Biomedical subjects

I Jacobs

Publications and source records attributed to I Jacobs.

At least 55 records · Page 3Linked to original sources

PubMed1998

Effects of UV on the migration and function of epidermal antigen presenting cells.

Depletion of epidermal Langerhans cells (LC) and the concomitant depression of the skin immune system after excessive exposure to ultraviolet B light (UVB) has been established in the international literature for some time. Our investigations were intended to determine whether or not these phenomena occurred as a direct result of increased LC migration being triggered by the UVB exposure. To test this hypothesis, a sheep model was established in which the lymphatic vessels draining a defined region of skin were cannulated and the cells migrating towards the regional lymph node continuously collected. Cell populations in these collections were identified and enumerated by indirect immunofluorescence and flow cytometry. These experiments showed there was a significant, dose-dependent increase in the rate of LC migration from sheep skin after exposure to doses of UVB light exceeding 1 minimal erythemal dose (MED). In a series of parallel experiments, the functional characteristics of dendritic cells (DC) migrating from normal or UVB irradiated sheep were studied. To assay them, enriched preparations of DC were collected via cannulated afferent lymphatic vessels and pulsed with antigen prior to incubation with autologous peripheral blood lymphocytes. The relative efficiency of antigen presentation was determined by the ability of DC to induce T cell proliferation. Our data clearly demonstrate that there is a profound loss of normal antigen-presenting cell function after exposure to UVB light. Various experiments were undertaken to determine the mechanism(s) associated with these changes in migration kinetics and cellular function. Electron microscopic examinations of LC migrating from normal or UVB irradiated skin have demonstrated a profound loss of dendritic processes after UVB exposure. This provides a possible explanation for the changes in skin immunity after UVB exposure.

Animals↗

PubMed1998

Effects of caffeine, ephedrine and their combination on time to exhaustion during high-intensity exercise.

This study investigated the effects of acute ingestion of caffeine (C), ephedrine (E) and their combination (C+E) on time to exhaustion during high-intensity exercise. Using a repeated-measures, double-blind design, eight male subjects exercised on a cycle ergometer at a power output that led to exhaustion after about 12.6 min during a placebo (P) control trial. They did this 1.5 h after ingesting either C (5 mg x kg[-1]), E (1 mg x kg[-1]), C+E, or P. Trials were separated by 1 week. Venous blood was sampled before and during exercise. The mean (SD) times to exhaustion were 12.6 (3.1) (P), 14.4 (4.1) (C), 15.0 (5.7) (E) and 17.5 (5.8) (C+E) min. Only the C+E treatment significantly increased time to exhaustion compared to P. Oxygen consumption (VO2), carbon dioxide production (VCO2), minute ventilation (VE) and the respiratory exchange ratio (RER) were similar during exercise for all trials. Heart rate during exercise was significantly increased for the C+E and C trials compared to P. Subjective ratings of perceived exertion during exercise were significantly lower after C+E compared to P. All treatments significantly increased lactate levels. Free fatty acid (FFA) levels were significantly increased by C ingestion. Glycerol levels were increased by C+E and C ingestion. Glucose levels were also higher with the drug treatments compared to P. Increased monamine availability after C+E treatment was suggested by measurements of catecholamines and dopamine. In conclusion, the combination of C+E significantly prolonged exercise time to exhaustion compared to P, while neither C nor E treatments alone significantly changed time to exhaustion. The improved performance was attributed to increased central nervous system stimulation.

Adult↗

PubMed1998

Ovarian cancer screening.

Despite advances in molecular biology, surgical oncology, and chemotherapy, the prognosis for ovarian cancer remains poor. The excellent survival rates for stage I disease provide the rationale for efforts to screen for early-stage ovarian cancer. However, there are doubts about the feasibility of screening related to the natural history of the disease, the performance of the available tests, and health economic considerations. The investigators use the World Health Organization criteria for a screening program as a framework for discussing current issues in ovarian cancer screening. These include screening modalities and strategies, high- and low-risk populations, and the acceptability, psychological impact, and cost of screening. As a result of developments during the last decade, there are now real prospects for practical and effective ovarian cancer screening programs. Research to date has made important progress, but information about the impact of screening on mortality from ovarian cancer is still awaited. Three large randomized controlled trials of ovarian cancer screening are currently recruiting volunteers and will yield important results in the next few years.

Algorithms↗

PubMed1997

Physical damage to rat cortical axons mimics early Alzheimer's neuronal pathology.

We investigated the reactive cytoskeletal changes following physical damage to axons in the rodent neocortex and compared these with the earliest neuronal alterations seen in Alzheimer's disease (AD). Insertion of a 25 gauge needle into the rodent somatosensory cortex resulted in ring- and club-like axonal changes characterized by an accumulation of neurofilaments. Morphologically and neurochemically identical abnormal axons were present within neocortical beta-amyloid deposits of individuals in the early stages of AD. Physically damaged rat cortical axons may therefore serve as a model for the early neuronal pathology of AD. Furthermore, these results suggest that insoluble beta-amyloid deposition may physically damage local axons, with further neurofibrillary changes due to the reactive neuronal response to this type of injury.

Aged↗

PubMed1997

Creatine ingestion increases anaerobic capacity and maximum accumulated oxygen deficit.

The purpose of this study was to test the hypothesis that ingestion of creatine monohydrate increases anaerobic exercise capacity, as reflected by the maximal accumulated oxygen deficit (MAOD). Subjects were assigned, double-blind, to placebo (PL, n = 12) or creatine (CR, n = 14) groups and ingested 5-g doses 4 times daily of artificial sweetener or artificially sweetened creatine monohydrate, respectively, for 5 days. On a separate day subjects exercised to exhaustion at 125% VO2max. After two familiarization trials, MAOD was again determined before treatment, after 5 days of PL or CR treatment, and 7 days later. MAOD increased after CR treatment from 4.04 +/- 0.31 to 4.41 +/- 0.34 L (p < .001) and remained elevated for another 7 days (4.31 +/- 0.33, p < .001). Time to exhaustion also increased in CR from 130 +/- 7 to 141 +/- 7 s (p < .01) and remained increased for another 7 days (139 +/- 8 s, p < .01). These data demonstrate that ingesting creatine monohydrate for 5 days increases the MAOD, and is likely to have an ergogenic effect on supramaximal exercise performance that persists for at least a week after treatment.

Administration, Oral↗

PubMed1997

Effect of upper respiratory tract infection in patients with neuromuscular disease.

Respiratory muscle strength during acute upper respiratory tract infection (URI) was assessed in patients with various forms of neuromuscular disease. Vital capacity (VC), oxygen saturation, end-tidal PCO2, maximal inspiratory pressure (MIP), and maximal expiratory pressure (MEP) were determined in 25 stable patients with various forms of neuromuscular disease. Thirteen episodes of URI developed in 10 patients. Respiratory parameters were reassessed within 24-36 h following the onset of symptoms in each patient. In patients with URI, mean baseline VC, MIP, and MEP were 1.16 L +/- 0.14, 49.2 cm H2O +/- 6.8, and 35.5 cm H2O +/- 3.8 and fell to 1.01 L +/- 0.15, 37.1 cm H2O +/- 6.2, and 25.5 cm H2O +/- 3.0 during URI (p < 0.05 for each), respectively. Mean baseline PCO2 and oxygen saturation were 39.1 mm Hg +/- 1.1 and 95.1% +/- 1.0, and during URI, 43.9 mm Hg +/- 2.1 (p < 0.05) and 95.0% +/- 1.0 (NS), respectively. Five episodes of significant hypercapnia were observed in 4 patients. All parameters returned to near baseline values following recovery. We conclude that patients with various forms of neuromuscular disease develop reductions in respiratory muscle strength in association with URI. Unlike normal subjects, however, these decrements in respiratory muscle function may result in symptoms of shortness of breath, reductions in vital capacity, and acute hypercapnia in this patient population.

Acute Disease↗

PubMed1997

The normal pediatric larynx on CT and MR.

PURPOSE: To determine the MR and CT appearance of the normal pediatric larynx. METHODS: Fifteen CT scans and 15 MR examinations of children with normal larynges and airways were reviewed retrospectively. Characteristics that were noted included the level of the hyoid bone, calcification and signal intensity within separate laryngeal components, amount of paraglottic fat, anteroposterior airway diameters, and airway contours. Two cadaveric larynges were imaged by CT and MR and were then sectioned at corresponding levels and section thicknesses. RESULTS: The larynx is higher in children than in adults, with the hyoid bone found at the C2-3 level in the youngest children (newborn to 2 years). The subglottic airway was narrowest in the youngest children. The hyoid bone was the only laryngeal structure ossified in any of the children. A thin line of high density was seen in the expected location of the thyroid cartilage in some children. The featureless circumferential soft tissue seen around the airway represented the uncalcified laryngeal cartilaginous structures. This was confirmed on gross sectioning of cadaveric larynges. The supraglottic airway contour was triangular or oval, the glottis was shaped like a teardrop, and the subglottic contour was oval. Contours were confirmed on histologic examination of necropsy specimens. CONCLUSIONS: This preliminary study suggests that the pediatric larynx differs from the adult larynx with respect to size, position, consistency, and shape, and these differences are reflected on CT and MR studies.

Adolescent↗

PubMed1997

Respiratory muscle fatigue during simulated air combat maneuvering (SACM).

HYPOTHESIS: This study tested the hypothesis that respiratory muscle fatigue occurs during a simulated air combat maneuver (SACM) centrifuge profile. METHODS: Six subjects (four males, two females) were exposed to a SACM consisting of alternating +4 Gz to +7 Gz plateaus until volitional fatigue. Electrical activities of the diaphragm, scalene, intercostal and external oblique muscles were monitored along with esophageal pressure and ventilation. RESULTS: SACM times averaged 358 +/- 115 s. The mean frequency of the electromyographic signal of the diaphragm and scalenes during inspiration, and the intercostals during the static expiratory portion of the anti-G straining maneuver (AGSM), decreased significantly (p < 0.05) over the course of the SACM by about 9%, 10% and 4%, respectively, indicating muscle fatigue. Esophageal pressure (PES) during the straining portion of the AGSM decreased significantly from 72 +/- 20 to 66 +/- 21 mmHg (mean +/- SD). Ventilation increased significantly both at +4 Gz and +7 Gz (32 +/- 16 L.min-1 to 56 +/- 19 L.min-1 at +4 Gz and 27 +/- 5 to 35 +/- 9 L.min-1 at +7 Gz) over time. PES during a maximal AGSM at +1.4 Gz (baseline) was decreased post- vs. pre-SACM (p = 0.0575). PES exerted during a maximal static inspiratory maneuver at residual lung volume was not changed after the SACM. Inspiratory work increased significantly during the SACM. The elastance of the respiratory system did not change during the SACM, but it was significantly increased when tested after the SACM. CONCLUSION: Increased inspiratory work, decreased pressure generation during a maximal AGSM and EMG frequency shifts suggest respiratory muscle fatigue coincides with the termination of SACM.

Acceleration↗

PubMed1996

Somatic and germline mutations of the BRCA2 gene in sporadic ovarian cancer.

The breast and ovarian cancer susceptibility gene BRCA2 has recently been isolated. A role for BRCA2 in sporadic breast and ovarian cancer has been suggested by loss of heterozygosity (LOH) studies which show frequent LOH in the BRCA2 region at chromosome 13q12. In addition, the observation of nonrandom loss of the wild-type chromosome in a breast/ovarian cancer family which shows linkage to BRCA2 suggests it may act as a tumor suppressor gene. To determine the extent of somatic alteration involving BRCA2 in sporadic ovarian cancer, 50 tumors were analyzed for mutations throughout the entire BRCA2 coding region. Mutations predicted to result in truncation of the BRCA2 protein were detected in four tumors. Analysis of germline DNA revealed two of these alterations to be of somatic origin. In addition, all four tumors exhibited loss of the second BRCA2 allele as predicted by Knudson's hypothesis for a tumor suppressor gene. These results suggest that, as is the case with BRCA1, somatic mutations of BRCA2 are infrequent in sporadic ovarian cancer, despite the relatively high frequency of LOH detected around the BRCA2 locus.

BRCA2 Protein↗

PubMed1996

Influence of respiration on calculation and delivery of the prescribed dose in external radiotherapy.

During the delivery of the prescribed dose in external beam radiotherapy, respiration alters the patient's body outline and consequently the basis for dose calculations. The influence of this effect was studied on both healthy volunteers and patients. In a subgroup of volunteers, we measured that respiratory movements modify a person's thickness, in particular in the antero-posterior direction at the lower abdominal level, by more than 4% implying a variation in absorbed dose of more than 2%. In view of the I.C.R.U. requirements for absorbed dose accuracy, these variations must be taken into account. Extension of the study to a group of 160 patients confirmed that for a subgroup of about 25%, respiration induces an important deviation from the prescribed dose as dose calculations are based on a body outline taken at an unknown stage during the respiratory cycle. Our results indicate that dose calculations should be based on an average body outline which takes the respiratory movements into account.

Adolescent↗

PubMed1996

No ergogenic effect of ginseng ingestion.

The purpose of this study was to examine the effects of ginseng extract ingestion on physiological responses to intense exercise. Subjects performed a control ride (CN) on a cycle ergometer, followed by placebo (PL) and ginseng (GS) treatments. Ginseng was ingested as 8 or 16 mg/kg body weight daily for 7 days prior to trial GS. Venous blood was sampled for FFA, lactate, and glucose analyses. Due to similar findings for both dose groups, the subjects were considered as one group. Lactate, FFA, VO2, VE, and RPE increased significantly from 10 through 40 min. RER increased during the first 10 min of exercise and then remained stable, with no intertrial differences. Glucose did not vary significantly from 0 to 40 min or among treatments. RPE was significantly greater and time to exhaustion was significantly less during trial CN than PL or GS, while PL and GS trials were similar. The data indicated that with 1 week of pretreatment there is no ergogenic effect of ingesting the ginseng saponin extract.

Adult↗

PubMed1996

Diet and muscle glycogen concentration in relation to physical performance in Swedish elite ice hockey players.

The effects of carbohydrate (CHO) loading on physical characteristics including muscle fiber distribution, muscle glycogen concentration, and physical performance were studied in two top Swedish ice hockey teams. Players were randomly allocated to two groups: those consuming a CHO-enriched diet (CHO group) and those consuming a mixed diet (controls). Biopsies from the vastus lateralis muscle were taken three times: after Game 1, before Game 2, and after Game 2. Muscle fiber distribution averaged 50 +/- 2% slow twitch fibers (mean +/- 1 SEM). Muscle glycogen concentrations (measured in mmol glucose units . kg-1 wet muscle) were as follows: after Game 1, 43 +/- 4 (all players); before Game 2, 99 +/- 7 (CHO group) and 81 +/- 7 (controls); and after Game 2, 46 +/- 6 (CHO group) and 44 +/- 5 (controls). Distance skated, number of shifts skated, amount of time skated within shifts, and skating speed improved with CHO loading. It was concluded that individual differences in performance could be related to muscle glycogen metabolism.

Adult↗

PubMed1995

Response of olfactory Schwann cells to intranasal zinc sulfate irrigation.

The response of olfactory Schwann cells was assessed at 2, 4, and 7 days following intranasal zinc sulfate irrigation in 1-month-old mice. Ultrastructural and immunohistochemical observations showed dramatic differences between experimental and control mice which had been washed with saline intranasally. Two days after zinc sulfate treatment, many olfactory nerve bundles contained patchy areas of axonal degeneration, while the cell bodies of the olfactory Schwann cells appeared to have increased in electron density and to have shifted peripherally. Some of the cell bodies protruded from the surface of the axon fascicle, suggesting that the olfactory Schwann cells were in the initial process of migrating away. On the fourth day when most of the olfactory axons had degenerated, some olfactory Schwann cells were aligned immediately beneath the basal lamina of the olfactory epithelium. These cells were immunopositive for the S-100 protein and possessed an expanded perinuclear space. Many olfactory Schwann cells were present in the region beneath the cribriform plate, while some appeared to have passed through the gaps between the bony plates to reach the olfactory bulb. Hence, the results showed that many olfactory Schwann cells migrated towards the olfactory bulb following loss of axonal contact. Furthermore, on the seventh day following zinc sulfate treatment, some olfactory Schwann cells in the vicinity of the olfactory bulb appeared phagocytic, as indicated by their extension of processes around fragments of cell debris and the presence of lysosome-like organelles in the perikaryon. The control mice which had been intranasally irrigated with saline did not demonstrate massive olfactory axonal degeneration, and the morphology of the nasal cavity region was similar to that of normal mice.

Animals↗

PubMed1995

Molecular approaches to prevention and detection of epithelial ovarian cancer.

More than 90% of epithelial ovarian cancers arise from single cells. Malignant transformation can be associated with a number of molecular alterations including upregulation of tyrosine kinases and phosphatases, physiologic activation o ras, mutation of p53, amplification of myc, and increased activity of matrix metalloproteinases 2 and 9. Proliferation of transformed epithelial cells can be enhanced through the persistence of autocrine growth stimulation by TGF-alpha, loss of autocrine growth inhibition by TGF-beta, as well as paracrine growth stimulation by macrophage derived cytokines and OCAF, a novel lyso-phospholipid. Ascites tumor cells retain responsiveness to growth inhibition by TGF-beta which induces apoptosis in malignant ovarian epithelial cells, but not in normal ovarian surface epithelium. Proliferation of surface epithelial cells following ovulation may contribute to the pathogenesis of ovarian cancer. Use of oral contraceptives that suppress ovulation has been associated with reduced risk of ovarian cancer in later life. Retinoids also deserve further evaluation for chemoprevention. Treatment with fenretinide was associated with decreased incidence of ovarian cancer. Additive or synergistic inhibition of ovarian tumor cell proliferation has been observed with TGF-beta in combination with all-trans-retinoic acid. Early detection of ovarian cancer could improve survival. Transvaginal sonography (TVS) and serum markers such as CA-125 have been evaluated in multiple clinical trials. The former lacks adequate specificity, whereas the latter is not sufficiently sensitive. Use of multiple serum markers can improve sensitivity. A combination of CA-125, M-CSF and OVX-1 has detected > 95% of Stage I ovarian cancers. If similar results are obtained with different data sets, multiple serum markers could be used to trigger the performance of TVS, providing a potentially cost effective screening strategy. Prospective trials will be required to demonstrate that screening for early stage ovarian actually impacts on survival.

Diagnosis, Differential↗

PubMed1995

Electron microscopic examination of factors influencing the expression of filamentous surface structures on clinical and environmental isolates of Aeromonas veronii Biotype sobria.

Strains of Aeromonas veronii biotype sobria isolated from clinical and environmental sources were examined for their expression of surface structures under a variety of culture conditions. When grown on solid media at 37 degrees C, more than 95% of bacteria from the majority of strains isolated from human diarrheal feces and chicken carcasses were non-piliated or expressed only a few pili of long, flexible morphology per cell. Strains isolated from water or other foods were much more likely to express pili. Heavily piliated strains (all sources) possessed pili of several morphological types, including long, flexible pili of varying widths and rigid pili of varying lengths. Expression of Pili was favored by growth at temperatures ca. 20 degrees C and below and growth in liquid medium. Most fecal strains expressed some pili under these conditions. In addition, other surface structures (fibrillar aggregates, fibrillar networks bundle-forming pili) were seen on some strains from most sources. These were also seen most frequently when bacteria were grown in liquid media at temperatures ca. 20 degrees C and below. Pili expression was not dramatically influenced by growth under anaerobic conditions, or in iron-depleted media, or by combinations of the above conditions. The role of the above surface structures in Aeromonas pathogenicity remains to be elucidated.

Aeromonas↗

PubMed1995

Variability of time to exhaustion during submaximal exercise.

Exercise time to exhaustion (TE) is commonly used to evaluate the success or failure of such treatments as endurance training programs or nutritional supplements. The present study determined the variability of TE during submaximal exercise at 80% VO2max. Fifteen males performed cycle exercise to exhaustion on five occasions at the same time of day with a minimum of 72 hrs between sessions. There was no difference in TE (0.1 > p > 0.05) among the trials, with values ranging from 14.4 +/- 1.1 min for Test 1 to 18.2 +/- 2.4 min during the final test. Substantial variability in TE over the five trials was observed among subjects with coefficients of variation (CV) ranging from 2.8 to 31.4%. Subjects were divided into two groups using the median CV for TE. For the low CV group (n = 8), TE was significantly increased during Test 3 (14.9 +/- 1.3 min) compared with Test 1 (12.8 +/- 1.0 min) and Test 5 (12.5 +/- 1.2 min). For the high CV group (n = 7), TE was increased during Test 5 (24.7 +/- 3.7 min) compared with the other tests (18.5 +/- 2.2 min). CV for VO2, VE, pH, Pco2, and rectal temperature were less than 5% and did not differ between groups. Post hoc power calculations revealed that if all subjects were considered as one group, sample size would have to increase to 40 to increase the power to 0.8. Due to the variability in TE that may be observed with males of average fitness, it is concluded that TE should not be the only dependent measure used to evaluate treatment effects during submaximal exercise.

Adult↗

PubMed1995

Plasma glucose turnover during cold stress in humans.

To clarify the source of increased carbohydrate oxidation during cold stress, six males rested for 3 h at 29 and 10 degrees C dressed only in shorts. After priming the blood glucose and bicarbonate pools, [U-13C6]glucose was infused for 3 h in each condition to determine the plasma glucose rate of appearance (Ra) or turnover under relative steady-state conditions. Plasma enrichment (mol %excess) was determined by selective ion-monitoring gas chromatography-mass spectrometry. Cold exposure decreased rectal temperature and mean skin temperature and increased heat debt, metabolic rate, and whole body lipid and carbohydrate oxidation (CHOox) compared with the same subjects at thermal neutrality (P < 0.05). Cold exposure significantly increased Ra from 13.18 +/- 0.70 to 16.22 +/- 0.43 mumol.kg-1.min-1 (P < 0.05). Plasma glucose clearance was elevated commensurately by the cold (from 2.68 +/- 0.16 to 3.55 +/- 0.14 ml.kg-1.min-1; P < 0.05). If we assume that Ra is completely oxidized (thus equivalent to maximum rates of plasma glucose oxidation) [J. A. Romijn, E. F. Coyle, L. S. Sidossis, A. Gastaldelli, J. F. Horowitz, E. Endert, and R. R. Wolfe. Am. J. Physiol. 265 (Endocrinol. Metab. 28): E380-E391, 1993], the minimum rates of glycogen and lactate oxidation in the cold would be the difference between CHOox and glucose oxidation (approximately 14.0 +/- 3.0 mumol.kg-1.min-1). Therefore, under the present laboratory conditions, 54% of CHOox would be fueled by plasma glucose oxidation, whereas the remaining 46% would be derived from the combination of glycogen and lactate oxidation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

Effect of triazolam on responses to a cold-water immersion in humans.

Managing alertness of soldiers during sustained operations is a source of serious concern for military unit commanders. A frequently employed strategy is to induce sleep before an operation, especially operations requiring prolonged travel. Sleep-inducing drugs could have an action on thermoregulation through their effect on alertness and a possible direct effect on the brain. The goal of this study was therefore to evaluate the effect of a commonly prescribed triazolam (Halcion) on thermoregulatory responses to cold-water immersion. Eight subjects were immersed twice in 18 degrees C water for up to 90 min in the morning; once after ingesting 0.25 mg triazolam (TRZ) the prior evening, and again after placebo (PLB) treatment. There were no significant differences between trials for mean duration of the immersion, the change in rectal temperature and mean skin temperature. Total metabolic heat production was similar for both conditions: 767 +/- 107 vs. 781 +/- 105 kj.m-2 for TRZ and PLB, respectively. The results should be considered in light of a large variation among the subjects in sensitivity to TRZ, which was unrelated to biometrical characteristics such as surface area-to-mass ratio, lean body mass, % body fat, and physical fitness. Although not statistically significant, there was a trend for a smaller increase in plasma free fatty acid and glycerol concentrations after water immersion with TRZ. The results suggest that the ingestion of a single dose of triazolam 11 h prior to a cold-water immersion is not likely to accelerate the rate of onset of hypothermia. Individual sensitivity, however, may predispose some sensitive subjects to negative effects in this regard.

Adipose Tissue↗