The effect of aspirin on blood cell nucleotides in vivo.
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Adenine Nucleotides↗
Biomedical subjects
R Jacobs
Publications and source records attributed to R Jacobs.
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
Reference intervals for feline cerebrospinal fluid: cell counts and cytologic features.
Reference intervals for feline CSF cell counts and cytologic variables were determined. Values were derived from 58 adult cats that had normal neurologic examination findings and did not have histologic lesions of the CNS. Effect of age or gender was not apparent for any CSF variable, and no CSF variable was significantly correlated with its corresponding blood value. Total WBC count and neutrophil and eosinophil percentages were positively correlated with the CSF RBC count. Thus, proposed reference intervals for feline CSF were derived from 33 cats with CSF RBC count of less than 31 cells/ul. Data for CSF samples with range between 31 and 1,700 RBC/microliters were also determined. Erythrocyte count was not significantly different in CSF collected, using 20- or 22-gauge spinal needles.
Animals↗
Colostral and serum IgG, IgA, and IgM concentrations in Standardbred mares and their foals at parturition.
Immunoglobulin G, IgM, and IgA concentrations were measured in serum collected from 36 Standardbred mares within 12 hours of foaling, in colostrum collected within 6 hours of foaling, and in serum collected from foals 24 to 48 hours after birth. In serum collected from mares after parturition, mean concentrations of IgG, IgM, and IgA were 2,463.9 +/- 1,337.3 mg/dl, 136.4 +/- 218 mg/dl, and 305.2 +/- 237.5 mg/dl, respectively. In serum from foals, mean concentrations of IgG, IgM, and IgA were 1,953.3 +/- 1,635 mg/dl, 33.8 +/- 30.4 mg/dl, and 58.4 +/- 42.2 mg/dl, respectively. In colostrum, mean concentrations of IgG, IgM, and IgA were 8,911.9 +/- 6,282.2 mg/dl, 957 +/- 1088.1 mg/dl, and 122.9 +/- 77.3 mg/dl, respectively. The IgG concentrations in foal serum were poorly correlated with IgG concentrations in colostrum (r = 0.462, P less than 0.01). Correlations of IgM or IgA concentrations in serum from foals with IgM or IgA concentrations in colostrum and correlations of IgG concentrations in serum from mares with those in colostrum were not significant (P less than 0.01). Of 36 foals, 1 (2.8%) had a serum IgG concentration less than 400 mg/dl. Of 36 foals monitored for 4 months, 6 developed infectious respiratory tract disease requiring antimicrobial therapy at ages varying from 55 to 113 days; these infections were probably not related to failure or partial failure of passive transfer of antibody.
Animals↗
Pathogenetic mechanisms in the Mycoplasma arthritidis polyarthritis of rats.
Mycoplasma arthritidis is the causative agent of severe polyarthritis in rats and mice, which resembles human rheumatoid arthritis (RA). Several mechanisms are involved in this disease. M. arthritidis releases substances acting on polymorphonuclear granulocytes (PMNs), i.e. oxygen radical formation stimulating substances (500-3,000 daltons), a chemotactic substance (400 daltons) and an aggregating substance (500 daltons). These products were separated from the cell-free culture supernatant by gel chromatography on Sephadex G-15 and G-10 columns. Isolated membranes of M. arthritidis possesses toxic properties for rats, mice, and chicken embryos. Hemolytic activities for sheep red blood cells and toxic effects on fetal rat skin fibroblasts were detected for this 170,000 dalton substance. Cross-reactivity between M. arthritidis and rat tissues was demonstrated in several investigations with polyclonal and monoclonal antibodies. Polyclonal antibodies against M. arthritidis showed a strong reaction in immunofluorescence tests with rat chondrocytes. In Western blot analysis six corresponding protein bands were observed in M. arthritidis membranes and rat chondrocytes, favoring the idea of several shared epitopes. Monoclonal antibodies were established reacting with M. arthritidis as well as with rat and human chondrocytes in the immunofluorescence test and in the enzyme immunoassay. Cross-reactivity could be observed also on the cellular level. T-cell lines of the OX 19 and W 3/25 type were established that could be stimulated by M. arthritidis antigens and by syngeneic chondrocytes. In the initial stage of the arthritis, toxic processes seem to be predominant that are continued by autoimmune reactions in the progressing disease.
Animals↗
Use of plasma histamine levels to monitor cutaneous mast cell degranulation.
A simple, minimally invasive procedure for monitoring cutaneous mast cell degranulation in vivo in man is described. Plasma histamine levels in venous blood draining the site of intradermal histamine, morphine, and antigen challenges were determined with a modified radioenzymatic assay. Elevations in plasma histamine above baseline levels of 0 to 0.6 ng/ml were measured after intradermal histamine; levels of 1.4 to 85.2 ng/ml were obtained after a 2 microgram intradermal challenge in 16 subjects. After antigen testing, peak plasma histamine levels ranged from 1.1 to 24.4 ng/ml (n = 9), and after morphine sulfate skin testing peak plasma histamine levels ranged from 2.3 to 12.7 ng/ml (n = 4). The time to achieve peak plasma histamine levels ranged from 2 to 10 minutes after histamine, from 5 to 15 minutes after antigen, and from 1 to 8 minutes after morphine challenges. Plasma levels returned to baseline within 30 minutes after histamine and morphine challenges but took more than 60 minutes for antigen challenges. With careful choice of the skin test site in relation to venous drainage, plasma histamine increases after either histamine or antigen were reproducible and reliable. Plasma histamine levels peaked 5 to 10 minutes before maximal development of the wheal-and-flare responses after histamine, antigen, or morphine skin tests. The wheal-and-flare skin tests continued to increase in magnitude despite rapidly declining plasma histamine levels. Thus skin tests eliciting reactions ordinarily seen in an allergist's office cause measurable increases in plasma histamine levels that can be used to directly monitor mast cell degranulation in man in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)
Allergens↗
Failure of intravenous vancomycin and intravenous metronidazole to prevent or treat antibiotic-associated pseudomembranous colitis.
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Enterocolitis, Pseudomembranous↗
Blood histamine concentrations are not elevated in humans with septic shock.
Histamine has been suggested as an important mediator of the cardiovascular abnormalities during septic shock. To determine if blood histamine levels were increased during human sepsis and septic shock, plasma histamine was measured using a very sensitive radioenzyme assay employing histamine N-methyltransferase (HNMT) in the following patient groups: normal controls (n = 76), nonseptic critically ill (n = 12), nonseptic shock (n = 2), sepsis without shock (n = 28), and septic shock (n = 41). Using this enzyme binding assay, all these groups had similar, normal plasma histamine concentrations, except those patients with septic shock whose mean histamine measurements were significantly reduced (p less than .002). This decrease was found to be due to an artifact of the assay: plasma contained a circulating inhibitor that falsely lowered the measured histamine level. Fractionation of septic shock plasma using molecular exclusion membranes and gel filtration revealed a 5000 MW inhibitory factor. After removal of this inhibitor from plasma, septic shock plasma histamine levels were normal. Thus, septic shock patients may have a circulating inhibitor of the HNMT enzyme, but plasma histamine concentrations are normal. Histaminemia is unlikely to play an important role in the pathogenesis of septic shock in humans.
Chromatography, Gel↗