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Biomedical subjects

M Halpern

Publications and source records attributed to M Halpern.

At least 91 records · Page 5Linked to original sources

Chemical and immunological analysis of prey-derived vomeronasal stimulants.

We have isolated seven proteins from earthworm preparations that are chemoattractive to garter snakes. Three of these proteins have been purified to homogeneity: two from aqueous earthworm wash (EWW) and one from electric shock-induced earthworm secretion (ESS). One of the two highly purified proteins from EWW has a relative molecular mass of 20 kDa and contains free sulfhydryl groups that appear to play a functional role in its chemoattractivity. The other purified protein from EWW has a molecular mass of 3 kDa (low molecular weight protein, LMW). The highly purified chemoattractive protein (ES20) from ESS is a glycoprotein having a minimum molecular mass of 15.4 kDa calculated from its amino acid and carbohydrate contents. It consists of a single polypeptide chain. The sequence of terminal 15 amino acid residues from its amino (NH2-) terminal has been determined. It binds specifically to the membranes of vomeronasal sensory epithelium in a saturable and reversible fashion with a Kd value of about 0.3 microM and Bmax value of 0.4 nmol/mg of protein. This protein causes an increase in firing rate of individual neurons in the accessory olfactory bulb of garter snakes, the projection site for vomeronasal neurons. All the isolated chemoattractive proteins from both earthworm preparations can be divided immunologically into three groups: (i) those closely related to the ES20 snake-attractive protein, (ii) those closely related to the LMW snake-attractive protein, and (iii) those unrelated to either ES20 or the LMW protein.

Amino Acids↗

Regulation of the low affinity IgE Fc receptor (CD23) in atopic dermatitis.

Alterations in the production of CD23, the IgE Fc receptor, may play a role in the etiology of atopic dermatitis and other allergic conditions. Interleukin-4 (IL-4), interferon-gamma (IFN-gamma), and interferon-alpha (IFN-alpha) are involved in coordinate regulation of CD23. IL-4 stimulates production of both CD23 and IgE. IFN-gamma also stimulates production of CD23, but suppresses production of IgE and inhibits IL-4-mediated production of CD23. IFN-alpha also suppresses these IL-4-mediated activities and, in addition, suppresses IFN-gamma-mediated stimulation of CD23 production. Changes in this coordinate regulation may be involved in the development of atopic dermatitis. Expression of CD23 by Langerhans cells is stimulated by IL-4 and IFN-gamma. Further, levels of CD23-positive T cells are elevated in atopic dermatitis subjects as compared to non-atopic controls, and observed skin changes appear to be related to changes in CD23-positive mononuclear cell populations. Coordinate regulation of CD23 by IFN-gamma and IL-4 may also be important in other allergic conditions, parasitic infections, and a variety of disease states.

Dermatitis, Atopic↗

Renal aspergilloma: an unusual cause of infection in a patient with the acquired immunodeficiency syndrome.

The case of a 36-year-old man with the acquired immunodeficiency syndrome (AIDS) and a renal aspergilloma is reported. Aspergillus infections are uncommon in patients with AIDS. Isolated renal aspergillomas have rarely been reported in the non-AIDS population (14 cases) and have never been reported in a patient with AIDS. The patient we describe was clinically symptomatic and initially treated medically, but he did not respond to intravenous amphotericin and oral itraconazole. He eventually required nephrectomy; however, there was local recurrence of the aspergilloma postoperatively. We comment on some issues in the spectrum of Aspergillus infections in AIDS and review the literature on the manifestations and treatment of renal aspergillomas.

Acquired Immunodeficiency Syndrome↗

Immunological analysis of chemoattractive proteins from earthworm to garter snakes.

1. Two sets of polyclonal antibodies to two highly purified prey-derived snake-attractive proteins, a low molecular weight (3000) protein and a 20,000 mol. wt protein, were generated in rabbits. 2. They are immunospecific for their respective purified immunogens and do not cross-react with each other. 3. Eight prey-derived proteins that elicit attack by garter snakes (Thamnophis sirtalis) from earthworms (Lumbricus terrestris) were analyzed with these antibodies, and can be assigned to three distinct groups on the basis of their antigenic properties. 4. Unfolding or denaturation of the low molecular weight protein did not alter its antigenic activity to its polyclonal antibodies, suggesting the antigenic epitopes contain contiguous amino acid sequences. 5. In contrast, unfolding of the 20,000 mol. wt protein resulted in a loss of its binding with antibodies, suggesting that the epitope of this protein contains noncontiguous amino acid sequences. 6. The snake-attractivity of the 20,000 mol. wt protein could not be neutralized by reacting it with its antiserum, suggesting that the antigenic determinant (the epitope) of the antigen is not an integral part of the attractive domain of the ES20 protein. 7. In contrast, the attractivity of the purified low molecular weight protein could be neutralized by the polyclonal antibodies.

Animals↗

Prevention of low back pain: basic ergonomics in the workplace and the clinic.

Redesigning the job is a strategy for preventing low back injuries at work or for accommodating injured employees who return to work. An evaluation of the physical job demands is necessary in either strategy. Several job demands are associated with low back pain and injury--heavy physical work, static or postural effort, dynamic work-load and exposure to wholebody vibration. Traditional work measurement studies emphasize a rigorous task analysis. By adding biomechanical, physiological and psychophysical measurements, a comprehensive evaluation is possible. There is no standard scheme for a workplace evaluation. The method depends on the end use of the analysis. Job evaluation for workplace design requires an emphasis on equipment and work conditions; evaluation for placement of injured employees should emphasize the operational demands of the tasks. Few studies considered the multifactorial aetiology of low back pain. Most studies that measured the magnitude of biomechanical, physiological and psychophysical stresses attempted to define peak work-loads. The attempt to evaluate the effects of subacute cumulative traumas is only in the beginning. Most ergonomic intervention programmes modify the loads, the design of objects handled, lifting techniques, workplace layout and task design. The effectiveness of these interventions in controlling medical costs or morbidity has not been clearly demonstrated. Consequently, occupational risk factors may be more important for evaluating disability. Job familiarity is the key to effective medical management. Ergonomic analysis procedures may be useful within rehabilitation settings that also provide placement services. The reason is that they facilitate communication between all elements involved in the rehabilitation process. Proper communication procedures are also crucial in implementing ergonomic interventions in the workplace. A health care provider should be part of a task force that oversees these interventions. Future effort should be directed to finding a method that health care practitioners could be competent to carry out effectively in a clinical setting. Expert systems offer promising results in disseminating ergonomic knowledge in primary and secondary health care facilities.

Ambulatory Care Facilities↗

Endometrioid carcinoma of the ovary presenting as primary carcinoma of the breast. A case report and review of the literature.

A case is presented of endometrioid carcinoma of the ovary, metastasizing to the breast in a 63-year old woman. Differentiation of metastatic cancer to the breast for primary breast carcinoma and discovering the primary tumor site are rather important for treatment and prognosis. Lumpectomy, followed by panhysterectomy, was performed and six courses of cisplatinum and cyclophosphamide were given. No signs of recurrence or metastasis are apparent 16 months after the discovery of the breast lesion.

Adenocarcinoma↗

Unusual renal deposit in mixed connective tissue disease.

We describe a patient with clinical signs of mixed connective tissue disease who developed nephrotic syndrome. The kidney biopsy revealed glomerular and vascular deposits that stained positive with Congo red and showed a green birefringence. The Congo red positivity became negative in sections treated with potassium permanganate. Peroxidase-antiperoxidase staining with anti-AA antibodies was strongly positive. Ultrastructurally, although the deposits were similar to amyloid, they were about twice the size of amyloid fibrils. To our knowledge, the deposition of an amyloidlike material that shows the histochemical and immunohistochemical features of amyloid AA but is lacking the distinctive ultrastructural characteristics of amyloid fibrils has not been described.

Amyloid↗

Incorporation of 3H-thymidine in the embryonic vomeronasal and olfactory epithelial of garter snakes.

Previous studies have shown that the vomeronasal and olfactory epithelia of adult vertebrates provide good models for studying normal neuronal turnover and regeneration in response to axotomy. However, little is known about the cell dynamics in the embryonic vomeronasal and olfactory epithelia or the origins of different cell types in these structures. By using 3H-thymidine autoradiography, both in vivo and in vitro, the origins of receptor and supporting cells and the survival of labelled cells in the embryonic vomeronasal and olfactory epithelial of garter snakes were examined. The results of this study suggest that the receptor and supporting cells of both epithelial arise from separate stem cells and that two subpopulations of stem cells exist for receptor cells in the embryonic vomeronasal epithelium. One subpopulation generates cells that migrate through the receptor cell columns, while another subpopulation remains at the base of the epithelium for approximately 50 days. Although it is unclear how long receptor cells in the embryonic olfactory epithelium survive, the results of this study suggest that they survive at least 37 days and may survive over 56 days. In addition, the development of these sensory epithelia appears different in early versus late embryos, and regeneration in the vomeronasal and olfactory epithelia of adult garter snakes appears similar to development during late gestation. Cells in the developing receptor cell layer of the olfactory epithelium lose their ability to incorporate 3H-thymidine before those in the vomeronasal epithelium, suggesting that the onset of neuronal maturation occurs earlier in the olfactory epithelium than in the vomeronasal epithelium.

Animals↗

Incorporation of 3H-thymidine in telencephalic structures of the vomeronasal and olfactory systems of embryonic garter snakes.

Previous studies have shown that the vomeronasal and, possibly, olfactory systems are functional in newborn garter snakes. However, little is known about neurogenesis in these chemosensory pathways. In the companion paper, we describe the embryonic growth of the sensory epithelia for both the vomeronasal and olfactory systems. In the present study, we examine neurogenesis in the telencephalic structures of these chemosensory systems by using 3H-thymidine autoradiography (ARG). The majority of neurogenesis appears to occur before birth in the accessory and main olfactory bulbs and their principal projection sites, the nucleus sphericus and lateral cortex, respectively. The data suggest that some postnatal neurogenesis may occur in the accessory and main olfactory bulbs and in the nucleus sphericus. Although the neuronal constituents of the accessory and main olfactory bulbs appear to mature concurrently, those of the lateral cortex appear to mature before those of the nucleus sphericus. Along with previous findings, this latter result supports the hypothesis that the olfactory system develops before the vomeronasal system in garter snakes. There appears to be a rostral to caudal gradient of neurogenesis within the mural layer of the nucleus sphericus. However, an "outside to inside" gradient of neurogenesis was not observed in the mantle layer of the lateral cortex, as described for other reptiles. Similarities and differences observed by other investigators in other reptilian species and mammals are discussed.

Animals↗

Snake aggregation pheromones: source and chemosensory mediation in western ribbon snakes (Thamnophis proximus).

Aggregation with conspecifics is a robust phenomenon among snakes that is mediated by chemical cues, although the source of such cues is unknown. Adult western ribbon snakes (Thamnophis proximus) discriminated between skin lipid extracts from conspecifics and those from a sympatric heterospecific snake, the corn snake (Elaphe guttata). Additionally, ribbon snakes were attracted to conspecific skin lipid-marked shelters when paired with control-marked shelters, but no preference was exhibited when shelters marked with E. guttata skin lipids were paired with control-marked shelters. Furthermore, prevention of chemical access to the vomeronasal organs of T. proximus eliminated the ability to respond to conspecific skin lipids. These results indicate that epidermal lipids are the source of chemical cues mediating attraction to shelters marked by conspecifics and that such signals are detected by the vomeronasal system.

Animals↗

Purification and characterization of a chemoattractant from electric shock-induced earthworm secretion, its receptor binding, and signal transduction through the vomeronasal system of garter snakes.

Following shocks with low voltage electric current, earthworms, Lumbricus terrestris, secrete a yellow mucus that has alarm properties for conspecifics and chemoattractive properties for garter snakes, Thamnophis sirtalis. A proteinaceous chemoattractant for garter snakes has been isolated and purified to homogeneity from such secretions by means of permeation chromatography and semipreparative nondenaturing polyacrylamide gel electrophoresis. The purified protein is highly attractive to garter snakes; it loses its activity after proteolytic digestion. It is a glycoprotein consisting of a single polypeptide chain with an NH2-terminal alanine. This chemoattractant has a minimum molecular mass of 15.4 kDa calculated from its amino acid and carbohydrate contents and an apparent molecular mass of about 20 kDa as estimated from sodium dodecyl sulfate-polyacrylamide gel electrophoresis. It has a pI of about 4.0, and it binds wheat germ agglutinin but not concanavalin A. This chemoattractant shows a protein to carbohydrate ratio of 2.0 +/- 0.08 (n = 5) and a ratio of total sugar to amino sugar of 1.9 +/- 0.08 (n = 3). The sequence of its NH2-terminal 15 amino acid residues has been determined. Studies were also conducted on the chemosignal transduction through the vomeronasal sensory system of the garter snake. Dot blot analysis showed that the purified chemoattractant bound to snake vomeronasal sensory epithelial membrane fractions. It did not bind to membrane extracts of the nonsensory epithelium of the vomeronasal mushroom body. The chemoattractant also bound specifically to vomeronasal sensory epithelial membrane in a reversible and saturable fashion with Kd and Bmax values of about 0.3 microM and 0.4 nmol/mg of protein, respectively. In electrophysiological studies, the chemoattractant applied to the vomeronasal epithelium caused an increase in firing rate of individual neurons in the accessory olfactory bulb of garter snakes, the projection site for vomeronasal neurons. The present results are the first clear biochemical and electrophysiological evidence for a vomeronasal epithelium response to a purified nonvolatile odorant, and this makes the garter snake vomeronasal system ideal for studying the mechanisms of chemosignal transduction.

Amino Acids↗

Embryonic and neonatal development of the vomeronasal and olfactory systems in garter snakes (Thamnophis spp.).

Newborn, unfed garter snakes (Thamnophis spp.) respond preferentially to aqueous extracts of natural prey items, and these responses are mediated by the vomeronasal system (VNS). Since the VNS, and possibly the olfactory system (OS), are functional at birth, we examined the ontogeny of VNS and OS structures in four embryonic stages and two postnatal ages in garter snakes. The results of this study show 1) significant changes in thickness of the receptor epithelia for both systems; 2) temporal differences in the innervation of the telencephalon for each system; and 3) concurrent development of primary and secondary projection sites in both systems. Possible interactions between different cell populations and their significance for morphogenesis are discussed.

Animals↗