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Biomedical subjects

L Myers

Publications and source records attributed to L Myers.

At least 19 recordsLinked to original sources
PubMed1992

Differential effects of sequential, simultaneous, and single agent interleukin-3 and granulocyte-macrophage colony-stimulating factor on megakaryocyte maturation and platelet response in primates.

Recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) following interleukin-3 (IL-3) priming has been shown to increase thrombopoiesis. To elucidate the comparative abilities of IL-3 and GM-CSF in influencing megakaryocyte development in vivo, serial bone marrow analyses were performed on rhesus monkeys treated with 5 micrograms/kg/d of IL-3 and 5 micrograms/kg/d of GM-CSF sequentially for 4 days each, simultaneously for 8 days, and as single agents for 8 days. Platelet counts maximally increased to a mean of 7.5 x 10(5)/microL (n = 3) on days 11 through 12 in monkeys treated with sequential IL-3/GM-CSF. In contrast, neither IL-3 alone nor simultaneously administered IL-3/GM-CSF elicited increases in thrombopoiesis between days 3 and 15. GM-CSF elicited a variable platelet response. Megakaryocyte ploidy distributions were significantly (P < .001) shifted between days 7 and 10 in monkeys treated sequentially and between days 3 and 15 in monkeys treated with combined IL-3/GM-CSF and with GM-CSF alone but not in monkeys treated with IL-3 alone. The changes in mean DNA content and megakaryocyte size, as determined by digital image analysis, were larger in monkeys treated with sequential IL-3/GM-CSF and with GM-CSF alone than in simultaneously treated monkeys. In addition, sequentially but not simultaneously treated monkeys showed increased numbers of megakaryocytes on bone marrow biopsy. We conclude that administration of IL-3 followed by GM-CSF treatment increases thrombopoiesis by sequentially increasing megakaryocyte numbers and maturation and that these effects are diminished by simultaneous administration of the two cytokines.

Animals↗
PubMed1992

Evaluation of 9-dimethylaminomethyl-10-hydroxycamptothecin against xenografts derived from adult and childhood solid tumors.

The topoisomerase I inhibitor 9-dimethylaminomethyl-10-hydroxycamptothecin (topotecan) was evaluated against a panel of xenografts comprising four lines of adult colon adenocarcinoma, three colon tumors derived from adolescents, six childhood rhabdomyosarcomas from previously untreated patients as well as sublines selected in vivo for resistance to vincristine and melphalan, and three lines of childhood osteogenic sarcoma. Efficacy was determined at maximal tolerated dose levels using intermittent i.p. administration [every 4 days for 4 doses (q4dx4)] or daily p.o. or i.p. administration 5 days per week for up to 20 courses. On a q4dx4 schedule, the maximum tolerated dose (MTD) was 12.5 mg/kg per administration, which caused marked weight loss and lethality in approximately 5% of the tumor-bearing mice. This schedule caused significant growth inhibition (but no tumor regression) in advanced adult colon adenocarcinomas. The minimal treated/control (T/C) ratios were 0.49, 0.54, and 0.3 for three of the tumor lines and were achieved at 18-21 days after the initiation of treatment. In contrast, rhabdomyosarcomas were considerably more sensitive, with T/C ratios being < 0.1 for three lines, whereas topotecan was less active against two other rhabdomyosarcoma xenografts (minimal T/C ratios, 0.17 and 0.14). As inhibitors of topoisomerase I have been demonstrated to have activity in the replication phase of the cell cycle (S-phase-specific), prolonged administration schedules were examined. Mice received topotecan 5 days per week for 3 weeks either by i.p. injection or by oral gavage (p.o.). In selected experiments, p.o. administration was continued for up to 20 weeks. Oral administration for 3 weeks (2 mg/kg per dose) resulted in complete regression of all six lines of rhabdomyosarcoma, with two lines demonstrating no regrowth during the period of observation (> or = 84 days). Similar results were obtained after i.p. administration, suggesting significant schedule dependency for these tumors. For colon tumors, the daily administration schedule (i.p. or p.o.) demonstrated some advantage over the intermittent schedule, resulting in partial regressions and significant inhibition of the growth of several colon adenocarcinoma lines. In rhabdomyosarcoma Rh12 and VRC5 colon adenocarcinoma, both of which demonstrated intermediate sensitivity to topotecan, and in osteosarcoma OS33, protracted p.o. administration for 13-20 weeks (1.0-1.5 mg/kg per dose given daily x 5 days) caused complete regression without regrowth in Rh12 and OS33 tumors and partial regression of all VRC5 tumors. No toxicity was observed using this schedule of administration. Topotecan demonstrated significant activity against all three osteosarcoma xenografts examined, with optimal schedules causing complete regression in two lines.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenocarcinoma↗
PubMed1992

Pathology induced by interleukin-6.

Interleukin 6 (IL-6) is a multi-functional cytokine which plays an important role in the immune response, hemopoiesis and host defense. Recombinant human IL-6 (rhIL-6) was administered at high doses to mice, rats and non-human primates. In all species IL-6 had an immunostimulatory and hemopoietic (especially on megakaryocytes) effect. An acute phase response was most pronounced in non-human primates, which was not, however, associated with any major histopathological liver change. Finally, no evidence of glomerular pathology was found. Neutralising antibodies were detected within 10 days of rhIL-6 administration in all species.

Animals↗
PubMed1992

High-dose methylprednisolone therapy for acute graft-versus-host disease associated with matched unrelated donor bone marrow transplantation.

Acute graft-versus-host disease (aGVHD) is a major barrier to successful bone marrow transplantation (BMT) with matched unrelated donors. Eight of eight recipients of matched unrelated donor BMT developed aGVHD. We used a regimen of high-dose methylprednisolone (5 mg/kg/day for 4 days with responders continuing on treatment, and dose escalation to 10 mg/kg/day for non-responders) as initial therapy of aGVHD. One patient died on the second day of steroid administration. Each of the seven remaining patients responded to methylprednisolone, five at the 5 mg/kg/day dose and two at the 10 mg/kg/day dose. Three of five patients developed flare of aGVHD during reduction of the corticosteroid dosage and died with aGVHD and infection. Two patients have undergone reduction of methylprednisolone at a modified rate without a flare. Infectious complications during methylprednisolone treatment were very common and contributed to the death of the three patients with flare of aGVHD. Four patients in whom aGVHD was in remission survived serious systemic infections. High-dose methylprednisolone is effective initial therapy for aGVHD associated with matched unrelated BMT, but is associated with a high risk of serious infections.

Acute Disease↗
PubMed1991

Myxedema coma.

Myxedema coma is a rare condition associated with high mortality. The pathophysiology is complex and often involves profound hypothyroidism as well as an inciting event. The diagnosis should be suspected based on the clinical presentation, and treatment should not be delayed while awaiting confirmatory laboratory data. In critically ill patients, laboratory differentiation between severe hypothyroidism and the euthyroid-sick syndromes is difficult and may require measurement of free hormone levels. Treatment consists of correction of electrolyte abnormalities, passive rewarming, treatment of infections, respiratory and hemodynamic support, administration of stress-dose glucocorticoids, and thyroid hormone replacement. Intravenous thyroxine, between 200 and 500 micrograms as the initial dose followed by 50 to 100 micrograms/day, is recommended. Concurrent therapy with triiodothyronine can also be considered.

Coma↗
PubMed1990

A role for the neural cell adhesion molecule, NCAM, in myoblast interaction during myogenesis.

The Ca2(+)-independent neural cell adhesion molecule, NCAM, is expressed by both nerve and muscle cells and has been shown to mediate both nerve-nerve and nerve-muscle cell interaction. A role for NCAM in muscle-muscle cell interaction has been proposed but not demonstrated. Here we report evidence that NCAM is expressed by embryonic chick muscle cells during in vitro development and functions together with Ca2(+)-dependent adhesion molecules in mediating myoblast interaction during the formation of multinucleate cells.

Animals↗
PubMed1990

A role for the Ca2(+)-dependent adhesion molecule, N-cadherin, in myoblast interaction during myogenesis.

The formation of multinucleate skeletal muscle cells (myotubes) is a Ca2(+)-dependent process involving the interaction and fusion of mononucleate muscle cells (myoblasts). Specific cell-cell adhesion precedes lipid bilayer union during myoblast fusion and has been shown to involve both Ca2(+)-independent (CI)2 and Ca2(+)-dependent (CD) mechanisms. In this paper we present evidence that CD myoblast adhesion involves a molecule similar or identical to two known CD adhesion glycoproteins, N-cadherin and A-CAM. These molecules were previously identified by other laboratories in brain and cardiac muscle, respectively, and are postulated to be the same molecule. Antibodies to N-cadherin and A-CAM immunoblotted a similar band with a molecular weight of approximately 125,000 in extracts of brain, heart, and pectoral muscle isolated from chick embryos and in extracts of muscle cells grown in vitro at Ca2+ concentrations that either promoted or inhibited myotube formation. In assays designed to measure the interaction of fusion-competent myoblasts in suspension, both polyclonal and monoclonal anti-N-cadherin antibodies inhibited CD myoblast aggregation, suggesting that N-cadherin mediates the CD aspect of myoblast adhesion. Anti-N-cadherin also had a partial inhibitory effect on myotube formation likely due to the effect on myoblast-myoblast adhesion. The results indicate that N-cadherin/A-CAM plays a role in myoblast recognition and adhesion during skeletal myogenesis.

Animals↗
PubMed1989

Evaluation of N-(5-indanylsulfonyl)-N'-(4-chlorophenyl)-urea against xenografts of pediatric rhabdomyosarcoma.

N-(5-indanylsulfonyl)-N'-(4-chlorophenyl)-urea (LY186641), a novel anticancer compound, was evaluated against six lines of rhabdomyosarcoma xenografts, each of which was established from tissue biopsies from untreated patients, and additional sublines selected as xenografts for primary resistance to vincristine, melphalan, and ifosfamide. LY186641 was given by oral gavage twice daily for 10 consecutive days or as 5-day courses repeated at 7-day intervals. At the optimal schedule, complete regressions of advanced tumors were obtained in each of the six rhabdomyosarcoma lines. There was no apparent cross-resistance in RMS lines selected for vincristine resistance or against multiple-drug-resistance KB cells in vitro. There was slight cross-resistance in xenografts selected for melphalan resistance, but not in an ifosfamide-resistant line. These results indicate that LY186641 may have significant clinical activity in the treatment of childhood rhabdomyosarcoma.

Animals↗
PubMed1989

Penile and finger sensory thresholds in young, aging, and diabetic males.

To investigate the possible role of sensory function in conditions affecting sexual function, sensory thresholds were compared between young healthy men (n = 14, means age = 29.8), aging men (n = 15, means age = 67.3), and men suffering from diabetic impotence (n = 15, means age = 45.0). Using the psychophysical method of forced choice, vibrotactile and electrical stimulation thresholds were deterlmined in two separate sessions at two body sites: the fingertip and the ventral surface of the penis, just proximal to the glans. Vibrotactile penile thresholds (VTP) were lowest for young (Y) subjects and much higher for both aging (A) and diabetic (D) subjects. Electrical stimulation of the penis (ESP) showed the same trends, although the differences only approached significance (p = 0.06). The vibrotactile finger threshold (VTF) was significantly higher for A subjects as compared with Y and D subjects, but there was no difference between the Y and D groups. Diabetic patients had significantly higher thresholds for electrical stimulation of the finger (ESF), in contrast to the VTF finding. Finger thresholds were significantly lower than penile thresholds for all groups, and the change in threshold from finger to penis was greater in both aging and diabetic than in young subjects. Age was positively correlated with thresholds for ESF, ESP, VTF, and marginally for VTP when all three groups were analyzed together. However, in general the results of threshold determinations could not be attributed merely to age. Based on a detailed questionnaire of sexuality, VTP was negatively correlated with sexual activity and both ESP and VTP were negatively correlated with erectile capacity. The data are consistent with a genital sensory role for age-related and diabetic changes in sexual function.

Adult↗
PubMed1988

The long march of the cerebrospinal fluid profile indicative of clinical definite multiple sclerosis; and still marching.

Much progress has been made, especially in the last two decades, in laboratory aids to diagnosis and to follow the course of patients with multiple sclerosis (MS). The cerebrospinal fluid (CSF) profile indicative of MS, though not pathognomonic of MS, is present in almost every case of clinical definite MS in a chronic progressive phase (probably also true for early MS). The cardinal aspect of the profile is intra-blood-brain barrier (BBB) IgG synthesis which can be qualitatively detected by determining unique CSF oligoclonal IgG bands and quantitated by rate formula, mg/day. We believe that intra-BBB IgG synthesis is caused by a persistent antigen, most likely a virus, possibly measles. A number of issues about the profile are proposed and opportunities are presented to resolve them.

Antibodies↗
PubMed1987

The primary care physician and psychiatric services.

This article describes the relationship of self-assessed psychiatric skill among primary care physicians to their role in treating mental disorders. Physicians rated diagnostic skills more favorably than therapeutic skills. Factor analysis was used to identify three dimensions of physician skill: confidence in treatment of major disorders; confidence in treatment of anxiety; and diagnostic confidence. These variables were found to be associated with the reported number of patients with specific mental disorders managed by the physician.

Anxiety Disorders↗
PubMed1985

Human alpha-lymphoblastoid interferon. A phase I study including pharmacokinetics and effects on hematologic stem cells (CFU-GMs).

Human alpha lymphoblastoid interferon (Wellferon) was administered to 33 patients in a phase I study. Patients received Wellferon intramuscularly every 12 hours for 14 doses in nine dosage levels ranging from 0.75 X 10(6) units to 50.0 X 10(6) units. Toxicity tended to be dose dependent and included fever/chills, malaise, hematologic toxicity, and digestive tract toxicity. Thirty X 10(6) u q 12 h was felt to be the maximum tolerated dose. Three partial responses (renal cell carcinoma, diffuse histiocytic lymphoma, Hodgkin's disease) were achieved. Interferon rapidly (2 to 3 hours after the initial injection) reached peak serum levels which varied generally with dose and exceeded 500 u/ml at the 30 and 50 X 10(6) u dosages. Multiple doses of interferon resulted in cumulative peak levels substantially higher than first dose levels (greater than 500 u/ml at dosages greater than 3 X 10(6) u/ml and greater than 1,500 u/ml at dosages greater than or equal to 18 X 10(6) u). Interferon given at high dosages persisted up to 10 days beyond the final injection. Despite hematologic toxicity, inhibition of CFU-GM was not seen.

Dose-Response Relationship, Drug↗