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Biomedical subjects

R Jacobs

Publications and source records attributed to R Jacobs.

At least 19 recordsLinked to original sources
PubMed1992

CD16- CD56+ natural killer cells after bone marrow transplantation.

Natural killer (NK) cells are phenotypically defined as lymphocytes expressing the antigens CD56 and mostly CD16 (Fc gamma RIII), but lacking CD3. A small CD3- CD16- CD56+ NK cell subset has been described in normal individuals representing less than 2% of peripheral blood lymphocytes. We analyzed here 70 patients for their reconstitution of the immune system during follow-up after autologous or allogeneic bone marrow transplantation. In 35% of these patients, two different NK cell subsets, namely CD56+dim and CD56+bright cells, were observed. The mean duration of these two subsets after transplant was 4 months. Sixty-five percent of the patients exhibited an increased number of NK cells, but only the typical CD16+ CD56+dim population. The CD56+bright subpopulation represented a particular CD3- CD16- NK subset, with posttransplant frequencies up to 70% of all NK cells and 40% of peripheral blood lymphocytes, respectively. In contrast to normal CD56+dim NK cells, CD56+bright cells coexpressed the activation antigens p75 beta-chain of interleukin-2 receptor (IL-2R), CD2R, and CD26, but were negative for CD16. NK and antibody-dependent cellular cytotoxicity activity of CD56+bright cells was low compared with CD56+dim NK cells. But using IL-2 and interferon gamma, their cytotoxicity could be enhanced even more than in CD56+dim lymphocytes. These different subsets may reflect distinct activation or differentiation steps of NK cells during reconstitution of the immune system. Their differential response to IL-2 may be of functional importance for posttransplant cytokine therapy.

Adult↗
PubMed1992

Production of anti-NC1 antibody by affected male dogs with X-linked hereditary nephritis: a probe for assessing the NC1 domain of collagen type IV in dogs and humans with hereditary nephritis.

Some patients with hereditary nephritis (HN) who have received a renal transplant have been shown to form antibody with specificity for the NC1 domain of collagen type IV, a major constituent of glomerular basement membranes (GBM). We attempted to duplicate this phenomenon in a family of dogs with X-linked HN, a model for human X-linked HN, by immunizing affected male dogs with normal dog NC1 domain. A collagenase digest was prepared from normal dog GBM, the NC1 domain was separated into dimer (approximately 50 kDa) and monomer (24 kDa and 26 kDa) components by SDS-PAGE, and injected into two affected male dogs. Antisera obtained from both dogs contained antibody which reacted with the NC1 domain of dog and human GBM by a plate-binding radioimmunoassay, bound to the dimer and 26 kDa monomer bands by Western blotting, and staining dog and human GBM by immunofluorescence (IF). The affected male dog antiserum reacted equally by radioimmunoassay with the NC1 domain isolated from GBM of unaffected, affected male, and carrier female dogs in the family with X-linked HN, and bound by Western blotting to dimers and the 26 kDa monomer band of the NC1 domain of GBM in each group of dogs. However, the affected male dog antiserum differentiated these dogs by IF; it produced global staining of GBM of unaffected dogs, failed to stain GBM of affected male dogs, and produced segmental staining of GBM of carrier female dogs. Absorption of the affected male dog antiserum with normal dog NC1 domain eliminated the staining of dog GBM by IF, whereas staining persisted after absorption with affected male dog NC1 domain. The abnormal staining patterns of GBM seen by IF in the affected male and carrier female dogs and the results of the absorption studies imply an abnormality of one or more determinants in the 26 kDa monomer band of the NC1 domain of their GBM. Amino acid sequencing of this band identified the alpha 1(IV) chain of collagen type IV, a finding that has implications for the pathogenesis of canine X-linked HN. Absent and segmental staining respectively were also seen by IF in GBM of a male and female patient with HN, using the affected male dog antiserum. Thus, the results obtained in affected male and carrier female dogs with X-linked HN may also be relevant to patients with this disease.

Amino Acid Sequence↗
PubMed1992

The importance of visual feedback on the accuracy of jaw and finger positioning in man.

The anatomical position of the mandible means that direct visual feedback is not possible. To clarify the role of visual information, several jaw- and finger-positioning tasks were designed, both in a 'free-movement' and an 'isolated' (arm or head fixed) state, with or without a visual feedback display of the target position. The subjects had to position the mandible or the index finger of the preferred hand on to a movable metal bar and to maintain a defined position coinciding with the target level provided on an oscilloscope screen. The position signal was tape recorded and computer analysed off-line. Digital filtering differentiated between the drift and the oscillations around the target (root mean square). The results demonstrated a lack of precision in the free-movement, finger-positioning task after withdrawal of visual feedback. For jaw opening and closing muscles, position control was less impaired when a visual feedback display was abolished. It was suggested that the efficiency of jaw positioning is not primarily determined by visual feedback.

Adult↗
PubMed1992

Intermuscular coordination in a sprint push-off.

This study was designed to investigate the patterns of intermuscular coordination during a sprinting event. In previous research it was found that despite the indeterminacy problem of movement control, movements like vertical jumping, speed skating and cycling are performed in a stereotyped manner. It was hypothesized that this might be due to constraints associated with the transformation of joint rotations into the desired translation. The objective of the present study was to determine the extent to which the intermuscular coordination patterns during other movements also are performed in a stereotyped manner and, if that is true, whether this can be understood on the basis of such constraints. Seven elite sprint runners were instructed to execute an explosive sprinting dash. Ground reaction forces and cinematographic data were recorded for the second stance phase of the sprint. Simultaneously, electromyographic activity of nine leg muscles was recorded telemetrically. Linked-segment modeling was used to obtain net joint moments and net joint powers. Different athletes appeared to perform the sprint in a stereotyped manner. The muscle coordination pattern is characterized by a proximo to distal sequence in timing of the monoarticular muscles. When compared to the sequential pattern found in jumping, the biarticular hamstrings and rectus femoris muscles behave differently; in the sprint a more pronounced reciprocal activity between these muscles exists. The resulting movement pattern is characterized by a sequence of upper leg extension and plantar flexion. The observed sequence in timing of muscle activation patterns is aimed at solving the problems associated with the earlier identified geometrical and anatomical constraint. However, the coordination pattern cannot be fully understood on the basis of these constraints. A specific constraint is identified with respect to the direction of the ground reaction force, which explains the pronounced reciprocal activity of the biarticular hamstring and rectus femoris muscles. The intermuscular coordination pattern in the sprint can be seen as a compromise between the specific requirement of the sprint and the advantageous effect of a proximo to distal sequence as found previously for jumping.

Adult↗
PubMed1992

Influence of temperature and foil hardness on interocclusal tactile threshold.

Determinations of interocclusal tactile threshold levels so far have involved neither appropriate psychophysical approaches nor an assessment of the mechanical and thermal properties of the foils used. Twenty subjects (12 females) aged 18 to 50 (mean age 35) were tested for their absolute threshold level (RL). Both the method of limits and the staircase method were applied to determine the active or passive RL. For the active RL assessment, foils of different thicknesses were placed between edge-to-edge opposed incisors during gentle biting. Inner ear receptors of the blindfolded subjects were blocked by broad band noise applied through earphones, because vibrations induced by occlusal contact and conducted through bone might be perceived by these receptors. The foils presented were aluminum (Al), tin (Sn), polyester (PE) and calibrated steel (St) (thickness ranging from 8 to 50 microns) which offer different physical and thermal properties. The range of RL of the group varied between 8 microns for aluminum to 46 microns for polyester for 50% correct assessments. Increasing the foil temperature from room temperature (20 degrees C) to body temperature (35 degrees C) significantly increased the RL for conducting materials (one-way blocked ANOVA). These results indicate that temperature exchange takes place while presenting conducting foils at 20 degrees C (cold stimulus) interocclusally, which influences the RL by activating thermosensitive receptors. The passive RL determination with classical von Frey-hairs resulted in a mean axial RL of 3.0 g. Both psychophysical RL assessments (method of limits, staircase method) gave reproducible and similar results as ascertained by ANOVA. Furthermore, a positive correlation was established between active and passive RL (Pearson correlation test).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Control of an external force in leg extensions in humans.

1. We investigated the hypothesis that mono- and bi-articular muscles perform different functions: the former are chiefly dependent on their mechanical advantage, while the latter are considered to be mainly concerned with controlling the direction of an external force. 2. Seven subjects were asked to exert a constant external force in various directions from three different positions. Feedback was given on the amplitude (300 and 600 N) and direction of the force vector. 3. During each trial the position of the subject was registered. Ground reaction force and muscle activity (EMG) from the main mono- and bi-articular upper leg muscles were recorded. Link segment modelling was used to obtain net moments about the knee and hip joints. For each muscle the mechanical advantage was calculated in each force direction. 4. The task of controlling the ground reaction force was performed with little interindividual variation as reflected by the variability of the different force and EMG variables. 5. A linear relationship between the difference in activity of rectus femoris and hamstrings and the difference in net moment around the knee and hip was found. This relationship showed very high correlation coefficients of 0.96 (300 N) and 0.97 (600 N) and was independent of position. Mean correlations between this activity difference and the angle of the force vector were also high: -0.95 (300 N) and -0.94 (600 N). 6. The mono- as well as the bi-articular muscles increased in activity when a larger mechanical advantage could be obtained from them, except for the biceps femoris (short head). 7. The results support the hypothesis that bi-articular muscles have a unique role in controlling the distribution of net moments about the joints, and as a consequence, in controlling the direction of the external force exerted on the environment.

Biomechanical Phenomena↗
PubMed1991

Predictors of morbidity and mortality in neonates with herpes simplex virus infections. The National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group.

BACKGROUND: In a controlled trial comparing acyclovir with vidarabine in the treatment of neonatal herpes simplex virus (HSV) infection, we found no significant difference between the treatments in adjusted mortality and morbidity. Hence, we sought to define for the entire cohort (n = 202) the clinical characteristics that best predicted the eventual outcome in these neonates. METHODS: Data were gathered prospectively at 27 centers between 1981 and 1988 in infants less than one month of age who had virologically confirmed HSV infection. We examined the outcomes by multivariate analyses of 24 variables. Disease was classified in one of three categories based on the extent of the involvement at entry into the trial: infection confined to skin, eyes, or mouth; encephalitis; or disseminated infection. RESULTS AND CONCLUSIONS: There were no deaths among the 85 infants with localized HSV infection. The mortality rate was significantly higher in the 46 neonates with disseminated infection (57 percent) than in the 71 with encephalitis (15 percent). In addition, the risk of death was increased in neonates who were in or near coma at entry (relative risk, 5.2), had disseminated intravascular coagulopathy (relative risk, 3.8), or were premature (relative risk, 3.7). In babies with disseminated disease, HSV pneumonitis was also associated with greater mortality (relative risk, 3.6). In the survivors, morbidity was most frequent in infants with encephalitis (relative risk, 4.4), disseminated infection (relative risk, 2.1), seizures (relative risk, 3.0), or infection with HSV type 2 (relative risk, 4.9). With HSV infection limited to the skin, eyes, or mouth, the presence of three or more recurrences of vesicles was associated with an increased risk of neurologic impairment as compared with two or fewer recurrences.

Consciousness↗
PubMed1991

Can cycle power predict sprint running performance?

A major criticism of present models of the energetics and mechanics of sprint running concerns the application of estimates of parameters which seem to be adapted from measurements of running during actual competitions. This study presents a model which does not perpetuate this solecism. Using data obtained during supra-maximal cycle ergometer tests of highly trained athletes, the kinetics of the anaerobic and aerobic pathways were modelled. Internal power wasted in the acceleration and deceleration of body limbs and the power necessary to overcome air friction was calculated from data in the literature. Assuming a mechanical efficiency as found during submaximal cycling, a power equation was constructed which also included the power necessary to accelerate the body at the start of movement. The differential equation thus obtained was solved through simulation. The model appeared to predict realistic times at 100 m (10.47 s), 200 m (19.63 s) and 400 m (42.99 s) distances. By comparison with other methods it is argued that power equations of locomotion should include the concept of mechanical efficiency.

Aerobiosis↗
PubMed1991

The precision of motor control in human jaw and limb muscles during isometric contraction in the presence of visual feedback.

Experiments showed that the human capacity to maintain a particular isometric force in the presence of visual feedback during a force-level, pursuit-tracking experiment is less developed for the jaw-closing muscles than for the limb muscles. This finding may indicate that the projection on the trigeminal motoneurone pool from visual inputs is poor, or that the trigeminal effector system itself is less finely tuned.

Adult↗
PubMed1991

A case of Rhodococcus equi brain abscess.

We treated a patient with acquired immunodeficiency syndrome for a brain abscess caused by Rhodococcus equi, an actinomycete that usually infects the lung in immunosuppressed hosts. Rhodococcus equi brain abscess is an extremely rare lesion that has never been reported in a patient with acquired immunodeficiency syndrome. The infection was cured by lengthy therapy with multiple antibiotics after aspiration of the lesion to identify the infective organism and determine its sensitivity to antibiotics.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Renal disease in carrier female dogs with X-linked hereditary nephritis. Implications for female patients with this disease.

Male dogs with X-linked hereditary nephritis (HN) serve as a model for studying male patients with this disease. In the present study, carrier female dogs were found to resemble female patients in showing a broad range of renal dysfunction. Of 37 carrier female dogs studied, all were healthy up to 5 years of age; however, all had proteinuria develop at 2 to 3 months, and focal segmental glomerulosclerosis (FSGS) was detected after 7 months. After 5 years, 4 of 13 dogs remained healthy and showed mild FSGS on renal biopsy; 4 had mild renal dysfunction develop and their kidneys showed extensive FSGS; 5 died prematurely of renal failure with end-stage kidneys. By immunofluorescence, using antibody to the NC1 domain of collagen type IV, segmental staining of glomerular basement membranes (GBM) was seen in all dogs before 3 to 4 years, and lesions of FSGS were negative. Thereafter, a transition to global staining of GBM was noted and lesions of FSGS became positive. Lens capsule and basement membranes in lung and choroid plexus showed discontinuous staining in two young carrier female dogs and continuous staining in one older carrier female dog. By electron microscopy, multilaminar splitting of some GBM was seen up to 4 years, and thereafter, splitting took on a compressed appearance, with the layers becoming apposed though still detectable. The authors conclude that: 1) carrier female dogs with X-linked HN are mosaics for an abnormality in the NC1 domain of GBM and other basement membranes; 2) FSGS develops in all carrier female dogs in glomerular capillary loops that possess an abnormal NC1 domain, and progresses to a variable extent in different dogs; and 3) the abnormality of NC1 in GBM of carrier female dogs appears to diminish with age, but this does not prevent progression of renal disease. Similar conclusions may apply to females with X-linked HN.

Animals↗
PubMed1991

Dietary modification reduces splitting of glomerular basement membranes and delays death due to renal failure in canine X-linked hereditary nephritis.

Affected male (AM) Samoyed dogs with X-linked hereditary nephritis (HN) demonstrate splitting of all of their glomerular basement membranes (GBM) and rapidly develop renal failure within the first year of life, features reminiscent of those seen in male patients with X-linked HN. In contrast, carrier female (CF) dogs with X-linked HN show only isolated foci of splitting of GBM, and renal failure is never seen at such an early age. In the present study, we assessed whether a diet designed for dogs in renal failure could modify the changes seen in GBM of AM and CF dogs and improve the clinical outcome in the AM dogs. Beginning at 35 days of age, one group of dogs (unaffected, AM, and CF) was fed a regular diet, while a second group was fed a modified diet (i.e., restricted in protein, lipid, calcium, and phosphorus). AM dogs fed the modified diet showed less of a reduction in glomerular filtration rate than AM dogs fed the regular diet, indicative of a delay in the onset and a decrease in the severity of renal damage. Nevertheless, all of the AM dogs eventually died of renal failure regardless of diet. However, the onset and progression of renal failure were delayed and the severity of splitting of GBM was reduced in the AM dogs fed the modified diet; these dogs lived 53% longer than AM dogs fed the regular diet. CF dogs fed the modified diet also showed a reduced severity of splitting of GBM. In addition, when two CF dogs on the modified diet were switched to the regular diet, splitting of their GBM increased, indicating that continual administration of the modified diet was required to maintain the reduced rate of splitting. These studies indicate that dietary modification is beneficial in canine X-linked HN, and suggest that similar benefits (i.e., reduction in severity of splitting of GBM and delay in development of renal failure) might be observed in patients with HN who are treated with an appropriately modified diet.

Animals↗
PubMed1990

5-Fluorouracil with oral leucovorin and hydroxyurea and concomitant radiotherapy for stage III non-small cell lung cancer.

Twenty-three patients with regionally advanced non-small cell lung cancer (NSCLC) (Stage III) were treated with continuous infusion 5-fluorouracil (5-FU) augmented by high-dose oral leucovorin and hydroxyurea and concomitant radiotherapy. This chemoradiotherapy regimen was administered during 5 days of every other week for six cycles (total radiation dose, 6000 cGy). Three patients (13%) had stable disease, 13 patients (57%) had a partial response (PR), and 1 patient (4%) had a complete response (CR). The overall response rate was 61% (95% confidence interval, 41% to 81%). At a median follow-up time of 19 months, the median survival time for all 23 patients was 12 months. The median time to disease progression was 6 months. Twelve patients have had disease progression outside of the chest, and only 3 patients have had intrathoracic disease progression as the site of first failure. The toxicities of this regimen consisted of mild to moderate myelosuppression and moderate degree dermatitis and mucositis. It was concluded that concomitant chemoradiotherapy with this regimen results in high local activity at acceptable toxicity. However, the systemic activity of this regimen was low, resulting in a high distant recurrence rate and a median survival time that was not different from that achieved with standard therapy. Therefore, its use, as defined in this study, cannot be recommended.

Administration, Oral↗
PubMed1990

Antibodies to cardiolipin and intermediate filaments: a study of autoimmunity in rheumatoid arthritis.

Autoantibodies to cardiolipin and intermediate filaments have both been reported with increased frequency in rheumatoid arthritis. We evaluated the frequency, pathological significance, and diagnostic relevance of these autoantibodies in a series of 124 patients and controls. We studied 81 patients with rheumatoid arthritis, 23 with osteoarthritis, and 20 normals. Antibodies to cardiolipin were measured by an ELISA method and antibodies to intermediate filaments were measured by indirect immunofluorescence using HEp2 cells. Antibodies to cardiolipin were present in 58% of rheumatoid patients and antibodies to intermediate filaments were present in 55% rheumatoid patients. They were both predominantly of IgM class, and were more frequent than in normal or osteoarthritic controls. Correlating levels of both these autoantibodies to clinical and laboratory measures of disease activity such as Ritchie articular index and C-reactive protein level showed that no consistent relationships existed. They were not related to other auto-antibodies such as rheumatoid factors and anti-nuclear antibodies, nor to each other. These results show that antibodies to cardiolipin and intermediate filaments in rheumatoid arthritis are of no diagnostic value, they are not related to disease activity, and have no relationship to other autoimmune disturbances. We suggest that several pathological mechanisms must be involved in the development of autoantibodies in rheumatoid arthritis.

Adult↗
PubMed1990

A subset of CD16-natural killer cells without antibody-dependent cellular cytotoxicity function.

The low affinity IgG receptor, CD16 (Fc gamma RIII), is expressed on almost all peripheral blood natural killer (NK) cells. A small subset of CD3- CD16- CD56+ NK cells, representing less than 1% of peripheral blood lymphocytes, expands during in vivo IL-2 treatment. To analyze this CD16- NK cell subset in more detail, NK clones have been generated. One of them (TNK2) has been used to study the function of these cells in more detail. It is demonstrated that TNK2 exerts normal NK activity and displays large granular lymphocyte morphology. Since this clone lacks CD16 expression, antibody-dependent cellular cytotoxicity cannot be exerted. CD16 monoclonal antibodies fail to induce cytotoxic activity against NK-resistant target cells. These studies reveal that the lack of CD16 detection is not due to the modulation or the stage of activation of these NK cells. TNK2 is representative of this small subset of peripheral blood NK cells, expanded during IL-2 treatment, which does not express Fc gamma RIII and therefore cannot perform antibody-dependent cellular cytotoxicity.

Antibodies, Monoclonal↗
PubMed1990

Reference intervals for feline cerebrospinal fluid: biochemical and serologic variables, IgG concentration, and electrophoretic fractionation.

Reference intervals are reported for feline CSF biochemical and serologic variables, IgG concentration, and electrophoretic fractionation, derived from 58 clinically normal adult cats that did not have histologic lesions of the CNS. There was no apparent effect of age on any variable. The CSF total protein concentration was significantly (P = 0.012) greater in males than in females, but all other variables were unaffected by gender. The only variable that had a statistically significant correlation with its corresponding blood concentration was IgG. Blood contamination of the CSF affected the following CSF variables: total protein concentration, activities of lactate dehydrogenase and creatine kinase, IgG ratio, and gamma-globulin percentage. The reference intervals proposed for feline CSF were derived from 33 cats with CSF RBC count less than 31 cells/microliters. Reference limits for CSF with 31 to 1,700 RBC/microliters also are reported.

Animals↗
PubMed1990

Augmentation of the effect of doxorubicin with low-dose tumor necrosis factor in experimental liver metastasis.

The antitumor activity of recombinant human tumor necrosis factor was studied in vivo as a single agent and in combination with a conventional chemotherapeutic agent. Dosages of tumor necrosis factor of 100 micrograms, 50 micrograms, and 25 micrograms were injected intraportally in Sprague-Dawley rats containing hepatic implants of Walker carcinosarcoma. An effect on the tumor was seen but was associated with a significant acute mortality. Lower dosages of tumor necrosis factor, 10 micrograms, 5 micrograms, and 1 microgram, administered with 10 mg/kg of doxorubicin (Adriamycin) significantly enhanced the antitumor effect of doxorubicin without an acute mortality. This suggests that lower dosages of tumor necrosis factor with conventional chemotherapy may augment the latter's effect without any added toxicity.

Animals↗