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Biomedical subjects

R E Morris

Publications and source records attributed to R E Morris.

At least 145 records · Page 8Linked to original sources
PubMed1995

Health risk behavioral survey from 39 juvenile correctional facilities in the United States.

PURPOSE: The study surveyed adolescents in juvenile detention facilities to determine the incidence of health risk behaviors. METHODS: A modified version of the United States Centers for Disease Control Youth Risk Behavior Surveillance System was administered to 1801 minors at 39 facilities in the United States. RESULTS: Risky behavior begins early, the initiation plateauing at age 15 or 16 years. Girls and boys reported comparable rates of drinking, binge drinking, and illicit drug use. North American Natives and those individuals who designated themselves as being other than any of the offered choices for racial designation ("Other") began drinking at earlier ages, had more binge drinking, more illegal drug use, and the most fight-related behavior. By age 12 years 62% reported onset of sexual intercourse and by age 14 years 89% were sexually active. Fighting was reported by 69% of detainees. Fight-related injuries within the past year were reported by 25% of the respondents. Nearly 47% belonged to a gang. Drug/alcohol use, fighting, and gang membership were related. Suicide was considered by 22% of the detainees, planned by 20%, tried by 16%, 8% were injured because of a suicide attempt. Younger teens (White, N.A. Natives, and "Other") had the most frequent suicide ideation. Drug/alcohol use correlated with suicidal thoughts. Onset of sexual intercourse was at an average age of 12. Multiple partners and pregnancy, was highest among blacks and "Others". Blacks had the highest sexually transmitted disease (STD) rate. Less than half of all respondents used condoms at last intercourse. STDs were related to being female, being black, and having multiple sexual partners. Pregnancy was related to multiple sexual partners and violent behavior. CONCLUSION: Male and female detainees report a high incidence and early onset of risky behaviors. N.A. Natives and those of "other" races reported the highest incidence of risk behaviors.

Adolescent↗
PubMed1995

Surfactant protein A-polylysine conjugates for delivery of DNA to airway cells in culture.

Surfactant protein A (SP-A) was modified by covalent linkage with polylysine of average M(r) 21 kD ([Lys]21kD-SP-A) and utilized to transfect human airway epithelial cells (H441) in vitro. Transfection of H441 cells was more efficient with [Lys]21kD-SP-A than with polylysine-DNA or unmodified SP-A-DNA complexes. Transfection with [Lys]21kD-SP-A was effective at a protein-to-DNA molar ratio of 400:1 and in the presence of an exogenous surfactant preparation, Survanta. Transfection with [Lys]21kD-SP-A was reduced in the presence of unmodified SP-A consistent with the concept of a receptor mediated uptake of protein-DNA complexes. Increased transfection efficiency correlated with decreasing diameter of the [Lys]21kD-SP-A-DNA complexes, and these complexes bound to the cell surface and pseudopodia of H441 cells. Transfection was enhanced by co-incubation with replication-deficient adenovirus. Cotransfection by [Lys]21kD-SP-A-DNA and [Lys]10kD-SP-B resulted in an additive level of reporter gene (CAT) expression. [Lys]21kD-SP-A-DNA is likely to be useful as a component of a surfactant-based DNA delivery system for transfection of airway cells.

Adenoviridae↗
PubMed1995

Immunosuppression in cardiac transplantation: a new era in immunopharmacology.

During the past 5 years, there has been a concerted effort to identify new immunosuppressive agents for organ transplantation that have greater efficacy and fewer side effects than current therapies (corticosteroids, azathioprine, cyclosporine, anti-T cell antibodies). These new drugs can be generally classified according to their varying structures or mechanisms of action: xenobiotic molecules (FK506, rapamycin, cyclosporine analogues); antimetabolites (mycophenolate mofetil, mizoribine, brequinar sodium); and those agents with novel or incompletely defined mechanisms of action (leflunomide, 15-deoxyspergualin). Many of the newer agents offer better therapeutic indexes, and some even show promise in the treatment of two of the major obstacles currently facing cardiac allograft transplantation: antibody-mediated accelerated humoral rejection and chronic vascular rejection (also known as accelerated graft coronary artery disease). With the increasing shortage of donor organs in recent years, there has been a resurgence of interest in xenotransplantation; some of the new immunosuppressants demonstrate efficacy in prolonging xenograft survival. Most of these agents will probably find their niches as components of low-dose combination regimens designed to maximize effective immunosuppression and minimize drug toxicities and opportunistic infections.

Graft Rejection↗
PubMed1995

Mechanisms of action of new immunosuppressive drugs.

More immunosuppressive drugs than ever have recently graduated from the laboratory to extensive clinical trials of their safety and efficacy in transplant patients. None of these drugs is perfect, but they control different forms of rejection in stringent animal models more effectively than other immunosuppressants, and these novel molecules suppress the immune system far more specifically than steroids and regimens that cause lymphopenia. Cyclosporin A and FK506 are the only drugs that selectively inhibit T-cell proliferation by blocking cytokine synthesis. The primary action of rapamycin appears to be inhibition of the actions of cytokines and growth factors on T, B, and some nonimmune cells. T and B cells are more sensitive than nonimmune cells to the depletion of purines and pyrimidines caused by mizoribine, mycophenolate mofetil, brequinar sodium, and leflunomide. Nucleotide depletion causes interruption of DNA synthesis and glycosylation of adhesion molecules in immune cells. Further differentiation of T and B cells after proliferation into fully functional immune cells is inhibited by unknown mechanisms of brequinar and deoxyspergualin. On the basis of preclinical studies, these drugs may effectively suppress clinical rejection that is acute (all), chronic (rapamycin, leflunomide, mycophenolate mofetil), or antibody mediated (brequinar, deoxyspergualin, mycophenolate mofetil, rapamycin, leflunomide). Some drugs (FK506, deoxyspergualin, mycophenolate mofetil, rapamycin, leflunomide) may reverse acute rejection refractory to conventional immunosuppression. Not only do these new drugs block different biochemical steps that normally lead to fully functional T and B cells after stimulation by alloantigen, but their toxicity profiles also differ. Results from preclinical studies predict that use of selected combinations of these drugs will be more effective, less nephrotoxic, less myelotoxic, and less broadly immunosuppressive than current regimens based on cyclosporine, T-cell depletion, steroids, and azathioprine.

Animals↗
PubMed1995

Caries experience in a selected group of children in Kuwait.

A study to set base-line data for future interventions to develop young children's oral health care was carried out in November 1993 in Kuwait. The study population comprised a random sample of 450 3- to 7-year-old children drawn from the students in Kindergarten and Primary Departments of Kuwait English School in the Salwa District of Kuwait. The mean dmft and mean d values were highest at the age of 6 (4.1, SD = 3.6, and 2.1, SD = 2.4, respectively) and lowest at the age of 4 (1.4, SD = 2.5, and 1.0, SD = 2.0, respectively). The proportion of caries-free children (dmft = 0) was 39%. Molars and maxillary incisors were most prevalently affected by caries. There seems to be a distinct need for both organized dental health care and preventive programs for the very young children in Kuwait.

Age Factors↗
PubMed1995

Epipolarization microscopic immunogold assay: a combination of immunogold silver staining, enzyme-linked-immunosorbent assay and epipolarization microscopy.

We describe a new immunoassay which combines an immunosorbent assay, immunogold silver staining and epipolarization microscopy. Our new assay procedure features multiple samples on a single microscope slide, and high sensitivity of epipolarization microscope for detection of silver-enhanced colloidal gold as a final immunoassay product. We call the new immunoassay "on slide immunogold assay" (OSIGA). This new method uses biotinylated antibody and streptavidin-gold reaction with silver enhancement technique. With OSIGA it is possible to investigate 30 samples on a single microscopic slide. Our preliminary studies used 10-20 microliter samples and detected nanogram quantities of a standardized protein solution. Unlike enzyme linked immunosorbent assay (ELISA), which has a limited time for reading the final color products, the OSIGA specimens can be dried or resin mounted for longer storage and future reference.

Animals↗
PubMed1994

Efficacy of rapamycin and FK 506 in prolonging rat hind limb allograft survival.

OBJECTIVE: Graft rejection and the toxicity of current immunosuppressive regimens preclude the application of microsurgical advances to transplantation of limbs or other nonessential parts. If limb transplantation is to become a clinical reality, newer, safer, more effective immunosuppressive agents are needed. SUMMARY BACKGROUND DATA: Rapamycin (RPM) and FK 506 are fungal macrolide antibiotics with effective immunosuppressive properties demonstrated in several animal models. RPM is more potent and effective than is FK 506 in rat cardiac allografts and has demonstrated synergy with cyclosporine (CsA) in limb allograft models. METHODS: An orthotopic rat hind limb allograft model (Brown-Norway [RT-1n] to Lewis [RT-1(1)] rats was used. RPM (doses, 3.0, 4.5, and 6.0 mg/kg/day) was administered intraperitoneally on postoperative days 1 to 14. FK 506 (6 mg/kg/day) was administered orally on postoperative 1 to 14 and 1 to 90 and at rejection onset (10 mg/kg/day for salvage). CsA with RPM (postoperative days 1 to 14) was used to assess synergy, with CsA alone serving as the control. Other controls included untreated and placebo-treated allografted animals. The permutation test and Mann-Whitney test were applied to the data. RESULTS: The mean survival times were assessed as follows: (1) control (placebo, untreated), 5 days; (2) RPM groups, 9.5, 10.6, and 8.7 days; (3) 14-day FK 506, 28 days; (4) 90-day FK 506, > 90 days; (5) CsA, 17.3 days; and (6) CsA with RPM, 19.3 days. FK 506 significantly prolonged graft survival compared with RPM (Permutation Test, p < 0.001 and Mann-Whitney Test, p < 0.05). FK 506 salvage reversed early rejection. High-dose RPM produced significant toxicity. Synergy between CsA and RPM was not demonstrated. CONCLUSIONS: FK 506 prolongs allograft survival, reverses early rejection, and prevents rejection without clinical toxicity when given continually. RPM does not prevent rejection in this model and produces significant toxicity at high doses. FK 506 may be a first step in making limb transplantation a clinical reality in reconstructive surgery.

Animals↗
PubMed1994

Immortalization of subpopulations of respiratory epithelial cells from transgenic mice bearing SV40 large T antigen.

Murine lung epithelial (MLE) cell lines were produced from lung tumors derived from transgenic mice bearing the viral oncogene, SV40 large T antigen, under transcriptional control of the promoter-enhancer region of the human surfactant protein C (SP-C) gene. Cells were selected on the basis of increased murine cystic fibrosis transmembrane conductance regulator (mCFTR) mRNA content and were dilution cloned to produce distinct immortalized epithelial cell lines. MLE-13a3 cell lines expressing high levels of mCFTR mRNA also expressed apolipoprotein J (apoJ) mRNA, a developmentally regulated glycoprotein expressed preferentially in fetal lung. SP-A, -B, and -C were not detected or were present at low levels in the MLE cells that contained abundant CFTR and apoJ mRNA. In contrast, MLE cells, cloned on the basis of abundant surfactant protein mRNAs, expressed apoJ and mCFTR mRNAs at low levels. Forskolin-stimulated short-circuit current, typical of CFTR-mediated chloride transport activity, was generated by monolayers of subclones of the MLE-13a3 cell lines. Tumor necrosis factor-alpha stimulated mCFTR mRNA, whereas dexamethasone, retinoic acid, and phorbol ester had no effect on the levels of mCFTR mRNA in MLE-13a3 cells.

Animals↗
PubMed1994

Optimal visualization of immunogold-silver staining of hepatic PEPCK with epipolarized light microscopy.

We used immunogold-silver staining to localize phosphoenolpyruvate carboxykinase in 10 microns cryosections of 4% paraformaldehyde perfusion-fixed normal male rat liver. The resolution and sensitivity of detection were improved by epipolarized light microscopy of 0.5 microns semi-thin plastic sections prepared from these pre-embedding immunogold-silver-enhanced 10-microns thick cryosections. Epipolarized light combined with transmitted light simultaneously demonstrated antigenic sites (visualized with epipolarized light illumination) and tissue morphology (revealed by transmitted light). To optimize the conditions for high resolution, an oil immersion objective lens (x 100) with adjustable iris diaphragm was used with different intensity settings for both light sources. Our observations indicate that if the intensity of the transmitted light is too high, the visibility of the gold-cored silver grains by epipolarized illumination is decreased; if the intensity of epipolarized light is too strong, haloes appear around the gold-cored silver particles. By adjusting the aperture in the objective lens and the neutral density filter in the transmitted light pathway to balance the intensities of transmitted and epipolarized light, an optimal image is obtained that shows the maximal number of antigenic sites and excellent morphology.

Animals↗
PubMed1993

Immunogold-silver staining and epipolarized light microscopic detection of phosphoenolpyruvate carboxykinase and glycogen phosphorylase in rat liver.

The subcellular distribution of enzymes related to carbohydrate metabolism was determined in sections of paraformaldehyde fixed and polyethylene glycol-1540-embedded rat liver and in cryostat sections. For this purpose, goat anti-rat phosphoenolpyruvate carboxykinase (PEPCK) serum and rabbit anti-rat glycogen phosphorylase (GP) serum were used as primary antibodies to localize the corresponding antigens. The primary antibodies were localized by 5 nm colloidal gold labeled secondary antibodies (either rabbit anti-goat IgG for PEPCK or goat anti-rabbit IgG for GP), and the gold particles were enhanced by silver staining using appropriate development reagents. The silver enhanced gold particles were detected by epipolarized light microscopy. PEPCK and GP immunoreactive molecules were found only in glycogen-containing areas of the cytosome of hepatocytes, and not in other cells. No immunocytochemical staining of hepatocytes was found when normal serum replaced the primary antibody in the procedures. Visio-Bond semithin (0.35-1.0 micron) sections provided higher resolution for subcellular immunostaining of PEPCK and GP than cryosections of 10 microns. Epipolarized light microscopy provided detection at high sensitivity of the gold-labeled antibody, and combined with transmitted light, allowed simultaneous visualization of the tissue morphology.

Animals↗
PubMed1993

The immunopharmacology of immunosuppression by 15-deoxyspergualin.

We have used two murine bioassays, a nonprimarily vascularized heart transplant model and a host-versus-graft (HvG) popliteal lymph node (PLN) hyperplasia assay, to study the novel immunosuppressant, 15-deoxyspergualin (DSG). Using these methods, we investigated DSG's immunosuppressive potency, efficacy, and mechanisms of action. Dose-response studies showed that prolongation of heart allograft survival by DSG was dose dependent with an ED50 +/- SD of 1.45 +/- 0.39 mg/kg/day and that DSG was nearly seven times more potent than cyclosporine. Low maintenance doses of 0.25 or 1.0 mg/kg/day of DSG that followed an initial 14-day course of 5.0 mg/kg/day DSG enabled heart allografts to survive for more than 200 days without recipient weight loss or other signs of overt toxicity. When used as treatment for ongoing acute rejection, DSG prolonged graft survival. Although a 30-day course of 5.0 mg/kg/day of DSG caused significant but reversible body-weight loss, no overt, gross, or histopathologic evidence of significant tissue toxicity was observed in mice treated with 5.0 mg/kg/day DSG for 13 consecutive days. Frequent, intermittent administration of DSG was more immunosuppressive than less frequently administered high doses of DSG, but continuous infusion did not augment drug efficacy or reduce its toxicity. Isobologram analysis of graft survival in recipients treated with both DSG and CsA showed that this drug combination produced synergistic immunosuppression. In contrast to DSG's efficacy when administered posttransplant, the survival of grafts in recipients that were treated with DSG for 30 days posttransplant was only minimally prolonged. When recipients were sensitized by primary grafts, administration of DSG only during the period of sensitization or only immediately after implantation of secondary grafts failed to prevent accelerated rejection. If, however, graft recipients were treated with DSG both before and after implantation of secondary grafts, accelerated graft rejection was prevented. DSG induced partial alloantigen-specific unresponsiveness, since in DSG-treated C3H recipients of primary BALB/c grafts, secondary BALB/c grafts survived longer than third-party C57BL/6 secondary grafts. A dose of DSG that prolonged graft survival maximally did not suppress the in vivo lymphoproliferative response to alloantigen in the PLN assay. In contrast, doses of CsA that prolonged graft survival minimally suppressed the HVG response significantly. Thus, these studies showed that DSG was a more potent and effective immunosuppressant than CsA, and that DSG treatment prolonged graft survival substantially without apparent toxicity. Furthermore, unlike CsA, a dose of DSG that prolonged heart allograft survival did not suppress alloantigen-stimulated lymphoproliferation in vivo.(ABSTRACT TRUNCATED AT 400 WORDS)

Acute Disease↗