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Biomedical subjects

L E Clemens

Publications and source records attributed to L E Clemens.

At least 19 recordsLinked to original sources
PubMed2001

The role of the rheumatologist in managing arthritis.

When and why should a patient with arthritis see a rheumatologist? To establish or confirm the diagnosis: aim for diagnosis within six weeks of onset. To plan an optimal management program: early, aggressive treatment is essential to achieve the best outcome in patients with inflammatory arthritis. To assess the response to treatment: failure to respond to treatment requires a change in drug regimen--objective measures of disease activity should be used.

Aged↗
PubMed1998

Pharmacokinetics and biological actions of subcutaneously administered human brain natriuretic peptide.

Human brain natriuretic peptide (hBNP) has demonstrated favorable hemodynamic effects in patients with congestive heart failure; however, the peptidic nature of this compound has focused clinical testing on protocols involving intravenous delivery. We have studied subcutaneous delivery as an alternative method of administering hBNP. Administration of 30 microgram/kg hBNP by either subcutaneous or intravenous delivery protocols resulted in significant hBNP-immunoreactive material in the plasma with area under the plasma concentration-time curve values of 310 +/- 20 nmolxmins/liter and 187 +/- 47 nmolxmins/liter, respectively. Plasma cyclic GMP, a surrogate marker of activation of the biological receptor for hBNP, was elevated for a longer period of time following subcutaneous delivery compared with intravenous delivery. Subcutaneous delivery of 30 microg/kg hBNP resulted in natriuresis, diuresis and reduced systolic blood pressure in anesthetized normotensive rabbits, effects similar in magnitude yet prolonged in duration compared with those elicited by the same dose of hBNP delivered intravenously. Systolic blood pressure following hBNP treatment remained below base-line values for 50 and 150 min following intravenous and subcutaneous delivery protocols, respectively. These results suggests that subcutaneous delivery of hBNP may be a viable therapeutic alternative to intravenous modes of delivery.

Amino Acid Sequence↗
PubMed1997

Human brain natriuretic peptide reduces blood pressure in normotensive and acute norepinephrine-induced hypertensive rabbits.

Human brain natriuretic peptide (hBNP) is a cardiac-derived peptide hormone with potent hemodynamic and renal effects in dogs, monkeys, and humans, but not in rats. At present there is no small animal model to study the actions of hBNP. These studies describe the effects of hBNP in New Zealand White rabbits in normotensive and acute norepinephrine-induced hypertensive states. Intravenous administration of hBNP (1, 3, 10, and 30 microg/kg) to anesthetized rabbits resulted in a dose-dependent diuresis and natriuresis and a decrease in systolic blood pressure. Bolus administration of hBNP resulted in a time- and dose-dependent accumulation of plasma cyclic GMP, consistent with activation of a particulate guanylyl cyclase receptor. The hemodynamic actions of hBNP suggest clinical utility for the management of acute hypertension associated with numerous surgical procedures, a condition linked to catecholamine activation. In rabbits with norepinephrine-induced acute hypertension, bolus and continuous infusion of hBNP markedly reduced blood pressure. These studies demonstrate that the rabbit is a useful species to study the hemodynamic and renal effects of hBNP and that this peptide may have therapeutic utility for the acute reduction of hypertension associated with catecholamine activation.

Animals↗
PubMed1991

Demonstration of local immunosuppression with methylprednisolone in the sponge matrix allograft model.

This study evaluated the effect of locally delivered methylprednisolone on the systemic and local immune response in the sponge matrix allograft model. Polyurethane sponges were coated with peritoneal exudate cells from DBA/2 (H-2d) or C57Bl/6 mice (H-2b) and placed subcutaneously in C57BL/6 recipients 24 hr later. Each mouse received both a syngeneic and an allogeneic sponge graft. Local immunosuppression was effected by placement on day 0 of cellulose/matrix pellets containing a preparation of increasing quantity of controlled release MP or by daily intrasponge injection of MP. Local immunosuppression was demonstrated by decreased cytotoxicity on day 12 in the allogeneic sponge receiving MP directly, as compared with the groups that received MP in the opposite syngeneic sponge or no MP. This effect was noted at a specific MP dose (0.5 mg/kg/day). Absolute numbers of precursor cytolytic cells and mature cytolytic cells (determined by limiting dilution analyses) infiltrating the allografts were also decreased in the sponges receiving MP directly, relative to the groups receiving MP in the opposite syngeneic sponge. Maintenance of systemic (in contrast to local) immunity was also demonstrated. Animals treated with local MP into a simultaneously placed syngeneic sponge or in whom no MP was delivered became sensitized to a synchronous DBA/2 sponge and rejected a subsequent DBA/2 skin graft in second-set fashion. Conversely, animals that received local MP into their synchronous DBA/2 sponge rejected a subsequent DBA/2 skin graft or a third-party graft with first-set kinetics. The presence of local MP at the initial graft site prevented the animals from becoming sensitized to the presented alloantigen but did not keep the animal from developing a rejection response to a third-party skin graft with first-set kinetics. It appears that delivery of MP locally to the site of antigen is an effective method to modulate alloreactivity. In addition, the sponge matrix allograft appears to be a useful model for studying local immunosuppression.

Animals↗
PubMed1989

Schistosoma mansoni: insulin independence.

Several authors have reported that schistosomes are affected by host hormones, including insulin. We found that insulin in a 10,000-fold range of concentrations failed to affect glucose consumption of males, females, or pairs of Schistosoma mansoni incubated for periods up to 24 hr. Insulin, vasopressin, or tetradecanoyl phorbol acetate (an insulin mimic) did not affect the uptake and incorporation of [14C]glucose and [14C]deoxyglucose over the active transport range. Competitive binding studies using 125I-insulin and 125I-insulin-like growth factor II, with varying concentrations of unlabeled hormones, demonstrated only nonspecific binding to intact worms or subcellular fractions. This generalized nonspecific uptake of label was also shown by autoradiography, suggesting that specific insulin receptors are absent from S. mansoni. We conclude that plasma glucose levels are sufficient to supply the metabolic requirements of schistosomes by diffusion, and that no insulin-dependent mechanisms have evolved in these parasites.

Animals↗
PubMed1989

Schistosoma mansoni: reversible destruction of testes by procarbazine.

1. The anticancer drug procarbazine is profoundly damaging to the testes of Schistosoma mansoni when administered at 200 mg/kg or more to the mouse host. Somatic tissues appear entirely unaffected. 2. Within 2 days the meiotic process is disrupted, and primary and secondary spermatocytes and spermatids are destroyed and replaced by amorphous granular material. 3. The testes regenerate within about 15 days, apparently from surviving spermatogonial resting cells near the germinal epithelium of the testis. 4. Livers of mice treated once 7 weeks earlier have numerous egg granulomas and give rise to many miracidia, suggesting that full testis function is regained. 5. Male worms given the drug at 200 mg/kg at 19 days of age and fixed 7 weeks later have on average one testis less than control worms, indicating that about 15% of immature testes are unable to regenerate, whereas mature worms given the drug regenerate the normal number of testes. 6. The drug did not have significant antispermatogenic effects when male worms were incubated for a week with various concentrations in vitro, suggesting that a host metabolite is the active agent.

Animals↗
PubMed1989

Schistosoma mansoni: effect of transferrin and growth factors on development of schistosomula in vitro.

We have studied the role of human transferrin and of exogenous iron on early growth and development of schistosomula of Schistosoma mansoni in vitro, as determined by developmental achievement and thymidine incorporation. To help define an adequate serumless medium we also utilized fibroblast growth factor, platelet-derived growth factor, epidermal growth factor, and multiplication-stimulating activity, all present in the hepatic environment of developing schistosomula, as well as certain commercial serum substitutes. Supplementation of basal medium with transferrin in the range of 250-1,000 micrograms/ml provided development equal or superior to serum-supplemented medium, at least within the first 2 wk of culture. Serum-free medium supplemented with Nutridoma-HU or -SP stimulated development to a lesser extent. The stimulatory effect of iron (as ferric sulfate) on thymidine incorporation was removed by deferroxamine, a chelating agent. Competitive inhibition studies with 125I-labeled and unlabeled transferrin indicated the presence of nonsaturable binding sites on schistosomula.

Animals↗
PubMed1988

Lower limb amputation secondary to large vessel involvement in scleroderma.

A 34-year-old woman with scleroderma was admitted to hospital with pain and weakness of her left foot. She was subsequently shown to have developed a popliteal artery occlusion associated with progressive lower limb ischaemia. This culminated in below-knee amputation. Marked intimal hyperplasia of the large vessels in the leg was noted histologically. An increasing number of cases of large vessel involvement in scleroderma, a disease that primarily affects the microvasculature, has been reported. Scleroderma should be regarded as a rare cause of large vessel peripheral vascular disease.

Adult↗
PubMed1985

Sibling pairs affected by chronic arthritis of childhood: evidence for a genetic predisposition.

Twelve families with a sibling pair affected by seronegative juvenile chronic arthritis (JCA) were studied. The ratio of HLA haplotype sharing was significantly different from that expected. No common haplotype was found. All 10 sibling pairs concordant for pauciarticular disease shared 2 haplotypes and the other 2 pairs shared one haplotype. These findings are evidence of a genetic predisposition to develop pauciarticular onset JCA in the families studied and suggest the presence of a disease susceptibility gene or genes within the major histocompatability complex.

Antibodies, Antinuclear↗
PubMed1983

A comparison of low dose levamisole and penicillamine in rheumatoid arthritis.

Levamisole (150 mg once weekly) was compared with penicillamine (250 mg daily) in a single blind independent observer study in 28 patients with rheumatoid arthritis over twelve months. Fifty percent (8/16) of patients stopped levamisole, five within three months of starting, while only two of twelve stopped penicillamine. In those patients able to tolerate treatment for twelve months, both regimens produced a significant and comparable reduction in disease activity, with the onset of action of penicillamine occurring at three months compared with six to nine months for levamisole. Radiological progression of disease occurred in both groups. Levamisole in low dose may improve parameters of disease activity in rheumatoid arthritis but poor patient tolerance, slow onset of action and failure to prevent radiological progression limit its usefulness.

Arthritis, Rheumatoid↗
PubMed1983

HLA studies in IgM rheumatoid-factor-positive arthritis of childhood.

The clinical course of children with IgM rheumatoid-factor-positive chronic arthritis closely resembles that of seropositive rheumatoid disease in adults. The frequency of HLA DR4 is known to be increased in adults with seropositive rheumatoid arthritis, but the first major report on childhood arthritis did not suggest a correlation, though only 8 seropositive cases were included. Fifty-two children with polyarthritis beginning before the age of 16 who persistently carried IgM rheumatoid factor were studied. HLA DR4 was present in 60% of these children but was found in only 29% of 93 patients with seronegative juvenile arthritis and 27% of a normal adult population. These results suggest immunogenetic similarities in patients with seropositive arthritis irrespective of age of onset.

Adolescent↗
PubMed1979

Immunologic regulation in pregnancy.

Theories to explain the failure of rejection of the fetus by the mother during pregnancy include immunologic privilege of the uterus as a graft site, lack of transplantation antigen expression on the trophoblast, weakening of maternal cellular immunity during pregnancy, and separation of maternal and fetal circulations. Evidence for and against each of these theories is discussed. Local concentration of a variety of hormones, including human chorionic gonadotropin (HCG), sex steroids, alpha-fetoprotein, and immunoglobulins, could provide a blocking mechanism to prevent maternal cellular immune attack. Possibly, progesterone, antibodies, and immune complexes are important in protecting the placenta and ultimately the fetus from rejection. Elucidation of regulatory mechanisms in pregnancy may be applicable to other problems in immunology.

Antibodies↗
PubMed1975

Physiologic significance of 17beta-estradiol binding in the rabbit Fallopian tube.

Rabbit Fallopian tube contractility was recorded in vitro during perfusion with either Locke's solution or that solution containing CN-55, 945-27 (CN; or CI-628), a nonsteroidal estrogen antagonist (Endocrinology 79: 153, 1966). Contractility was inhibited and 17beta-estradiol (E2) displaced from both its cytoplasmic (8S) and nuclear (4S) receptors in the presence of the above agent. These effects result from a direct interaction between CN and the E2-receptor complexes. Two types of evidence show the specificity of the foregoing responses: (1) nonspecific binding of E2 to serum proteins was unaffected by the antagonist and (2) CN had no effect on contractility of a nontarget tissue, i.e., rabbit ileum. In addition, Fallopian tube contractions induced by strong electrical stimulation of K-depolarized tissues (i.e., in the absence of normal ionic gradients) were inhibited by CN and a decrease in the binding capacities of 8S and 4S receptors was again observed. Thus, antagonism of specific E2 binding inhibits the contractile mechanism at a level other than the cell membrane. These observations, and additional findings concerning the reversibility of CN action, indicate that E2 binding is essential for contractility of the rabbit Fallopian tube.

Animals↗