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Biomedical subjects

R L Jacobson

Publications and source records attributed to R L Jacobson.

At least 37 records · Page 2Linked to original sources

HIV infection and associated sexually transmitted diseases in women.

We determined the prevalence of other sexually transmitted diseases (STDs) in 56 women infected with the human immunodeficiency virus (HIV) and compared the usefulness of this prevalence to that of standard risk assessment alone in identifying HIV-infected women. Of the 56 women studied, 54 were infected with HIV. These women received instruction as to the modes of transmission and were then placed in standard risk groups based on their own assessments. A history of previous or current STD was obtained and followed by appropriate testing. We found that combining standard risk assessment with a current or previous STD enabled us to identify a greater percentage of women who are infected with HIV.

Female↗

Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment. Pediatric AIDS Clinical Trials Group Protocol 076 Study Group.

BACKGROUND AND METHODS: Maternal-infant transmission is the primary means by which young children become infected with human immunodeficiency virus type 1 (HIV). We conducted a randomized, double-blind, placebo-controlled trial of the efficacy and safety of zidovudine in reducing the risk of maternal-infant HIV transmission. HIV-infected pregnant women (14 to 34 weeks' gestation) with CD4+ T-lymphocyte counts above 200 cells per cubic millimeter who had not received antiretroviral therapy during the current pregnancy were enrolled. The zidovudine regimen included antepartum zidovudine (100 mg orally five times daily), intrapartum zidovudine (2 mg per kilogram of body weight given intravenously over one hour, then 1 mg per kilogram per hour until delivery), and zidovudine for the newborn (2 mg per kilogram orally every six hours for six weeks). Infants with at least one positive HIV culture of peripheral-blood mononuclear cells were classified as HIV-infected. RESULTS: From April 1991 through December 20, 1993, the cutoff date for the first interim analysis of efficacy, 477 pregnant women were enrolled; during the study period, 409 gave birth to 415 live-born infants. HIV-infection status was known for 363 births (180 in the zidovudine group and 183 in the placebo group). Thirteen infants in the zidovudine group and 40 in the placebo group were HIV-infected. The proportions infected at 18 months, as estimated by the Kaplan-Meier method, were 8.3 percent (95 percent confidence interval, 3.9 to 12.8 percent) in the zidovudine group and 25.5 percent (95 percent confidence interval, 18.4 to 32.5 percent) in the placebo group. This corresponds to a 67.5 percent (95 percent confidence interval, 40.7 to 82.1 percent) relative reduction in the risk of HIV transmission (Z = 4.03, P = 0.00006). Minimal short-term toxic effects were observed. The level of hemoglobin at birth in the infants in the zidovudine group was significantly lower than that in the infants in the placebo group. By 12 weeks of age, hemoglobin values in the two groups were similar. CONCLUSIONS: In pregnant women with mildly symptomatic HIV disease and no prior treatment with antiretroviral drugs during the pregnancy, a regimen consisting of zidovudine given ante partum and intra partum to the mother and to the newborn for six weeks reduced the risk of maternal-infant HIV transmission by approximately two thirds.

Adult↗

Haemoglobin inhibits the development of infective promastigotes and chitinase secretion in Leishmania major cultures.

Haemoglobin or blood in the growth medium of Leishmania major inhibited the formation of infective promastigotes and the secretion of chitinases. Inoculation of mice with stationary-phase parasites from control medium caused infections in 20/29 mice, compared to 3/20 mice injected with parasites grown with 10% rabbit blood, or 1/30 mice that received parasites grown with rabbit haemoglobin. The concentration of peanut lectin (PNA) required to agglutinate promastigotes was used as an index of their infectivity, ranging from a high concentration for infective populations to a low concentration for relatively non-infective populations. Agglutination of 50% of the parasites from control medium or from medium containing rabbit haemoglobin required 4.1 micrograms PNA/ml and 0.1 microgram PNA/ml, respectively. Chitinase activities/10(7) parasites decreased from 4.8 units chitinase and 12.5 units N-acetylglucosaminidase (NAGase) in the control to 2.0 units chitinase and 8.5 units NAGase in cultures containing rabbit haemoglobin. Rabbit, human, bovine and pigeon haemoglobins had various inhibitory effects on the activity of chitinases and not on the virulence, as expressed by PNA agglutination. The relevance of the results to the cycle of Leishmania is discussed.

Acetylglucosaminidase↗

Mortality of Leishmania major in Phlebotomus papatasi caused by plant feeding of the sand flies.

The plant feeding of Phlebotomus papatasi and the effects of plant diets on the Leishmania major infections were investigated. Plant-fed flies had small free particles and membranous shreds in their gut that were stained by calcofluor as cellulosic plant tissues. They were found in 34.0% of the female and 14.3% of the male sand flies following feeding on the caper plant (Capparis spinosa). No plant residues were found in 54 females that had been fed on plant-derived honeydew secretions of Aphis craccivora offered on a branch of the host plant. Calcofluor-stained particles were also absent from the gut lumen of unfed flies. The proportion of sugar feeding, regardless of the intake of plant tissue, in the series that had been offered caper plant or honeydew was estimated by testing for the presence of fructose in the gut. The proportion of fructose-positive flies in each series, among both males and females, was 45%. Plant feeding in the field was demonstrated by finding tissue residues in the gut of 32.8% of female and 10.3% of male P. papatasi from the Jordan Valley. Feeding on specific plants was demonstrated using baits of branches suffused with food dye and finding the dye marker in wild-caught P. papatasi. The influence of plant diets on L. major infections in P. papatasi was as follows: Malva nicaeensis and the honeydew of Icerya purchasi produced thriving parasitemias; however, feeding on Ricinus communis, Capparis spinosa, and Solanum luteum caused > 50% mortality and deformation of parasites in 88%, 55%, and 46% of the infections, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Leishmania infections damage the feeding mechanism of the sandfly vector and implement parasite transmission by bite.

Leishmania parasites are transmitted by the bites of infected female sandflies by a mechanism that has not been clarified. Leishmania infections in the vector develop only in the gut, and the parasites' exit is through the food channel in the proboscis. The problem is how during the bite, when blood flows in, parasites are emitted through the same channel in the opposite direction. It is well documented that infected sandflies maintained on sugar diets are potent vectors, whereas transmission fails after constant feeding on blood. Hence to study the mechanism of transmission, we fed these diets to Phlebotomus papatasi infected with L. major. Histological examination demonstrated that only in the sugar-fed flies did the cuticle lining of the cardiac valve detach and other valve tissues degenerate gradually. The injury of the main valve of the food pumps hindered gorging of most flies when force-fed from capillaries, and they regurgitated the gut contents with fluids from the capillaries. We suggest that infections are caused by parasites regurgitated from the stomach that are deposited in the host tissue. We found that secretion of chitinolytic enzymes by cultured L. major parasites is inhibited by blood or hemoglobin, and hence these enzymes are apparently absent from the blood-fed infected flies, where the cardiac valve appears undamaged. We therefore presume that lysis of the chitin in the cuticle lining of the valve leads to exposure and degeneration of the underlying tissues.

Animals↗

Chitinase secreted by Leishmania functions in the sandfly vector.

Leishmania major parasites ingested with host blood by the sandfly Phlebotomus papatasi multiply confined within the peritrophic membrane. This membrane consists of a chitin framework and a protein carbohydrate matrix and it is secreted around the food by the insect midgut. Histological sections of infected flies show lysis of the chitin layer in the anterior region of the peritrophic membrane that permits the essential forward migration of a concentrated mass of parasites. Both the location and the nature of this disintegration are specific to infected flies. At a later stage the parasites concentrate in the cardiac valve region and subsequently this segment of the fore gut loses its cuticular lining. We have found that chitinase and N-acetylglucosaminidase are secreted by cultured L. major promastigotes, but not by sandfly guts. Hence lysis of the chitin layer of the peritrophic membrane could be catalysed by these enzymes of the parasites. Activity of both enzymes was also observed in other trypanosomatids, including L. donovani, L. infantum, L. braziliensis, Leptomonas seymouri, Crithidia fasciculata and Trypanosoma lewisi.

Animals↗

Transfer of aspirin across the perfused human placental cotyledon.

Pregnancy-induced hypertension is associated with a reduction in prostacyclin synthesis that is relative to normotensive pregnancy, whereas thromboxane A2 synthesis is unchanged or increased. The net effect is a decreased prostacyclin/thromboxane ratio that may result in the reduced fetal-placental blood flow seen in pregnancy-induced hypertension because thromboxane is known to constrict this circulation. Low-dose aspirin (acetylsalicylic acid), which is used to treat pregnancy-induced hypertension, selectively inhibits thromboxane synthesis and therefore may alter fetal-placental blood flow. We have investigated the transfer of acetylsalicylic acid in the perfused human placental cotyledon and its effects on fetal-placental perfusion pressure. Human placental cotyledons were perfused with tissue culture medium 199 plus 5% polyvinylpyrrolidone that was gassed with 95% oxygen/5% carbon dioxide at flow rates of 10 ml/min (maternal) and 4 ml/min (fetal). Acetylsalicylic acid (10(-5) mol/L) was added to the maternal circuit, and cotyledons were perfused for 1 hour with aliquots taken from a closed fetal circuit every 5 minutes. Acetylsalicylic acid was assayed by spectrofluorometry at 306/412 nm. Our data indicate an initial rapid transfer of acetylsalicylic acid during the first 5 minutes into the fetal-placental circulation, the concentration then decreased to a steady state at 0.4 x 10(-5) mol/L. Resting perfusion pressure of both maternal and fetal circulation did not change after the addition of acetylsalicylic acid to maternal perfusate and transfer to the fetal circulation.

Aspirin↗

Serodiagnosis of canine visceral leishmaniasis in Portugal: comparison of three methods.

Sera collected in Portugal from 43 dogs were screened for specific antibodies to Leishmania donovani antigens. Three different techniques were compared: an indirect immunofluorescence assay (IFA), a direct enzyme-linked immunosorbent assay (ELISA) and a competitive-ELISA (C-ELISA) using two species-specific monoclonal antibodies, D2 and D13. By IFA, 22 of the sera examined showed positive reactions, compared with 26 by ELISA or 27 by C-ELISA. There was no direct correlation observed between the serum titre by IFA and the strength of the reaction in ELISA or inhibition in C-ELISA. However, a good correlation was observed between sera identified as positive (95.5%) by all three techniques. Western blotting on leishmanial membranes showed that common antigens with Mr of 26,000 and 70-84,000 were recognized by all infected dog sera, regardless of the serum titre. In large scale studies, ELISAs are preferred to IFA for the rapid diagnosis of canine visceral leishmaniasis because of their greater simplicity.

Animals↗

Prenatal diagnosis of fetal left ventricular aneurysm: a case report and review.

Fetal echocardiography in a 30-year-old black woman, gravida 4, para 3, demonstrated left ventricular aneurysm. This was confirmed by color flow pulsed Doppler techniques. After delivery, neonatal echocardiography and magnetic resonance imaging further confirmed the diagnosis. The infant was followed closely and underwent surgical correction at 8.5 months of age. Before surgery, cardiac catheterization demonstrated normal hemodynamic function. A review of the literature revealed a paucity of information. Issues of prenatal diagnosis, antenatal surveillance, method of delivery, and neonatal follow-up are not well defined in either the obstetric or pediatric cardiology literature. A rationale for our approach to this complex problem is presented.

Adult↗

Oviposition diapause and other factors affecting the egg-laying of Phlebotomus papatasi in the laboratory.

Stimuli which modulate oviposition of P. papatasi were investigated to improve insectary breeding efficiency. Oviposition and survival of gravid females were observed weekly during April-December 1987, in plastic cages at 28 +/- 1 degrees C with L:D 17:7. Oviposition of controls was subject to seasonal variation despite the relatively uniform insectary conditions. From April to mid-October (summer), mean weekly oviposition ranged from 11.6 to 18.6 eggs per fly, dropping to 1.4 eggs/fly in November (winter). Monthly yields of eggs were found to correlate with the seasonal cycle of ultraviolet (UV) radiation in sunlight. This was attributed to an endogenous rhythm since the flies were not normally exposed to UV under insectary conditions. Short exposure to UV sources of 254 nm and 312 nm, but not white light, raised the low rate of oviposition in October-November from 1.4 to 16.8-29.6 eggs/female/week, but female mortality also increased highly significantly. It is suggested that the seasonal oviposition cycle of P.papatasi is set by levels of UV irradiation. In the warm season oviposition was promoted, as compared to controls, by furrows in plaster of Paris lining the bottom of cages (29.6 v. 10.2 eggs/female) and by cow manure in the cages (39.7 v. 18.2 eggs/female), but the combination of both stimuli gave no greater fecundity (40.9 v. 20.9 eggs/female). Oviposition decreased when larvae were present (3.9 v. 15.0 eggs/female) and in half-volume cages (3.9 v. 12.5 eggs/female/week). Under standard insectary conditions, mean weekly mortality-rates of P.papatasi females were 18.3 +/- 4.8% in October-November and 36.5-59.1% during the warmer months. None of the experimental conditions yielded any significant improvement in survival-rates.

Animals↗

Changing surface carbohydrate configurations during the growth of Leishmania major.

Surface carbohydrates of leishmanial promastigotes change during their growth cycle. These changes were monitored in a cloned line of Leishmania major in 2 media. A freshly isolated virulent strain was also examined. Infectivity, surface sugar moieties, and released glycoconjugates (EF) were examined and compared during the growth cycle. When promastigotes of the same clone were grown in different media, their lectin-mediated agglutination profiles were dissimilar, and both quantitative and qualitative variation was seen in the antigenic glycoconjugates released into the media. When labeled with fluorescent lectins, the virulent strain showed no loss of galactose, an increase of N-acetylglucosamine, and a midcycle decrease of N-acetylgalactosamine. Promastigotes of this strain were infective to hamsters throughout the growth cycle. The results presented indicate that culture medium components regulate carbohydrate surface configurations and, thereby, antigenic expression. Infectivity of the virulent strain was not dependent on the expression of a single surface carbohydrate.

Agglutination Tests↗

Surface reaction of Leishmania. IV. Variation in the surface membrane carbohydrates of different strains of Leishmania major.

Eleven strains of Leishmania major were characterized by enzyme electrophoresis, excreted factor serotyping and lectin specificity determination. Nine of the 12 enzyme mobilities were identical for all the strains. Variation was seen in 6PGD, NH and AK. Seven serological entities were recognized, including a non-EF producing strain. A panel of six lectins and sugar inhibitors was used to determine surface membrane carbohydrate configurations, which displayed considerable variation.

Agglutination Tests↗

Leishmaniasis in the Jordan Valley: differential attraction of dispersing and breeding site populations of Phlebotomus papatasi (Diptera: Psychodidae) to manure and water.

The response of Phlebotomus papatasi Scopoli to traps baited with manure or water was used to compare the behavior of flies near rodent burrows (breeding sites) and dispersing flies in fallow fields. The degree of response in each biotype was defined for each bait by the difference between catches in baited and unbaited traps. Manure bait attracted twice as many flies near the burrows and 2.7 times more flies in the field compared with unbaited traps. In both locations, the manure bait increased the capture of males and nongravid females, whereas gravid females were attracted only near burrows and not in the fields. The catch in the fields with water bait was similar to the unbaited control. However, near burrows, water bait captured more males and gravid females, but not nongravid females. These results demonstrate specific behavioral patterns of the dispersing P. papatasi population.

Animals↗

The cellular and humoral immune response in subjects vaccinated against cutaneous leishmaniasis using Leishmania tropica major promastigotes.

In vitro lymphocyte transformation was studied in 24 subjects 12 months after vaccination with live Leishmania tropica major vaccine, in 10 normal control subjects and in three controls residing in an endemic area. The vaccines had lesions in various stages of clinical development. Lymphocytes from all the subjects were studied for their response to stimulation with L. tropical major promastigotes. Lymphocytes of vaccinated subjects responded to low concentrations of antigen whereas the lymphocyte response of the controls tended to be depressed by the same concentration of the antigen. Serum from each subject was subjected to a study of the humoral antibody titre against L. tropica major and L. donovani using indirect immunofluorescence. A humoral response to L. donovani was present in a majority of vaccinees who had developed a positive lesion whereas no such responses was present in any of the controls. The data suggest that high humoral responses were accompanied by relatively low cell-mediated responses and vice versa. No significant humoral response to L. tropica major could be demonstrated in any of the subjects. A combination of both the cell-mediated and humoral mechanisms may participate in the immune response although their usefulness in the assessment of the protectivity of leishmania vaccines has not been established.

Antibody Formation↗