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Biomedical subjects

R E Smith

Publications and source records attributed to R E Smith.

At least 199 records · Page 11Linked to original sources

Immunopathology of chronic experimental histoplasmic choroiditis in the primate.

A nonhuman primate model of ocular histoplasmosis was developed that enabled the authors to define the choroidal cellular immunopathology of both the acute and chronic phases of experimental histoplasmic choroiditis. Anti-human monoclonal antibodies were used to identify the inflammatory cell subsets and to calculate their relative percentages in the choroidal inflammatory lesions. Comparison of the acute (less than or equal to 65 days) and chronic (greater than or equal to 1 yr) phases suggested possible variations in the evolution of these lesions, resulting in the development of immunopathologically distinct chronic lesions. In this model, these late lesions could be differentiated by the presence or absence of dense lymphocytic foci, comprised predominantly of mature B-lymphocytes, located within the more diffuse inflammatory cell background. The chronic lesions containing these B-cell foci had significantly higher percentages of both mature B-cells (P less than 0.0001) and helper-inducer T-cells (P less than 0.05) than did the chronic lesions without B-cell foci. The increase in helper-inducer T-cells in the chronic lesions with B-cell foci resulted in a higher mean helper-suppressor T-cell ratio (mu = 0.60) than that seen in lesions lacking foci (mu = 0.33). These findings suggest that, even in the same eye, individual chronic histoplasmic choroidal lesions, which clinically resemble "histo spots" in humans, may have different immunopotentials.

Acute Disease↗

Repair of retinal detachment caused by cytomegalovirus retinitis in patients with the acquired immunodeficiency syndrome.

Twenty-two eyes of 19 patients with the acquired immunodeficiency syndrome who had pars plana vitrectomy and silicone-oil injection after retinal detachment caused by cytomegalovirus retinitis were studied. All patients but one were monitored until time of death. The postoperative survival time and the factors that predicted anatomic success (retinal attachment) and functional success (visual acuity) were analyzed. No intraoperative complications were encountered. The mean survival time after surgery was four months. Of all of the preoperative and intraoperative factors studied, only the duration of cytomegalovirus retinitis was predictive of survival (P less than .03). The anatomic success rate was 89.5% (17 of 19 patients). None of the factors showed a trend or statistical significance in relation to anatomic success. Fifteen of 19 patients (79%) had lost at least two lines of Snellen visual acuity at time of death. Vision declined in a bimodal pattern (within the first postoperative month and after four months postoperatively). The optic nerve was pink and well perfused preoperatively in 16 of 19 patients (81.8%), but optic-nerve atrophy was observed postoperatively in 18 of 19 patients (95.5%). There was a trend for functional success to be influenced by increased intraocular pressure and optic-nerve atrophy, although our sample size was too small for statistical significance.

Acquired Immunodeficiency Syndrome↗

Quantitation of plasma factor XIIIa activity using fibrin-coated microscopic latex beads.

Following exposure to thrombin, monodisperse microscopic polystyrene-divinylbenzene beads coated with a mixed film of lecithin and fibrinogen aggregate as a consequence of interbead fibrin polymerization. These bead aggregates rapidly dissociate in 5 M urea. Treatment of aggregates with factor XIIIa results in a dose-dependent decrease of the rate of aggregate dissociation in urea. The rate of disaggregation is readily quantitated by turbidimetry. We have exploited this phenomenon to develop a rapid and sensitive method for quantitating factor XIIIa activity in plasma. Using 20 microliter of human plasma the method measures the activity of factor XIIIa to a level of 0.03 U ml-1 with a precision of +/-5%.

Fibrin↗

Measurement of left ventricular heat production in man.

A system to measure left ventricular heat production phi iv in conscious human subjects is described. Using phi iv and the rate of energy supply to the myocardium, the mechanical efficiency of the left ventricle is calculated. Heat carriage in left ventricular myocardial blood flow phi cs is calculated from coronary sinus flow and the transcoronary temperature difference. Diffusional heat loss phi diff is derived from the ratio of areas under temperature/time curves recorded in the aorta and coronary sinus after a bolus injection of cold saline into the pulmonary artery. The sum of phi cs, phi diff and phi chem (the energy of endothermic reactions with haemoglobin) gives phi iv. The estimated errors in the derived values of heat production and mechanical efficiency are less than 17 per cent. At basal heart rates 17 patients with good left ventricular function had a transcoronary temperature difference of 0.16 +/- 0.03 degrees C (mean +/- standard deviation), left ventricular flow blood of 145.3 +/- 81.5 ml min-1, and phi iv of 3.1 +/- 1.8 W. Left ventricular oxygen extraction was strongly correlated with phi iv (r = 0.925, p less than 0.001). Left ventricular mechanical efficiency was 0.33 +/- 0.11, at basal heart rates, which fell to 0.18 +/- 0.15 (p less than 0.001) on atrial pacing at 100 beats min-1.

Aged↗

Proteinase activities in bovine atrium and the possible role of mast cell tryptase in the processing of atrial natriuretic factor (ANF).

1. Using low salt, Triton X-100 and high salt extracts of bovine atria, two main proteinases were identified by means of fluorogenic oligopeptide substrates. 2. An acidic proteinase, extracted in low salt and Triton X-100 was identified as cathepsin B, but it caused little hydrolysis of the Z-Gly-Pro-Arg- containing substrate that resembles the cleavage site for activation of pro-ANF. 3. An alkaline proteinase was extracted only with high salt and had characteristics of the serine proteinase tryptase. It cleaved Z-Gly-Pro-Arg- containing substrates more efficiently than others tested and was localized in and around mast cells histochemically. Previously, Imada et al., 1988 (J. biol. Chem. 263, 9515-9519) found an identical enzyme would cleave ANF from pro-ANF. 4. These results suggest therefore that mast cell tryptase may be involved in the activation of ANF from pro-ANF.

Amino Acid Sequence↗

Renal 11 beta-hydroxysteroid dehydrogenase activity: effects of age, sex and altered hormonal status.

The enzyme 11 beta-hydroxysteroid dehydrogenase, by converting cortisol and corticosterone to their receptor-inactive 11-keto metabolites cortisone and 11-dehydrocorticosterone, appears crucial to the aldosterone-selectivity of renal mineralocorticoid receptors. Levels of enzyme activity in the rat kidney, measured by conversion of cortisol to cortisone, are unaltered by changes in adrenal or thyroid status, or by castration in either sex; in contrast, oestrogen administration increases enzyme activity in male rats.

11-beta-Hydroxysteroid Dehydrogenases↗

Ion chromatographic determination of inositol tris- and tetrakisphosphates in rat brain.

Ion chromatography has been applied to the determination of inositol 2,4,5-trisphosphate (Ins 2,4,5-P3), inositol 1,3,4-trisphosphate (Ins 1,3,4-P3), inositol 1,4,5-trisphosphate (Ins 1,4,5-P3), and inositol 1,3,4,5-tetrakisphosphate (Ins 1,3,4,5-P4). Other common polyanionic metabolites, including ATP and GTP, do not interfere with the determinations even at concentrations exceeding those normally found in tissue extracts. Assay of rat brain for Ins 1,4,5-P3 and Ins 1,3,4,5-P4 by the method of standard addition gives values which are within 10% of the amount calculated by external calibration. When rat brain homogenates are spiked with Ins 1,4,5-P3, the recoveries are greater than 90%. Treatment of animals with lithium chloride and pilocarpine produces increases in total inositol trisphosphates from 14 to 64 nMol/g wet weight, and increases in Ins 1,3,4,5-P4 from 0.9 to 18 nMol/g wet weight in tissue extracts obtained from the cerebral cortex. Using chemically suppressed conductivity, detection limits in brain are estimated to be 50 pMol/g wet weight for inositol trisphosphates and 22 pMol/g wet weight for inositol tetrakisphosphate.

Adenosine Triphosphate↗

Post-partum anovulation in nursing mothers.

An analysis of breastfeeding and ovulation data from 72 nursing mothers is presented. A proportional hazards model of the data strengthens the hypothesis that a pattern of short, frequent bouts of nursing defines a risk-set of women less susceptible to post-partum ovulation than those who choose to nurse on a schedule of relatively lengthy and infrequent bouts. In contrast, no effect of maternal weight-for-height on the month-specific rate of post-partum ovulation could be detected in the study population comprised of American mothers trained in self-observation of fertility signs.

Anovulation↗

Donor cornea bacterial contamination.

The incidence of culture-positive cornea rims from 446 consecutive donor corneas cultured at the Doheny Eye Institute between 1986 and 1988 was determined. Both the identity and antibiotic sensitivities of the contaminating organisms were reviewed. Sixty-three (14.1%) of 446 cornea rims were culture-positive, but none of the 63 patients who received these contaminated donor corneas developed endophthalmitis. Streptococcus (26 of 63), Propionibacterium (15 of 63), Stphylococcus (14 of 63) species and diptheroids (8 of 63) were the most common cornea rim contaminants, and in most cases were resistant to gentamicin (i.e., 21 of 26 or 81%, 9 of 15 or 60%, 10 of 14 or 71%, 4 of 8 or 50%, respectively). Virtually all of the gentamicin-resistant bacteria isolated from cornea rims were found to be sensitive to vancomycin. Eye banks should consider the addition of other antibiotics to storage media to reduce donor cornea contamination. Surgeons performing corneal transplantation should also consider these results when selecting antibiotics for use at the time of surgery and in the postoperative period.

Anti-Bacterial Agents↗

Variations in clinical features of the Vogt-Koyanagi-Harada syndrome.

Forty-eight cases of the Vogt-Koyanagi-Harada (VKH) syndrome occurring in patients residing in southern California were reviewed. Thirty-six patients were Hispanic and 12 of other racial groups. Symptoms of meningismus, predominantly headache, were present in 32 (67%) cases, but the other characteristic neurologic symptoms, i.e., tinnitus and dysacusis, were present in only eight (17%) and six (13%) cases, respectively. Dermatologic changes were rare; vitiligo occurred in five (10%) patients, alopecia in six (13%), and poliosis in three (6%). In this patient population, extraocular signs and symptoms of the VKH syndrome, other than headache, were unusual. The ocular manifestations of the VKH syndrome are more constant and include iridocyclitis, vitritis, diffuse swelling of the choroid, serous retinal detachment, and optic disc hyperemia. Procedures that may aid in the diagnosis include lumbar puncture, fluorescein angiography, and standardized echography. The ophthalmologist must be prepared to make this diagnosis and initiate treatment with high-dose systemic steroids based on the typical ocular findings even in the absence of other (extraocular) manifestations of this disease.

Adolescent↗

Coronary vasodilatation induced by endotoxin in the rabbit isolated perfused heart is nitric oxide-dependent and inhibited by dexamethasone.

The coronary vasoconstriction induced by the thromboxane mimetic U46619 (9, 11 dideoxy methanoepoxy 9 alpha, 11 alpha prostaglandin F2 alpha, 3-30 nM) was significantly attenuated in hearts obtained from rabbits treated with endotoxin (lipopolysaccharide, LPS, 200 micrograms kg-1, i.v.) 4 h before isolation of the heart. Under these conditions the vasoconstriction induced by two inhibitors of nitric oxide (NO) synthase, NG-monomethyl-L-arginine (L-NMMA) and N-iminoethyl-L-ornithine (L-NIO) (1-100 microM for each) was significantly enhanced when compared to that induced in hearts from control animals. Both the decreased response to U46619 and the increased response to inhibitors of NO synthase were significantly attenuated by administration of dexamethasone (4 mg kg-1, i.v.) 90 min before treatment with LPS. These data are consistent with the induction, by LPS, of an NO synthase, and the inhibition of this induction by dexamethasone. The enhanced NO synthesis contributes to the haemodynamic changes known to occur in endotoxin shock.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Sequences from myeloblastosis-associated virus MAV-2(O) and UR2AV involved in the formation of plaques and the induction of osteopetrosis, anemia, and ataxia.

Recombinant viruses were made between myeloblastosis-associated virus MAV-2(O) and UR2AV to examine the relationship between regions of the MAV-2(O) genome and disease induction. The env-long terminal repeat (LTR) portion of MAV-2(O), when substituted into UR2AV, was sufficient to induce osteopetrosis identical to that caused by the parent MAV-2(O). When this region was reduced to the gp37 and LTR of MAV-2(O), osteopetrosis more severe than that caused by the parent virus was induced. Recombinant viruses that contained all or part of the MAV-2(O) env gene in the absence of the MAV-2(O) LTR induced a severe, chronic anemia and late-onset osteopetrosis, leading to the conclusion that the MAV-2(O) LTR, in addition to env, was required for rapid induction of osteopetrosis. A viral recombinant, pEU, which contained the gp85 segment of UR2AV substituted into MAV-2(O), induced an ataxia/cerebellar dysfunction not seen during infection with the other chimeric or parent viruses. In vitro studies of the parent and recombinant viruses demonstrated that the ability to form plaques on chicken embryo fibroblasts correlated with the presence of the MAV-2(O) gp37 and LTR except for construct pEU. When the viruses were inoculated into 10-day-old chickens, chimeras containing the env-LTR of gp37-LTR region of MAV-2(O) induced severe regenerative anemia similar to that induced by MAV-2(O). pEU was the exception, suggesting that the unique configuration of this chimera is responsible for its unusual pathogenic properties.

Anemia↗

Eosinophilic leukemia: a myeloproliferative disorder distinct from the hypereosinophilic syndrome.

Evidence to support the existence of eosinophilic leukemia (EL) as an autonomous eosinophilic proliferation analogous to other myeloproliferative disorders has been somewhat confusing. Partially obscuring the existence of EL as a distinct entity is the proposal that EL merely represents a clinically aggressive form of hypereosinophilic syndrome. This report details the clinical and pathologic findings in a case of EL. The presence of trisomy 8 and trisomy 21; morphologic, cytochemical, and ultrastructural findings of granular abnormalities and nuclear/cytoplasmic dysynchrony; and a clinical course similar to that of other myeloproliferative disorders support the existence of EL as a rare but distinct entity within the spectrum of myeloproliferative diseases.

Adult↗

Bone remodelling after growth factor and cyclosporine A therapy for aplastic anemia.

We describe a patient with viral induced aplastic anemia who developed severe bone pain after treatment with multiple courses of antithymocyte globulin, cyclosporine A, recombinant human granulocyte macrophage colony stimulating factor and deferoxamine. Radiographs and bone biopsy revealed extensive new trabecular bone formation in long bone diaphyses and adjacent periosteal reaction. The effects of hematopoietic growth factors, cyclosporine A and deferoxamine on bone metabolism are reviewed.

Adolescent↗

Adventitial cystic disease of the lesser saphenous vein.

Adventitial cystic disease or degeneration of the blood vessel wall is an unusual form of peripheral vascular disease that occurs almost exclusively in the popliteal artery and accounts for an estimated one in 1200 cases of claudication. The cause of adventitial cystic disease is unknown, but it has been attributed to repeated trauma, an ectopic ganglion, or primary dysplasia of the vascular connective tissue. We describe an unusual case of adventitial cystic disease of the lesser saphenous vein located adjacent to the ankle joint. Only a handful of cases of venous adventitial cystic disease have been reported in the English literature, and, to our knowledge, none involved the lesser saphenous vein.

Adult↗