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Biomedical subjects

R Jacobs

Publications and source records attributed to R Jacobs.

At least 37 records · Page 2Linked to original sources

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

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

Alzheimer's disease as a capillary dementia.

In addition to the well known structural stigmata which accompany the senile dementia of Alzheimer, attention is called to the presence of a group of robust changes which affect the fine vessels (capillaries, capillary arterioles and capillary venules), particularly of the cerebral cortex. These alterations include irregular pouches and excrescences on the vessels (a "lumpy-bumby" appearance), general thickening of the basement membrane, loss of the fine perivascular neuronal plexus which seems to invest each vessel, no matter how small, and the appearance of pits or lacunae in the vessel walls of about one half of the Alzheimer patients studied. None of these changes have been seen in a group of approximately age-matched, non-demented controls. Much of this perivascular neural plexus originates within a few specific subcortical fields, especially the locus ceruleus and the nucleus basalis of Meynert and basal forebrain area. These also happen to be included among those brain areas which experience the most marked neuronal atrophy or loss in Alzheimer's disease. Since there is some evidence suggesting that surgically induced vascular denervation in myocardium produces dramatic changes in vascular wall structure we wonder whether neuronal pathology developing initially in these subcortical areas may not play a significant role in the development of the characteristic neuropathology in Alzheimer's disease. These speculations emphasize the possible importance of a failing blood brain barrier in the development of the disease.

Alzheimer Disease

Developing an AIDS prevention education program for persons with developmental disabilities.

The AIDS epidemic poses a serious threat to people with developmental disabilities, the magnitude of which has not yet been fully realized by many professionals working with this population. Models for effective AIDS prevention education have been developed, however, within other populations. Key principles utilized in existing models were discussed and recommendations presented on how to adapt these models when designing programs for people who have developmental disabilities, most specifically, those in the mild/moderate range of mental retardation.

Acquired Immunodeficiency Syndrome

Evidence that epinephrine acutely redistributes blood flow to experimental intrahepatic tumors.

Tumor microcirculation was studied in Sprague-Dawley rats with solitary intrahepatic implants of Walker carcinosarcoma tumors. Thioflavine S (TS), a fluorescent dye that stains capillary endothelium acutely, was injected intraportally or intra-arterially in order to demonstrate patterns of blood flow through normal liver tissue and through tumor. The dye was given immediately after intraportal injection of 10 micrograms of epinephrine in some animals and 3 minutes after the epinephrine in others. Control animals received TS alone. Additional animals were given TS immediately after intra-arterial epinephrine. The degree of resulting fluorescence in tumor and liver was graded subjectively from 0 to 3+. In the controls and in animals receiving TS 3 minutes after epinephrine, fluorescence in the centers of tumors was absent or, at most, faintly present. In contrast, all animals given epinephrine either intraportally or intra-arterially immediately before the dye showed intense fluorescent staining within the centers of the tumors. Subjective grading averaged 0.6 +/- 0.1 in the controls, 2.2 +/- 0.1 in those receiving intraportal epinephrine immediately before TS, and 1.0 +/- 0.3 in those receiving TS 3 minutes after epinephrine. Results were significantly higher in the latter group (p less than 0.01). Subjective grading in animals receiving intra-arterial epinephrine immediately before TS averaged 2.5 +/- 0.3. These experiments confirm previous studies in this laboratory that demonstrated an acute short-lived redistribution of blood flow into the centers of intrahepatic tumors after administration of epinephrine.

Animals

[Severe chronic Epstein-Barr virus infection with natural killer cell defect].

Chronic Epstein-Barr virus infection was confirmed serologically in a 27-year-old man with pneumonia, splenomegaly, pancytopenia, arthritis, neuropathy and psychological changes. Immunological tests revealed a defect in the cytotoxic activity of the natural killer cells. Treatment with high doses of acyclovir intravenously and of antimycotic drugs dramatically and lastingly improved the patient's condition.

Acyclovir

Small intestinal myeloid metaplasia.

Extramedullary hematopoiesis is rarely found in the gastrointestinal tract. A patient with postpolycythemic myeloid metaplasia who previously underwent splenectomy presented with recurrent, protracted gastrointestinal tract hemorrhage. Elaborate workup failed to reveal the source of bleeding. Intraoperative endoscopy with transillumination disclosed multiple submucosal lesions along the entire small bowel, which proved to be extramedullary hematopoiesis. After institution of hydroxyurea therapy, the rate of bleeding diminished considerably.

Aged

Increased capillary flow in intrahepatic tumors due to alpha-adrenergic effects of catecholamines.

Chemotherapy of liver metastases is dependent on adequacy of tumor microcirculation. Attempts have been made, experimentally, to improve tumor blood flow with appropriate vasoactive agents. Capillary blood flow within intrahepatic Walker carcinosarcomas and normal liver were measured with a laser doppler needle probe. Tumor capillary blood flow increased briefly but significantly with intraportally administered epinephrine. This effect was blocked by phenoxybenzamine but not by propranolol. The response of capillary flow in normal liver to epinephrine was dose related, with decreased flow with higher doses, and slight increase with lower doses. Norepinephrine and phenylephrine produced brief increases in capillary flow in tumor and liver, and isoproterenol caused a decreased flow. In studies with injected silicone rubber (Microfil, Canton Bio-Medical Products, Boulder, CO) performed previously, and on electron microscopic examination, there was evidence of increased vascular filling within central areas of tumors after epinephrine. These studies suggest that the brief but potent effect of epinephrine on tumor capillary flow could be useful in improving delivery of chemotherapeutic agents to liver tumors.

Animals

Natural cytotoxicity of rat hepatic natural killer cells and macrophages against a syngeneic colon adenocarcinoma.

The in vitro cytotoxic activity of two types of hepatic sinusoidal cells, i.e., natural killer (NK) cells and macrophages (Kupffer cells), was tested against a syngeneic rat colon adenocarcinoma cell line (DHD-K12). Purified hepatic NK cells (85% cells with large granular lymphocyte morphology) were spontaneously cytolytic, whereas Kupffer cells (90% pure) were not able to kill the DHD-K12 cells. This carcinoma cell line was found to be resistant to the action of mouse recombinant tumor necrosis factor which is considered as the major cytolytic molecule secreted by macrophages. However, colon carcinoma cells were readily lysed by soluble factors present in the culture supernatant of NK cells. It is postulated that hepatic NK cells, which are strategically located within the lumen of the sinusoids, may form a first line of defense to metastasizing colon carcinoma cells.

Adenocarcinoma

The effects of steroidal and nonsteroidal anti-inflammatory agents on uptake of Evans blue in experimental metastasis.

The effects of anti-inflammatory drugs on uptake of Evans blue were studied in solitary Walker carcinosarcomas implanted in the livers of Sprague-Dawley rats. Animals were sacrificed at 5 min, 30 min, and 6 hr after administration of the anti-inflammatory drugs and Evans blue, and spectrophotometric measurements of the Evans blue in tumor and normal liver tissue were carried out. Uptake of Evans blue in the tumors was significantly decreased at all time periods after the injection of the following, as compared to controls: steroids (cortisol, methylprednisolone, and triamcinolone), the antihistamine diphenhydramine, and nonsteroidal anti-inflammatory agents (naproxen, ibuprofen, indomethacin, and phenylbutazone). The effects of these drugs on uptake of Evans blue in the normal liver were more variable.

Animals

Role of dietary factors in cell replication and colon cancer.

Human studies and experimental data from animals suggest that high rates of colonic epithelial cell replication enhance the development of colon cancer. Vegetarians and individuals following a prudent diet have lower rates of colorectal cell proliferation than subjects at high risk for colon cancer. Animal studies show that colonic cell proliferation is stimulated by feeding in general and specifically by a number of dietary fibers, fats, bile acids, and short-chain fatty acids. Many of these growth factors also increase the induction of experimental tumorigenesis. On the other hand factors that reduce cell growth, including ascorbic acid and butylated hydroxyanisole, inhibit colon carcinogenesis. These results support the concept that dietary chemoprevention is feasible and could significantly reduce the rate of colon cancer development in high risk populations.

Animals

Effect of 1,2-propanediol and dimethylsulphoxide on the meiotic spindle of the mouse oocyte.

At ovulation, the mouse oocyte is arrested at metaphase of the second meiotic division. Since microtubules are thermo-and chemosensitive structures, the effects of 1.5 M dimethylsulphoxide and 1.5 M 1,2-propanediol were studied at room temperature on the morphology of the meiotic spindle. Oocytes incubated at 37 degrees C or at room temperature served to estimate the effect of temperature in the experiment. The meiotic spindle was visualized by immunogold-silver staining of microtubules. In the control group at 37 degrees C, 88% of oocytes had normal spindles. After incubation at room temperature for the same time, 89% of oocytes showed abnormal spindles. In the oocytes exposed to dimethyl-sulphoxide or 1,2-propanediol at room temperature a protective effect on spindle morphology could be recognized. Subsequent incubation at 37 degrees C resulted in partial restoration of the observed abnormalities after cooling to room temperature and after exposure to dimethylsulphoxide. Incubation at 37 degrees C after exposure to 1,2-propanediol at room temperature induced spindle absence in the majority of oocytes. Although this latter condition allowed fertilization without increased incidence of ploidy abnormalities, a role for 1,2-propanediol as an activating agent is hypothesized.

Animals

Pure motor hemiplegia secondary to a saccular basilar artery aneurysm.

Pure motor hemiplegia is the most commonly encountered lacunar syndrome and is classically associated with small infarctions in the contralateral internal capsule or basis pontis. Pure motor hemiplegia has also been observed secondary to a wide variety of other vascular and nonvascular focal central nervous system processes. We describe a patient with pure motor hemiplegia associated with a saccular basilar artery aneurysm causing a lacunar infarction of the cerebral peduncle.

Aged

The effect of prolonged hypobaric hypoxia on growth of fetal sheep.

The effect of prolonged hypobaric hypoxia on fetal sheep was studied. Pregnant ewes were subjected to an atmospheric pressure of 429 torr from 30 days to 135 days gestation (long-term study). Average fetal weight for the hypoxaemic group (3.35 +/- 0.53 kg; n = 4; mean +/- SD) was significantly lower than for the controls (4.23 +/- 0.29 kg; n = 7; P less than 0.05). A short-term study was undertaken with fetuses (n = 8) which were catheterized at 110 days gestation and whose dams were subjected to hypobaric hypoxia from 120 to 141 days gestation. The mean carotid PO2 of fetuses in the hypoxic group was 12.7 +/- 0.7 torr compared to 22.7 +/- 0.7 torr for the control group (n = 9; P less than 0.001) throughout the period of treatment. Fetal arterial oxygen content fell from 6.5 +/- 1.7 to 4.9 +/- 0.4 ml/dl (P less than 0.05), but rose to control values after 7 days due to an increase in fetal haemoglobin concentration (9.6 +/- 1.1 to 13.0 +/- 1.9 g/dl, P less than 0.001) and packed cell volume (33 +/- 3 to 45 +/- 4%, P less than 0.001). In the hypoxaemic fetuses, pH fell initially from 7.34 +/- 0.02 to 7.28 +/- 0.03 (P less than 0.05) and then recovered to 7.32 +/- 0.03 within 24 h. Mean fetal weight of the short-term hypoxic group was 3.46 +/- 0.72 kg compared to 4.15 +/- 0.51 for the control group (P less than 0.05). Both long- and short-term hypoxia produced a similar reduction in fetal body weight. The adrenal glands were significantly heavier in the hypoxic fetuses than in controls. Placental weight was not effected by hypoxia, but exposure from 30 days gestation reduced the average size of cotyledons (P less than 0.05). It is concluded that the fetal sheep increases its ability to acquire and transport oxygen in response to chronic hypoxia, but this compensation is not sufficient to prevent growth retardation or changes to the pattern of tissue growth.

Altitude Sickness