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Biomedical subjects

A Patel

Publications and source records attributed to A Patel.

At least 505 records · Page 28Linked to original sources

The mechanism by which adenosine and cholinergic agents reduce contractility in rat myocardium. Correlation with cyclic adenosine monophosphate and receptor densities.

The adenosine analogue phenylisopropyladenosine decreased the basal and isoproterenol-stimulated contractile state of isolated rat left atria. The ED50 levels for both responses were similar, suggesting that direct and antiadrenergic effects may be mediated by the same receptor. Phenylisopropyladenosine decreased the cyclic adenosine monophosphate content of isolated atria and inhibited isoproterenol-stimulated adenylate cyclase activity in membranes prepared from atria and ventricles, but not as much as did methacholine. A maximally effective concentration of phenylisopropyladenosine or methacholine greatly reduced atrial contractility measured in the presence of either isoproterenol (1 microM) or Ro7-2956 (a phosphodiesterase inhibitor, 1 mM); however, in the presence of isoproterenol plus Ro7-2956, the contractile effects of phenylisopropyladenosine and methacholine were greatly attenuated. From the contractile data and cyclic adenosine monophosphate analyses, we conclude that direct and antiadrenergic contractile effects of both phenylisopropyladenosine and methacholine result primarily from their effects on cyclic adenosine monophosphate metabolism. The densities of adenosine, muscarinic, and beta-adrenergic receptors in rat atrial membranes were found to be 30, 551, and 24 fmol/mg protein, respectively, based on equilibrium-binding assays conducted with 125I-aminobenzyl-adenosine, [3H]quinuclidinyl benzilate, and 125I-labeled pindolol. The greater effectiveness of methacholine than phenylisopropyladenosine as a negative inotropic agent and an inhibitor of adenylate cyclase in atria may be related to the relative densities of muscarinic and adenosine receptors.

1-Methyl-3-isobutylxanthine↗

Advances in the isolation of HTLV-III from patients with AIDS and AIDS-related complex and from donors at risk.

During the last 2 yr more than 100 independent isolates of human T-cell leukemia virus type III have been obtained in this laboratory. Most isolates were from peripheral blood T-lymphocytes established in cell culture from acquired immunodeficiency syndrome (AIDS) and acquired immunodeficiency syndrome-related complex (ARC) patients and healthy donors at risk for AIDS. Several were also obtained from leukocytes from bone marrow, lymph node, and brain tissue and from body excretions, e.g., saliva and semen. In addition HTLV-III was found in cell-free plasma. The incidence (number of isolates per number of patients or donors tested) of virus isolation was approximately 80% for ARC patients, approximately 50% for AIDS patients, and approximately 30% for healthy individuals at risk for AIDS. Inclusion of hydrocortisone in cell culture medium greatly facilitated the isolation of virus from primary leukocytes from AIDS/ARC patients and also promoted its transmission to fresh leukocytes in vitro. Biological analysis of cells from infected patients or donors, as well as from normal peripheral blood mononuclear cells exposed to virus in vitro, demonstrated that OKT4/leu3a+ T-lymphocytes were preferentially infected and were subjected to a characteristic cytopathic effect. In addition to the well-defined individuals at risk for AIDS, heterosexual transmission of HTLV-III with its subsequent pathological manifestations was found. Virus was isolated from males with heterosexual promiscuity as their only recognized risk factor and from the spouses of these and other AIDS and ARC patients.

Acquired Immunodeficiency Syndrome↗

[Technic of C1-C2 fixation by posterior screwing].

A posterior screw fixation technique for C1-C2 is described which respects strict anatomical relations and allows associated posterior arthrodesis limited to C1-C2, using a single approach route. This method of posterior fixation can be used even when anomalies of the posterior arch of C1 or C2 exist, of whatever origin, as well as in the presence of a laminectomy. Four patients were operated upon using this method without any postoperative complications.

Axis, Cervical Vertebra↗

Rapid agonist-induced decrease of 125I-pindolol binding to beta-adrenergic receptors. Relationship to desensitization of cyclic AMP accumulation in intact heart cells.

Cyclic AMP accumulation in embryonic chick heart cells and binding of the beta-adrenergic antagonist 125I-pindolol to intact cells has been examined during the first 30 min of (-)-isoproterenol-induced desensitization. Myocardial beta-adrenergic receptors exist in two states which bind agonists with high (KD congruent to 10 nM) and low (KD congruent to 10 microM) affinities. Both activation and desensitization of cyclic AMP accumulation were mediated by (-)-isoproterenol binding to high affinity receptors. (-)-Isoproterenol-induced desensitization of cyclic AMP accumulation occurred with a t1/2 of 3.8 min. Desensitization was accompanied by a decrease in the number of 125I-pindolol binding sites assessed by equilibrium radioligand binding assays conducted at 4 degrees C or short (80 s) binding assays conducted at 37 degrees C. There was an excellent temporal correlation between loss of binding and loss of (-)-isoproterenol-stimulated cyclic AMP accumulation. After (-)-isoproterenol-induced desensitization, most of the remaining receptors assayed at 4 degrees C bound (-)-isoproterenol with high affinity. A rapid (-)-isoproterenol-induced decrease in the number of 125I-pindolol binding sites also occurred in adult canine heart cells and rat adipocytes. The data suggest that agonists do not cause uncoupling of surface receptors. Receptors may be uncoupled as a consequence of rapid sequestration into a hydrophobic compartment.

Animals↗

A study of an infected bone tissue (osteomyelitis) by small-angle X-ray scattering.

The small-angle X-ray scattering method has been applied to evaluate various macromolecular parameters such as the specific inner surface, the transversal lengths, the length of crystallinity, the range of amorphous zone and the percentage of porosity in pure human bone and osteomyelitis, an infection of bone tissue. The hydroxyapatite crystals of bone being uniformly dispersed throughout the hydrated collagenous matrix creating a large mineral matrix interface, we found the bone samples to behave as a densely packed two phase system. The theories of Kratky and Porod have been utilized to evaluate the macromolecular parameters. These findings may shed light on tertiary structural deformation of human bone when it is infected.

Bone and Bones↗

Comparison of latex agglutination and immunofluorescence for direct Lancefield grouping of streptococci from blood cultures.

Simulated positive blood cultures with 84 known stock strains of streptococci were used to comparatively evaluate the direct identification of these organisms by fluorescein-tagged antibody staining (immunofluorescence [IF]) and latex agglutination (LA). IF was not evaluated for Lancefield group D strains (a total of 81 strains tested) and had 89% sensitivity and 91% specificity. IF was least sensitive for the identification of Lancefield group F, in which three of seven strains showed no fluorescence with the group F reagent. Since LA was more convenient and revealed comparable sensitivities and specificities on 84 simulated cultures, we tested this procedure using an additional 29 fresh positive clinical blood cultures, for a total of 113 cultures tested by this technique. Of 11 Streptococcus pneumoniae strains, 9 reacted with the LA group C reagent, a problem not observed with IF. However, all these strains were identified by a rapid modified bile solubility test. Of the 12 Streptococcus faecalis strains, 4 were falsely negative with the group D reagent, but all were correctly identified by a rapid litmus milk reduction test. Of 12 group A strains, 1 was not detected. Of all 113 strains tested by LA, eliminating S. faecalis and S. pneumoniae, the sensitivity and specificity were 97 and 98%, respectively. LA was simple and reliable in the rapid identification of streptococci from blood cultures and appeared to be preferable to IF. When LA is used, the group D reagent should not be used, and all samples reacting with the group C reagent should be tested by a modified rapid bile solubility test to exclude S. pneumoniae.

Blood↗

A homogeneous immunoassay for cyclic nucleotides based on chemiluminescence energy transfer.

A chemiluminescent derivative of cyclic AMP, aminobutylethylisoluminol succinyl cyclic AMP (ABEI-scAMP), was synthesized in order to develop a homogeneous immunoassay based on non-radiative energy transfer. ABEI-scAMP was chemiluminescent (5.1 X 10(18) luminescent counts X mol-1 at pH 13), pure (greater than 95%) stable and immunologically active. A conventional immunoassay was established using ABEI-scAMP and a solid-phase anti-(cyclic AMP) immunoglobulin G which could detect cyclic AMP at least down to 25fmol. A homogeneous immunoassay for cyclic AMP was established by measuring the shift in wavelength from 460 to 525nm which occurred when ABEI-scAMP was bound to fluorescein-labelled anti-(cyclic AMP) immunoglobulin G. The assay was at least as sensitive as the conventional radioimmunoassay using cyclic [3H]AMP and could measure cyclic AMP over the range 1-1000nM. The homogeneous chemiluminescent energy transfer assay was also able to quantify the association and dissociation of antibody-antigen complexes. Chemiluminescence energy transfer occurred between fluorescein-labelled antibodies and several other ABEI-labelled antigens (Mr values 314-150000) including progesterone, cyclic GMP, complement component C9 and immunoglobulin G. The results provide a homogeneous immunoassay capable of measuring free cyclic AMP under conditions likely to exist inside cells.

Animals↗

Chemiluminescence energy transfer: a new technique applicable to the study of ligand--ligand interactions in living systems.

Chemiluminescent molecules can be readily detected in the range 10(-15) to 10(-18) mol, and potentially at least down to 10(-20) mol reacting/s. The chemiluminescent compound aminobutylethylisoluminol (ABEI) and its isothiocyanate derivative have been synthesized. The ABEI was coupled to rabbit immunoglobulin and cyclic AMP. These labeled antigens were stable for at least 9 months and were used to establish chemiluminescent immunoassays. When these chemiluminescent-labeled antigens bound to their respective fluorescein-labeled antibodies, a wavelength shift towards the green was detected in the chemiluminescence. This was due to chemiluminescence energy transfer and used to establish an homogenous immunoassay which could measure these antigens in biological samples at least as sensitively as conventional radioimmunoassays.

Animals↗

Intraarterial 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and systemic chemotherapy for malignant gliomas: a follow-up study.

Twenty-five adults who harbored malignant gliomas received 72 courses of intraarterial 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) (100 mg/m2) and 67 courses of systemic vincristine (1.0 mg/m2) and procarbazine (100 mg/m2) as induction therapy (BVP) followed by 106 courses of systemic 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (methyl-CCNU) (130 mg/m2), vincristine, and procarbazine as maintenance therapy (MVP). With a 6-week interval between each treatment, the median and range for the number of courses of BVP were 3 and 1 to 4 and those for MVP were 3 and 0 to 14, respectively. Fifteen patients (60%) responded to both BVP and MVP, and 10 (40%) did not. The overall median survival time was 12.7 months (range, 1.8 to 48.5+ months). Two of 3 patients who had recurrent gliomas responded and survived for 37+ to 45+ months. Seven of 10 who had nonirradiated glioblastomas responded and survived for 9 to 22 months. Four who had nonirradiated anaplastic astrocytomas all responded and survived for 38+ to 48.5+ months. Two who also received radiotherapy (1 glioblastoma and 1 primitive neuroectodermal tumor) benefited and survived for 16.9 and 28.5+ months. All who did not respond favorably died within 8 months. During the infusion of BCNU, complications included transient orbital and head pain, periorbital and scleral erythema in all patients, and a focal seizure in 1 (4%). During the 6-month induction periods, leukopenia and thrombocytopenia occurred in 1 (4%), deep vein thrombosis occurred in 9 (36%), pulmonary emboli occurred in 8 (32%), upper respiratory infections occurred in 6 (24%), pneumonia occurred in 9 (36%), and herpes zoster occurred in 1 (4%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Homogeneous immunoassay based on chemiluminescence energy transfer.

The chemiluminescent compound aminobutylethyl-isoluminol (ABEI) and its isothiocyanate derivative have been coupled to a range of haptens (progesterone, cyclic AMP, cyclic GMP) and protein antigens (IgG, C9). All the derivatives were chemiluminescent, immunologically active, and stable for more than six months. When the ABEI-labeled antigens bind to their respective fluorescein-labeled antibodies, there is a shift in the ratio of chemiluminescence at 460 nm (blue) to that at 525 nm (green). This nonradiative energy transfer was used to establish homogeneous immunoassays, which require no separation step. These assays were at least as sensitive as the conventional radioimmunoassays and could accurately measure substances in serum (i.e., for IgG, results correlated by r = 0.96 relative to those by 125I assay) and tissue extracts (cyclic AMP, r = 0.91 relative to 3H assay), and also were used to evaluate the kinetics of antibody-antigen binding. Chemiluminescence energy transfer provides a new method for quantifying ligand-ligand interactions in the 10(-15) to 10(-18) mol range without first separating bound and free ligand. This provides a unique opportunity to investigate chemical events in single cells and intact cells.

Antigens↗

[Acute primary infection due to slow-growing anaerobes after total hip arthroplasty (author's transl)].

Most early post-operative infections in total hip arthroplasty are due to aerobic bacteria. Anaerobes infections are less common and less easy to diagnose since the organisms are growing slowly. In the three patients reported the responsible organisms were detected by a strict bacteriological technique including cultures lasting more than 48 hours. Treatment consisted of re-operation and appropriate antibiotic therapy. The slow development of anaerobic bacteria makes antibiotic sensitivity tests particularly difficult to read. The need for cultures prolonged beyond 48 hours partly explains the frequency of overt suppuration in cases where standard bacteriological methods had given negative results.

Acute Disease↗

Treatment of infected pseudoarthrosis of limbs.

It was not difficult to treat an infected pseudoarthrosis without loss of bone substance by "excision-decortication-drainage" in one stage. Union was obtained in 90% of the cases. The rest required additional bone grafts. In only one case out of 41 was there persistent infection. The problem of infected pseudoarthrosis with loss of bone substance and a sizeable defect was more difficult to solve. None of the several methods of treatment employed were without complications. When the overlying skin defect was large and impossible to close in the presence of persistent sepsis at the pseudoarthrosis defect, Papineau's two stage technique of wide excision first followed by insertion of spongious autologous grafts through the granulating defect, appeared secure with minimal risk of residual osteitis in nearly 90% of the cases. 15% of the cases had poor skin healing, requiring further treatment and 20% (nearly one in five) had a stress fracture through the grafted area. One out of 35 cases had persistent pseudoarthrosis and two had persistent infection. In ten selected cases of infected pseudoarthrosis of the tibia with large skin and bone defect, a one stage method of excision, bone grafting and primary skin cover with a local gastrocnemius flap was attempted. In seven cases, primary skin healing and bone union was achieved, one patient required further bone grafting and two had recurrence of sepsis. If properly planned, this one stage method may be indicated in selected cases of infected pseudoarthrosis of the tibia.

Anti-Bacterial Agents↗

Fractures of cervical spine with neurological lesion treated by reduction and fixation with plates.

A series of 61 cases of cervical spine fracture and dislocation with neurological deficit treated operatively were reviewed. All were reduced and internally fixed with plates and screws. The operative technique was not easy and required a great deal of care and experience. Surgery did not significantly alter the neurological recovery in 12 cases with root involvement and 23 cases with complete tetraplegia. Neurological recovery seemed to be better after surgical intervention in the case of incomplete tetraplegias; 18 out of 26 being able to walk eventually. The main value of surgical fixation of these injuries was to allow early rehabilitation without any external cervical support. However, intensive care of the neuro-cardio-respiratory complications in the post-operative period was necessary to evert the high risk of mortality and morbidity from surgery.

Adolescent↗