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Biomedical subjects

M Stein

Publications and source records attributed to M Stein.

At least 145 records · Page 8Linked to original sources

Measurement of anti-inflammatory effects of glucocorticoids on human keratinocytes in vitro. Comparison of normal human keratinocytes with the keratinocyte cell line HaCaT.

There are only few objective in vitro methods available for the testing of anti-inflammatory pharmaceutical products. One possibility is in the stimulation of cytokine production in cultivated human keratinocytes by UV light and the subsequent testing of suppressing activities. From the dermatological aspect the interleukins 6 and 8 are especially interesting because they are elevated in psoriatic skin. In the present work three glucocorticoids were tested in cultures of normal human keratinocytes and in the permanent keratinocyte cell line HaCaT. Both cell species produced IL-6 and IL-8 spontaneously, albeit in very small amounts. After UV irradiation the interleukin production increased in a dose dependent manner. The IL-6 and IL-8 induction could be suppressed by each of the glucocorticoids tested. The thymidine incorporation rate of the cells was not affected by the glucocorticoids indicating that the observed suppression of cytokine induction was not the result of a generalised cell damage. The response of both HaCaT keratinocytes and primary human keratinocytes to UV irradiation and glucocorticoid application was similar indicating the possible use of the generally available HaCaT cells for the pharmacological testing of anti-inflammatory activities in vitro.

Anti-Inflammatory Agents↗

Enteropathogenic E. coli exploitation of host epithelial cells.

Enteropathogenic E. coli (EPEC) is a leading cause of neonatal diarrhea worldwide. These organisms adhere to the intestinal cell surface, causing rearrangement in the epithelial cell surface and underlying cytoskeleton, resulting in a structure termed an attaching/effacing (A/E) lesion. A/E lesion formation is thought necessary for EPEC-mediated disease. EPEC secretes several proteins that trigger signal transduction, intimate adherence, and cytoskeletal rearrangements in epithelial cells. Additionally, it produces intimin, an outer membrane product that mediates intimate adherence. Together these various bacterial molecules contribute to the intimate relationship that is formed by EPEC with host epithelial cells which results in A/E lesion formation and diarrhea.

Adhesins, Bacterial↗

A pathogenic bacterium triggers epithelial signals to form a functional bacterial receptor that mediates actin pseudopod formation.

Enteropathogenic E. coli (EPEC) belongs to a group of bacterial pathogens that induce actin accumulation beneath adherent bacteria. We found that EPEC adherence to epithelial cells mediates the formation of fingerlike pseudopods (up to 10 microm) beneath bacteria. These actin-rich structures also contain tyrosine phosphorylated host proteins concentrated at the pseudopod tip beneath adherent EPEC. Intimate bacterial adherence (and pseudopod formation) occurred only after prior bacterial induction of tyrosine phosphorylation of an epithelial membrane protein, Hp90, which then associates directly with an EPEC adhesin, intimin. These interactions lead to cytoskeletal nucleation and pseudopod formation. This is the first example of a bacterial pathogen that triggers signals in epithelial cells which activates receptor binding activity to a specific bacterial ligand and subsequent cytoskeletal rearrangement.

Actins↗

Eye manifestations of congenital toxoplasmosis.

PURPOSE: To determine the natural history of treated and untreated congenital toxoplasmosis and impact of this infection on vision. METHODS: In this prospective, longitudinal study, 76 newborns were treated with pyrimethamine and sulfadiazine for approximately one year, and 18 individuals not treated during their first year of life entered the study after age 1 year (historical patients). RESULTS: Chorioretinal scars were the most common eye finding in all patients and were most common in the periphery (58% of treated and 82% of historical patients). Macular scars were present in 54% of the treated patients; 41% were bilateral. Macular scars were present in 76% of the historical patients; 23% were bilateral. Visual acuity in the presence of macular lesions ranged from 20/20 to 20/400. Of the patients followed up from the newborn period and treated, 29% had bilateral visual impairment, with visual acuity for the best eye of less than 20/40. Causes for this visual impairment in eyes with quiescent lesions included macular scars, dragging of the macula secondary to a peripheral lesion, retinal detachment, optic atrophy, cataract, amblyopia, and phthisis. There were recurrences in both treated (13%, 7/54) and previously untreated historical patients (44%, 8/18). The total, median, and range of years of follow-up during which recurrences were observed were, for treated patients, 189 years (total), five years (median), and three to ten years (range) and, for historical, untreated patients, 160 years (total), 11 years (median), and three to 24 years (range). New lesions occurred in previously normal retinas and also contiguous to older scars. Active lesions appeared to become quiescent within ten to 14 days after beginning pyrimethamine and sulfadiazine therapy. CONCLUSION: Many children with congenital toxoplasmosis have substantial retinal damage at birth and consequent loss of vision. Nonetheless, vision may be remarkably good in the presence of large macular scars. Active lesions become quiescent with treatment.

Adolescent↗

Treatment efficacy: aphasia.

This article presents a brief overview of aphasia, followed by a summary of research studies and program evaluation data addressed to answering the question of the efficacy of treatment for aphasia. Selected studies are reviewed in terms of the quality of evidence they present. In addition, a number of questions that remain unanswered are also presented. Several tables, designed to provide clarifying information concerning several aspects of research design (number and types of patients studied, examples of well-designed small-group or single-subject studies, clinical techniques for which efficacy data are available), are included. The conclusion of this review is that, generally, treatment for aphasia is efficacious.

Aphasia↗

Congenital toxoplasmosis transmitted from an immunologically competent mother infected before conception.

Congenital transmission of Toxoplasma gondii from a mother who was apparently immunologically competent and who had toxoplasmic lymphadenitis 2 months before conception is described. Since no T. gondii-specific serological data were available for this mother from the time her lymph node biopsy specimen was obtained, the specimen was studied by polymerase chain reaction (PCR) to determine whether the T. gondii B1 gene was present. The predictive diagnostic value of histologic findings previously considered to be classic signs of T. gondii lymphadenitis also was studied. This was done by correlation of serological tests diagnostic of acute acquired T. gondii infection and presence of characteristic findings in biopsy specimens from persons without known immunocompromise. Both PCR and review of the characteristic features of her lymph node biopsy specimen confirmed the diagnosis of preconceptual infection in the mother. We also discuss two other cases in which apparently immunologically competent mothers with preconceptually acquired infection transmitted this parasite to their fetuses.

Animals↗

The Abbreviated Injury Scale. A valuable tool for forensic documentation of trauma.

Anatomic trauma scoring systems are fundamental to trauma research. The Abbreviated Injury Scale (AIS) and its derivative, the Injury Severity Score (ISS), are the most frequently used scales. We assessed the applicability of the AIS and the ISS systems for postmortem forensic documentation of trauma. In a prospective study, all trauma autopsies performed between January 1 and June 30, 1993, were coded according to the AIS and ISS method. All cases were reviewed by a consultant in forensic medicine and a traumatologist. Cases were grouped in three categories according to ISS values: 0-14, 16-66, and 75. These categories represent minor, major, and incompatible-with-life injuries, respectively. All autopsy findings in which ISS was < or = 14 were peer-reviewed to establish mechanism and cause of death. In the 6-month period, 279 trauma-related autopsies were studied. Age at death averaged 37.1 +/- 18.7 (mean +/- SD). Eighty-six percent of the victims were male. Penetrating trauma was the mechanism of injury in 67%. ISS was 0-14 in 19 cases, 16-66 in 150 cases, and 75 in 110 cases. In conclusion, AIS and ISS scoring systems are applicable to trauma forensic documentation. Using these methods for coding postmortem findings may help in establishing a database for trauma research, and this information could constitute a major part of continuous quality improvement of trauma management. Low ISS values may serve as a warning, sometimes indicating preventable death.

Abbreviated Injury Scale↗

Transaxial gunshot injuries.

OBJECTIVE: To define the clinical characteristics of gunshot injuries across the truncal midline (transaxial injuries). DESIGN: A retrospective case-control study MATERIALS AND METHODS: Analysis of a consecutive series of 223 patients with gunshot injuries to the torso treated at one trauma center. Sixty-three patients with transaxial injuries were compared to 148 patients with unilateral bullet trajectories. MAIN RESULTS: The incidence of cardiac (8%), vascular (17%), and spinal (29%) injuries and the mortality rate (29%) were significantly higher among the 63 patients with transaxial injuries compared with 148 patients with unilateral injuries. Initial operative access to the wrong visceral cavity (10%), missed injuries (14%), and early reoperations (19%) were also more common in the transaxial group. CONCLUSIONS: A transaxial bullet trajectory identifies a distinct injury pattern associated with a high incidence of major visceral damage, intraoperative misadventures, and very high mortality.

Abdominal Injuries↗

Blast injuries: bus versus open-air bombings--a comparative study of injuries in survivors of open-air versus confined-space explosions.

OBJECTIVES: To compare injury patterns resulting from explosions in the open air versus within confined spaces. METHODS: Medical charts of 297 victims of four bombing events were analyzed. Two explosions occurred in the open air and two inside buses. Similar explosive devices were applied in all four incidents. The incidence of primary blast injuries, significant penetrating trauma (Abbreviated Injury Scale score > or = 2), burns, Injury Severity Score, Revised Trauma Score, and mortality were compared between the two populations. RESULTS: A total of 204 casualties were involved in open-air bombings, 15 of whom died (7.8%). Ninety-three victims were involved in bus bombings, 46 of whom died (49%). The difference in mortality rate was highly significant, p < 0.00001. Primary blast injuries were observed in 25 and 31 victims (34.2% and 77.5% of admitted victims), respectively (p = 0.00003). Median Injury Severity Score was 4 versus 18, respectively (p < 0.0001). CONCLUSION: Explosions in confined spaces are associated with a higher incidence of primary blast injuries, with more severe injuries and with a higher mortality rate in comparison with explosions in the open air.

Adolescent↗

Characterization of EspC, a 110-kilodalton protein secreted by enteropathogenic Escherichia coli which is homologous to members of the immunoglobulin A protease-like family of secreted proteins.

Enteropathogenic Escherichia coli (EPEC) secretes at least five proteins. Two of these proteins, EspA and EspB (previously called EaeB), activate signal transduction pathways in host epithelial cells. While the role of the other three proteins (39, 40, and 110 kDa) remains undetermined, secretion of all five proteins is under the control of perA, a known positive regulator of several EPEC virulence factors. On the basis of amino-terminal protein sequence data, we cloned and sequenced the gene which encodes the 110-kDa secreted protein and examined its possible role in EPEC signaling and interaction with epithelial cells. In accordance with the terminology used for espA and espB, we called this gene espC, for EPEC-secreted protein C. We found significant homology between the predicted EspC protein sequence and a family of immunoglobulin A (IgA) protease-like proteins which are widespread among pathogenic bacteria. Members of this protein family are found in avian pathogenic Escherichia coli (Tsh), Haemophilus influenzae (Hap), and Shigella flexneri (SepA). Although these proteins and EspC do not encode IgA protease activity, they have considerable homology with IgA protease from Neisseria gonorrhoeae and H. influenzae and appear to use a export system for secretion. We found that genes homologous to espC also exist in other pathogenic bacteria which cause attaching and effacing lesions, including Hafnia alvei biotype 19982, Citrobacter freundii biotype 4280, and rabbit diarrheagenic E. coli (RDEC-1). Although these strains secrete various proteins similar in molecular size to the proteins secreted by EPEC, we did not detect secretion of a 110-kDa protein by these strains. To examine the possible role of EspC in EPEC interactions with epithelial cells, we constructed a deletion mutant in espC by allelic exchange and characterized the mutant by standard tissue culture assays. We found that EspC is not necessary for mediating EPEC-induced signal transduction in HeLa epithelial cells and does not play a role in adherence or invasion of tissue culture cells.

Amino Acid Sequence↗

Pelvic abscesses: transvaginal US-guided drainage with the trocar method.

The effectiveness of the trocar technique of catheter placement for transvaginal sonographically guided drainage of pelvic abscess was assessed in seven women who presented with pelvic pain, fever, and presumed pelvic abscess. Endovaginal ultrasound was performed to document fluid collection before drainage. All procedures were performed in less than 1 hour, without complications. Catheters were left in place for 1-3 days. Catheter placement was curative in six of seven patients (86%).

Abscess↗

Treatment efficacy: cognitive-communicative disorders resulting from traumatic brain injury in adults.

Traumatic brain injuries (TBI) may result in a broad array of cognitive-communicative impairments. Cognitive-communicative impairments are the result of deficits in linguistic and nonlinguistic cognitive functions. The speech-language pathologist functions as a member of the multidisciplinary team of professionals that collaboratively assess and treat individuals with TBI. The role of the speech-language pathologist includes assessment of all aspects of communication, as well as the communicative implications of cognitive deficits, and swallowing; treatment planning and programming, as determined by the individual's stage of recovery; client and family training/counseling; and interdisciplinary consultation. The effectiveness of speech and language intervention for specific cognitive deficits (e.g., attention, memory, executive functions) as well as general issues of social-skills training and early intervention are illustrated by scientific and clinical evidence from group-treatment and single-subject studies as well as case studies.

Activities of Daily Living↗