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Biomedical subjects

S G Allen

Publications and source records attributed to S G Allen.

At least 19 recordsLinked to original sources
PubMed2000

The development of immunoassays to four biological threat agents in a bidiffractive grating biosensor.

A critical need exists for a field deployable biosensor to detect environmental infectious agents in collected air samples rapidly, with sensitivity and specificity approaching that of standard laboratory procedures. The ideal sensor would analyze unknown samples in minutes, have programmable operation for unattended sample analysis, and be capable of multiple agent analysis for a number of agents. The goal of this project was to further the development of the bidiffractive grating biosensor (BDG) created through collaboration between Battelle Memorial Institute (BMI), Hoffman LaRoche (HLR), and the Naval Medical Research Command (NMRC). This manuscript details the development, optimization, and evaluation of this device as a potential field deployable biosensor. Well-characterized immunochemical reagents developed by the Biological Defense Research Department (BDRD) at NMRI were employed to develop assays in the BDG. These results were compared to those obtained with antigen capture enzyme linked immunosorbent assays (ELISAs). Four separate antigens were evaluated: Staphylococcus aureus enterotoxin B (SEB), ricin (RIC), Francisella tularensis (FT), and Clostridium botulinum toxin (BOT).

Biological Warfare↗
PubMed1996

Phase equilibria of absorbed liquids and the structure of porous media.

The phase equilibria of water within porous silica has been studied by proton and deuteron magnetic resonance. Proton signal amplitude as a function of filling factor was measured. These protons arise from the proton-deuterium equilibrium that is established between the liquid and the absorbed layer on the pore wall. The results for temperatures below 0 degree C show a maximum as a function of filling factor, theta. This suggests that the pores fill from either a surface layer or from the crevices and interstices into the center. Another experiment used cryoporometry to study the size of crystals formed within the pores as a function of theta and leads to the same conclusion.

Magnetic Resonance Spectroscopy↗
PubMed1994

Co-infection and synergy of human immunodeficiency virus-1 and herpes simplex virus-1.

The human immunodeficiency virus (HIV-1) uses the CD4 molecule, expressed by T helper cells and activated macrophages, as a receptor for entry into host cells. In tissues co-infected with herpes simplex type 1 (HSV-1), HIV-1 virions were observed to infect keratinocytes, which, because they lack the CD4 molecule, are normally incapable of being infected by HIV-1. Although a number of other viruses have been reported to enhance HIV-1 viral transcription in vitro, this is the first in-vivo report to our knowledge of reciprocal enhancement of viral replication associated with co-infection of keratinocytes and macrophages by HIV-1 and HSV-1 in patients with AIDS and non-genital herpes simplex lesions. The virions in the co-infected cells were larger, morphologically atypical, and appear to be hybrids; most contain the HIV-1 envelope necessary for infectivity. The increased viral load and the proximity of the virions to the cutaneous surface may lead to increased risk of transcutaneous transmission of both viruses. These findings point to the need for incorporation of suppressive treatment for herpes simplex in the treatment of AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Expression of the L-fucose moiety on infrainfundibular follicular keratinocytes of terminal follicles, its decreased expression on vellus and indeterminate follicles of androgenetic alopecia, and re-expression in drug-induced hair regrowth.

The distribution of various glycoprotein molecules on the surface of follicular keratinocytes was studied with a panel of lectins with specificity for various sugar moieties on biopsy specimens from both bald/balding scalp and normal occipital scalp, of 23 patients with androgenetic alopecia as well as on biopsies of normal forearm skin of four patients. The most significant differences between bald and normal scalp biopsy were noted with Ulex europaeus agglutinin I (UEA I). We noted an increased (91.8% +/- 3.1; mean +/- SE) expression of UEA I binding sites on the infra-infundibular follicular keratinocytes in anagen terminal scalp hairs, compared to 28.5% +/- 5.2 in the indeterminate (anagen) hairs of balding scalps, and 23.2% +/- 6.3 in the anagen follicles of vellus fore-arm hairs. By contrast, the telogen hairs demonstrated minimal UEA I staining: 4.0% +/- 0.8, mean +/- SE in telogen scalp hairs, 1.8% +/- 0.5 in telogen hairs of balding scalps (0% in completely bald scalps, in which all the hairs were in the telogen phase), and 1.9% +/- 0.2 in telogen forearm hairs. The percentage of UEA I staining correlated with the length of the infra-infundibular follicles in all cases studied. In three cases of hair regrowth after hair growth promotors, the UEA I staining increased to 80.6% +/- 6.1 in anagen hairs and correlated with increased length of infra-infundibular follicles. Our data indicate that there are 1) marked differences between anagen and telogen follicles in UEA I binding to infra-infundibular follicular keratinocytes; 2) the percentage of UEA I staining reflects the size (length) of the infra-infundibular hair follicle; and 3) the anagen follicles of balding scalps (indeterminate hairs) show UEA I staining resembling that exhibited by anagen follicles of vellus hairs.

Adult↗
PubMed1992

Expression of the L-fucose moiety on epidermal keratinocytes in psoriasis induced by the Koebner phenomenon: a sequential study.

The expression of Ulex europaeus agglutinin (UEA I) binding sites on cell-surface glycoproteins has been used as a marker for terminal differentiation. Increased number of UEA I binding sites of L-fucose specificity have been demonstrated in psoriatic epidermis. The results of lectin-binding studies in a series of biopsies taken sequentially (0 min, 5 min, 24 h, 7 days and 8 weeks) after tape-stripping of uninvolved skin in 12 psoriatic patients (three of whom were taking diltiazem, a calcium blocker at the time of the study) and six controls are presented. UEA I binding sites, which were expressed on the granular layer and upper layers of the stratum spinosum of pre-tape stripped uninvolved skin in psoriatic individuals, were progressively more numerous, with the expression of the L-fucose moiety on the lower stratum spinosum keratinocytes in the 7-day post-tape-stripping biopsies and 8-week biopsies, correlating with a moderate and marked increase in the proliferative index, respectively. In the Koebner-negative and non-psoriatic individuals who failed to develop psoriasis after tape-stripping, the UEA I binding sites were not expressed on keratinocytes of the lower stratum spinosum in any of the biopsies, although a mild increase in the proliferative index was noted in the 7-day biopsies. Our data suggest that the increased commitment of keratinocytes to terminally differentiate may be involved in the psoriatic process.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium↗
PubMed1991

Mitozantrone and prednimustine in the treatment of advanced breast cancer--a toxic regimen with low activity.

The combination of mitozantrone and prednimustine has been reported to elicit response rates of around 50% in patients with advanced breast cancer. In the present trial, either three or nine courses of this combination were given to previously untreated patients with advanced breast cancer. Mitozantrone was given at 12 mg/m2 on day 1 and prednimustine was given orally at 130 mg/m2 on days 1-5; treatment was repeated every 4 weeks. A total of 34 patients were treated; the performance status was 0-1 in 29 subjects and 2 in 5 cases. Locoregional disease only was present in 13 patients; 9 showed lung involvement; 8, liver; 3, bone; and 1, stomach involvement. A total of 10 subjects had received no prior hormone therapy. The median disease-free interval from the time of initial diagnosis was 24 months (range, 0-144 months). In all 14/23 patients exhibited an oestrogen receptor level of greater than 20 fmol. Grade 1 nausea and vomiting occurred in 16 patients and that of grade 2-3, in 11 subjects; nausea was prolonged for greater than 10 days in 7 cases. Grade 4 neutropenia occurred in 2 patients. The response rate was 21% (95% confidence interval, 8%-38%). The combination of mitozantrone and oral prednimustine is toxic and displays low activity.

Adult↗
PubMed1991

Efficacy of cyclophosphamide in toxic epidermal necrolysis. Clinical and pathophysiologic aspects.

In this article we describe the immunocytochemical and electron microscopic findings in five patients with toxic epidermal necrolysis. They indicate the occurrence of necrotic keratinocytes with nuclear disintegration associated with apposed dendritic cells with the nuclear chromatin configuration of T lymphocytes. These findings, including the presence of blebbing of the keratinocytes and membrane defects associated with cytoplasmic processes from these apposed lymphoid cells, fit known electron microscopic criteria that suggest the involvement of T lymphocyte-mediated cytolysis of drug-altered target keratinocytes in toxic epidermal necrolysis. The effector cell appears to be a dendritic subset, with the phenotypic characteristics (CD3+, CD4-, CD8+, CD2+, DR+) of a T cell subset. There is some evidence that tumor necrosis factor alpha, secreted by activated macrophages, may play a role in necrolysis of the epidermis. The dramatic response of our patients to cyclophosphamide, which is known to inhibit cell-mediated cytotoxicity by inhibiting both the recognition and lethal hit stages, together with the rapid regrowth of the epidermis within 4 days to a week in patients who received adequate dosage of the drug, supports the preceding concepts.

Adult↗
PubMed1991

Focal endothelial cell degeneration and proliferative endarteritis in trauma-induced early lesions of necrobiosis lipoidica diabeticorum.

Microangiopathy is an essential component in diabetic vascular pathology. We report ultrastructural observations of ballooning degeneration involving isolated endothelial cells of cutaneous capillaries, while leaving adjacent endothelial cells relatively intact in six diabetic patients with early lesions of necrobiosis lipoidica induced by trauma. Focal proliferation of endothelial cells encroaching upon the vascular lumina (obliterative endarteritis) was also observed. Lectin studies on biopsy specimens of older lesions of necrobiosis lipoidica revealed paucity of dermal blood vessels. These observations enable us to gain further insight into the pathophysiological mechanisms that underlie diabetic microvascular disease.

Aged↗
PubMed1991

Electron microscopic and immunocytochemical studies of the sequence of events in psoriatic plaque formation following tape-stripping.

Electron microscopic and immunocytochemical studies were performed on sequential biopsies following the tape-stripping of the uninvolved skin in 12 patients with psoriasis. In the biopsies taken after 5 min for up to 7 days during the pre-psoriatic phase, there were initial lymphocyte-Langerhans cell interactions as well as interactions between lymphocytes and keratinocytes. In biopsies taken after 6-8 weeks during the proliferative phase there were lymphocyte-macrophage interactions. In the 24-h and 7-day biopsies there were close contacts between epidermal lymphocytes and keratinocytes via microvilli, with blebbing of the keratinocyte plasma membranes and granular cytoplasmic changes around these microvilli. Few basal keratinocyte herniations were noted during this phase. The 6-8-week biopsies of Köbner-positive patients were characterized by a marked increase in lymphocyte-macrophage interactions via similar microvillous processes with associated electronlucent areas suggestive of cytotoxicity.

Adult↗
PubMed1991

Predominance of CD8 subset in id eruption of poison oak-induced dermatitis.

The pathophysiology and immune mechanisms involved in the clinical syndrome of autoeczematization remain a mystery. In this study of nickel dermatitis without autoeczematization and poison oak dermatitis with autoeczematization, it was noted that the process of autoeczematization was associated with the presence of CD8+ lymphocytes within the epidermis and the expression of HLA-DR antigens on epidermal keratinocytes. It is surmised that since CD8+ clones are induced by poison oak antigen but not by nickel, the inability of nickel to induce CD8+ lymphocytes may explain why uncomplicated nickel dermatitis does not autoeczematize. Since the selective adherence of CD8+ lymphocytes to keratinocytes, probably via the expression of adhesion molecules such as ICAM-1, the generation of antigens on endothelial cells of high endothelial venules involved in lymphocyte trafficking, and the expression of HLA-DR antigens on epidermal keratinocytes are all due to the activity of interferon-8, it is deduced that this lymphokine may play a key role in id eruptions induced by contact allergens.

CD8 Antigens↗
PubMed1991

Alpha-1 antitrypsin deficiency in a patient with widespread prurigo nodularis.

Skin lesions associated with alpha 1-antitrypsin deficiency are becoming better defined and understood. Deficiency in this major antiproteinase, which neutralizes multiple proteolytic enzymes ranging from collagenases and elastases to trypsin and chymotrypsin, thus results in significant tissue autodigestion. This anti-proteinase is secreted by activated lymphocytes and macrophages, suggesting the existence of homeostasis which titrates the release of proteolytic enzymes by these cells, and the adequate neutralization of these proteases in order to prevent excessive tissue autodigestion each time these inflammatory cells are activated. We report a patient with alpha 1-antitrypsin deficiency who, following insect bites and cellulitis developed widespread itching and scratching, leading to widespread lesions of prurigo nodularis. The colonization of his multiple skin lesions with Staphylococcus aureus and the release of potent T cell mitogens, such as Protein A and enterotoxin A from the bacterial cell membrane may have resulted in the release of additional proteolytic enzymes by the activated lymphocytes and macrophages, without the concomitant secretion of alpha 1-antitrypsin with subsequent aggravation of his pruritus. These concepts are supported by electron microscopic evidence of excessive tissue autodigestion, and by immunocytochemical data identifying the presence of T helper and T cytotoxic/suppressor lymphocytes as well as macrophages within the upper dermis.

Humans↗
PubMed1990

Basement membrane changes in psoriatic patients on long-term topical corticosteroid therapy.

It has been observed that the beneficial anti-inflammatory effects of topical steroids in psoriasis are counteracted by increasing instability of the disease, with rebound phenomena associated with the cessation of these drugs. We report the occurrence of multi-layered fragmentation and disorganization of the basal laminae in active, untreated psoriatic lesions, resolving and uninvolved, inadvertently steroid-treated psoriatic skin, as well as in a variety of non-psoriatic dermatoses treated with fluorinated topical steroids for prolonged periods. These changes, which were associated with a moderate to severe loss of dermal collagen, were not found in untreated and treated psoriatic controls, with or without concomitant alpha 1-antitrypsin deficiency, who had not received steroids, suggesting that they were probably the consequence of prolonged fluorinated steroid use. This conclusion is supported by the observation that the largest number of layers (10-15) of fragmented basal laminae was noted in the patients who had received fluorinated steroids for 6 years or more, while those on 4 years or less of fluorinated steroid therapy exhibited only three to seven layers of fragmented basal laminae. In psoriatic lesions, the fragmentation of the basal lamina was associated with the presence of basal keratinocyte herniations (BKH), the frequency of which has been shown to parallel clinical psoriatic activity. The persistence of these electron-microscopic markers of psoriatic activity (i.e. BKH) in psoriatic plaques treated with prolonged fluorinated steroids suggests that loss of integrity of the basement membrane, as indicated by the presence of multi-layered fragmentation of the basal lamina, may account for the instability of the psoriatic lesions treated with prolonged topical fluorinated steroids.

Administration, Topical↗
PubMed1990

Tannic-acid staining material on high endothelial venules and lymphocytes in skin and peripheral lymph nodes in Staphylococcus aureus-associated erythroderma.

The recognition and binding of glycoprotein receptors on lymphocytes to specific antigens present on high endothelial venules (HEV) precedes the egress of lymphocytes from the blood stream into the tissues. In this paper, we report the presence of HEVs with tannic-acid staining material (TASM+ HEVs) in Staphylococcus aureus-associated erythroderma, which allow the migration of CD8+ lymphocytes from the bloodstream into the epidermis. TASM positivity is also expressed on lymphocytes within the regional lymph nodes, and by intravascular lymphocytes prior to leaving the TASM+ HEV. It is proposed that TASM positivity may represent a molecule, which may function in binding lymphocytes to HEVs prior to egress from the HEV. (TASM is lost from lymphocytes after leaving the HEVs). The expression of TASM positivity may form an essential part of the CD8+ lymphocyte-HEV recognition system, and may be the means whereby CD8+ lymphocytes generated in the regional lymph nodes by various mitogens (in this case by staphylococcal mitogens) may 'home' to specific sites within the epidermis. TASM positivity on both the HEVs and lymphocytes may serve as a convenient marker of such a system.

Dermatitis, Exfoliative↗
PubMed1989

Lack of host cellular immune response in eruptive molluscum contagiosum.

A lack of cellular immunity on the part of the host has been incriminated as the cause of the persistence of the cutaneous lesions of molluscum contagiosum. We present a patient in the eruptive phase of the disease, confirming the absence of T-lymphocyte and natural killer cell subsets in the base of these typical lesions, using a panel of monoclonal antibodies. We also report the observation of lipid material ultrastructurally (confirmed by osmium staining on fresh-frozen tissue), as well as cross-reactivity immunocytochemically of the antigens on these molluscum bodies with antigens normally present on macrophages, as defined by DAKO-macrophage monoclonal antibodies. We have considered the possible role of these findings in the lack of host cellular responsiveness in the eruptive phase of the disease.

Adult↗
PubMed1989

An electron microscopic study of the epidermal infiltrate in recurrent herpes simplex.

Host immunity has been suspected of playing a role in recurrent herpes simplex. In this preliminary ultrastructural study of two patients with acute herpetic eruption, it was noted that the keratinocytes exhibiting the most severe damage are those adjacent to large granular lymphocytes. In contrast, many keratinocytes filled with viral particles of herpes simplex show little or no signs of keratinocyte damage. These observations suggest that in recurrent herpes simplex the epidermal damage may be due, at least in part, to cell-mediated host immunity as well as to the viral infection.

Adult↗
PubMed1988

High endothelial venules in involved and uninvolved psoriatic skin: recognition by homing receptors on cytotoxic T lymphocytes.

We report the presence of tannic acid staining material in the intercellular spaces between adjacent endothelial cells of the high endothelial venules (HEVs) in psoriatic skin, which appears to be recognized by T8 (cytotoxic/suppressor) lymphocytes, as the presence of HEVs was found to be related to the presence of T8 lymphocytes in the epidermis. As HEVs with similar tannic acid staining material were also observed in peripheral lymph nodes, we suggest that this material may serve as a marker for HEVs recognized by the T8 lymphocyte subset. T8 + lymphocytes were found in the epidermis at 5 min and I h after tape-stripping of uninvolved skin of psoriatic patients with active disease, but not until 24 h in a psoriatic patient in remission. The prior existence of HEVs in uninvolved psoriatic skin could account for the rapid egress of T8 lymphocytes from the vasculature to the epidermis in response to trauma.

Antibodies, Monoclonal↗
PubMed1987

Electron microscopic features in generalized pustular psoriasis.

Basal keratinocyte herniations (BKH) have been used as markers of psoriatic activity. Abnormal multipolypoid forms herniating through large gaps in the basal lamina have been found to characterize biopsies from psoriatic patients with concomitant alpha 1-antitrypsin deficiency, and appear to be a marker of excessive proteolytic activity. The finding of similar multipolypoid BKH in patients with generalized pustular psoriasis of the von Zumbusch variety (but not in patients with psoriasis vulgaris), in the absence of concomitant alpha 1-antitrypsin deficiency, would support the concept of the presence of large amounts of proteolytic enzymes in the dermis of patients with this syndrome. The large proportion of BKH directly associated with dermal neutrophils, and the presence of clusters of high-density BKH overlying collections of dermal neutrophils, suggests that neutrophilic proteases are largely responsible for BKH formation in patients with this syndrome.

Adult↗