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Biomedical subjects

P Siegel

Publications and source records attributed to P Siegel.

At least 19 recordsLinked to original sources
PubMed2001

Pharmacologic properties of brewery dust extracts in vitro.

STUDY OBJECTIVES: To study the effects of extracts of brewery dust on isolated guinea pig tracheal smooth muscle in vitro. DESIGN: Parallel pharmacologic intervention on guinea pig tracheal rings that were obtained from the same animal. SETTING: Mount Sinai School of Medicine, Department of Pulmonary Medicine. MATERIAL: The isolated guinea pig tracheal tissue of 18 guinea pigs. INTERVENTIONS: Pretreatment of guinea pig rings by mediator-modifying agents before challenge with the brewery dust extracts. MEASUREMENTS AND RESULTS: The effect of brewery dust extracts on isolated guinea pig tracheal smooth muscle was studied using water-soluble extracts of dust obtained from brewery materials, including hops, barley, and brewery yeast. Dust extracts were prepared as a 1:10 (wt/vol) aqueous solution. Dose-related contractions of nonsensitized guinea pig tracheas were demonstrated using these extracts. The dust extracts contained significant quantities of bacterial components (eg, endotoxin and n-formyl-methionyl-leucyl-phenylalanine), but these agents were not thought to contribute directly to the constrictor effect of the dusts. Pharmacologic studies were performed by pretreating guinea pig tracheal tissue with the following drugs known to modulate smooth muscle contraction: atropine; indomethacin; pyrilamine; LY171883; nordihydroguaiaretic acid; captopril; thiorphan; verapamil; and TMB8. The constrictor effects of the dust extracts were inhibited by a wide variety of agents, the patterns of which depended on the dust extract. Atropine consistently and strikingly reduced the contractile effects of these extracts. These observations may suggest an interaction of the extracts with parasympathetic nerves or, more directly, with muscarinic receptors. The inhibition of contraction by the blocking of other mediators was less effective and varied with the dust extract. CONCLUSIONS: We suggest that brewery dust extracts cause a dose-related airway smooth muscle constriction by nonimmunologic mechanisms involving a variety of airway mediators and, possibly, cholinergic receptors. This effect is not dependent on presensitization of the guinea pigs.

Animals↗
PubMed2000

SM5-1: a new monoclonal antibody which is highly sensitive and specific for melanocytic lesions.

Antibodies such as HMB-45 and anti-S100 protein have been widely used as markers of malignant melanoma despite evidence that HMB-45 has a sensitivity of only 67-93% and S100 is nonspecific for melanoma. Using a subtractive immunization protocol in a mouse model of human melanoma, we have generated several monoclonal antibodies with putative specificity for melanoma. After initial screenings, the antibody SM5-1 was chosen because of its intriguing reactivity with melanocytic tumors in both frozen and paraffin sections. The immunohistochemical staining of SM5-1 was studied in paraffin-embedded specimens of 401 melanomas (n = 401; 250 primary melanomas, 151 metastases), melanocytic nevi of the skin (n = 16), nonmelanocytic neoplasms (n = 84). The results were compared with HMB-45 and anti-S100 staining. All antibodies reacted with nevi and 97-99% with primary melanomas. Whereas both SM5-1 and anti-S100 stained 96% (146/151) of melanoma metastases, HMB-45 correctly identified only 83% (126/151). All HMB-45-negative metastases were positive for SM5-1. Whereas neither SM5-1 nor HMB-45 stained any of 84 specimens from 40 different nonmelanocytic neoplasms, anti-S100 was positive in 21/84 (25%). While the staining pattern of SM5-1 was mostly homogeneous, small tumor areas in some metastases remained unstained. Staining with SM5-1 was also observed in perivascular dendritic cells, in plasma cells, some myofibroblasts and the secretion of eccrine sweat glands. Nonactivated epidermal melanocytes, keratinocytes, endothelial cells, smooth muscle cells and peripheral nerves were all negative for SM5-1. These results suggest that SM5-1 is highly specific, as well as sensitive, for melanocytic lesions and is useful in the immunohistochemical evaluation of melanoma.

Animals↗
PubMed1998

Reciprocal regulation of neu tyrosine kinase activity and caveolin-1 protein expression in vitro and in vivo. Implications for human breast cancer.

Neu (c-erbB2) is a proto-oncogene product that encodes an epidermal growth factor-like receptor tyrosine kinase. Amplification of wild-type c-Neu and mutational activation of Neu (Neu T) have been implicated in oncogenic transformation of cultured fibroblasts and mammary tumorigenesis in vivo. Here, we examine the relationship between Neu tyrosine kinase activity and caveolin-1 protein expression in vitro and in vivo. Recent studies have suggested that caveolins may function as negative regulators of signal transduction. Our current results show that mutational activation of c-Neu down-regulates caveolin-1 protein expression, but not caveolin-2, in cultured NIH 3T3 and Rat 1 cells. Conversely, recombinant overexpression of caveolin-1 blocks Neu-mediated signal transduction in vivo. These results suggest a reciprocal relationship between c-Neu tyrosine kinase activity and caveolin-1 protein expression. We next analyzed a variety of caveolin-1 deletion mutants to map this caveolin-1-dependent inhibitory activity to a given region of the caveolin-1 molecule. Results from this mutational analysis show that this functional in vivo inhibitory activity is contained within caveolin-1 residues 32-95. In accordance with these in vivo studies, a 20-amino acid peptide derived from this region (the caveolin-1 scaffolding domain) was sufficient to inhibit Neu autophosphorylation in an in vitro kinase assay. To further confirm or refute the relevance of our findings in vivo, we next examined the expression levels of caveolin-1 in mammary tumors derived from c-Neu transgenic mice. Our results indicate that dramatic reduction of caveolin-1 expression occurs in mammary tumors derived from c-Neu-expressing transgenic mice and other transgenic mice expressing downstream effectors of Neu-mediated signal transduction, such as Src and Ras. Taken together, our data suggest that a novel form of reciprocal negative regulation exists between c-Neu and caveolin-1.

Animals↗
PubMed1998

Effects of recycled paper dust extracts on isolated guinea pig trachea.

The effect of paper dust collected at two different locations in a paper recycling plant (PD1 and PD2) on isolated nonsensitized guinea pig tracheal smooth muscle was studied in vitro. Dust extracts were prepared as a 1:10 w/v aqueous solution. Dose-related contractions of guinea pig tracheal rings were elicited with both PD1 and PD2. Pharmacologic studies were performed with atropine (10(-6) M), indometacin (10(-6) M), pyrilamine (10(-6) M), LY171883 (10(-5) M), nordihydroguaiaretic acid (10(-5) M), and TMB8 (10(-5) M). The possible role of endogenous neuropeptides in this constrictor process was studied by depleting neural mediators with capsaicin (5 x 10(-6) M) before challenge with dust extracts. Constrictor effects were partially inhibited by a wide variety of the mediator blocking agents. The effects of both extracts were almost totally inhibited by the anticholinergic agent atropine, suggesting that a principal pathway mediating this response may involve the parasympathetic nervous system. The intracellular calcium-blocking agent TMB8 also induced a reduction of the contractile responses to PD1 and PD2 consistent with the well established role of intracellular calcium in smooth muscle constriction. Pretreatment with capsaicin significantly increased the contractile activity of paper dust extracts but only at the higher doses of these extracts. This suggests that the effect of paper dust is not initiated by the release of mediators stored in sensory nerves but that the prerelease of these mediators may enhance the constrictor effects of these dusts. We suggest that paper dust extracts cause dose-related airway smooth muscle constriction possibly associated with the release of cholinergic as well as other mediators. The constrictor effect does not require tissue presensitization or the release of neuropeptides from sensory nerves.

Animals↗
PubMed1997

Nucleotide sequence comparison of the IgE constant region in patients with atopic dermatitis and non-atopic individuals.

In order to answer the question whether the Fc portion of the IgE molecule in patients with atopic dermatitis is altered by somatic replacement mutations, we amplified and sequenced the respective C epsilon 2 and C epsilon 3 domain genes. Five patients with atopic dermatitis and 6 non-atopic individuals were studied. Neither within the C epsilon 2 nor the C epsilon 3 domain could any common nucleotide substitutions be detected. Therefore, the conclusion can be drawn that, in patients with atopic dermatitis, there are no protein sequence differences within the Fc part of the IgE which could be responsible for distinct functional features with regard to Fc epsilon-receptor binding and signal transduction or could account for the frequent occurrence of anti-IgE autoantibodies in these individuals.

Base Sequence↗
PubMed1995

Telomerase activity in normal and malignant murine tissues.

Telomere shortening may contribute to the limited lifespan of somatic cells and telomerase, the enzyme that elongates telomeric DNA and maintains telomere length, may be essential for unlimited cell proliferation in vivo and in vitro. Telomerase is not expressed in most human somatic cells but is a nearly ubiquitous tumour marker, being activated in malignant cells from many cancers. Inhibition of telomerase may lead to telomere shortening and eventually limit the proliferative capacity of malignant cells and hence be of therapeutic value. With the intent of characterizing an animal model for inhibition studies, we investigated telomerase activity during mammary tumorigenesis in transgenic mice overexpressing the neu gene. We detected activity in primary mammary tumours and lung metastases but also in normal mammary glands and other organs. Activity was elevated in tumors versus normal tissues and was enhanced by short-term culturing of normal cells. Telomerase activity was also present in somatic tissues from the non-transgenic parental strain and the outbred Mus spretus strain. As we recently detected telomerase activity in normal human hemopoietic tissues, mouse models of tumorigenesis may provide useful experimental systems for assessing the outcome of in vivo inhibition of telomerase in both malignant and normal cells.

Animals↗
PubMed1995

What they didn't know may have helped us: how the Supreme Court misinterpreted the role of sign language interpreters.

In Zobrest v. Catalina Foothills School District (1993), the Supreme Court ruled that using state monies to pay for a sign language interpreter's services in a parochial school setting did not violate the Establishment Clause. That decision was based on a flawed reading of the role played by sign language interpreters and the implications of that role within the rubric of traditional First Amendment jurisprudence. This article explores why the interpreter's role is constitutionally significant. It then contrasts the two competing models set before the Court, the mechanical model and the full participant model. After finding that the latter model is the more accurate depiction of the interpreter's role, the article examines several unique features of interpreting between spoken and spatial languages that suggest a more sophisticated Court would have ruled against the Zobrests.

Deafness↗
PubMed1993

An anti-lipid A antibody obtained from the human fetal repertoire is encoded by VH6-V lambda 1 genes.

The human hybridoma cell line CB-201 has been obtained from a fusion of fetal spleen lymphocytes (31st gestational week) with heteromyeloma cells. The IgM (lambda) secreted was found to bind to lipid A, whereas other endogenous and exogenous antigens were not recognized. The CB-201 antibody is encoded by the unmutated VH6 gene recombined with DN4 and JH3 elements and a V lambda subgroup 1 gene. Therefore, a VH gene, which was previously described to be over-represented in the fetal repertoire and to be expressed in autoantibody-producing B cells, may encode an anti-bacterial specificity.

Antibodies, Monoclonal↗
PubMed1992

Studies of hospital social stays in the frail elderly and their relationship to the intensity of social work intervention.

The elderly frequently suffer long lengths of hospital stay (LOS). These long stays are often associated with long social care stays which occur when patients no longer require acute care and are awaiting post-discharge services. In this study, actual acute care LOS and social care LOS were studied specifically in hospitalized frail elderly. Our data demonstrate that frail elderly receiving only acute care do not suffer markedly prolonged total LOS (TLOS). However, in hospitalized frail elderly patients who experience acute care and social care stays, social care LOS accounts for over half of all hospital days. When patients were grouped and studied according to the type of post-discharge services being sought by the health care team, significant differences in acute LOS and social care LOS were noted. Subgroups of patients were also identified among the various groups which differed significantly in their LOS parameters. Patients who required more than one discharge plan during the course of hospitalization experienced the longest hospital stays of all groups, and spent almost 70% of these days receiving non-acute social care. In a study of the relationship between the intensity of social work intervention and social care LOS in the frail elderly, a statistically significant relationship was noted between the timing and frequency of social work intervention and the actual length of social care stays. Early and frequent social work interventions were associated with significantly shorter social care LOS. We conclude that the study of TLOS should include acute LOS and social care LOS to obtain a reliable measure of the course and cost of hospital care for the frail elderly. The study of social care subgroups may facilitate future investigations to define the social care problems which contribute most to TLOS, and the patient populations which should be most heavily targeted for early and intensive social work intervention.

Aged↗
PubMed1991

Lesbian and gay rights as a free speech issue: a review of relevant caselaw.

The legal struggles waged by lesbian and gay male litigants almost invariably involve issues of freedom of expression, broadly construed. To illustrate this point, a wide array of caselaw is examined--ranging from classic "access to a forum" controversies to those concerning symbolic conduct and freedom of association (including marriage and child custody law), employment discrimination, and proscriptions against deviant sexual conduct. In each category, claims to a right of freedom of expression are manifested. Cautionary notes are offered concerning those cases in which gay litigants try to protect their rights by inhibiting the speech of others. A brief concluding section assesses the long-term and short-term efficacy of raising First Amendment arguments (as opposed to privacy or equal protection arguments) in lesbian/gay male litigation.

Adult↗
PubMed1984

Severe bronchopulmonary dysplasia. Predictors of survival and outcome.

Predictors of survival and outcome were evaluated following severe bronchopulmonary dysplasia in 35 neonates, 15 of whom died during the initial hospitalization and four following discharge. There was no difference in the clinical characteristics between those infants who survived or died. The survival rate was 47 percent when the length of stay in the hospital was three months and was 17 percent when the length of stay was five months. The survival rate was 27 percent when the time receiving oxygen was three months. There were no survivors when the time receiving oxygen was longer than five months. Follow-up of 13 survivors revealed that four had neurologic sequelae, and two had severe retrolental fibroplasia. When comparing infants with a mean mental developmental index of less than 84 (n = 8) to those with more than 85 (n = 5) on the Bayley Scales of Infant Development, mean length of hospitalization was 125 days vs 72 days (p less than 0.05), and the time receiving oxygen was 84 days vs 46 days (p less than 0.05). When comparing infants with growth parameters below the 5th percentile (n = 4) to those above the 5th percentile (n = 9), the mean time receiving oxygen was 94 days compared to 58 days (p less than 0.05). Severe bronchopulmonary dysplasia is associated with a high mortality and morbidity, both in and beyond the neonatal period.

Birth Weight↗
PubMed1979

The interaction of stressors in the induction of increased levels of fluctuating asymmetry in the laboratory rat.

Recent studies on fluctuating dental asymmetry have isolated single stressors as causative agents. Since most stressors are composite in nature, the present study was designed to determine the effects of the interaction of stressors in the induction of fluctuating dental asymmetry. Pregnant rats were assigned to one of six treatment groups and stressed with various combinations of heat, cold, noise and protein deprivation. The levels of fluctuating dental asymmetry were assessed and it was found that all protocols produced higher levels of asymmetry than found for control animals. Noise and reduced protein exhibited an additive effect and the interaction of stressors produced a reduction in litter size. Suggestions were offered for further research in this expanding field.

Animals↗