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Biomedical subjects

E J Lewis

Publications and source records attributed to E J Lewis.

At least 19 recordsLinked to original sources

Evaluation of the recovery of waterborne Giardia cysts by freshwater clams and cyst detection in clam tissue.

The Asian freshwater clam, Corbicula fluminea, inhabits environments recognized to be contaminated with waterborne Giardia cysts. Sixty-four tissue samples of Giardia-free clams were spiked with various numbers of Giardia duodenalis cysts within the range of 50-700 cysts. Regression analysis showed that paired numbers of spiked (x) versus recovered (y) cysts regressed significantly (P < 0.01) according to the equation y = 42.57 +/- 1.81x (+/- 64.3). The cyst detection threshold was 43 cysts/clam, the coefficient of determination was 77%, and the overall sensitivity of cyst detection was 42.9%. All 20 values of cyst numbers in clam tissue samples that were processed blind were located within the 95% prediction limits of the linear regression equation. The cyst retention rate of 160 clams kept in an aquarium with 38 l of water spiked with 1.00 x 10(5) G. duodenalis cysts was approximately 1.3 x 10(3) cysts/clam. No waterborne cysts were detected by the membrane filtration method 90 min after spiking the aquarium water. G. duodenalis cysts were detected in clam tissue up to 3 weeks post-exposure. Filtration of water by clams substantially depleted the aquarium water of its particulate matter. The sampling program demonstrated that the population of 160 clams examined during the study could be accurately assessed for exposure to waterborne Giardia cysts by random sampling of 86 (54%) clams. The results indicate that C. fluminea clams can be used for biological monitoring of contamination with Giardia.

Analysis of Variance

A case of bullous frostbite following recreational snowmobiling.

Frostbite is the occurrence of localized tissue freezing and injury. It results following cold exposure of sufficient magnitude or duration to cause acute tissue damage. Although there are several conditions that predispose to frostbite, all are at risk if subject to sufficient cold exposure. We discuss a case of frostbite presenting with bullae localized to the neck resulting from extreme cold encountered while snowmobiling at night in Minnesota, an entity known by some local practitioners as "polaris vulgaris."

Anti-Infective Agents, Local

AP1 proteins mediate the cAMP response of the dopamine beta-hydroxylase gene.

Neurotransmitter biosynthesis is regulated by environmental stimuli, which transmit intracellular signals via second messengers and protein kinase pathways. For the catecholamine biosynthetic enzymes, dopamine beta-hydroxylase and tyrosine hydroxylase, regulation of gene expression by cyclic AMP, diacyl glycerol, and Ca2+ leads to increased neurotransmitter biosynthesis. In this report, we demonstrate that the cAMP-mediated regulation of transcription from the dopamine beta-hydroxylase promoter is mediated by the AP1 proteins c-Fos, c-Jun, and JunD. Following treatment of cultured cells with cAMP, protein complexes bound to the dopamine beta-hydroxylase AP1/cAMP response element element change from consisting of c-Jun and JunD to include c-Fos, c-Jun, and JunD. The homeodomain protein Arix is also a component of this DNA-protein complex, binding to the adjacent homeodomain recognition sites. Transfection of a dominant negative JunD expression plasmid inhibits cAMP-mediated expression of the dopamine beta-hydroxylase promoter construct in PC12 and CATH.a cells. In addition to the role of c-Fos in regulating dopamine beta-hydroxylase gene expression in response to cAMP, a second pathway, involving Rap1/B-Raf is involved. These experiments illustrate an unusual divergence of cAMP-dependent protein kinase signaling through multiple pathways that then reconverge on a single element in the dopamine beta-hydroxylase promoter to elicit activation of gene expression.

Animals

Ro 32-3555, an orally active collagenase selective inhibitor, prevents structural damage in the STR/ORT mouse model of osteoarthritis.

OBJECTIVE: To determine the efficacy of a selective inhibitor of collagenases in an animal model of osteoarthritis (OA). METHODS: Ro 32-3555, an orally active collagenase selective inhibitor, was administered to STR/ORT mice. Microfocal x-ray-generated images of the hind limbs were visually scored for joint space narrowing, osteophyte formation, and calcification of tendons. Histologic sections of the knees were scored for cartilage changes including loss of surface matrix, fibrillation, and eburnation. RESULTS: Significant inhibition of joint space narrowing and osteophyte formation was achieved in groups of animals treated with 10-50 mg/kg(-1) of Ro 32-3555. These effects were confirmed histologically in the same groups of animals: histologic analysis revealed that Ro 32-3555 protected cartilage from degradative changes. CONCLUSION: Ro 32-3555, a collagenase selective inhibitor, inhibits both the cartilage and bone changes in this mouse model of OA, and thus shows great potential as a treatment of OA in humans.

Animals

A simple inflammation model that distinguishes between the actions of anti-inflammatory and anti-rheumatic drugs.

OBJECTIVE AND DESIGN: To determine the effects of anti-inflammatory and anti-rheumatic drugs on paw swelling and changes in plasma levels of acute phase proteins (APPs) during acute inflammation in the rat. MATERIALS AND METHODS: Inflammation was induced in rats by the injection of adjuvant and the animals were bled five days later and plasma levels of seromucoid, haptoglobin, caeruloplasmin and albumin were determined spectrophotometrically using a Cobas-bio centrifugal analyzer. The effects of daily administration of a variety of drugs used to treat arthritis were determined on paw swelling and APP levels. RESULTS: Injection of the adjuvant induced a pronounced change in APP levels which correlated with the increase in paw swelling. In general, the NSAIDs tested significantly reduced paw swelling and significantly increased levels of haptoglobin and caeruloplasmin in a dose-related manner. Two dose-levels of steroids were administered, the higher dose reduced swelling, and reduced levels of seromucoid, haptoglobin and caeruloplasmin, but raised albumin levels; the lower dose also reduced paw swelling, but the only change in APPs was increased albumin levels. Anti-rheumatic drugs such as gold salts reduced levels of some APPs (seromucoid, haptoglobin and caeruloplasmin) without reducing paw swelling. Immunomodulators had a variety of effects on inflammation and APPs depending on mechanism of action. CONCLUSIONS: The different classes of anti-inflammatory/anti-rheumatic drug tested show distinct profiles of activity against APPs and paw swelling. These differential effects may result from modulation of cytokine activity.

Acute-Phase Proteins

Renal pathology patterns in type II diabetes mellitus: relationship with retinopathy. The Collaborative Study Group.

BACKGROUND: The glomerular and retinal vessels are both affected in patients with type I and type II diabetes mellitus. However, the prevalence of the nodular form of diabetic glomerular sclerosis (Kimmelstiel Wilson lesion) and other forms of glomerular pathology including diffuse mesangial sclerosis and their clinical correlates in type II diabetes are less well known. In addition, although recent studies have suggested that non-diabetic glomerular disease was a common cause of proteinuria in type II diabetes, the prevalence of other diseases is unknown. The literature on this subject is clouded by clinical bias regarding patients with diabetes who undergo renal biopsy. METHODS: Glomerular and retinal pathology and clinical correlates were studied in 36 patients enrolled in a prospective clinical trial of patients with type II diabetes mellitus, proteinuria, renal insufficiency, and hypertension. RESULTS: Seventeen biopsies had diabetic glomerular sclerosis with Kimmelstiel Wilson nodules; 15 biopsies had glomerular changes characteristic of the diabetic state including enlarged glomeruli and an increase in mesangial matrix without Kimmelstiel Wilson nodules (mesangial sclerosis lesion); and two had other primary glomerular diseases (IgA and membranous nephropathy). Patients with Kimmelstiel-Wilson nodules had elevated serum creatinines compared to patients with mesangial sclerosis lesions, but there were no other significant differences. Patients with Kimmelstiel Wilson nodules had more severe overall retinopathy than those with mesangial sclerosis lesions (P = 0.0043): six of seven with proliferative retinopathy had Kimmelstiel Wilson nodules, and seven of the eight patients without retinopathy had mesangial sclerosis lesions. CONCLUSIONS: The two discrete patterns of glomerular pathology and the correlation between diabetic retinopathy and the Kimmelstiel-Wilson lesion but not the mesangial sclerosis lesion suggest that the Kimmelstiel Wilson and mesangial sclerosis lesions of diabetic glomerulosclerosis are caused by different pathogenetic mechanisms. In this study, diabetic glomerulosclerosis was responsible for the clinical renal abnormalities in 94%, of patients with type II diabetes mellitus.

Adult

Survival of infectious Cryptosporidium parvum oocysts in seawater and eastern oysters (Crassostrea virginica) in the Chesapeake Bay.

Oocysts of Cryptosporidium parvum placed in artificial seawater at salinities of 10, 20, and 30 ppt at 10 degrees C and at 10 ppt at 20 degrees C were infectious after 12 weeks. Those placed in seawater at 20 ppt and 30 ppt at 20 degrees C were infectious for 8 and 4 weeks, respectively. These findings suggested that oocysts could survive in estuarine waters long enough to be removed by filter feeders such as oysters. Thereafter, 30 Eastern oysters, Crassostrea virginica, were collected with a dredge or with hand tongs at each of six sites within Maryland tributaries of the Chesapeake Bay in May and June and in August and September of 1997. Hemocytes and gill washings from all oysters were examined for the presence of Cryptosporidium oocysts and Giardia cysts by immunofluorescence microscopy utilizing a commercially available kit containing fluorescein isothiocyanate-conjugated monoclonal antibodies. Giardia was not detected by this method from any of the 360 oysters examined. Presumptive identification of Cryptosporidium oocysts was made in either hemocytes or gill washings of oysters from all six sites both times that surveys were conducted. In addition, during August and September, for each of the six sites, hemocytes from the 30 oysters were pooled and gill washings from the oysters were pooled. Each pool was delivered by gastric intubation to a litter of neonatal mice to produce a bioassay for oocyst infectivity. Intestinal tissue from two of three mice that received gill washings from oysters collected at a site near a large cattle farm and shoreline homes with septic tanks was positive for developmental stages of C. parvum. These findings demonstrate for the first time that oysters in natural waters harbor infectious C. parvum oocysts and can serve as mechanical vectors of this pathogen.

Animals

Giardia sp. cysts and infectious Cryptosporidium parvum oocysts in the feces of migratory Canada geese (Branta canadensis).

Fecal droppings of migratory Canada geese, Branta canadensis, collected from nine sites near the Chesapeake Bay (Maryland), were examined for the presence of Cryptosporidium parvum and Giardia spp. Cryptosporidium sp. oocysts were found in feces at seven of nine sites, and Giardia cysts were found at all nine sites. The oocysts from three sites were infectious for mice and molecularly identified as the zoonotic genotype of Cryptosporidium parvum. Waterfowl can disseminate infectious C. parvum oocysts in the environment.

Animals

Furocoumarin-induced epidermal melanogenesis does not protect against skin photocarcinogenesis in hairless mice.

Topical 6,4,4'-trimethylangelicin (TMA) plus UVA was used to induce intense epidermal pigmentation in inbred HRA.HRII-c/+/Skh hairless pigmented mice over a 13 day period. Subsequent UVB/UVA exposure was used to assess the photoprotective properties of this tan using skin tumors as an endpoint. Comparisons were always made with sibling albino mice. The TMA/UVA treatment was shown to be not carcinogenic when treated mice were compared with untreated control mice over 25 weeks. The tan faded despite daily exposure to UVB/UVA and did not afford any protection when TMA/UVA-treated mice with subsequent UVB/UVA were compared with pigmented mice treated with UVB/UVA only. In one group, the TMA-induced tan was maintained by application of TMA three times a week prior to UVB/UVA for the duration of the experiment. This treatment was associated with a significant increase in tumor risk in both pigmented and albino mice compared to groups treated with UVB/UVA alone. Although pigmented mice had a significant photoprotective advantage, it was shown to be outweighed by the carcinogenic risks of the TMA maintenance treatment when they were compared with mice that did not have this treatment. Nonpretanned pigmented mice developed mild pigmentation during UVB/UVA treatment that was shown to have no protective effect when those mice were compared with albinos. We conclude that induced epidermal tanning with or without furocoumarin enhancement is not an effective way to prevent skin cancer in the HRA.HRII-c/+/Skh mouse model.

Animals

Localized crusted scabies of the scalp and feet.

An atypical case of crusted scabies in a patient with acquired immunodeficiency syndrome is presented in which lesions at the time of evaluation were confined to the scalp and feet. Because of the unusual presentation, the scalp involvement (which clinically mimicked seborrheic dermatitis) was initially missed. Although both the crusted variant of scabies and scabietic involvement of the scalp are well documented to occur in immunocompromised patients, to our knowledge scabies confined to the scalp and feet has not been previously reported.

AIDS-Related Opportunistic Infections

Scalp metastases mimicking alopecia areata. First case report of placental site trophoblastic tumor presenting as cutaneous metastasis.

BACKGROUND: Placental site trophoblastic tumor (PSTT) is a rare neoplasm of intermediate trophoblastic cells of the placenta. There is a wide range of biologic behavior, with metastases occurring in about 15% of cases. Cases with metastases have all presented with abnormal vaginal bleeding or gynecological symptoms. METHODS: We describe a 31-year-old G3P3003 woman who presented with several alopecic patches resembling alopecia areata, which on biopsy proved to be metastatic, previously unsuspected, PSTT. CONCLUSIONS: This represents the first case in which PSTT presented initially with metastases, and specifically, with cutaneous metastases. A new primary tumor source of alopecia neoplastica is presented. The role of mitotic counts in predicting prognosis in PSTT is supported. Alopecia areata was mimicked very closely. Dermatologists should be alert to any features atypical of alopecia areata, including erythema, induration, or palpability, and maintain a low threshold for biopsy in atypical cases.

Adult

Detection of Cryptosporidium oocysts and Giardia cysts in the tissues of eastern oysters (Crassostrea virginica) carrying principal oyster infectious diseases.

The potential cross-reactivity of the combined Cryptosporidium/Giardia direct immunofluorescence antibodies (IFA) of MERIFLUOR and HYDROFLUOR-COMBO tests was examined against tissues containing known developmental stages of 12 pathogens causing the principal infectious diseases in oysters. Spores of Haplosporidium nelsoni and Haplosporidium costale produced positive acid-fast stain (AFS) reactions similar in intensity to Cryptosporidium parvum oocysts. Hexamia nelsoni trophozoites produced positive IFA reactions in both IFA tests; however, the intensity of fluorescence was considerably lower and the fluorescein-staining pattern different than those of Giardia cysts. The applicability of AFS for screening oysters for Cryptosporidium oocysts is low, and positive identification of Cryptosporidium oocysts cannot be accomplished based on the AFS. Presumptive IFA identification of the Cryptosporidium oocysts or Giardia cysts in the oyster tissue should fulfill 3 criteria, i.e., bright-green fluorescence of the same intensity as C. parvum oocysts and Giardia cysts in the positive control, correct size and shape of the fluorescein-stained objects, and oocyst or cyst shell clearly visible.

Animals

Report of a nipple nevus and an overview of accessory mammary tissue.

Supernumerary nipples, also known as accessory nipples, are the most frequently encountered congenital anomaly of the breast. Once associated with fertility or divine powers, they are now widely held to be of cosmetic significance only. During the past 20 years, however, there has been a steady number of articles reporting the suspected association of supernumerary nipples with numerous benign and malignant medical conditions. We describe a previously unreported accessory nipple variant occurring as a nevoid nodule surmounting an otherwise normal primary nipple. The patient was otherwise healthy. The embryogenesis of this anomaly is hypothesized to result from in utero nipple dichotomy, rather than a failure of regression along the embryonic milk line.

Adult

The homeodomain protein Arix interacts synergistically with cyclic AMP to regulate expression of neurotransmitter biosynthetic genes.

Transcription of the neurotransmitter biosynthetic genes tyrosine hydroxylase and dopamine beta-hydroxylase (DBH) is regulated by cell type-specific transcription factors, including the homeoprotein Arix, and second messengers, including cyclic AMP. The cis-acting regulatory sites of the DBH gene which respond to Arix and cAMP lie adjacent to each other, between bases -180 and -150, in a regulatory element named DB1. Neither Arix nor cyclic AMP analogs alone effectively stimulate transcription from the DBH promoter in non-neuronal cell cultures. However, when Arix is present together with cAMP, transcription is substantially activated. Synergistic transcription from the DBH promoter can also be elicited by cotransfection of Arix with an expression vector encoding the catalytic subunit of protein kinase A. Nuclear extracts from PC12 cells display a cAMP-induced complex binding to the DB1 element, and antisera to transcription factors CREB, CREM, Fos, and Jun indicate that these proteins, or closely related family members, interact with DB1. A dominant negative construct of CREB inhibits the response of the DBH promoter to protein kinase A. These results demonstrate a synergistic interaction between a homeodomain protein and the cAMP signal transduction system and suggest that similar interactions may regulate the tissue-specific expression of neuroendocrine genes.

Animals