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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

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

Plasmodium berghei adoptive transfer and immunosuppression of immunity in allogenic neonates.

Outbred female rats were hyperimmunized with Plasmodium berghei and mated to produce progeny. Spleen cells from the immunized rats and from normal control mothers were adoptively transferred to their 48 hr old neonates. Some neonates from immune mothers were fostered to normal mothers and vice versa. Weanling rats were challenged 35 days after birth with Plasmodium berghei; immune and normal litters which had not received cells were also challenged at the same time. Rats which had received immune spleen cells from their mothers but were fostered on to non-immune mothers showed significantly lower parasitaemias and higher fluorescent antibody titres than any other combination of cell transfer and maternal milk. GVH reaction was minimal. These results suggest that the immune response to P. berghei was suppressed in the presence of passively transferred maternal antibody.

Animals

Hear! Hear!

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Communication

The passage of serum immunoglobulins through the gut of Sarcophaga falculata, Pand.

Rabbits were immunized with brain, muscle or haemolymph of adult Sarcophaga falculata, and groups of Sarcophaga were then fed on serum collected from the immune rabbits. Rabbit serum immunoglobulins on the tissues of the fed flies were demonstrated by the indirect fluorescent antibody method, using fluorescent goat-anti-rabbit IgG. The antibodies were specifically demonstrated in the tissues that had been used as immunizing antigen. It was also shown that antibodies unrelated to fly antigens pass through the fly gut and react with the specific antigens.

Animals

Patterns of clinical response and plasma dopa levels in Parkinson's disease.

Serial determinations of plasma dihydroxyphenylalanine (dopa) in 16 Parkinson's disease patients receiving levodopa showed a negative correlation between plasma dopa levels and disability scores among patients who exhibited daily fluctuations of signs and symptoms. This suggests that the amount of levodopa delivered to the brain from the periphery is of major importance in the production of the "on-off" phenomenon. A close relationship between plasma dopa levels and abnormal involuntary movements was present in six patients. In three a striking dissociation between control of Parkinson's disease and abnormal involuntary movements was present, suggesting that in some patients these two effects are mediated through different underlying mechanisms. Administration of levodopa in such a way as to prevent both high and low levels of dopa in plasma minimizes disability in Parkinson's disease and may lessen abnormal involuntary movements in patients with the "on-off" effect.

Adult

Catecholamine content of cerebral tissue after occlusion or manipulation of middle cerebral artery in cats.

The authors determined by fluorimetry the norepinephrine-epinephrine content (NE-E) of cerebral tissue from 38 cats, to ascertain whether constriction of hypersensitive arterial vessels by vasoactive agents in ischemic cerebral tissue could cause extension of cerebral infarcts and worsening of neurological deficits. Twenty-three cats had the left middle cerebral artery (MCA) occluded transorbitally, and 10 cats had sham operations. Five cats had only the surgical procedures necessary for obtaining tissue; mean NE-E content was 0.30 mug/gm (SD=0.041). For the other 33 cats, including those with sham operations, values were variable, ranging from 0.07 to 0.60 mug/gm. Low values usually were obtained for ischemic hemispheres 24 hours and 7 days after MCA occlusion, but at other times values could be high or low on either side. Many factors unrelated to tissue damage, including arterial manipulation, influence the catecholamine content of cerebral tissue.

Animals

Released glycoconjugate of indigenous Leishmania major enhances survival of a foreign L. major in Phlebotomus papatasi.

The effect of Leishmania glycoconjugate in the vector was investigated using Phlebotomus papatasi artificially infected with a Leishmania major strain that this vector does not transmit in nature. Glycoconjugate of the vector-specific strain of L. major was added to the infective meals of some fly groups and the success of infections with or without this substance was compared 4 d later. In the absence of glycoconjugate the parasites survived in 15.6% of the flies, while the addition of 0.5 mg/ml and 2 mg/ml raised the rate of infection to 34.3% and 63.0% respectively. Undigested blood was found in the stomach of 7.8% of the infected flies, whereas following meals with parasites and 2 mg/ml glycoconjugate it was present in 37% of the flies. The results demonstrated that this glycoconjugate increased the viability of the parasites in the unsuitable vector and delayed digestion of the infective meals. In a parallel experiment the glycoconjugate of L. donovani did not affect the survival of the parasites.

Animals