2R mRNA in the stimulated Tat transfectants. Inhibition of IL-2 and IL-2R expression by the HIV-1 Tat protein may contribute to the immune suppression that characterizes HIV-1 infection.

Cell Line↗
PubMed1992

CD28-stimulated IL-2 gene expression in Jurkat T cells occurs in part transcriptionally and is cyclosporine-A sensitive.

CD28 is a glycoprotein expressed as a homodimer on the surface of a major subset of human T cells. Previous studies have shown that proliferation of peripheral blood T cells involving the CD28 pathway is associated with cyclosporine A (CsA) resistant IL-2 gene expression. This pathway was shown to specifically regulate the stability of mRNA for several lymphokines including IL-2. We have investigated the expression of the IL-2 gene in the Jurkat cell line, J32 clone, induced by CD28 stimulation. Cross-linked anti-CD28 mAb alone was sufficient to induce the release of small amounts of IL-2 (256 U/ml). The CD28-mediated IL-2 release was enhanced with simultaneous engagement of CD28 and CD2 or CD28 and CD3 molecules. Hybrid constructs in which the human IL-2 gene 5' flanking region drives luciferase expression (pIL-2-Luc) were used to help delineate whether the CD28 pathway activates the IL-2 gene transcriptionally. Costimulation of cells with CD28 mAb and either PHA or CD2 mAb induced a 20- to 90-fold increase in the expression of pIL-2-Luc as well as IL-2 release. Costimulation with CD28 mAb plus PMA gave only five- to sevenfold increase in enhancer activity. In contrast, no enhancer activity was detected after stimulation with CD28 or CD2 mAb alone. Both IL-2 release and pIL-2-Luc activity were inhibited by CsA in J32 cells. The degree of CsA inhibition was concentration dependent and was similar in cells stimulated with either CD28 mAb or CD3 mAb. Maximum inhibition was achieved with 1 microgram/ml of CsA. Studies with internal deletion mutations of the IL-2 gene 5' flanking sequence revealed that as with stimulation through the TCR pathway, the CD28 pathway requires 5' flanking sequences located within 500 bp of the transcription start site. These results are the first direct evidence that the triggering of CD28 molecule is sufficient to induce IL-2 release in J32 cells. Furthermore these studies strongly indicate that IL-2 gene expression induced by CD28 stimulation occurs, in part, transcriptionally and is CsA sensitive in these cells.

Antigens, CD↗
PubMed1992

Travel at low energetic cost by swimming and wave-riding bottlenose dolphins.

Over the past 50 years there has been much speculation about the energetic cost of swimming and wave-riding by dolphins. When aligned properly in front of the bow of moving ships in the stern wake of small boats, on wind waves, and even in the wake of larger cetaceans, the animals appear to move effortlessly through the water without the benefit of propulsive strokes by the flukes. Theoretically, body streamlining as well as other anatomical and behavioural adaptations contribute to low transport costs in these animals. The economy of movement permitted by wave-riding has been perceived as an energetic advantage for the swimming dolphin, but has been hard to prove in the absence of physiological data for exercising cetaceans. Here we determine the aerobic and anaerobic costs of swimming and wave-riding in bottlenose dolphins and find that the minimum cost of transport for swimming dolphins is 1.29 +/- 0.05 J kg-1 m-1 at a cruising speed of 2.1 m s-1. Aerobic costs are nearly twice as high for swimming seals and sea lions, and 8-12 times higher for human swimmers. Wave-riding by dolphins provides additional benefits in terms of speed. The results indicate that behavioural, physiological and morphological factors make swimming an economical form of high-speed travel for dolphins.

Animals↗
PubMed1992

Whipple's disease involving the mesenteric lymph nodes diagnosed by fine-needle aspiration.

Although it traditionally presents with signs and symptoms of small intestine involvement, such as diarrhea and malabsorption, Whipple's disease (WD) can involve many other organs. Typically, WD diagnosis is established by biopsy of the small intestine. A case of WD, established by duodenal biopsy, in a 36-yr-old male is presented. This patient developed mesenteric lymphadenopathy, prompting computerized-tomography guided fine-needle aspiration (FNA), which showed typical features of WD. Electron microscopy (EM) studies confirmed the diagnosis. To our knowledge, this is the first reported case of lymph-node involvement in WD diagnosed by FNA biopsy.

Adult↗
PubMed1992

The TCF8 gene encoding a zinc finger protein (Nil-2-a) resides on human chromosome 10p11.2.

The TCF8 gene encodes a zinc finger protein (Nil-2-a). Nil-2-a inhibits T-lymphocyte-specific interleukin 2 (IL2) gene expression by binding to a negative regulatory domain 100 nucleotides 5' of the IL2 transcription start site. Southern hybridization and somatic cell hybrids are used to demonstrate that the murine and human genomes contain related genes for Nil-2-a. TCF8 resides on human chromosome 10. Fluorescent in situ hybridization is employed to localize TCF8 to 10p11.2.

Blotting, Southern↗
PubMed1992

Verification of the pressure provocative test in carpal tunnel syndrome.

Three provocative tests (pressure, Phalen's test, and Tinel's sign) were studied in 30 patients with carpal tunnel syndrome and 30 control subjects. The pressure provocative test had a sensitivity of 100%. In contrast, Phalen's test was 88% sensitive and Tinel's sign only 67% sensitive. The pressure provocative test is a sensitive indicator of median nerve compression at the wrist with a faster reaction time than Phalen's test (mean time of 9 seconds vs 30 seconds). It is an appropriate provocative test in patients with stiff or painful wrists when wrist flexion is restricted.

Adult↗
PubMed1992

Primary pulmonary hypertension in association with human immunodeficiency virus infection. A possible viral etiology for some forms of hypertensive pulmonary arteriopathy.

Recent reports have suggested a possible association between HIV-1 infection and primary pulmonary hypertension (PPH), but most of the patients described to date have either had acquired immunodeficiency syndrome (AIDS) with concurrent lung infections or have administered Factor VIII intravenously for hemophilia. We report three human immunodeficiency virus type 1 (HIV-1)-positive homosexual white males with clinical and hemodynamic diagnoses of PPH. None of the patients had any opportunistic lung infections or other pulmonary pathology, nor were they hemophiliacs. They had no histories of intravenous drug use. Lung tissue from two of the patients revealed hypertensive arteriopathy consistent with PPH and no other pulmonary pathology. Attempts at localizing HIV-1 infection to the vascular endothelium with electron microscopy, immunohistochemistry, DNA in situ hybridization, and polymerase chain reaction techniques did not reveal direct pulmonary artery infection with the virus. These data and the finding of tubuloreticular structures on electron microscopy suggest that HIV-1 may play a role in the pathogenesis of these cases of PPH through mediator release associated with HIV-1 infection rather than by direct endothelial infection.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Psychomotor slowing is associated with distal symmetrical polyneuropathy in adults with diabetes mellitus.

To test the hypothesis that diabetes mellitus is associated with cognitive dysfunction, a battery of neuropsychological tests was administered to 75 diabetic adults and an equal number of demographically similar nondiabetic control subjects. Compared with control subjects, diabetic subjects performed significantly more poorly on measures of psychomotor efficiency and spatial information processing. In contrast, no between-group differences appeared on measures of verbal intelligence, learning, memory, problem solving, or simple motor speed. Results from multiple regression analyses showed that clinically significant distal symmetrical polyneuropathy was strongly associated with psychomotor slowing, whereas, glycosylated hemoglobin values were weakly associated with both psychomotor slowing and spatial processing. No other biomedical variables predicted cognitive test performance. These neurobehavioral data are consistent with the hypothesis that a "central neuropathy" may be associated, at least in part, with chronic hyperglycemia.

Adult↗
PubMed1991

Identification of a zinc finger protein that inhibits IL-2 gene expression.

Transient activation of the interleukin-2 (IL-2) gene after antigen recognition by T lymphocytes is crucial for subsequent T cell proliferation and differentiation. Several IL-2 gene regulatory elements and binding factors necessary for activation of the IL-2 gene have been defined. However, little is known about negative regulation of IL-2 expression, which is likely to be important in the rapid shut-off of IL-2 transcription. A nucleotide sequence element (NRE-A) that negatively regulates IL-2 expression has been identified within the IL-2 gene. T cell nuclear extracts contained an NRE-A binding activity. A complementary DNA was isolated that encodes a zinc finger-containing protein that suppressed IL-2 gene expression. The observation of negative regulation of the immunoglobulin heavy chain gene enhancer by an element similar to NRE-A suggests that related proteins may regulate multiple immune response genes.

Amino Acid Sequence↗
PubMed1991

Fuel homeostasis in the harbor seal during submerged swimming.

1. The turnover rates and oxidation rates of plasma glucose, lactate, and free fatty acids (FFA) were measured in three harbor seals (average mass = 40 kg) at rest or during voluntary submerged swimming in a water flume at 35% (1.3 m.s-1) and 50% (2 m.s-1) of maximum oxygen consumption (MO2max). 2. For seals resting in water, the total turnover rates for glucose, lactate, and FFA were 23.2, 26.2, and 7.5 mumols.min-1.kg-1, respectively. Direct oxidation of these metabolites accounted for approximately 7%, 27%, and 33% of their turnover and 3%, 7%, and 18% of the total ATP production, respectively. 3. For swimming seals, MO2max was achieved at a drag load equivalent to a speed of 3 m.s-1 and averaged 1.85 mmol O2.min-1.kg-1, which is 9-fold greater than resting metabolism in water at 18 degrees C. 4. At 35% and 50% MO2max, glucose turnover and oxidation rates did not change from resting levels. Glucose oxidation contributed about 1% of the total ATP production during swimming. 5. At 50% MO2max, lactate turnover and anaerobic ATP production doubled, but the steady state plasma lactate concentration remained low at 1.1 mM. Lactate oxidation increased 63% but still contributed only 4% of the total ATP production. Anaerobic metabolism contributed about 1% of the total ATP production at rest and during swimming. 6. The plasma FFA concentration and turnover rate increased only 24% and 37% over resting levels, respectively, at 50% MO2max. However, the oxidation rate increased almost 3.5-fold and accounted for 85% of the turnover.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1991

The effect of submergence on heart rate and oxygen consumption of swimming seals and sea lions.

Respiratory, metabolic, and cardiovascular responses to swimming were examined in two species of pinniped, the harbor seal (Phoca vitulina) and the California sea lion (Zalophus californianus). 1. Harbor seals remained submerged for 82-92% of the time at swimming speeds below 1.2 m.s-1. At higher speeds, including simulated speeds above 1.4 m.s-1, the percentage of time spent submerged decreased, and was inversely related to body weight. In contrast, the percentage of time spent submerged did not change with speed for sea lions swimming from 0.5 m.s-1 to 4.0 m.s-1. 2. During swimming, harbor seals showed a distinct breathhold bradycardia and ventilatory tachycardia that were independent of swimming speed. Average heart rate was 137 beats.min-1 when swimming on the water surface and 50 beats.min-1 when submerged. A bimodal pattern of heart rate also occurred in sea lions, but was not as pronounced as in the seals. 3. The weighted average heart rate (WAHR), calculated from measured heart rate and the percentage time spent on the water surface or submerged, increased linearly with swimming speed for both species. The graded increase in heart rate with exercise load is similar to the response observed for terrestrial mammals. 4. The rate of oxygen consumption increased exponentially with swimming speed in both seals and sea lions. The minimum cost of transport calculated from these rates ranged from 2.3 to 3.6 J.m-1.kg-1, and was 2.5-4.0 times the level predicted for similarly-sized salmonids. Despite different modes of propulsion and physiological responses to swimming, these pinnipeds demonstrate similar transport costs.

Aerobiosis↗
PubMed1991

Expression of c-erbB-2 in human pancreatic adenocarcinomas.

The c-erbB-2 (neu) gene encodes a transmembrane phosphoglycoprotein (p185erbB-2) which resembles a growth factor receptor-like molecule closely related to the epidermal growth factor receptor. Overexpression of c-erbB-2 induces cell transformation in vitro. Poorer survival rates and elevated recurrence rates following treatment have been shown in patients whose breast adenocarcinomas demonstrate increased c-erbB-2 expression. Using immunoprecipitation and immunoperoxidase staining, we surveyed human cell lines for p185erbB-2. Cell lines from most tumor types (e.g. lymphomas, neuroblastomas, melanomas) demonstrated negligible p185erB-2; however, 3 of 6 pancreatic cell lines overexpressed c-erbB-2. Southern blot analysis revealed that c-erbB-2 was amplified in two of these cell lines and was both rearranged and amplified in one of them. Based on these findings, we examined tissue sections from archival specimens of primary human pancreatic adenocarcinomas. A substantial proportion of specimens had increased p185erbB-2, as judged by increased immunostaining of the tumor cells. In such pancreatic tumors p185erbB-2 may contribute to the malignant phenotype and could provide a target for immunodiagnostic or immunotherapeutic strategies.

Adenocarcinoma↗
PubMed1991

Steal-prone coronary anatomy and myocardial ischemia associated with four primary anesthetic agents in humans.

To examine the relationship between myocardial ischemia in patients with steal-prone coronary anatomy and the administration of isoflurane anesthesia, we reviewed coronary angiograms of 955 patients who had participated in a randomized trial of the use of one of four primary anesthetics for coronary artery bypass operations. Steal-prone anatomy was found in 31.8% of patients who had received enflurane; 40.0%, halothane; 32.6%, isoflurane; and 31.7%, sufentanil. Detected by greater than or equal to 0.1 mV ST segment displacement, ischemia during anesthesia occurred in 290 (30.4%) of all patients with no difference in the incidence among the four primary anesthetics (27.5%-32.9%). Patients with steal-prone anatomy did not suffer more ischemia than patients who needed coronary artery bypass surgery but with other varieties of coronary anatomy. In patients with steal-prone coronary anatomy, the incidence of myocardial ischemia by primary anesthetic was 24.0% with enflurane, 34.4% with halothane, 32.1% with isoflurane, and 38.2% with sufentanil. Systolic blood pressure less than 90 mm Hg during anesthesia occurred in 416 (45.6%) patients and was twice as common during administration of volatile anesthetics than during that of sufentanil. Hypotension did not increase ischemia frequency in patients with steal-prone anatomy with use of any of the four primary anesthetics including isoflurane. Ischemia was temporally related to hypotension in only 9 patients (0.9%). In none of the 42 patients who had steal-prone anatomy and hypotension during isoflurane anesthesia was ischemia temporally related to hypotension.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthetics↗
PubMed1990

Dependence of oxygen consumption on oxygen delivery in children with hyperdynamic septic shock and low oxygen extraction.

We studied the effect of increasing systemic oxygen delivery (DO2) by packed RBC (PRBC) transfusion on oxygen consumption (VO2) in children with hyperdynamic septic shock. After routine resuscitation with volume loading and pharmacologic support, patients were studied if they had significant derangements of oxygen transport variables defined as: baseline VO2 less than 180 ml/min.m2 and oxygen extraction (O2 extr) less than 24%. Eight studies were performed. PRBC transfusion increased DO2 from 636 +/- 167 to 828 +/- 266 ml/min.m2 (p less than .01) without increasing cardiac index (5.2 +/- 1.3 vs. 5.0 +/- 1.4 L/min.m2). VO2 increased from 112 +/- 36 to 157 +/- 60 ml/min.m2 (p less than .01) while O2 extr was unchanged (18 +/- 3% vs. 19 +/- 6%). Despite initial low O2 extr, VO2 can be increased in pediatric septic shock by a further increase in DO2. Since VO2 correlates with survival, one should consider enhancing DO2 further despite initial low O2 extr and high DO2. Effects on morbidity and mortality require further study.

Adolescent↗
PubMed1990

Percutaneous catheterization of the axillary vein in infants and children.

The axillary vein was evaluated as an alternative access site for central venous catheterization in critically ill infants and children. Children were placed in the Trendelenberg position (when possible) with arm abducted 100 to 130 degrees. The vein was entered parallel and inferior to the artery. Success rate for catheterization was 79% (41/52). Catheter diameter range was 3 to 8.5 F and catheter length range was 5 to 30.5 cm. Median patient weight was 7.0 kg (3.0 to 59 kg). Median age was 0.91 years (14 days to 9 years). All central lines ended in the subclavian, innominate, or superior vena cava. Median catheter duration was 8 days (2 to 22 days). A total of 338 patient catheter-days were studied. Central venous pressure was successfully monitored in five of five attempts. Complications with insertion (3.8% of attempts) included one pneumothorax and one hematoma. Complications during catheter duration (9.8% of catheters, 1.1% per catheter-day) included one instance each of venous stasis, venous thrombosis, catheter sepsis, and parenteral nutrition infiltration. No complication contributed to a patient mortality. Success and complication rates were comparable with those in jugular catheterization studies in children. The axillary approach is an acceptable route for central venous catheterization in critically ill infants and children.

Axillary Vein↗