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Biomedical subjects

N Desai

Publications and source records attributed to N Desai.

At least 55 records · Page 3Linked to original sources
PubMed1997

Transgenic plants: an emerging approach to pest control.

Insect pests are a major cause of damage to the world's commercially important agricultural crops. Current strategies aimed at reducing crop losses rely primarily on chemical pesticides. Alternatively transgenic crops with intrinsic pest resistance offer a promising alternative and continue to be developed. The first generation of insect-resistant transgenic plants are based on insecticidal proteins from Bacillus thuringiensis (Bt). A second generation of insect-resistant plants under development include both Bt and non-Bt proteins with novel modes of action and different spectra of activity against insect pests.

Animals↗
PubMed1997

Use of Synthetic Serum Substitute and alpha-minimum essential medium for the extended culture of human embryos to the blastocyst stage.

This study was designed to provide further information on mouse and human embryo development in alpha-modified minimum essential medium (alphaMEM). First, we compared the development and implantation potential of murine in-vitro fertilized (IVF) embryos cultured in alphaMEM, in the presence and absence of co-culture cells. No significant difference was observed in blastocyst rate between alphaMEM alone (76.2%) and alphaMEM plus co-culture (79.9%). The percentage of hatched blastocysts was, however, higher with co-culture (47.5 versus 40%, P < 0.01). Transfer of blastocysts to pseudopregnant foster mothers resulted in similar live birth rates (14.9% alphaMEM alone versus 19.8% alphaMEM/co-culture). alphaMEM was also introduced into our clinical IVF programme for culture of human embryos beyond day 3. Spare human embryos were cultured under oil in microdrops of alphaMEM supplemented with 10% synthetic serum substitute. Blastocysts were evaluated for maturity and the presence and organization of the inner cell mass. A total of 206 embryos from 53 IVF patients underwent extended culture. The overall blastocyst rate was 45.1%. An inner cell mass was observed in 76 blastocysts (81.7%). With regard to developmental maturity, approximately 73% of blastocysts that had been frozen were expanding (cavity > 50% embryo volume) or fully expanded. These data suggest that alphaMEM in conjunction with a commercial protein preparation such as Synthetic Serum Substitute may be a good basal medium for culture of human embryos to the blastocyst stage.

Animals↗
PubMed1997

Regulation of EBNA gene transcription in lymphoblastoid cell lines: characterization of sequences downstream of BCR2 (Cp).

During Epstein-Barr virus (EBV) latent infection of B lymphocytes in vitro, six EBV nuclear antigens (EBNAs) are expressed from one of two promoters, Cp and Wp, whose activities are mutually exclusive. Upon infection, Wp is initially active, followed by a switch to Cp for the duration of latency. In this study, the impact on Cp and Wp activity of sequences downstream of the distal EBNA gene promoter, Cp, was assessed in two lymphoblastoid cell lines. Cp activity was detected in constructs extending from just upstream of oriP to the first W1 exon. In contrast, Wp activity required the presence of the next downstream exon, W2. Viral sequences from -2199 to +2680 bp, relative to the Cp transcription start site, were dispensable for Wp activity. Sequences from +155 to +2680 bp, relative to the Cp transcription start site, were dispensable for Cp activity. Deletion of a 200-bp region from +2680 to +2880 bp downstream of Cp decreased both Cp and Wp activity two- to fivefold. Wp activity was also significantly diminished by deletion of the sequences from +2880 to +3000 bp downstream of the Cp transcription initiation site, which encompassed the Wp CCATT box. Based on deletion analyses of 10.3 kb of viral genomic sequence extending from just upstream of oriP to the first Wp, the only deletions which significantly upregulated Wp activity were those which abrogated Cp activity. However, reporter constructs in which the orientation of Cp was reversed displayed Wp activity comparable to that of reporter constructs in which Cp was deleted, even though the steady-state level of Cp-initiated transcripts from the inverted promoter was indistinguishable from that observed with Cp in normal orientation. This is the first direct evidence to support transcriptional interference as the mechanism for the mutually exclusive behavior of Cp and Wp.

Cell Line↗
PubMed1997

A fast hemoglobin variant on newborn screening is associated with alpha-thalassemia trait.

Alpha thalassemia trait (alpha-thal-1) is a common cause of microcytosis in black and Asian populations. A small amount of hemoglobin Barts (2-8%) is transiently present in affected infants at birth and detectable in many newborn screening laboratories; it is a fast-moving hemoglobin on electrophoresis. In order to determine whether a report of a "fast hemoglobin variant" on newborn hemoglobinopathy screening is associated with a diagnosis of alpha thalassemia trait, hemoglobin concentration, red blood cell indices, and peripheral blood smear examination were performed on 18 infants referred for hematologic evaluation of a "fast hemoglobin variant" on newborn screening. All 18 infants with this diagnosis referred for consultation were black; ages ranged from 24 to 86 days (median 40 days). Six of 18 infants (33%) were mildly anemic for age and all 18 were microcytic. The prevalence of a "fast variant" among infants born at our institution is 2.5%. In that conditions other than alpha-thal-1 that cause microcytosis in early infancy are very uncommon, we conclude that all 18 of our infants with a fast hemoglobin on newborn screening likely have alpha-thal-1. The newborn screening result is thus a commonly and readily available laboratory report that specifically supports a diagnosis of alpha-thal-1, a diagnosis with significant clinical and genetic implications that is usually made only by exclusion.

Hemoglobins↗
PubMed1996

Prospective angiographic study of the abnormalities of systemic venous connections in congenital and acquired heart disease.

UNLABELLED: Angiographic definition of systemic venous connections was obtained prospectively in 780 consecutive patients with congenital heart disease and 102 patients with acquired valvular heart disease undergoing cardiac catheterization. Attempts were made to enter the innominate vein and perform a balloon occlusion angiogram in each patient. In patients with congenital heart disease, bilateral superior vena cava were present in 32/771 patients (approximately 4%) with levocardia and 3/9 patients with dextrocardia. Among patients with bilateral superior vena cava (n = 35), an innominate vein of variable size that could be entered was present in six patients. Small tributaries connecting the right and left superior vena cava were found and entered in six patients. The superior vena cava was entered via its connection to morphologic left atrium in five patients and via the coronary sinus in 17 patients. Abnormalities of the inferior vena cava were seen in 7/780 patients. The following abnormalities of the inferior vena cava were noted: azygous continuation of rightsided inferior vena cava in levocardia -- 3 patients, hemiazygos continuation of the leftsided inferior vena cava in levocardia -- 1 patient, azygos continuation of the leftsided inferior vena cava in dextrocardia -- 1 patient, interruption of inferior vena cava below the liver with a plexus of veins joining the azygos vein -- 1 patient, and an inferior vena cava draining into the leftward aspect of the common atrium -- 1 patient. Abnormalities of the systemic venous connections were seen in 2/102 patients with acquired heart disease: bilateral superior vena cava in 1 patient and bilateral inferior vena cava in 1 patient. CONCLUSIONS: Abnormalities of systemic venous connections were seen in approximately 5% patients with congenital heart disease and approximately 2% patients with acquired heart disease. Small tributaries or an innominate vein of variable size often connect left and right superior vena. Contrast material can be injected into these connections to document the presence of bilateral superior vena cava.

Adolescent↗
PubMed1996

Optimizing expression of transgenes with an emphasis on post-transcriptional events.

Introducing a foreign gene into a new plant host does not always result in a high level of expression of the incoming gene. Numerous promoters have been used to express foreign genes in different plant tissues, but there are sometime various features of the new gene which are deleterious to expression in the new host. There are a number of post-transcriptional steps in the expression of a gene and sometimes sequences present in a particular coding region can resemble the signals which initiate these processing steps. When aberrantly carried out, these steps diminish the level of expression. By removing such fortuitous signals, one can dramatically increase expression of a transgene in plants. Ensuring proper protein folding and/or targeting the protein product to a particular cellular compartment can also be used to increase the level of protein obtained. The various methods used to optimize expression of a foreign gene in plants by concentrating on post-transcriptional events are discussed.

Chloroplasts↗
PubMed1996

B19 parvovirus infection and transient aplastic crisis in a child with sickle cell anemia.

Transient aplastic crisis is reported in a young child with sickle cell anemia with acute B19 parvovirus infection. She also developed acute chest syndrome and bone marrow/bone infarction involving the right ilium. The clinically unsuspected bone marrow infarction in this patient may have contributed to acute chest syndrome secondary to pulmonary fat embolism. Transient cessation of erythropoiesis as a result of B19 parvovirus infection, and not the localized bone marrow infarction, was the probable cause of reticulocytopenia and worsening of anemia in this child.

Acute Disease↗
PubMed1995

Active transport of cimetidine into human milk.

Most xenobiotics are transferred from blood into breast milk by passive diffusion. However, an active transport mechanism has been speculated for cimetidine, and the purpose of this study was to characterize cimetidine transfer into human milk. Twelve healthy lactating volunteers received single oral doses of 100, 600, and 1200 mg cimetidine in a randomized, crossover design on 3 different days. Blood and milk specimens were collected and assayed for cimetidine. In vitro measurements, including skim to whole milk concentration ratio, milk pH, and free fractions in serum and milk were used for a diffusion model prediction of milk to serum concentration ratio of cimetidine; the mean milk/serum ratio (+/- SD) was 1.05 +/- 0.18. The observed milk/serum ratio (5.77 +/- 1.24) was 5.5 times higher than the milk/serum ratio predicted by diffusion. The observed milk/serum ratio for the three dosing regimens were not significantly different from one another. Time of peak concentration (tmax) in milk (3.3 +/- 0.7 hours) displayed a delay compared with serum tmax (1.7 +/- 0.6 hours). Oral clearance for 1200 mg cimetidine dose (0.47 +/- 0.11 L/hr/kg) was significantly lower compared with oral clearance values for 100 and 600 mg cimetidine doses (0.59 +/- 0.11 and 0.57 +/- 0.13 L/hr/kg, respectively). The maternal dose of cimetidine ingested by a suckling infant based on body weight was estimated to be 6.7%, which appears to be safe under normal conditions. This study provides the first definitive evidence of an active transport system for drug transfer into human milk, which may have broader consequences for the suckling infant.

Administration, Oral↗
PubMed1995

Anti-pneumococcal antibody levels three to seven years after first booster immunization in children with sickle cell disease, and after a second booster.

We measured pneumococcal antibody levels in 55 patients (ages 7 to 20 years) with sickle cell disease 3 to 7 years after the first booster immunization. Only 6 of the children had protective levels of antibodies (> 300 ng/ml) against all 12 serotypes tested. Thirty-two children (58%) had suboptimal levels against 1 to 3 serotypes; 17 had suboptimal levels against 4 to 10 serotypes. Ten patients from the latter group (ages 13 to 17 years) received a second booster 6 to 8 years after the first booster immunization, and had a marked increase in antibody levels against all serotypes with the exception of serotypes 3 and 4 in two patients and serotype 6A in one patient.

Adolescent↗
PubMed1995

Pharmacokinetics in lactating women: prediction of alprazolam transfer into milk.

1. Alprazolam, a triazolobenzodiazepine, is extensively prescribed for the treatment of anxiety disorders, which predominantly affect women of child-bearing age. The purpose of the present study was to assess the pharmacokinetics of alprazolam and its two hydroxylated metabolites: 4-hydroxy-alprazolam and alpha-hydroxy-alprazolam in lactating human volunteers and to test the predictability of four recently reported models for drug transfer into milk based on physicochemical properties. 2. Multiple milk and serum samples in eight lactating subjects were collected up to 36 h following single oral doses of 0.5 mg alprazolam; suckling of the infant was discontinued after drug administration. 4-Hydroxy-alprazolam was the predominant metabolite in serum samples while alpha-hydroxy-alprazolam was not detected. 3. The mean oral clearance of alprazolam was 1.15 +/- 0.32 ml min-1 kg-1. The time course of alprazolam in milk roughly paralleled the perspective plasma time profile (mean serum residence time = 16.42 +/- 4.69 h; mean milk residence time = 18.93 +/- 7.03 h). The mean terminal half-life in serum was 12.52 +/- 3.53 h. 4. Observed milk/serum concentration ratios were determined in vivo as AUCmilk/AUCserum (mean M/S(obs) = 0.36 +/- 0.11).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Deletion of donor-reactive T lymphocytes in adult mice after intrathymic inoculation with lymphoid cells.

Clonal deletion of self antigen-reactive T lymphocytes is known to be a dominant mechanism of tolerance induction in the normal immune system. This report considers whether deletion of antigen-reactive T cells is also the immunologic basis for the recently described model of transplantation tolerance that follows intrathymic inoculation with allogeneic lymphoid cells. We found that the outcome of injecting Mlsa- hosts with lymphocytes from Mlsa+ donors was depletion of V beta 6+ T cells (which are known to be reactive with the Mlsa superantigen). The process was found to be specific in that a similar reduction was not seen in an irrelevant T cell population (V beta 8+) in IT injected hosts. Deletion was observed in this model only if immunosuppression with ALS or anti-CD4 accompanied intrathymic injection. When the inoculum of allogeneic lymphocytes was administered intravenously instead of intrathymically only minimal deletion was observed. The induction of transplantation tolerance by intrathymic injection of donor lymphoid cells may prove especially efficacious since it relies on deletion of only those T cells specifically reactive to donor antigens, a process analogous to tolerance induction to self antigens.

Animals↗
PubMed1993

The specificity of alternative complement pathway-mediated lysis of erythrocytes: a survey of complement and target cells from 25 species.

Sera from 20 species of mammals were tested for their ability to lyse erythrocytes from 18 species of mammals and birds by the alternative complement pathway. Erythrocytes were not lysed by homologous complement, with one minor exception, but all erythrocytes tested were lysed by at least one complement source, and all sera tested except that of the horse lysed at least one type of erythrocyte. Control experiments indicated that lysis was via the alternative complement pathway and that antibodies were not involved. Complement from the various species could be ranked from most active to least active, and erythrocytes could be ranked from most susceptible to least susceptible. There was an inverse correlation between complement activity and erythrocyte susceptibility. The ranking of the orders of placental mammals, from strongest to weakest complement, was carnivore > artiodactyl (ruminants and swine) > primate = armadillo > rodent > rabbit > horse. Opossum serum had activity that placed it in the centre of this range. Ferret complement, the most potent tested, lysed all erythrocytes tested except for homologous erythrocytes, with APCH50 titres as high as 4000. Although the overall reactivity pattern was clear, there were several striking exceptions. For example, the only complement source which lysed ferret erythrocytes was sera of the mouse. The amount of sialic acid present on erythrocytes of 14 mammals was determined, and was, in general, directly correlated with resistance to alternative complement pathway lysis, although there were prominent exceptions to this correlation, involving erythrocytes of the horse, burro and human. All 20 types of complement were also tested for their ability to lyse antibody-coated human tumour cells, under conditions in which both the classical and alternative complement pathways were functional. The data obtained suggest that alternative pathway activation is, in some cases, a major factor determining the effectiveness of a particular complement source in the lysis of xenogeneic tumour cells.

Animals↗
PubMed1993

Hypertension as a paraneoplastic phenomenon in childhood Hodgkin's disease.

A 14 year old girl with Hodgkin's disease presented with hypertension as an unusual paraneoplastic phenomenon. The elevated plasma renin activity recorded in this patient was possibly a result of Hodgkin's disease. Hypertension as well as plasma renin activity declined to normal values following her successful response to chemotherapy.

Adolescent↗