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Biomedical subjects

R E Smith

Publications and source records attributed to R E Smith.

At least 271 records · Page 15Linked to original sources

Myelofibrosis: a concise review of clinical and pathologic features and treatment.

This paper reviews and clarifies the current understanding of the clinical and pathologic features and treatment of MF. Recent investigations indicate that MF may be mediated by platelet- and megakaryocyte-derived growth factors, impaired prostaglandin-mediated stem cell growth inhibition, or excessive endothelial cell and fibroblast proliferation. Immunologic disorders have been associated with MF. MF may be either a primary or a secondary phenomenon. Secondary MF often regresses with appropriate treatment of this underlying disorder. Primary MF may require androgen therapy, splenectomy, splenic irradiation, bone curettage, chemotherapy, or bone marrow transplantation.

Humans↗

Lambert-Eaton myasthenic syndrome: the lack of short-term in vitro effects of serum factors on neuromuscular transmission.

Serum was obtained from 7 patients with the Lambert-Eaton myasthenic syndrome (LES), 3 patients with small-cell carcinoma of the lung (SCCL), and 9 healthy control subjects. Serum samples were applied in vitro to the rat neuromuscular junction (for 1-3 h for control LES sera; 4 h for SCCL sera), following which the pre- and postjunctional physiological effects of serum factors were studied in the presence of 10 mM [Mg2+]o. All sera produced a marked reduction in the frequency of spontaneous miniature end-plate potentials (MEPPs), while causing slight to moderate changes in MEPP amplitude. There were no consistent changes in the quantum content of the impulse-evoked end-plate potentials, though the serum from one LES patient significantly and reversibly inhibited the evoked quantal release. No significant effect was found when a human intercostal muscle was exposed to serum from another LES patient for 2 h. Therefore, when applied in vitro on a short-term basis, the putative LES autoantibodies do not consistently react with voltage-dependent calcium channels in the motor nerve terminal and thus fail to reproduce the physiologic abnormality of the syndrome. We suggest that the pathogenic IgG molecules may require more than 3h of incubation in order to gain access to, and inhibit the function of, the prejunctional Ca2+ channels.

Action Potentials↗

Analysis of hematopoietic and lymphopoietic tissue during a regenerative aplastic crisis induced by avian retrovirus MAV-2(O).

Infection of 10-day-old chickens with an avian osteopetrosis virus resulted in a severe regenerative aplastic crisis. Hematopoietic and lymphopoietic tissues of chickens infected with myeloblastosis-associated virus (of subgroup B, inducing osteopetrosis, MAV-2(O] were analyzed for integrated and unintegrated viral DNA sequences, cell population shifts, weight changes, and morphological alterations. By 6 days postinfection (p.i.), DNA from bone marrow cells and peripheral blood leukocytes (PBL) contained between 0.50 and 0.70 copies of viral DNA per haploid genome. Erythrocytes and splenic leukocytes contained less than 0.10 copies/haploid genome. Granulocytes and precursor mesomyelocytes were absent from bone marrow, but numbers of erythrocytes, erythroblasts, and reticulocytes were normal. By 9 days p.i., bone marrow was severely hypoplastic and both granulopoietic and erythropoietic colonies were depleted. By 12 days p.i., erythrocytes and granulocytes were maximally depressed in peripheral blood and the amount of integrated virus in bone marrow and PBL decreased to less than 0.20 copies/haploid genome. In contrast, erythrocytes contained integrated viral DNA of up to 0.30 copies/haploid genome, indicating infection of erythrocyte precursors. At 18 days p.i., viral DNA was detected only in erythrocytes. Unintegrated viral DNA was not detected in any organs. Anemia was accompanied by splenomegaly and erythrophagocytosis. Viral DNA was never detected in thymus or bursa. Differential counting and flow cytometry of cells from bursa, thymus, and spleen, and of blood lymphocytes did not detect significant population shifts. These results suggest that MAV-2(O) infection of immunocompetent chickens occurs primarily in myelopoietic tissues, and tissues are selectively infected.

Anemia, Aplastic↗

Autopsy findings in the eyes of fourteen fatally abused children.

The eyes of fourteen fatally abused children and sixteen control cases were examined histopathologically. Ten of the abused children showed intraocular change. The most common ocular changes were subdural hemorrhage of the optic nerve and retinal hemorrhage which involved all the layers of the retina, but most commonly the nerve fiber layer, ganglion cell layer and inner nuclear layer. The presence of blood cavities within the retina partially supported the hypothesis of traumatic retinoschisis. The control cases of non-abused children rarely showed intraocular hemorrhage.

Child Abuse↗

Functional and structural alterations of the nervous system induced by avian retrovirus RAV-7.

Chickens infected as embryos with RAV-7 developed neurological signs including ataxia, lethargy, and imbalance. Evoked spinal cord potentials for RAV-7 infected SC chickens were considerably slower (64.8 m/s) than for uninfected SC (103.4 m/s), genetically hypothyroid (OS) (93.9 m/s) or special C (95.1 m/s) chickens. Conduction velocity measurements of sciatic nerves showed normal values for all the chickens examined in this study. Histopathological studies revealed non-suppurative meningoencephalomyelitis in RAV-7 infected SC chickens. The inflammatory infiltrate consisted of lymphocytes, macrophages, and occasional plasma cells. The cells in the infiltrate reacted with mouse monoclonal antibodies directed against la and T-cell antigens. Astrocytic hypertrophy and hyperplasia, demonstrated by the use of monoclonal antibody specific for glial fibrillary acidic protein (GFAP), was associated with the CNS lesions. The results of this investigation indicate that RAV-7 causes significant central nervous system lesions and functional impairment in the infected chicken. This system may serve as a useful model for studying retrovirus-induced neurological dysfunction.

Animals↗

Topical retinoid therapy for squamous metaplasia of various ocular surface disorders. A multicenter, placebo-controlled double-masked study.

In a prospective, double-masked clinical study, the authors evaluated the efficacy and safety of topically applied tretinoin ophthalmic ointment (0.01%) versus placebo in the treatment of squamous metaplasia associated with various ocular surface disorders involving dry eyes. Study parameters consisted of graded symptoms and signs, and serial impression cytologies. A total of 161 patients were enrolled in the study. Of these patients, 116 who had a minimum of 4 to 8 months of follow-up qualified for final statistical analysis. These patients were classified into two major groups: (1) keratoconjunctivitis sicca (KCS) and (2) conjunctival cicatricial diseases (Stevens-Johnson syndrome, inactive pemphigoid, radiation-induced dry eye, drug-induced pseudopemphigoid, and toxic epidermal necrolysis). An analysis of adjusted mean changes for KCS patients showed no statistically significant differences between active drug and placebo. A similar analysis of patients with conjunctival cicatricial diseases indicated a statistically significant (P less than 0.05) reversal of conjunctival keratinization in the temporal bulbar site after treatment with active drug, however, clinical symptoms and signs showed no significant improvement with active drug relative to placebo. Side effects were limited to blepharoconjunctivitis and were reversible upon tapering or stopping the drug.

Administration, Topical↗

Molteno implant for control of glaucoma in eyes after penetrating keratoplasty.

Seventeen patients (17 eyes) underwent implantation of a single plate Molteno implant for medically uncontrollable intraocular pressures after penetrating keratoplasty. Most of the eyes had extensive peripheral anterior synechiae, and 16 of 17 (94%) were pseudophakic or aphakic following keratoplasty. Other glaucoma procedures had been performed previously on 13 eyes: argon laser trabeculoplasty (one eye), trabeculectomy (seven eyes), transpupillary argon laser cyclophotocoagulation (three eyes), and cyclocryotherapy (three eyes). Follow-up ranged from 5 to 28 months (mean, 13 months). Three eyes underwent repeat Molteno implantation when intraocular pressure (IOP) was not satisfactorily reduced after the first procedure. Considering one eye with chronic hypotony as a failure, 12 of 17 eyes (71%) had IOPs of less than 21 mmHg at the time of the three most recent postoperative examinations after a single Molteno implant. Repeat implants in three eyes increased the number of eyes with IOPs of less than 21 mmHg to 14 (82%). Corneal allograft rejection after Molteno implantation occurred in seven eyes; two of these were successfully reversed with corticosteroid therapy. Three of the five eyes with irreversible graft rejection were regrafted, and two of these grafts have remained clear. Including the regrafted eyes, 13 eyes had clear grafts and controlled IOPs at the most recent postoperative examination. The Molteno implant may prove useful in the management of medically uncontrollable glaucoma following penetrating keratoplasty; however, there appears to be a substantial risk of postoperative graft rejection.

Adult↗

Rapid induction of B-cell lymphomas: insertional activation of c-myb by avian leukosis virus.

EU-8 is a recombinant avian leukosis virus (ALV) constructed in vitro, which carries long terminal repeats and gag and pol genes from ring-necked pheasant virus and the env gene from UR2AV. Unlike either parent virus, when injected into 10-day-old chicken embryos, EU-8 induces a high incidence of clonally arising B-cell lymphomas within an unusually short latent period, often causing death within 5 to 7 weeks after infection. These tumors differ from the classic lymphoid leukosis induced by ALV in several respects, both biologically and at the molecular level. Most notably, in all of the EU-8-induced tumors examined, the provirus was integrated in the c-myb locus, and in no tumors were c-myc integrations found. Most of the proviral integrations were downstream of the initiation codon of c-myb and thus presumably resulted in some truncation of the c-myb gene product, although not to the same extent as has been found in other cases of c-myb activation. In addition, several of the proviruses were integrated well upstream of the c-myb coding region. This is the first report of ALV interaction with the c-myb proto-oncogene and the first report of c-myb activation resulting in tumors of lymphoid rather than myeloid origin, suggesting that the target cell specificity of transformation by the myb gene is not as restricted as previously believed.

Animals↗

Chronic alcoholism and microbial keratitis.

In a series of 227 consecutive, non-referred patients with microbial keratitis an analysis of the accumulated hospital records showed that one-third were associated with chronic alcoholism. The diagnosis of alcoholism was usually unsuspected on admission to hospital. The microbial pathogenesis in these patients was distinctive; coagulase-negative staphylococci, alpha- and beta-streptococci, moraxellae, enteric Gram-negative bacilli, and polymicrobial infections were unusually prominent. Pseudomonas aeruginosa was uncommon. Trauma, exposure, bullous keratopathy, other external ocular diseases, and self-neglect were the major recognised predisposing causes. The nutritional, toxic and immunological sequelae of alcoholism may also have been contributory. Ophthalmologists should be alert to the diagnosis of chronic alcoholism in their patients. Chronic alcoholism may be an important and underrated risk factor for microbial keratitis.

Alcoholism↗

Pathogenesis of blepharoconjunctivitis complicating 13-cis-retinoic acid (isotretinoin) therapy in a laboratory model.

Systemic treatment of adult male New Zealand albino rabbits with 13-cis-retinoic acid (isotretinoin) resulted in a reduction in the size of the meibomian gland. Clinical signs of toxicity included weight loss, alopecia, dry skin and mild conjunctival erythema with crusting on the eyelid margin. Histopathologic findings included thickening of duct and ductule epithelium, decrease in acinar tissue, accentuation of basaloid cells and evidence of periacinar fibrosis. The model presents the first experimental data to indicate that systemic 13-cis-retinoic acid effects meibomian gland structure in a laboratory model. Future functional studies of this model may yield important insights into the relationships between meibomian gland morphology, function, the ocular surface and the pathogenesis of blepharo-conjunctivitis.

Alopecia↗

Cysteine proteinase activity in arthritic rat knee joints and the effects of a selective systemic inhibitor, Z-Phe-AlaCH2F.

The role of cathepsin B, H and L activities in arthritic processes was studied histochemically using specific synthetic substrates in a postcoupling method on unfixed and undecalcified cryostat sections of rat knee joints. Only cathepsin B in synoviocytes, chondrocytes and fibroblasts showed a strong increase in activity due to antigen induced arthritis. The addition of a tissue stabilizer, polyvinyl alcohol, to the incubation medium enabled us to demonstrate extracellular enzymic activity within the articular cartilage matrix of arthritic joints. Both intravenous and oral treatment of the animals with a selective inhibitor of cathepsin B, Z-Phe-Ala fluoromethyl ketone (CH2F), during the development of arthritis suppressed the degree of inflammation and resulted in decreased intracellular and extracellular cathepsin B activity as detected histochemically, and less cartilage damage. Our study indicates that (a) cathepsin B-like activity plays a role in the cascade of proteolytic cartilage destruction, (b) chondrocytes and fibroblasts may well be involved in the breakdown of cartilage and ligaments, and (c) Z-Phe-AlaCH2F could be of therapeutic value.

Administration, Oral↗

Sequential study of visceral lesions caused by isolates of an avian osteopetrosis virus (myeloblastosis-associated virus).

Ten-day-old chicken embryos were inoculated with isolates of myeloblastosis-associated virus that induced osteopetrosis of slow or rapid onset. Bursa of Fabricius, thymus, spleen, bone marrow, kidney, liver, and lung were examined at 15, 17, and 19 days in ovo and at 7 and 25 days after hatching by histologic and immunoperoxidase techniques. Tissues from 19-day-old in ovo embryos also were examined by electron microscopy. The lymphoid organs of embryos inoculated with all isolates manifested changes suggesting inhibited development. Virus was most often associated with macrophages, heterophils, and nonlymphoid stromal cells in these organs. Viral particles and antigen were abundant in tissues from embryos inoculated with slow-onset isolates, but cell necrosis was infrequent. The kidney and bursa had especially abundant viral particles and antigen. Conversely, viral particles and antigen were minimal in tissues from embryos inoculated with the rapid-onset isolate, yet intravascular cellular thrombi, substantial cell necrosis, and increased heterophils and hemocytoblasts were found.

Animals↗

Lymphoid immunohistochemistry of macaque primates.

The immunohistochemical localizations of 53 monoclonal antibodies with specificities expressed in human lymphoid tissue were investigated on lymph node tissues from Macaca mulatta, M. speciosa, and M. fascicularis using immunoperoxidase techniques. Thirty antibodies showed comparative cross-reactivity. The micro-anatomic distribution of these antigens was closely homologous to that observed in man and antigen densities appeared to be similar. A useful monoclonal antibody panel for immunopathological investigations in macaques was, thereby, defined. Of several pan-T antibodies studied, only OKT11(CD2) showed cross-reactivity. A detailed analysis of the immunocyto-architecture of five rhesus lymph nodes was undertaken. Automated flow cytometry of M. mulatta and M. speciosa peripheral blood showed a broadly similar pattern to man.

Animals↗

Lethality and bone alterations in chicken embryos and newly hatched chickens given bone-active agents.

Studies were undertaken to assess the chicken embryo and newly hatched chicken as models for studying the effects of bone-active agents. Initially, 1,25-dihydroxycholecaliferol (1,25[OH]2D3), sodium fluoride (NaF), parathyroid extract, epidermal growth factor, and prostaglandin E2, were tested for lethality over a broad dose range. One or 3 injections of 1,25(OH)2D3 into the yolk sac of chicken embryos resulted in death of embryos given greater than or equal to 0.1 ng/injection, whereas 0.01 ng was tolerated by the embryos. Administering 1,25(OH)2D3 intraperitoneally to newly hatched chickens as a single injection or weekly for 3 weeks resulted in no deaths at doses up to 50 ng. One or 3 IV injections of 800 micrograms of NaF were lethal to embryos, whereas injections of less than or equal to 400 micrograms were tolerated by the embryo. Giving chickens feed and water containing 2.4 g of NaF/kg was lethal, but no deaths occurred when chickens were given feed containing less than or equal to 1.2 g of NaF/kg. Mortality associated with the administration of epidermal growth factor to embryos was inconsistent, in that death occurred in embryos given a single injection of greater than or equal to 250 ng, but no deaths occurred in embryos given 3 injections at similar doses. Parathyroid extract and prostaglandin E2 were not lethal when administered to embryos and chickens in a single-injection or multiple-injection regimen. Overall, lethality in chicken embryos given a particular agent reflected the dose of bone-active agent injected, rather than the number of injections. Three of the bone-active agents were selected to characterize their microscopic bone effects in chicken embryos and chickens.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Biochemical detection of recurrent breast cancer.

When clinically obvious recurrence develops in breast cancer patients, a large tumor burden is usually present. The development of biochemical techniques to detect recurrence may allow early diagnosis and therapeutic benefit. Reviewed in detail is the use of 10 biochemical parameters, as well as chest x-rays and physical examinations. Present data indicate that serial chest x-rays, physical examinations, liver enzymes, and CEA are the most sensitive means of detecting recurrence.

Biomarkers, Tumor↗