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Biomedical subjects

R Jacobs

Publications and source records attributed to R Jacobs.

At least 199 records · Page 11Linked to original sources
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1988

[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↗
PubMed1988

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↗
PubMed1988

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↗
PubMed1988

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↗
PubMed1988

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↗
PubMed1988

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↗
PubMed1988

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↗
PubMed1988

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↗
PubMed1988

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↗
PubMed1988

Lymphoid microenvironments in the thymus and lymph node.

The three-dimensional architecture of the thymus and mesenteric lymph node reveals several different stromal cell types important in the development and function of T cells. In the thymic cortex, T cells proliferate and differentiate in a meshwork of epithelial-reticular cells. They then migrate towards the medulla where they may interact with interdigitating cells. T cells migrate from the thymus through perivascular spaces, surrounding large vessels at the cortico-medullary boundary. In this area also large thymic cystic cavities are found, their function remains at present unclear. Mature "selected" T cells leave the thymus most probably by the venous bloodstream, to enter peripheral lymph nodes. Upon entering the lymph node they cross the wall of high endothelial venules. On the other hand, lymph enters the node by afferent lymphatics draining into various types of sinuses. Here, macrophages are strategically located to phagocytose and process antigen. These cells then expose antigen to T cells and B cells within the lymph node parenchyma, thus creating a microenvironment for the onset of an immune response. The various microenvironments important in T cell development and T cell function are shown in this paper using scanning electron microscopy as a dissecting tool. We discuss our morphological findings in the light of recent data on the physiology of T cell differentiation and function.

Animals↗
PubMed1988

Changes to metabolite concentration in fetal sheep subjected to prolonged hypobaric hypoxia.

The effect of hypobaric hypoxaemia on the concentration of metabolic substrates in the ovine fetus and pregnant ewe with implanted vascular catheters, was investigated. At 120 to 141 days of gestation sheep were subjected to hypobaria (mean fetal carotid PO2 12.7 +/- 0.7 torr; n = 9) or normobaria (mean fetal carotid PO2 22.7 +/- 0.7 torr; n = 11; P less than 0.001). At 141 days gestation mean fetal weight was 3.46 +/- 0.72 kg in the hypobaric group compared to 4.15 +/- 0.51 in the normobaric group (P less than 0.05). Concentrations of glucose in maternal and fetal plasma and fructose in fetal plasma were similar in hypobaric and normobaric fetuses. The concentration of lactate in fetal plasma rose from 1.68 +/- 1.34 to 8.79 +/- 5.8 mmol/l (P less than 0.001) within 24 h of onset of hypoxia, but fell to 3.36 +/- 1.13 mmol/l by day 3 of treatment, though still significantly above the concentration of lactate in the control fetuses (1.47 +/- 0.47; P less than 0.001). There was no significant effect of hypoxia on the concentration of lactate or alanine in maternal plasma. Alanine concentration in the plasma of fetuses subjected to hypoxia significantly increased within 24 h of exposure (0.28 +/- 0.10 vs 0.58 +/- 0.39 mmol/l; P less than 0.01) and remained elevated for the duration of the study. There was no significant effect of gestational age on the concentration of metabolic substrates in either the control or experimental groups. Hypoxia is associated with a sustained rise in the concentration of plasma lactate and alanine in the fetus.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine↗
PubMed1987

Enhancement of tumor blood flow and tumoricidal effect of doxorubicin by intraportal epinephrine in experimental liver metastasis.

Laser Doppler capillary perfusion monitoring was performed in 25 Sprague-Dawley rats with solitary intrahepatic implants of Walker carcinosarcomas. Doses of intraportal epinephrine from 1 to 10 micrograms produced an immediate rise in capillary blood flow, reaching peak levels by 16 s. The increased flow lasted an average of 57 s. Because epinephrine selectively increased tumor blood flow, studies were performed to determine if enhancement of the chemotherapeutic effect of doxorubicin could be achieved. Forty-two rats with seven-day hepatic implants were treated sequentially with intraportal epinephrine (10 micrograms) and doxorubicin hydrochloride (10 mg/kg) or doxorubicin alone. After only two courses of chemotherapy, a significant difference in necrosis and cell viability was obtained in those animals treated with epinephrine intraportally prior to doxorubicin infusion. Enhancement of the tumoricidal effect of chemotherapy can be achieved by manipulating the blood flow to developing tumors pharmacologically.

Animals↗
PubMed1987

Intrauterine herpes simplex virus infections.

Neonatal herpes simplex virus (HSV) infection is usually acquired at birth, although a few infants have had findings suggestive of intrauterine infection. We describe 13 babies who had clinical manifestations of intrauterine HSV infection, including skin lesions and scars at birth (12), chorioretinitis (eight), microcephaly (seven), hydranencephaly (five), and microphthalmia (two). All infants had combinations of these defects. Infection was proved by viral isolation in each case; all isolates were HSV-2. Two infants died during the first week of life; 10 of the surviving infants had severe neurologic sequelae, and one infant was blind. Four mothers experienced an apparent primary genital HSV infection, and one had recurrent infection, at varying times during gestation. The remaining women denied a history of symptoms of genital HSV infection. These findings indicate that intrauterine HSV infection can occur as a consequence of either primary or recurrent maternal infection and has severe consequences for the fetus.

Abnormalities, Multiple↗