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Biomedical subjects

D M Patel

Publications and source records attributed to D M Patel.

At least 19 recordsLinked to original sources
PubMed2001

Intercellular exchange of class II major histocompatibility complex/peptide complexes is a conserved process that requires activation of T cells but is constitutive in other types of antigen presenting cell.

Activated T cells acquire antigen presenting cell- (APC) derived class II major histocompatibility complex glycoproteins (MHCII) but the role of TCR in this process is controversial. This study provides additional evidence that ligation of TCR initiates activation-dependent processes that independently mediate acquisition of APC-derived molecules. First, intercellular exchange of MHCII resulted in the constitutive accumulation of xenogeneic rat I-A on murine B cells, whereas naïve murine T cells required activation to adsorb xenogeneic I-A. Likewise, continuous lines of B cells, basophils, and MØ from various species such as rat, mouse, and human constitutively acquired xenogeneic I-A. Second, inhibitors of T-cell activation such as wortmannin, EGTA, or mAb against I-A, TCR, LFA-1, or CD4 inhibited I-A acquisition by rested T cells but not by preactivated T cells. In conclusion, exchange of MHCII is a conserved process that requires activation of T cells but is constitutive in other types of APC.

Androstadienes↗
PubMed2001

Intercellular exchange of class II MHC complexes: ultrastructural localization and functional presentation of adsorbed I-A/peptide complexes.

Activated rat T cells, like human T cells, synthesize class II MHC glycoproteins (MHCII) and absorb MHCII from neighboring T cells. This study focused on interactions of myelin basic protein (MBP)-specific T cells that either synthesized MHCII or absorbed MHCII during activation to assess cellular structures associated with presentation of functional MHCII/peptide complexes. Synthesis of MHCII by CD4(+)TCR(+) T cells involved I-A(+) multivesicular MHC class II-like compartments (MIIC), release of MHCII(+) vesicles, and expression of MHCII on a dendritic arborization. T-cell-mediated adsorption of MHCII was a saturable process that required close cell proximity, actin polymerization, and a permissive temperature. Adsorbed MHCII existed on vesicles that were intimately associated with the responder cell membrane. T cells bearing adsorbed vesicular MHCII presented antigen and were specifically lysed by CD4(+) T cell responders, but when labeled with anti-MHCII antibody were not susceptible to complement-mediated lysis. In summary, this study reveals vesicular compartments associated with synthesis and intercellular exchange of functional MHCII/peptide complexes.

Animals↗
PubMed2000

Desmethyl tirilazad improves neurologic function after hypoxic ischemic brain injury in piglets.

OBJECTIVE: Desmethyl tirilazad is a lipid-soluble free radical quencher. Deferoxamine reduces free radicals by chelating iron and reducing hydroxyl formation. Free radical inhibitors have shown promise in several hypoxic ischemic brain injury models, and we wished to see if this work could be extended to our newborn piglet model. DESIGN: Randomized controlled trial. SUBJECTS: Piglets (0 to 3 days old). INTERVENTION: Carotid snares and arterial and venous catheters were placed under 1.5% isoflurane anesthesia. In Experiment 1, piglets were randomly assigned to receive either 3 mg/kg desmethyl tirilazad or vehicle at -15 and 90 mins. In Experiment 2, piglets were randomly assigned to receive either 20 mg/kg desmethyl tirilazad at -15 mins followed by 8 mg/kg/hr for 90 mins or 100 mg/kg deferoxamine at -15 mins or vehicle. At time 0, both carotid arteries were clamped and blood was withdrawn to reduce the blood pressure to two-thirds normal. At 15 mins, inspired oxygen was reduced to 6%. At 30 mins, the carotid snares were released, the withdrawn blood was reinfused, and the oxygen was switched to 100%. On the third day after the hypoxic ischemic injury, the animals were killed by perfusing their brains with 10% formalin. We tested the timing of lipid peroxidation and inhibition of lipid peroxidation by these agents by freezing the brains of a subset of pigs in liquid nitrogen. MEASUREMENTS: Neurologic examination and brain pathology were scored by blinded observers. Thiobarbituric acid-reactive substance and oxidized and reduced glutathione were measured on frozen brains. MAIN RESULTS: Desmethyl tirilazad (20 mg/kg) and 100 mg/kg deferoxamine inhibit lipid peroxidation. Desmethyl tirilazad (20 mg/kg) improves neurologic exam, but 3 mg/kg Desmethyl tirilazad or 100 mg/kg deferoxamine does not. Neither desmethyl tirilazad nor deferoxamine improves pathologic results. CONCLUSIONS: High-dose desmethyl tirilazad improves neurologic function after hypoxic ischemic brain injury in the newborn piglet.

Animals↗
PubMed1999

Class II MHC/peptide complexes are released from APC and are acquired by T cell responders during specific antigen recognition.

T cell expression of class II MHC/peptide complexes may be important for maintenance of peripheral self-tolerance, but mechanisms underlying the genesis of class II MHC glycoproteins on T cells are not well resolved. T cell APC (T-APC) used herein were transformed IL-2-dependent clones that constitutively synthesized class II MHC glycoproteins. When pulsed with myelin basic protein (MBP) and injected into Lewis rats, these T-APC reduced the severity of experimental autoimmune encephalomyelitis, whereas unpulsed T-APC were without activity. Normal MBP-reactive clones cultured without APC did not express class II MHC even when activated with mitogens and exposed to IFN-gamma. However, during a 4-h culture with T-APC or macrophage APC, recognition of MBP or mitogenic activation of responder T cells elicited high levels of I-A and I-E expression on responders. Acquisition of class II MHC glycoproteins by responders was resistant to the protein synthesis inhibitor cycloheximide, coincided with transfer of a PKH26 lipophilic dye from APC to responders, and resulted in the expression of syngeneic and allogeneic MHC glycoproteins on responders. Unlike rested I-A- T cell clones, rat thymic and splenic T cells expressed readily detectable levels of class II MHC glycoproteins. When preactivated with mitogens, naive T cells acquired APC-derived MHC class II molecules and other membrane-associated proteins when cultured with xenogeneic APC in the absence of Ag. In conclusion, this study provides evidence that APC donate membrane-bound peptide/MHC complexes to Ag-specific T cell responders by a mechanism associated with the induction of tolerance.

Adoptive Transfer↗
PubMed1999

Role of postnatal penicillin prophylaxis in prevention of neonatal group B streptococcus infection.

This prospective study was designed to identify the role of postnatal penicillin prophylaxis in the prevention of neonatal group B streptococcus (GBS) infection. We studied 10 998 infants. Of these, 5389 were in the penicillin prophylaxis group (PP) and 5609 infants did not receive penicillin prophylaxis (NPP). Infants were allocated to treatment by month of birth, alternating 3-mo blocks or 2-mo blocks to the two groups after the first block was randomly assigned. The use of PP reduced the incidence of clinical sepsis (1.7% PP versus 2.5% NPP, p < 0.01), GBS infection (0.4% PP versus 0.9% NPP, p < 0.001) and deaths from sepsis (0.1% PP versus 0.3% NPP, p < 0.05). We conclude that the routine use of postnatal penicillin prophylaxis appears to be effective in reducing the incidence of clinical sepsis and death from sepsis in neonates.

Antibiotic Prophylaxis↗
PubMed1997

Immunogenicity of hepatitis B vaccine in healthy very low birth weight infants.

We studied the immunogenic response to hepatitis B vaccine of infants weighing < or = 1500 gm at birth. Infants were divided into two groups: those weighing < or = 1000 gm (n = 22) and those weighing 1001 to 1501 gm (n = 28). When immunized early (3 days of age, n = 25), these infants had a response rate (defined as antibody to hepatitis B surface antigen titer > 10 mIU/ml) of 68%, whereas when the first vaccine was given at 1 month of age (n = 25), a 96% response rate was noted, irrespective of birth weight and weight at the time of immunization (p < 0.02).

Hepatitis B↗
PubMed1995

AMPA antagonist LY293558 does not affect the severity of hypoxic-ischemic injury in newborn pigs.

BACKGROUND AND PURPOSE: LY293558 is a systemically active alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) excitatory amino acid antagonist. AMPA antagonists have shown promise in several adult hypoxic-ischemic brain injury models, and we wanted to see if this work could be extended to a newborn animal. METHODS: Seventy-six (beta error < .10) 0- to 3-day-old piglets under 1.5% isoflurane anesthesia underwent placement of carotid snares and arterial and venous catheters. While paralyzed with succinylcholine under 0.5% isoflurane, 50% nitrous oxide, piglets were randomly assigned to receive either 5 mg/kg or 15 mg/kg of LY293558 or saline at time--10 minutes and again 10 hours later. At time 0, both carotid arteries were clamped, and blood was withdrawn to reduce the blood pressure to two thirds of normal. At time 15 minutes, inspired oxygen was reduced to 6%. At time 30 minutes, the carotid snares were released, the withdrawn blood was reinfused, and the oxygen was switched to 100%. On the third day after the hypoxic-ischemic injury, the animals were killed by perfusion of the brain with 10% formalin. Brain pathology was scored by a blinded observer. RESULTS: There were no significant differences between the drug-treated and control groups. CONCLUSIONS: The systemically active AMPA antagonist LY293558, when given at a dose of 5 mg/kg or 15 mg/kg before injury and 10 hours later, does not affect the severity of hypoxic-ischemic brain injury in newborn piglets. Neither AMPA receptor activity nor NMDA receptor activity are important in brain injury in this model.

Animals↗
PubMed1994

Leucine kinetics during a brief fast in diabetes in pregnancy.

The effect of diabetes in pregnancy on leucine turnover and oxidation was examined in 12 insulin-dependent diabetic (IDDM) subjects and 12 gestationally diabetic (GDM) subjects during the third trimester of pregnancy. The data were compared with those in normal pregnant women studied during the same time period and reported previously. Eight of the IDDM subjects were on continuous subcutaneous insulin infusion (insulin pump), and four were on conventional twice-daily insulin treatment. Of the GDM group, seven were on insulin therapy and five were on dietary management. Leucine kinetics were quantified using [1-13C]leucine tracer in combination with respiratory calorimetry and measurement of lean body mass using the H2[18O] dilution method. In addition, glucose kinetics were measured in insulin-treated subjects using [6,6(2)H2]glucose tracer. Despite rigorous metabolic control, fasting plasma glucose (IDDM 5.5 +/- 1.9 mmol/L [P < .05], GDM 4.7 +/- 1.3 [P < .01], controls 3.6 +/- .6, mean +/- SD) and hemoglobin A1 ([HbA1] IDDM 7.9 +/- 1.9%, GDM 7.5% +/- 2.1%) levels were higher in diabetic subjects. Although total insulin levels were higher in insulin-treated diabetic subjects, free-insulin concentrations were similar in all groups. Rates of excretion of urinary urea nitrogen and respiratory quotients were also similar. The rate of glucose turnover was lower in insulin-treated subjects compared with normals. Leucine flux, a measure of the rate of protein breakdown, and leucine oxidation were higher in IDDM and insulin-treated GDM subjects. The rate of leucine oxidation was increased in conventionally managed IDDM and insulin-treated GDM subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Postnatal penicillin prophylaxis and the incidence of group B streptococcal sepsis in neonates.

We conducted a retrospective chart review of infants, born over a 3-year period, who had positive urine latex agglutination and/or positive blood culture for group B streptococci (GBS). Infants routinely received intramuscular aqueous penicillin for the first half of the study period, and no penicillin was given for the subsequent 18 months. Overall, infants who received penicillin prophylaxis had a decreased incidence of clinical sepsis and positive blood culture for GBS (4.8/1,000 versus 8/1,000 and 1.3/1,000 versus 5.4/1,000, respectively). The incidence of GBS sepsis during the time of penicillin prophylaxis was not different from that in previously reported studies. When analyzed by weight groups, no difference in clinical sepsis or positive blood cultures for GBS was seen in the subset of infants weighing < or = 2,500 g at birth. There were fewer positive blood cultures in the infants who received penicillin and met the criteria for clinical sepsis. Mortality from GBS sepsis was unchanged during these two study periods in all weight groups.

Female↗
PubMed1993

Demographic data of the neonatal intensive care population of a county hospital in Texas.

Morbidity and mortality associated with neonatal intensive care affect strongly the socioeconomic aspect of the health-care system. A retrospective study of the neonatal intensive care population at a county hospital in Texas showed that most deaths were related to nontreatable causes. Prematurity was a major cause both of increased mortality and morbidity. Although improved management of a premature infant with hyaline membrane disease using artificial surfactant improved survival, this treatment did not change the morbidity. The incidence of morbidity was related directly to the degree of prematurity. Illicit drug use also had a direct correlation with infants who had low birth weights. Overall, the mortality and morbidity data were consistent with incidence data reported nationally.

Black People↗
PubMed1992

Episodic release of luteinizing hormone and testosterone in Surti and Marwari bucks younger than one year of age.

Studies on the episodic release of luteinizing hormone (LH) and testosterone in Surti (n=2) and Marwari (n=2) bucks younger than one year of age (6 to 8 months) were carried out by collecting blood plasma during the breeding season. The studies revealed that definite pulsatile releases of LH and testosterone occur in both breeds of bucks. The overall number of LH and testosterone pluses over a 24 hour period was 9.1+/-1.00 and 7.5+/-0.28, respectively. The peak, basal and mean LH and testosterone concentrations did not show significant differences between the two breeds. The duration and interval of LH and testosterone pulses differed during light and dark hours. The time interval between LH peak followed by the testosterone peak was significantly (P<0.05) longer during the night than the day hours for both the breeds. The physiological basis of the findings are discussed.

Journal Article↗
PubMed1988

Cutaneous fistula communicating with the hip in a patient with a painful total hip prosthesis. Demonstration by radionuclide arthrography.

Radionuclide arthrography is becoming increasingly useful in the evaluation of femoral component loosening in patients with a painful total hip prosthesis. Additional potential advantages of radionuclide arthrography include detection of abnormal communications with the hip, such as bursae, abscess cavities, and fistulas. A case of cutaneous fistula communicating with the hip in a patient with loosening and infection of the femoral component of the total hip prosthesis that is clearly demonstrated by radionuclide arthrography is presented.

Aged↗
PubMed1987

ICMR task force study on hormonal contraception. Transfer of levonorgestrel (LNG) administered through different drug delivery systems from the maternal circulation into the newborn infant's circulation via breast milk.

The transfer of levonorgestrel (LNG) from the maternal plasma via breast milk to the infant was studied in 38 fully lactating and breast-feeding women at 4-6 weeks postpartum, for a duration of 28 days. These volunteers were provided with LNG contraceptive treatment delivered through three, different routes of drug delivery system: (i) intrauterine devices impregnated with LNG (LNG-IUD); (ii) subdermal implant (Norplant (R)-2); and (iii) minipills (LNG 30 micrograms daily). On the first day after either the LNG-IUD (n = 14 women) or Norplant (R)-2 (n = 14 women) insertion, the maternal blood and breast milk samples were collected at 2, 4 and 8 hourly intervals. This was followed by daily collection of these samples as well as infant's blood from days 2 to 4 and thereafter on days 7, 14 and 28. For infant's blood samples from LNG minipill users (n = 10 women), only a single 4-hour sample was collected on the first day and no samples were collected on days 3 and 4. The rest of the schedule for collection of maternal blood and breast milk as well as infant's blood samples were the same in minipill users as for the other two treatment groups. The study revealed a lower LNG percentage transfer from maternal sera to breast milk--11.8 +/- 2, 7 +/- 2 and 8 +/- 1 and relatively higher percentage LNG transfer from breast milk to infant's sera--75 +/- 17, 68 +/- 20 and 32 +/- 3, in LNG-IUD, Norplant (R)-2 and minipill users, respectively. Therefore, LNG contraceptive steroid is transferred into the infant's circulation, the biological significance of which remains to be established.

Administration, Oral↗
PubMed1986

Pharmacodynamic effects of levonorgestrel (LNG) administered either orally or subdermally to early postpartum lactating mothers on the urinary levels of follicle stimulating hormone (FSH), luteinizing hormone (LH) and testosterone (T) in their breast-fed male infants.

Pharmacodynamic effect of levonorgestrel (LNG) present in small amounts in infant's circulation has not yet been studied adequately. In our present study, nine women were taking oral minipills (LNG 30 micrograms daily) and 10 were using subdermal implants, Norplant(R)-2, during early postpartum period from four weeks to 15 weeks. These were healthy lactating women in age group 20 to 35 yrs, who had full-term normal delivery of male infants. Daily 4-hour urine samples (from 8 AM to 12 noon) were collected from four weeks onwards to 15 weeks for estimations by radioimmunoassays of follicle stimulating hormone (FSH), luteinizing hormone (LH) and testosterone (T) levels. No significant differences (P greater than 0.05) were found between geometric means of the total area under curve at weekly intervals for FSH, LH and T hormones between the male infants from control group (n=10) when compared with oral minipill or Norplant(R)-2 users. These results are reassuring for future sexual growth and development of children who are exposed to contraceptive steroids during their infancy; however, they do require further confirmation by long-term epidemiological studies incorporating monitoring and surveillance of such children.

Administration, Oral↗
PubMed1984

Effects of insulin and hydrocortisone on lung tissue phosphatidyl choline and disaturated phosphatidyl choline in fetal rabbits in vivo.

To determine the effects of insulin and hydrocortisone on lung tissue surfactant, the fetuses of New Zealand White rabbits were injected with insulin, saline (0.154 mol/l), insulin+hydrocortisone, insulin+saline or saline+hydrocortisone, or were sham-operated on day 27 of gestation. Twenty-four hours later (on day 28 of gestation) delivery was accomplished by Caesarian hysterectomy. The lung tissues were analysed for phosphatidyl choline and disaturated phosphatidyl choline. Both were higher in fetuses injected with insulin than in sham-operated control animals. The phosphatidyl choline and disaturated phosphatidyl choline were also higher in the fetuses injected with insulin+hydrocortisone than in fetuses injected with insulin or hydrocortisone alone. These results suggest that insulin increases the phosphatidyl choline and disaturated phosphatidyl choline content in lung tissue in fetal rabbits in vivo, and that in the presence of hydrocortisone, insulin appears to have an additive effect.

Animals↗
PubMed1984

Value of radionuclide angiogram for the diagnosis of Ebstein's anomaly.

A radionuclide angiogram in a patient with Ebstein's anomaly showed a very dilated right atrium with a minimally enlarged right ventricle and a normal sized left ventricle. This study led to the establishment of a definitive diagnosis by means of an echocardiogram. Late close of the tricuspid valve was demonstrated. In addition prolapse of the tricuspid and mitral valves was documented. A tricuspid valve prolapse has never been reported in this condition.

Blood Pressure↗