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Biomedical subjects

R L Jacobson

Publications and source records attributed to R L Jacobson.

At least 19 recordsLinked to original sources
PubMed2001

Phlebotomus papatasi and Leishmania major parasites express alpha-amylase and alpha-glucosidase.

Alpha-amylase and alpha-glucosidase activities were found in homogenates of young, unfed male and female Phlebotomus papatasi and in gut and salivary gland preparations. A significant increase in both enzyme activities in females and of alpha-amylase in males was recorded for flies that had fed overnight on a plant (Capparis spinosa). After plant feeding, alpha-amylase activity was relatively lower in female salivary glands and higher in guts, while in the males the activity in the salivary glands had increased. Alpha-glucosidase activity increased in guts of both sexes and in the salivary glands of the females. In addition, alpha-amylase activity was found in preparations of Leishmania major and L. infantum promastigotes, but not in those of L. donovani or L. tropica. Alpha-glucosidase activity was present in promastigote preparations of L. major, L. infantum, L. donovani, L. braziliensis, Crithidia fasciculata and Herpetomonas muscarum. It was lacking in similar preparations of L. tropica, Sauroleishmania agamae or Leptomonas seymouri. The growth rate of L. major promastigotes in medium supplemented with starch or with glucose was similar and it was significantly higher than in glucose poor medium. In this study, we demonstrate that P. papatasi and L. major possess the enzymes for hydrolyzing starch grains that are included in the plant tissue-diet of the sand flies.

Animals↗
PubMed1999

Filamentous proteophosphoglycan secreted by Leishmania promastigotes forms gel-like three-dimensional networks that obstruct the digestive tract of infected sandfly vectors.

Development of Leishmania parasites in the digestive tract of their sandfly vectors involves several morphological transformations from the intracellular mammalian amastigote via a succession of free and gut wall-attached promastigote stages to the infective metacyclic promastigotes. At the foregut midgut transition of Leishmania-infected sandflies a gel-like plug of unknown origin and composition is formed, which contains high numbers of parasites, that occludes the gut lumen and which may be responsible for the often observed inability of infected sandflies to draw blood. This "blocked fly" phenotype has been linked to efficient transmission of infectious metacyclic promastigotes from the vector to the mammalian host. We show by immunofluorescence and immunoelectron microscopy on two Leishmania/sandfly vector combinations (Leishmania mexicana/Lutzomyia longipalpis and L. major/Phlebotomus papatasi) that the gel-like mass is formed mainly by a parasite-derived mucin-like filamentous proteophosphoglycan (fPPG) whereas the Leishmania polymeric secreted acid phosphatase (SAP) is not a major component of this plug. fPPG forms a dense three-dimensional network of filaments which engulf the promastigote cell bodies in a gel-like mass. We propose that the continuous secretion of fPPG by promastigotes in the sandfly gut, that causes plug formation, is an important factor for the efficient transmission to the mammalian host.

Acid Phosphatase↗
PubMed1999

Sugar meals and longevity of the sandfly Phlebotomus papatasi in an arid focus of Leishmania major in the Jordan Valley.

The sugar diet and life-span of Phlebotomus papatasi were studied in a typical zoonotic focus of Leishmania major in an arid area of the Jordan Valley during 1996-1997. Plant-tissue residues (cellulose particles) were identified in the stained guts of 23% of P. papatasi and significant amounts of sugar were found in the gut of 16%. Feeding on different plants was demonstrated by using their branches, suffused with cellulose stain, as baits in the field. Ingested, stained cellulose was detected in 10% of the sandflies (6% of males, 12.5% of females) caught near bait-branches of common local plants, mostly Chenopodiaceae. The similar rates of plant and sugar feeding, with the observed absence of aphids (ruling out the availability of honeydew), implied that the sugar meals of sandflies were obtained directly from plants. The relative paucity of sugar meals in P. papatasi coincided with a short life-span, evaluated by daily growth lines in the cuticle. The age of the oldest females was estimated to be 8 days, and 6 days for males. Under local conditions, the first gonotrophic cycle can be completed in 6 days and the usual transmission of L. major is apparently afterwards, when females ingest blood to initiate another cycle. Only about 9% of P. papatasi females survived > 6 days.

Animals↗
PubMed1999

Lectins and toxins in the plant diet of Phlebotomus papatasi (Diptera: Psychodidae) can kill Leishmania major promastigotes in the sandfly and in culture.

Leishmania major promastigotes are agglutinated and die in their vector, Phlebotomus papatasi, after the sandflies feed on some plants that are found in their natural habitat. In in-vitro assays, extracts of Ricinus communis (Euphorbiaceae), Capparis spinosa (Capparaceae), Prosopis farcta (Mimosaceae) and Tamarix nilotica (Tamaricaceae) agglutinated and killed the parasites. This activity could be inhibited by specific carbohydrates, indicating that it was the result of various lectins in the extracts. An extract of Solanum luteum (Solanaceae) lysed the promastigotes under similar conditions and this cytotoxicity was not abated by the sugars tested. High mortality of promastigotes occurred in infected flies after they ingested an extract of R. communis, even when the extract fed to the flies had been pre-mixed with glucose, a carbohydrate that inhibited the agglutination caused by such an extract in vitro. The results indicate that the lectins and toxins found in the vegetation in L. major foci may decrease the transmission of the parasite.

Animals↗
PubMed1999

Recent advances in the pathophysiology and management of preterm premature rupture of the fetal membranes.

During the past few years, meaningful progress has been achieved in our understanding of the pathophysiology of preterm premature rupture of membranes. In addition, more evidence has been presented in favor of induction and delivery for rupture between 34 and 37 weeks and expectant management for rupture before 34 weeks. New approaches are being suggested to complement expectant management. The purpose of this article is to review this recent information about the pathophysiology and management of women with preterm premature rupture of membranes.

Female↗
PubMed1998

Frequency and yield of postoperative fever evaluation.

OBJECTIVE: In women undergoing major gynecologic surgery, we wish to determine the frequency and yield of blood culture, urine culture, and chest X-ray evaluation of postoperative fever. METHODS: A retrospective review of 537 consecutive patients undergoing major gynecologic surgery was performed. In patients who developed postoperative fever, it was determined whether blood culture, urine culture, and/or chest X-ray were performed, and, if so, the frequency of positive results was evaluated. RESULTS: Two hundred eleven patients (39%) developed postoperative fever. Blood cultures were obtained in 77 of 211 (37%) febrile patients, urine cultures in 106 of 211 (50%) febrile patients, and chest X-ray in 54 of 211 (26%) febrile patients. Zero of 77 blood cultures were positive, 11 of 106 (10%) urine cultures were positive, and 5 of 54 (9%) chest X-rays were positive. Logistic regression revealed that late onset fever predicted for positive urine cultures and early onset fever and advanced age predicted for pneumonia. Eighty percent of patients with pneumonia were symptomatic. In 92% of patients with postoperative fever, no infections or pathologic process were diagnosed. CONCLUSION: Although postoperative fever is frequently evaluated by blood culture, urine culture, and chest X-ray, evaluation rarely yields positive results.

Adult↗
PubMed1998

Resistance of Phlebotomus papatasi to infection with Leishmania donovani is modulated by components of the infective bloodmeal.

The circumstances which permit the establishment of Leishmania infections in sandflies were investigated by altering the growth conditions for L. donovani parasites in the unsuitable vector Phlebotomus papatasi. Only 5.0% of the sandflies harboured a few parasites 3 days after feeding on promastigotes in defibrinated blood. Heparinized blood or the addition of trypsin inhibitor to the meals allowed persistence of infections (day 6) in 9.9% and 25.8% of the flies respectively. Meals of erythrocytes, saline and amastigotes produced 44.4% fly infection on day 6, while similar promastigote-initiated infections remained in 70.3% of the flies. Proteolytic activities in the guts of sandflies fed on the above meals without parasites, were the highest after defibrinated bloodmeals. Erythrocytes with saline decreased the maximal alkaline protease level from 20.8 U to 13.5 U/fly; that of trypsin from 3.9 U to 1.8 U/fly and that of the aminopeptidase from 5.5 U to 3.9 U/fly. After meals of heparinized blood, the maximal alkaline protease activity (12.0 U/fly) was also much lower than after defibrinated blood-feeding. The different diets which resulted in comparatively low enzymatic activities, including blood with trypsin inhibitor, also promoted the survival of infections. This implies that the proteolytic activity in the sandfly gut modulates the vector susceptibility.

Aminopeptidases↗
PubMed1997

Phlebotomine sand fly control using bait-fed adults to carry the larvicide Bacillus sphaericus to the larval habitat.

Sugar meals of plant origin are an important component of the sand fly diet. We show that sugar solution baits have potential as vehicles for phlebotomine sand fly control. In the laboratory, adult Phlebotomus duboscqi Neveu-Lemaire and Sergentomyia schwetzi (Adler, Theodor, and Parrot) that have consumed an aqueous sucrose solution containing Bacillus sphaericus Neide toxins and are subsequently eaten by larvae produce significant larval death (P < 0.01). In the field, when vegetation near animal burrows and eroded termite mounds was sprayed with sucrose solution with or without incorporation of the larval toxicant B. sphaericus, 40% of female sand flies fed in situ. Dispersing B. sphaericus-carrier sand flies caused significant larval mortality (P < 0.01) in resting and breeding sites in animal burrows 10-30 m from the sprayed vegetation for 2-12 wk posttreatment. Also, adult sand fly populations breeding and resting inside animal burrows were significantly reduced (P < 0.01) following direct application of the sucrose/B. sphaericus solution to the burrow entrances. This control effect lasted 4-10 wk post-treatment. The effect was not seen for sand fly populations breeding and resting inside eroded termite mounds. This approach may be useful for the application of biological control agents against phlebotomine sand flies in biotypes where larvae and adults use the same habitats.

Animals↗
PubMed1996

Why is man an unsuitable reservoir for the transmission of Leishmania major?

Leishmania major strains cause human cutaneous leishmaniasis in various arid regions in the Old World. Nevertheless, there is apparently no anthroponotic transmission even when the incidence of cases is very high and the involvement of reservoir animals is obligatory. To investigate this phenomenon we compared the development of L. major in Phlebotomus papatasi artificially infected with parasites in human, rabbit, or sand rat blood. The parasites, sandflies, and reservoir rodents came originally from the Jordan Valley. Following meals of promastigotes in human blood, parasites were retained in 48.0% and heavy infections developed in 6.6% of the sandflies. Such meals with sand rat blood resulted in 76.9% infected, including 58.5% heavily infected flies, whereas rabbit blood produced intermediate results. Similar results were obtained when infections were initiated with amastigotes and the infection rates were significantly different. Only flies with heavy infections are considered as potential transmitters of leishmaniasis. The adverse effect of human blood was attributed to the erythrocytes after similar experiments in which sandflies ingested promastigotes either with human erythrocytes and rabbit plasma or rabbit erythrocytes and human plasma. Amastigotes of an Israeli strain of L. major died in medium containing 50% human blood. Also, addition of 20% human blood to growth media of parasites from Israel, Kenya, or Turkemenistan caused mortality of 70 to 80% of the initial inoculum in 24 hr. At that time there was a fivefold increase in the number of Israeli parasites cultured with sand rat blood. These results imply that the vector potential and the chances of transmission are drastically decreased when man is the source of L. major parasites.

Animals↗
PubMed1995

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1991

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↗