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Biomedical subjects

J Scherrer

Publications and source records attributed to J Scherrer.

At least 19 recordsLinked to original sources
PubMed2004

Solar wind-induced atmospheric erosion at Mars: first results from ASPERA-3 on Mars Express.

The Analyzer of Space Plasma and Energetic Atoms (ASPERA) on board the Mars Express spacecraft found that solar wind plasma and accelerated ionospheric ions may be observed all the way down to the Mars Express pericenter of 270 kilometers above the dayside planetary surface. This is very deep in the ionosphere, implying direct exposure of the martian topside atmosphere to solar wind plasma forcing. The low-altitude penetration of solar wind plasma and the energization of ionospheric plasma may be due to solar wind irregularities or perturbations, to magnetic anomalies at Mars, or both.

Journal Article↗
PubMed2002

Effect of MPC-11 myeloma and MPC-11 + IL-1 receptor antagonist treatment on mouse bone properties.

This study examines the effects of an IL-6-producing murine multiple myeloma cell line on trabecular and cortical mouse bone, and evaluates the efficacy of interleukin-1 receptor antagonist (IL-1ra) in mitigating bone destruction. Six-week-old BALB/c mice were assigned to two groups: normal controls and myeloma animals (5 x 10(7) MPC-11 cells on day 0). Myeloma animals were further assigned to three unique groups: MPC-11 only; MPC-11 treated with hyaluronic acid (HA); and MPC-11 + IL-1ra/HA (100 mg/kg). Disease development was assessed at 14 and 21 days via spleen, liver, and proximal tibia histology; histomorphometry at the femoral middiaphysis; and long bone composition and mechanical testing. Histologic analysis revealed marked myeloma infiltration into organs and bone marrow and gross bone resorption of the proximal tibia. IL-1ra tended to decrease bone resorption at the proximal tibia; however, it had no effect on quantitatively measured bone parameters. Whole femur and tibia, and tibial epiphysis, percent mineralization was decreased (3.0%, 2.9%, and 6.3%, respectively) in all MPC-11 groups. The presence of myeloma did not affect long bone stiffness, strength, or length over the 3 week study. The percent of the femoral endosteal perimeter showing excessive resorption ( approximately 60%) in the MPC-11 groups increased significantly after 21 days. MPC-11 cell presence caused no change in bone formation or morphology. Normal growth mechanisms were not impacted, as the bones lengthened and increased in size and mass despite the presence of myeloma. IL-1 does not appear to be a primary factor in in vivo bone destruction caused by the MPC-11 cell line. These findings reveal the stochastic nature of bone lesions in multiple myeloma and suggest that IL-1 is not a cytokine critical to this disease pathology.

Animals↗
PubMed2001

The identification and development of specific monoclonal antibodies to squamous cell carcinoma.

We have developed specific monoclonal antibodies to immunogenic glycoproteins expressed selectively on the cell membrane of squamous cell malignancies. These proteins serve to act as tumor markers that characterize this malignancy; there has be no evidence of cross reactivity to normal epithelial cells. Analysis of patterns of expression reveals that those membrane proteins identified by monoclonals AD7 and 5C6 appear early in cellular transformation to malignancy. At such a time, immunohistochemical recognition is seen in the presence of genotypic alterations, yet phenotypic changes may not be apparent. Of additional interest is that these monoclonal antibodies exhibit strong ADCC allowing the tumor proteins to not only serve as a marker of malignancy but as a target for therapeutic destruction.

Animals↗
PubMed2000

Combination benefit of treatment with the cytokine inhibitors interleukin-1 receptor antagonist and PEGylated soluble tumor necrosis factor receptor type I in animal models of rheumatoid arthritis.

OBJECTIVE: To determine the potential for additive or synergistic effects of combination therapy with the recombinant anticytokine agents interleukin-1 receptor antagonist (IL-1Ra) and PEGylated soluble tumor necrosis factor receptor type I (PEG sTNFRI) in established type H collagen-induced arthritis (CIA) and developing adjuvant-induced arthritis (AIA) in rats. METHODS: Rats with established CIA or developing AIA were treated with various doses of IL-1Ra in a slow-release hyaluronic acid vehicle or with PEG sTNFRI, either alone or in combination with the IL-1Ra. The effects of treatment were monitored by sequential caliper measurements of the ankle joints or hind paw volumes, final paw weights, and histologic evaluation with particular emphasis on bone and cartilage lesions. RESULTS: Combination therapy with IL-1Ra and PEG sTNFRI in rats with CIA resulted in an additive effect on clinical and histologic parameters when moderately to highly efficacious doses of each protein were administered. Greater-than-additive effects were seen when an inactive dose of IL-1Ra was given in combination with moderately to minimally active doses of PEG sTNFRI. Plasma levels associated with the latter effect (for both proteins) were similar to those seen in rheumatoid arthritis (RA) patients in clinical trials with these agents. Combination therapy in the AIA model generally resulted in additive effects, but some parameters showed a greater-than-additive benefit. CONCLUSION: The results provide preclinical support for the hypothesis that IL-1Ra administered in combination with PEG sTNFRI might provide substantially more clinical benefit to RA patients than either agent alone at blood levels that are currently achievable in patients.

Animals↗
PubMed1999

Neuroleptic influences on a lateralized behavioral bias in unoperated rats.

RATIONALE: Abnormalities of the ascending dopaminergic system have been associated with hemineglect, and evidence suggests that neuroleptic treatments normalize the right hemispatial attentional impairment that is sometimes observed in acutely psychotic schizophrenic patients. OBJECTIVE: A research program was initiated to develop an animal model of hemineglect-drug interactions. METHODS: Female rats were tested repeatedly on removing a "nuisance stimulus" - strips of surgical tape applied loosely to the forelimbs. Subjects were assigned to groups dependent upon showing a behavioral orientation preference (BOP) during pre-drug baseline tests. Animals representing left-BOP, right-BOP and no preference continued to be tested during chronic exposure either to a dopamine antagonist (0.05 mg haloperidol/kg) or agonist (1.0 mg d-amphetamine/kg) or vehicle only. RESULTS: Three weeks of haloperidol treatments to rats only with an initial right BOP gradually eliminated the response bias, as revealed by declines in choosing the right forepaw and the latencies between attending to the two forepaws. CONCLUSION: The results recommend right BOP female rats as a simple, non-invasive behavioral animal model for evaluating and comparing neuroleptic medications.

Amphetamine↗
PubMed1998

Effects of interleukin-1 receptor antagonist in a slow-release hylan vehicle on rat type II collagen arthritis.

PURPOSE: To determine the effect of hylan fluid (HA), a model slow release vehicle on the pharmacokinetic profile and efficacy of interleukin-1 receptor antagonist (IL-1ra) in rats with established type II collagen arthritis. METHODS: Female Lewis rats with type II collagen arthritis were treated daily, every other day or every third day with single subcutaneous (sc) injections of IL-1ra formulated in HA and the effects on arthritis determined. Results were compared to those obtained with IL-1ra in citrate buffered saline with EDTA and polysorbate (CSEP). Sequential blood levels were determined in rats injected sc with IL-1ra in CSEP or HA. RESULTS: Incorporation into HA led to slower release of IL-1ra into the bloodstream and maintained therapeutic blood levels of IL-1ra for a longer time compared to the IL-1ra/CSEP formulation. Single daily sc doses of 100 mg/kg IL-1ra in CSEP were ineffective in type II collagen arthritis. By contrast, once per day dosing of 100 mg/kg IL-1ra in HA provided 78% inhibition of paw swelling. Every other day dosing with 100 mg/kg IL-1ra in HA resulted in 62% inhibition. IL-1ra (100 mg/ kg in HA) given every third day provided 19% inhibition of arthritis. Improved efficacy correlated with improved pharmacokinetics. CONCLUSIONS: Administration of IL-1ra in the slow release vehicle HA improves pharmacokinetics and efficacy in rat type II collagen arthritis.

Animals↗
PubMed1996

Male reproductive systems under chronic fluoxetine or trimipramine treatment.

Adult male Long-Evans rats (n = 9 per group) received daily exposure for 4 weeks to fluoxetine (0.75 mg FLUOX/kg body weight) or trimipramine (1.6 mg TRIMI/kg body weight). Separate tests of copulation, sexual motivation, and intermale aggressive behaviors were used to evaluate functional changes during chronic exposure to either typical or atypical antidepressant drugs with more or less serotonin specificity. Circulating hormones, primary and secondary sex structures, and concentrations of dopamine (DA) and serotonin (5-HT) from mesolimbic tissue were assessed at necropsy. Results of tests with estrous females and untreated males revealed progressive disruption to sexual performance and aggressive responsiveness over time of treatment with TRIMI and, to a lesser extent, with FLUOX. By contrast, motivation, testosterone, and all measures of reproductive physiology were indistinguishable from controls. Ratios of transmitter metabolites relative to the parent compounds indicated similar reductions of 5-HT turnover with FLUOX and TRIMI. However, influences on DA turnover were significantly less with FLUOX than with TRIMI. Conclusions are that long-term intervention with antidepressant drugs may disrupt sociosexual exchanges without compromising male rats' interest in sexual contact or integrity of their reproductive physiology. Lessened disruption of sociosexual behaviors with this regimen of chronic FLUOX treatment may be related to the greater selectivity on serotonin relative to dopamine turnover.

Adrenal Cortex Hormones↗
PubMed1996

Nursing case management: relationships as a strategy to improve care.

MULTIPLE TRANSFERS, MULTIPLE caregivers, and an unpredictable hospital course may result in ineffective communication among patients, families, and the healthcare team, and a fragmented plan of care for complex patients. To address these concerns, CNSs in a tertiary hospital developed a nursing case management model for patients in a medical-surgical-neurological intensive care unit. Long-term relationships between nursing case managers (NCMs), patients, and families grounded the model. The NCM crossed traditional unit boundaries with the patient, improving communication among patient, family, and the healthcare team. Evaluation of the NCM's experience suggested four types of interventions: (a) telling the story, (b) advancing the plan of care, (c) maintaining values and beliefs, and (d) assisting with options and decisions. Case studies illustrate these interventions and demonstrate cost savings.

Case Management↗
PubMed1994

Endothelin-C-terminal hexapeptide increases grooming in mice.

Grooming behavior has been considered a response to stress, and a number of stress-related peptides have been demonstrated to modulate grooming behavior. In the experiments reported here, endothelin-C-terminal hexapeptide containing amino acid residues 16-21, ET[16-21], increased grooming with a maximum effect at 0.75 microgram. ET[16-21] did not significantly alter eating or locomotor behavior. Both alpha-helical CRF (10 micrograms) and neuropeptide Y (1 microgram) inhibited the grooming produced by ET[16-21].

Animals↗
PubMed1994

Endocrine interactions: adrenal steroids and precursors.

Adult male rats (n = 48) were castrated and treated daily for 4 wk with adrenal steroids in the presence or absence of adjuvant testosterone. Dehydroepiandrosterone (DHEA), DHEA sulfate, and androstenedione (2 mg/kg body wt) were administered as cyclodextrin complexes to mimic the pharmacodynamics of the endogenous products. Although they are the substrates for testosterone synthesis in target tissues, supplements of adrenal steroids alone were unable to maintain integrity of sociosexual responses and androgen target tissues after castration. More surprising, groups administered adrenal precursor plus testosterone showed substantial suppression of the typical restoration of reproductive systems in castrates receiving androgen therapy. The adrenal steroids, however, were not functionally identical. Each steroid interacted with testosterone to leave its own distinctive "footprint" on androgen-sensitive systems. The conclusion is that the endogenous adrenal products are not simply passive precursors of testosterone. Adrenal steroids may serve as endocrine regulators of androgen bioavailability and bioactivity.

Adrenal Glands↗
PubMed1985

Specific active immunotherapy in patients with adenocarcinoma of the colon utilizing tumor-associated antigens (TAA). A phase I clinical trial.

Twenty-two patients received specific active immunotherapy (TAA vaccine once per month for 3 months), with the duration of follow-up, as of July 1984, ranging from 3 months to 36 months (median, 21 months). Of these, seven had Dukes B2, seven had Dukes C, and eight had Dukes D lesions. All received surgical resection, and those with Dukes D disease underwent resection of all metastases where possible, with six clinically disease-free at the time of initiation of therapy. The age range of the 22 patients was 40 to 73 years (median, 60 years); sex distribution was 12 males and 10 females. All patients were monitored by physical examination and by laboratory parameters including complete blood count, liver and renal function tests, blood chemistries, urinalysis, chest x-ray, carcinoembryonic antigen levels, migration inhibition assays, complete immune complexes, serum chemistries, helper and suppressor and total T-cell and B-cell assays, and TAA antibody levels. As measured by delayed cutaneous hypersensitivity skin test and by migration inhibition assays (MIA), a strong postimmunization response is developed approximately 5 months after vaccination is completed. There were no clinical or biochemical manifestations of any type of systemic toxicity including hepatic, renal, gastrointestinal, respiratory, or neurologic during the period of follow-up. All patients developed skin ulcers at the vaccination and required 4 to 5 months to heal. With this small number of patients in a Phase I trial, survival is indicative of the safety of the vaccine only: 82% of the patients are alive (mean survival, 21 months) thus far, and 59% of the patients are without evidence of disease (NED) (mean NED, 22 months). These studies, therefore, justify a Phase II-III trial in a larger number of patients and have provided selection of appropriate monitoring tests for the larger trial.

Adenocarcinoma↗
PubMed1982

[Insomnia therapy and withdrawal of hypnotics].

The aim of this study is to evaluate the efficiency of a treatment prescribed, in the course of an hospital consultation for sleep pathology, to patients suffering from chronic insomnia not improved by longstanding and sustained medication with hypnotic drugs. The basis of the treatment is a progressive but total withdrawal of hypnotics in so far taken regularly. The withdrawal of hypnotics was prescribed to 79 patients: 33 aged 17 to 39 years (group 1, mean age 30) and 46 aged 40 to 70 years (group 2, mean age 51). 41 showed primary psychophysiological insomnia and 28 showed insomnia associated with psychiatric disorders. In patients of group 1, the average durations were 8 years for insomnia and 3 years for sustained hypnotic use; these durations were 15 and 5 years respectively in patients of group 2. Hypnotic drug withdrawal was achieved without placebos in 3 months in group 1 patients and 5 months in group 2 patients. 65 patients completely stopped the continual use of hypnotics. Subjective improvement of insomnia was reported by 51 of these patients (as well as by 6 patients who were given simultaneous antidepressant therapy). 16 of the 51 improved patients have resorted to hypnotics occasionally (at intervals of 10 days or more). After complete withdrawal, patients went on consulting for various lengths of time: 5 months average for group 1, 14 months average for group 2. This study of a fairly large group of insomniacs shows the frequent ineffectiveness of a sustained use of currently available hypnotics. It also shows that two times out of three the complete stop of sustained hypnotic medication proved beneficial to the patient.

Adolescent↗
PubMed1982

Pilot studies using melanoma tumor-associated antigens (TAA) in specific-active immunochemotherapy of malignant melanoma.

Highly purified melanoma TAA which induce melanoma-related cellmediated immune responses have been further characterized using hyperimmune TAA antisera after affinity chromatography for double immunodiffusion-immunoelectrophoresis and indirect immunofluorescence studies. An additional study of antigenic modulation was performed in 23 nonanergic and seven anergic melanoma patients, tested simultaneously with melanoma TAA prepared from primary and metastatic tumors, which had been obtained from one patient at different time periods. The results of pilot clinical trials are reported, including toxicity, timing and dosage studies in 20 patients and subsequent studies of patients with metastatic melanoma treated at three separate centers, using a single lot of purified, allogeneic melanoma TAA. The results of these latter studies in 51 patients with Stage III (distantly metastatic) melanoma and in five patients with earlier stages of disease indicate that: (1) when the interval from primary therapy to recurrence is greater than one year and when liver, bone and brain are not involved, partial or total clinical regression may be noted in up to 25% of patients with metastatic disease receiving immunochemotherapy; (2) when total regression does occur, the effect usually lasts from one to three years; (3) cytoreductive (debulking) surgery, when possible, in cutaneous, nodal retroperitoneal, and visceral regions may enhance the response to specific active immunochemotherapy, although some debulked patients had less tumor burden and this factor alone may lead to an improved prognosis in patients undergoing any subsequent treatment; (4) when circulating inhibitory factors are modified through preimmunization chemotherapy, an enhanced host response may be seen; and (5) Cancer Serum Indices (CSI) may be useful in predicting recurrence and in following tumor load and response to therapy. Information obtained from these studies suggest the need for further trials to determine the effect of immunization on patients with earlier stages of disease where recurrence rates remain high, and to evaluate the mechanisms of tumor rejection or tumor progression in the face of immune stimulation.

Adult↗
PubMed1979

Projections of the common fur of the muzzle upon the cortical area for mystacial vibrissae in rats dewhiskered since birth.

In normal adult rats, the mystacial vibrissae and the common fur of the snout project at different loci on the SI cortex. The surface area of the normal fur projection is 0.8 mm2, whereas the vibrissa field amounts to 3-4 mm2. In rats dewhiskered since birth, the vibrissa area can still be identified through the projections from ipsilateral vibrissae (undamaged side). It is shown that in the absence of the vibrissae since birth, the vibrissa area, and this alone, is invaded by projections from the contralateral fur (damaged side).

Animals↗