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Biomedical subjects

M H Allen

Publications and source records attributed to M H Allen.

At least 55 records · Page 3Linked to original sources
PubMed1997

CD44 variant expression in cutaneous T-cell lymphoma.

Expression of the lymphocyte homing receptor CD44 and its splice variants have been linked to tumour dissemination and poor prognosis in non-Hodgkin's lymphoma. Specifically, the in vitro expression of variant exon V6 confers metastatic potential in rat pancreatic carcinoma cell lines. In this study, we investigated the expression of CD44 splice variants in cutaneous T-cell lymphomas, including patients with mycosis fungoides (MF), Sezary syndrome (SS), large-cell anaplastic lymphoma (LCAL) and HTLV1-associated cutaneous lymphoma. In addition, 4 involved lymph nodes from 2 patients with MF and 1 patient with SS were examined. Inflammatory dermatoses, lichen planus and psoriasis, and normal skin were also studied. Immunohistochemistry was performed using a panel of monoclonal antibodies, including those with specificity for CD44H (standard isoform) and variant exons V3, V6 and V8-9. Normal epidermal keratinocytes were consistently CD44H and CD44 V3, V6 and V8-9 positive. In all the different clinicopathological subtypes and stages of cutaneous T-cell lymphomas, including involved lymph nodes, tumour cells consistently expressed CD44H, but were CD44 V3 and V6 negative. CD44 V8-9 was expressed on a majority of tumour cells in 2/5 LCAL and on occasional tumour cells in 2/5 LCAL. Occasional V8-9 positive tumour cells were also identified in 6/13 MF, 1/4 SS and 3/4 HTLV1. In 2/3 lymph node samples from 2 patients with tumour-stage MF, CD44 V8-9 expression was found on a small percentage of atypical mononuclear cells. Scattered V8-9 positive dermal mononuclear cells were present in sections of lichen planus and psoriasis. We have found no evidence to suggest that the metastasis-associated CD44 variant exon (V6) is expressed in cutaneous T-cell lymphoma, or that CD44H expression is associated with an adverse prognostic group. It is not clear whether the strong expression of CD44 V8-9 in 2 patients with CD30 positive LCAL reflects activation status or metastatic potential.

Alternative Splicing↗
PubMed1997

Localization of endothelial proliferation and microvascular expansion in active plaque psoriasis.

Expansion of the dermal microvasculature is a prominent feature of psoriasis. Although the pathogenetic process resulting in vascular morphological changes remains unclear, considerable evidence suggests the involvement of angiogenesis. To assess the degree and site of psoriatic microvascular expansion, immunohistochemical studies were performed on paired lesional and non-lesional specimens from 10 patients with active, untreated plaque psoriasis. Five-micron thick sections were labelled with monoclonal antibody JC/70A specific for the endothelial marker CD31, and vascular quantification was achieved using hue-saturation-intensity image analysis. Assessment of vasculature in the papillary dermis (superficial plexus) demonstrated a fourfold increase in endothelial surface area of lesional compared with non-lesional skin (P < 0.01), while there was no significant increase in vasculature of the upper reticular dermis. Subsequently, 18-micron thick sections were double-labelled with MIB-1 antibody to the nuclear proliferation marker Ki-67 and JC/70A. Endothelial cell proliferation was identified in the vertical limbs of capillary loops in eight out of 10 lesional biopsies and in no non-lesional biopsies. The endothelial MIB-1 labelling index was 3.1% of total endothelial cells of the superficial plexus. These findings confirm endothelial proliferation underlying psoriatic microvascular expansion, and indicate that this process is limited to a specific site in the dermal capillary bed.

Adult↗
PubMed1996

Definitive treatment in the psychiatric emergency service.

This article briefly reviews the history of psychiatric emergency services (PES) in the United States and concludes that the dominant model, the triage model, unnecessarily limits modern PES. Trends in the mental health system and the corresponding development of compensatory PES structures are described. These include observation units, outreach, and crisis residential treatment and other innovations. These new structures have had the effect of increasing the length of stay in emergency services, increasing the number and complexity of services provided in the PES and professionalizing emergency service personnel. A new model, the treatment model, is proposed for this type of PES. Strategies for the rapid initiation of definitive treatment of bipolar disorder, schizophrenia, major depression and opiate addiction are outlined for services with this capability.

Anxiety↗
PubMed1996

E-selectin binds to squamous cell carcinoma and keratinocyte cell lines.

E-selectin is an endothelial adhesion molecule that binds carbohydrate epitopes on leukocytes and has been implicated in a potential pathway of tumor metastasis. Keratinocyte cell lines express similar carbohydrate epitopes, one of which, sialyl Lewis X (SL-X) is a ligand for E-selectin and is also expressed by squamous cell carcinomas (SCC) in situ. The functional role of keratinocyte selectin ligands was investigated using a soluble E-selectin chimaeric protein (pE-sel-Ig) containing pig lectin-like and epidermal growth factor-like domains fused to human IgG. After incubation of keratinocyte cell lines (A431 and SVK14) and normal keratinocytes with pE-sel Ig, binding was quantified by flow cytometry. Frozen sections of SCC were overlaid with pE-sel Ig and binding was visualized immunoenzymatically. Immunolabeling was undertaken using monoclonal antibodies (CSLEX-1 and HECA-452), which label E-selectin ligands including sialyl Lewis X. E-selectin bound strongly to A431 and SVK14 cells; the degree of binding paralleled staining intensity with CSLEX-1 antibody. HECA-452 antibody stained A431 cells strongly but SVK14 cells only weakly. Normal keratinocytes and normal epidermis did not express CSLEX-1 or HECA-452 antigens or bind E-selectin. Serial sections of SCC revealed close correlation between fusion protein binding and antibody staining. Antibody pretreatment of tumor sections with CSLEX-1 blocked fusion protein binding, whereas HECA-452 antibody only slightly reduced fusion protein binding. pE-sel Ig pretreated with YT11.1 antibody failed to bind to A431 or SVK14 cells or to SCC. These studies provide functional evidence that SL-X/E-selectin pathways may be important in SCC metastasis and that A431 and SVK14 cells provide a good model to investigate these mechanisms.

Carcinoma, Squamous Cell↗
PubMed1996

Expression of E-cadherin in human epidermal non-melanoma cutaneous tumours.

E-cadherin is a calcium-sensitive, cell-to-cell, adhesion molecule that is expressed widely in normal human epithelial tissue. Abnormal expression has been described in colorectal, breast and nasopharyngeal squamous cell carcinomas, where loss of E-cadherin is associated with an increased metastatic potential. We have examined, by standard immunohistochemical techniques using the monoclonal antibody HECD-1 (E-cadherin monoclonal antibody), the distribution of E-cadherin in normal human skin and in non-melanoma neoplastic lesions. In the normal epidermis, E-cadherin was strongly expressed on the surface of keratinocytes and specialized epithelial structures. Staining was absent from the lower pole of basal keratinocytes in contact with the basement membrane. Weak cytoplasmic staining was also noted in basal keratinocytes. No reactivity was demonstrated in dermal structures. The assessment of cutaneous tumours demonstrated an altered pattern of staining in most cases. Cell surface expression was reduced in 28 of 30 cases of basal cell carcinomas (BCC). Twenty showed an additional feature of positive staining on the dermal aspect of peripheral cells of tumour lobules. In squamous cell carcinomas (SCC) (n = 16), surface expression was attenuated in eight and absent in a further four. Strong surface expression, similar to normal skin was seen in all examples of Bowen's disease (n = 6), viral wart (n = 3), seborrhoeic keratosis (n = 3) and actinic keratosis (n = 4). This study demonstrates that, in BCC and SCC, but not in premalignant lesions, cell-surface expression of E-cadherin is reduced, consistent with the observation that the loss of E-cadherin is associated with tumour invasion.

Cadherins↗
PubMed1995

Emergency psychiatric evaluation of "organic" mental disorders.

The emergency psychiatrist must first differentiate abnormal behavior with a medical etiology from that caused by so-called functional processes. Delays in diagnosis can be catastrophic and make a compelling argument for physician involvement in emergency mental health care.

Adolescent↗
PubMed1995

Social interventions in the care of human immunodeficiency virus (HIV)-infected pregnant women.

The incidence of infection with the human immunodeficiency virus (HIV) is increasing among women of childbearing age. Women now account for 18% of the total number of cases of the acquired immunodeficiency syndrome (AIDS), compared with 9% a decade ago. The medical care of pregnant HIV-infected women must take into account the high prevalence of substance abuse, preceded and often accompanied by significant levels of physical, emotional, and sexual trauma, and the concomitant stigmatization of these women in their families and communities. Pregnancy is often a time when women are motivated to make major positive behavioral and life-style changes. To do this, they need ongoing, multidisciplinary counseling and support, with recognition that progress may be intermittent and slow. The Special Prenatal Care Program at Bellevue Hospital is described to show the level of resource commitment that is needed as well as the nearly universal acceptance of voluntary HIV counseling and testing in these conditions. Trends in permanency planning for the children of HIV-infected women are described. Future research needs are outlined, including female-specific drug treatment and more effective contraceptive technology for both men and women.

Adult↗
PubMed1995

Tumour necrosis factor alpha is pro-inflammatory in normal human skin and modulates cutaneous adhesion molecule expression.

Tumour necrosis factor alpha (TNF-alpha) is a potent immunoregulatory cytokine produced by many cutaneous cells, including keratinocytes, mast cells and Langerhans cells. To explore its potential role in inflammatory skin disease, we have studied immunohistochemically the effects of intradermal recombinant human TNF-alpha (rHuTNF-alpha) on cutaneous inflammatory cells, adhesion molecules and Langerhans cells in normal human skin. Volunteers receive rHuTNF-alpha 100 U (group A), 5000 U (group B), or 100 U daily for 5 days (group C), and biopsies were taken at 6 h (groups A and B), or 6 h after the final injection (group C). An inflammatory cell infiltrate developed in all cases: following single injections of either 100 or 5000 U rHuTNF-alpha this was predominantly neutrophilic, whereas following multiple injections of 100 U few neutrophils were seen, although many lymphocytes (CD3+, CD4+) were present. In all groups there was an increase in cells of monocyte/macrophage lineage (CD36+). TNF-alpha induced a dose- and time-dependent decrease in CD1a+ epidermal Langerhans cell numbers and an increase in dermal CD1a+ cells, suggesting migration of Langerhans cells away from the epidermis. TNF-alpha induced endothelial E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in all groups, and adhesion molecule expression by interstitial dermal dendritic cells (ICAM-1 and VCAM-1) and keratinocytes (ICAM-1) was observed. These findings indicate that TNF-alpha is a potent modulator of cutaneous immune function in vivo, and this central role in the cutaneous immune response suggests that TNF-alpha may be an attractive target for therapeutic inhibition.

Antigens, CD↗
PubMed1995

Clinical effects of recent cocaine use on patients with acute schizophrenia.

OBJECTIVE: Dopamine function has been hypothesized to be involved in both producing schizophrenic symptoms and mediating cocaine's reinforcing properties. As a result, cocaine abuse in schizophrenic patients may be seen as a natural experiment that may alter the phenomenology and neurobiology of schizophrenia. This report concerns the clinical effects of cocaine abuse and cessation in schizophrenic patients at two times: when patients presented to the psychiatric emergency service and again after 4 weeks of hospitalization. METHOD: The subjects were 15 cocaine-abusing and 22 cocaine-abstaining schizophrenic patients. Diagnostic assessments were performed with the Structured Clinical Interview for DSM-III-R--Patient Version, which uses DSM-III-R criteria. All of the patients were assessed at both times with the Brief Psychiatric Rating Scale, the Scale for the Assessment of Positive Symptoms, and the Scale for the Assessment of Negative Symptoms. RESULTS: Cocaine-abusing schizophrenic patients showed fewer negative signs and more anxiety/depression at the hospital-admission assessment than their nonabusing counterparts. At retest, no group differences were detected in patients' negative signs or mood symptoms. Severity of positive symptoms was equal at both testing sessions. CONCLUSIONS: The significant difference in negative signs and mood symptoms at admission assessment was attributed to the neurobiological impact of cocaine. The role of psychostimulants in schizophrenic patients is discussed.

Acute Disease↗
PubMed1994

Langerhans' cell expression of the selectin ligand, sialyl Lewis x.

Cellular adhesion molecules play a central role in leucocyte migration through peripheral blood and tissues. A crucial stage in these events in selectin-mediated adhesion involving E-selectin expressed on activated endothelium interacting with a range of carbohydrate ligands expressed by specific subpopulations of leucocytes. As such mechanisms may be relevant to bone marrow-derived dendritic epidermal Langerhans' cell (LC) migration, expression of these carbohydrate ligands was assessed immunocytochemically in whole skin biopsies and in epidermal cell suspensions obtained from adult humans. Double-labelling experiments revealed that sialyl Lewis x, recognized by the monoclonal antibody CSLEX1, was expressed on epidermal LC (n = 9). Furthermore, expression was enhanced at 24 hr following epicutaneous application of antigen and in the inflammatory disorder psoriasis (n = 10). E-selectin was concomitantly strongly expressed on dermal endothelium in psoriasis and allergic contact dermatitis. Intradermal injection of the T-cell-derived cytokine interferon-gamma (IFN-gamma) led to increased LC expression of sialyl Lewis x. In epidermal cell suspensions, in contrast to keratinocytes, CD1a+ cells expressed sialyl Lewis x, intensity of which was enhanced after 4 days in culture. CSLEX1 staining could be abolished and CD15 (non-sialated Lewis x) expression induced by saponification and treatment with neuraminidase. Expression of other selectin ligands was also examined. While the cutaneous lymphocyte antigen defined by the monoclonal antibody HECA-452 reacted with a small minority of LC, sialyl Lewis a and sulphatide were not expressed under any experimental conditions. These studies indicate that E-selectin-sialyl Lewis x interactions are potentially important in LC migration, both into and out of skin.

Adult↗
PubMed1993

Expression of selectin ligands by cutaneous squamous cell carcinoma.

Recent evidence suggests that interactions between endothelial selectins and tumor surface selectin ligands may be of importance in cancer metastasis. To investigate the role of such mechanisms in cutaneous tumors, whole skin biopsies were examined immunohistochemically for a variety of selectin ligands including sialyl-Lewis-X, sialyl-Lewis-A (S-Le(a)), sulfatides, and CD15. In 12 of 12 squamous cell carcinomas (SCCs), there was expression of sialyl-Lewis-X and CD15, but no tumor expressed S-Le(a). Occasional keratinocytes in eight of 12 SCCs expressed sulfatides. All selectin ligands were absent on keratinocytes in basal cell carcinomas (BCCs, n = 8) and normal skin (n = 8), with the exception of one BCC that expressed S-Le(a). E-selectin was not present in normal skin, but was strongly expressed by dermal endothelium in both SCC and BCC. Keratinocyte cell lines A431, HaCaT, and SVK14 were investigated by flow cytometry, which demonstrated sialyl-Lewis-X and S-Le(a) expression by all three, whereas normal human keratinocytes did not express these molecules. These findings suggest a potential role for selectin-mediated events in early and late metastasis, and differential expression of these ligands by BCC and SCC may explain the relatively low metastatic potential of the former.

Basal Cell Carcinoma↗
PubMed1992

Occupancy of a C2-C2 type 'zinc-finger' protein domain by copper. Direct observation by electrospray ionization mass spectrometry.

The metal ion specificity of most 'zinc-finger' metal binding domains is unknown. The human estrogen receptor protein contains two different C2-C2 type 'zinc-finger' sequences within its DNA-binding domain (ERDBD). Copper inhibits the function of this protein by mechanisms which remain unclear. We have used electrospray ionization mass spectrometry to evaluate directly the 71-residue ERDBD (K180-M250) in the absence and presence of Cu(II) ions. The ERDBD showed a high affinity for Cu and was completely occupied with 4 Cu bound; each Cu ion was evidently bound to only two ligand residues (net loss of only 2 Da per bound Cu). The Cu binding stoichiometry was confirmed by atomic absorption. These results (i) provide the first direct physical evidence for the ability of the estrogen receptor DNA-binding domain to bind Cu and (ii) document a twofold difference in the Zn- and Cu-binding capacity. Differences in the ERDBD domain structure with bound Zn and Cu are predicted. Given the relative intracellular contents of Zn and Cu, our findings demonstrate the need to investigate further the Cu occupancy of this and other zinc-finger domains both in vitro and in vivo.

Copper↗
PubMed1992

HIV infection in women: presentations and protocols.

In the 11th year of the AIDS epidemic in the United States, it is clear that more and more women are becoming infected with HIV. Genital infections by other pathogens may be the first clue to the diagnosis. With progressive immunodeficiency, such infections may follow a protracted course or become recurrent, often requiring maintenance therapy.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Electrospray-ionization mass spectrometry for the detection of discrete peptide/metal-ion complexes involving multiple cysteine (sulfur) ligands.

Conditions have been developed to characterize the reversible interaction of one or more Zn(II) ions with cysteine (sulfur) ligands on metal-binding peptides by electrospray-ionization (ES) mass spectrometry. A 71-residue peptide with two separate clusters of four cysteine residues was selected as a model to optimize both the solution and electrospray variables most likely to affect the detection of stable cysteine (sulfur) ligand/Zn interactions. By infusing peptide in water alone, stable electrospray and ion signals were produced in both the absence and presence of up to 100 microM zinc sulfate. In the absence of Zn(II), the calculated mass of the fully reduced peptide (8248.5 Da) was observed (8248.4 +/- 0.4 Da). In the presence of Zn(II), peptides with zero, one and two bound Zn atoms were detected; all three species were present in several different charge states. The overall charge envelope was typically unchanged in the presence of Zn; the charge-state optimum (10+) observed for this peptide was apparently unaffected by the presence of bound Zn. The interaction of Zn(II) ions with sulfur ligands in this peptide appeared to result in tetracoordinate covalent bonds.(ABSTRACT TRUNCATED AT 250 WORDS)

Cysteine↗
PubMed1992

Differences in the conformational state of a zinc-finger DNA-binding protein domain occupied by zinc and copper revealed by electrospray ionization mass spectrometry.

Transition metal ions are important in biological regulation partly because they can bind to and stabilize protein surface domain structures in specific conformations that are involved in key molecular recognition events. There are two C2-C2 type zinc-finger sequences within the highly conserved DNA-binding domain of the estrogen receptor protein (ERDBD). Electrospray ionization (ESI) mass spectrometry has been used to demonstrate that the metal-binding sites within the 71-residue ERDBD can bind either Zn (up to 2) or Cu (up to 4). Evidence for the induction and/or stabilization of a different conformational state with bound Cu is revealed by a characteristic shift in the ESI charge envelope. The 10+ charge state is most abundant for the fully reduced ERDBD apopeptide and the ERDBD-Zn holopeptide (bound Zn does not alter the charge envelope). In contrast, the 8+ charge state is typically the optimum charge state observed for the ERDBD-Cu holopeptide; indeed, the entire charge envelope is frame-shifted to lower charge states with bound Cu. Interpretation of the altered charge states is simplified because (i) a single type of metal-binding ligand (sulfur) is involved in the case of both Zn and Cu binding, and (ii) the two different metal cations are both divalent. Thus, it is likely that the dissimilar charge envelopes represent different peptide conformers, each of which is stabilized by a different type of bound metal ion.(ABSTRACT TRUNCATED AT 250 WORDS)

Copper↗