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Biomedical subjects

L Sherman

Publications and source records attributed to L Sherman.

At least 19 recordsLinked to original sources

Adaptive correction of depth-induced aberrations in multiphoton scanning microscopy using a deformable mirror.

We demonstrate adaptive aberration correction for depth-induced spherical aberration in a multiphoton scanning microscope with a micromachined deformable mirror. Correction was made using a genetic learning algorithm with two-photon fluorescence intensity feedback to determine the desired shape for an adaptive mirror. For a 40x/0.6 NA long working distance objective, the axial scanning range was increased from 150 mm to 600 mm.

Microscopy, Confocal↗

Remifentanil by patient-controlled analgesia compared with intramuscular meperidine for pain relief in labour.

BACKGROUND: The pharmacokinetics of remifentanil suggests that it may be suitable for analgesia during labour. METHODS: In an open pilot study, 36 women requesting meperidine for analgesia were recruited early in labour and randomized to receive either meperidine i.m. or remifentanil given as patient-controlled analgesia (PCA). Pain severity, sedation and anxiety were assessed with visual analogue scales and overall effective analgesia was assessed by the woman and midwife. RESULTS: The pain scores were lower in the remifentanil group: median pain score at 60 min was 72 mm for meperidine and 48 mm for remifentanil (P=0.004) and median maximum pain score during the first 2 h was 82.5 mm for the meperidine group and 66.5 mm for the remifentanil group (P=0.009). Both the midwives' and the women's assessments of overall effective analgesia were higher in the remifentanil group [Likert scale (5 = excellent to 1 = poor): chi2=12.10, P=0.002 for mothers' assessment; chi2=12.80, P=0.002 for midwives' assessment]. CONCLUSION: In this pilot study, remifentanil by PCA gave better pain relief to mothers in labour than intramuscular meperidine. However, remifentanil is a potent respiratory depressant and adequate continuous monitoring is necessary.

Adolescent↗

Improving cognitive development of low-birth-weight premature infants with the COPE program: a pilot study of the benefit of early NICU intervention with mothers.

The purpose of this pilot study was to evaluate the effectiveness of a parent-focused intervention program (COPE) on infant cognitive development and maternal coping. A randomized clinical trial was conducted with 42 mothers of low-birth-weight (LBW) premature infants hospitalized in a neonatal intensive care unit (NICU), with follow-up at 3 months' and 6 months' corrected ages. COPE mothers received the four-phase educational-behavioral program that began 2-4 days postbirth and continued through 1 week following discharge from the NICU. Comparison mothers received audiotaped information during the same four time frames. Results indicated that COPE infants had significantly higher mental development scores at a 3 months' corrected age (M = 100.3) than did the comparison infants (M = 93.9), and this difference widened at 6 months' corrected age, with COPE infants scoring 14 points higher. COPE mothers were significantly less stressed by the NICU sights and sounds and had significantly stronger beliefs about what behaviors and characteristics to expect from their premature infants. Findings from this study support the need for further testing of early NICU interventions with parents to determine their effectiveness on parental coping and infant developmental outcomes.

Adaptation, Psychological↗

Identifying population health faculty in U.S. medical schools.

CONTEXT: An Association of American Medical Colleges (AAMC) panel has proposed the components of a population health (PH) curriculum for U.S. medical schools. Do schools have the trained faculty to teach these subjects well? OBJECTIVE: Determine the number and location of full-time medical school faculty formally trained in the population health sciences through an MPH degree, a public health (PH)-related doctoral degree, a residency in preventive medicine, or board certification in preventive medicine in 1990 and 1998. DESIGN: This is a descriptive study based on the AAMC Faculty Roster System that includes information about all full-time U.S. medical school faculty. RESULTS: In 1998, 2007 out of a total of 88,782 full-time medical school faculty had MPH degrees and 1214 had a PH-related doctoral degree. A total of 484 faculty had residency training in preventive medicine while 279 had passed the preventive medicine board examination. Faculty with these various degrees are distributed among multiple departments. Since 1990, most growth in new faculty formally trained in the population health sciences has been in family medicine, internal medicine, and pediatrics rather than preventive medicine. CONCLUSIONS: Full-time medical school faculty with MPH degrees and PH-related doctoral degrees have grown faster than total faculty since 1990. Faculty with residency training or board certification in preventive medicine have grown much more slowly. Faculty formally trained in the PH sciences are distributed among departments of preventive medicine, family medicine, internal medicine, and pediatrics, among others. Unfortunately, a significant number of medical schools have very few faculty formally trained in the PH sciences. The implications of this distribution for the education of medical students are discussed.

Certification↗

Progesterone receptor contains a proline-rich motif that directly interacts with SH3 domains and activates c-Src family tyrosine kinases.

Steroid hormones have rapid nongenomic effects on cell-signaling pathways, but the receptor mechanisms responsible for this are not understood. We have identified a specific polyproline motif in the amino-terminal domain of conventional progesterone receptor (PR) that mediates direct progestin-dependent interaction of PR with SH3 domains of various cytoplasmic signaling molecules, including c-Src tyrosine kinases. Through this interaction, PR is a potent activator of Src kinases working by an SH3 domain displacement mechanism. By mutagenesis, we also show that rapid progestin-induced activation of Src and downstream MAP kinase in mammalian cells is dependent on PR-SH3 domain interaction, but not on the transcriptional activity of PR. Preliminary evidence for the biological significance of this PR signaling pathway through regulatory SH3 domains was shown with respect to an influence on progestin-induced growth arrest of breast epithelial cells and induction of Xenopus oocyte maturation.

Amino Acid Motifs↗

More information on the nature of stereotyped body-rocking.

Body-rocking was exposed to kinematic analysis in two studies. In the first study, amplitude was larger in the natural body-rocking of individuals with mental retardation than in the natural body-rocking of college students. Variability did not differ. In the second study, natural body-rocking of people with mental retardation was compared with their artificial body-rocking. Amplitude and variability were larger in the artificial condition. However, this result was not clear. We suggest that group and condition differences might have been a function of practice.

Humans↗

Early development of stereotyped and self-injurious behaviors: I. Incidence.

From five programs with 457 eligible children, 39 children younger than 40 months who had developmental disabilities were studied. Video sampling, observation notes, parent reports, staff reports, and clinical records were the data sources. Twenty-one children, or 4.6% of the total number in the program, exhibited SIBs. Virtually all children in the sample who were motorically capable of it showed body-rocking in at least one position. The SIBs were directed mainly toward the head, and body-rocking occurred mainly in four-point and seated position.

Age Factors↗

Screening to the converted: an educational intervention in African American churches.

BACKGROUND: African American women have higher incidences of breast and cervical cancers and African American men present with more advanced stages of colon and prostate cancers than do their non-African American counterparts. Since the church is central to the organization of the African American community, the authors set out to determine whether a church-directed educational project could influence parishioners to obtain cancer screening. METHODS: Three African American churches having memberships of 250, 500, and 1,500, respectively, were selected for their different socioeconomic strata: one congregation was composed mostly of working poor, the second was more affluent, and the third consisted primarily of retirees. During a five-week summer period, appropriate literature, health fairs, testimonials by cancer survivors, and visits by representatives of the medical community were used to increase awareness of cancer screening. Surveys regarding cancer-screening behaviors were distributed at the end of church services. Using the guidelines established by the American Cancer Society, individual recommendations for screening examinations were developed and sent to parishioners based on their survey responses. RESULTS: Of 437 parishioners surveyed (73% female, 27% male), 75% were 40 years old or older. Many reported up-to-date screening for breast (84%), cervical (78%), colon (62%), and prostate (89%) cancers. The results were remarkably similar in all three churches. Telephone follow-up seven months after the survey directed at the 120 parishioners identified as noncompliant for at least one cancer screening revealed that 49% had obtained the appropriate screenings. CONCLUSIONS: These African American churchgoers were well screened compared with estimated national averages, possibly due to previous efforts of the activist ministers in the churches selected. The message for cancer screening is heeded when delivered through the African American church.

Adult↗

Deep venous thrombosis: detection by using indirect CT venography. The Pulmonary Angiography-Indirect CT Venography Cooperative Group.

PURPOSE: To assess the clinical benefits of performing indirect computed tomographic (CT) venography after pulmonary CT angiography to detect deep venous thrombosis (DVT) in patients suspected of having a pulmonary embolism. MATERIALS AND METHODS: The authors prospectively enrolled 541 consecutive patients who underwent pulmonary CT angiography for suspected pulmonary embolism at seven institutions. Using a protocol that optimizes venous enhancement without additional contrast material injection, the authors obtained contiguous images from the pelvis to the popliteal fossa. Ultrasonography (US) also was performed in 116 patients. RESULTS: DVT was found at indirect CT venography in 45 (8%), and pulmonary embolism was found at pulmonary CT angiography in 91 (17%) of 541 patients. Among the 45 patients with DVT, DVT occurred in 16 patients who had no pulmonary embolism at pulmonary CT angiography, which increased the diagnosis of thromboembolic disease by 18%. Among 116 patients who underwent US and indirect CT venography, 15 had DVT at US, and in all 15, DVT also was seen at indirect CT venography. In four additional cases, DVT was seen at only indirect CT venography. CONCLUSION: Among patients suspected to have pulmonary embolism, a substantial number had DVT in the absence of pulmonary embolism. Combined pulmonary CT angiography-indirect CT venography can depict these cases with accuracy comparable to that of US and thus could have a significant effect on patient care.

Adolescent↗

Differential hormone-dependent phosphorylation of progesterone receptor A and B forms revealed by a phosphoserine site-specific monoclonal antibody.

Human progesterone receptor (PR) is phosphorylated on multiple serine residues (at least seven sites) in a manner that involves distinct groups of sites coordinately regulated by hormone and different kinases. Progress on defining a functional role for PR phosphorylation has been hampered both by the complexity of phosphorylation and the lack of simple, nonradioactive methods to detect the influence of ligands and other signaling pathways on specific PR phosphorylation sites in vivo. Toward this end, we have produced monoclonal antibodies (MAbs) that recognize specific phosphorylation sites within human PR including a basal site at Ser 190 (MAb P190) and a hormone-induced site at Ser 294 (MAb P294). Biochemical experiments showed the differential reactivity of the P190 and P294 MAbs for phosphorylated and unphosphorylated forms of PR. Both MAbs recognize specific phosphorylated forms of PR under different experimental conditions including denatured PR protein by Western blots and PR in its native conformation in solution or complexed to specific target DNA. As detected by Western blot of T47D cells treated with hormone for different times, hormone-dependent down-regulation of total PR and the Ser 190 phosphorylation site occurred in parallel, whereas the Ser 294 phosphorylation site was down-regulated more rapidly. This difference in kinetics suggests that the Ser 294 site is more labile than basal sites and is acted upon by distinct phosphatases. A strong preferential hormone-dependent phosphorylation of Ser 294 was observed on PR-B as compared with the amino-terminal truncated A form of PR. This was unexpected because Ser 294 and flanking sequences are identical on both proteins, suggesting that a distinct conformation of the N-terminal domain of PR-A inhibits phosphorylation of this site. That Ser 294 lies within an inhibitory domain that mediates the unique repressive functions of PR-A raises the possibility that differential phosphorylation of Ser 294 is involved in the distinct functional properties of PR-A and PR-B.

Amino Acid Sequence↗

The presence of HPV 16, 18 and p53 immunohistochemical staining in tumor tissue of Israeli Jewish women with cervical and vulvar neoplasia.

The incidence of cervical neoplasia in Israeli Jewish women is persistently lower, while that of vulvar carcinoma is comparable to that in other populations. The aim of the present investigation was to assess the prevalence of HPV and of immunohistochemically detected mutant p53 in Israeli Jewish women with cervical and vulvar neoplasia compared with other populations. Tissue sections from formalin-fixed paraffin-embedded blocks of ten patients with CIN III, 29 with invasive squamous cell carcinoma, three with adenocarcinoma and 14 with invasive vulvar carcinoma, were examined for the presence of HPV 16 and HPV 18 DNA by PCR amplification, and for mutant p53 protein by immunohistochemical staining. HPV negative cases were re-examined with a sensitive primer. HPV DNA was detected in eight patients with CIN III and in 23 patients with invasive squamous carcinoma. In the remaining cervical squamous neoplasia tissue analysis with the sensitive primer could not be done. HPV DNA was also detected in two patients with adenocarcinoma and in nine (64.2%) patients with vulvar carcinoma. Positive p53 immunohistochemical staining was found only in one CIN III patient, in six (20.7%) squamous carcinoma and in 11 (78.6%) vulvar carcinoma patients. Of the p53 immunohistochemical staining positive tissues, two with cervical carcinoma and six with vulvar carcinoma were also HPV-positive. The prevalence of HPV and of positive p53 immunohistochemical staining in our series of Israeli Jewish women with cervical and vulvar neoplasia is similar to that in other populations, suggesting that the etiological factors are probably also alike.

Adult↗

Overexpression of activated neu/erbB2 initiates immortalization and malignant transformation of immature Schwann cells in vitro.

The neu/erbB2 protooncogene is overexpressed in numerous human cancers and is mutationally activated in N-ethyl-N-nitrosourea (ENU)-induced rodent tumors of the Schwann cell lineage. We investigated whether expression of activated neu in Schwann cells is sufficient to initiate their immortalization and transformation. Clones of embryonic dorsal root ganglia cells infected with a retrovirus bearing activated neu (NID cells) were selected based on their expression of Schwann cell-specific markers. Compared to embryonic Schwann cells infected with a virus encoding empty vector, we found that NID cells have altered shapes and disorganized cytoskeletons, grow in the absence of growth factors required for normal Schwann cell survival and proliferation, and can be repeatedly passaged. Furthermore, NID cells are invasive in an in vitro matrix invasion assay and form metastatic tumors when injected into syngeneic animals. The neu-induced growth and invasive phenotypes could be reversed by drugs that inhibit Ras and Src activity. Interestingly, later stage Schwann cells infected with activated neu failed to become immortalized. These findings indicate that constitutive activation of erbB2 is sufficient to initiate the immortalization and transformation of immature Schwann cells, and support the notion that Schwann cells have particular developmental stages during which they are susceptible to immortalizing and transforming events.

Animals↗

Tumor antigens are constitutively presented in the draining lymph nodes.

Tumor growth is rarely associated with a strong specific CTL response, suggesting that the immune system is ignorant of the presence of tumor because the Ags are not readily available to or are sequestered from potential effector cells. We studied the in vivo activation of naive TCR transgenic hemagglutinin (HA)-specific CD8+ T cells adoptively transferred into mice bearing HA-expressing tumor using 5,6-carboxy-succinimidyl-fluorescein-ester labeling, which allows the identification of proliferating HA-specific T cells. We demonstrate that tumor Ags are constitutively presented in the lymph nodes draining tumors and are powerfully mitogenic for responding T cells despite the absence of anti-tumor CTL responses. Importantly, this proliferative signal occurs throughout tumor growth and is still detectable 6 mo after tumor inoculation when tumor is not palpable. These results provide the first evidence that there is constitutive presentation of tumor Ags in draining lymph nodes.

Animals↗

HPV16 E6 oncoprotein inhibits apoptosis induced during serum-calcium differentiation of foreskin human keratinocytes.

Transfection of human papillomavirus (HPV) 16 E6 oncogene into foreskin primary human keratinocytes (PHKs) causes the formation of colonies of viable cells resistant to serum-calcium differentiation. To define the stage of keratinocyte differentiation inhibited by E6, we examined the response of PHKs to serum and calcium with respect to parameters of both growth and differentiation. The effect of HPV16 E6 was evaluated by infection with recombinant retroviruses encoding the E6 protein. Results of these studies indicated that terminal differentiation of cultured foreskin keratinocytes, triggered by serum and calcium, is a progressive process (2-3 weeks) that ends with cell death with characteristics of apoptosis. Human keratinocyte terminal differentiation was accompanied by time-related changes in the expression of cellular proteins involved in the control pathways of apoptosis, including downregulation of Bcl-2 and p53 and upregulation of Bax, which coincided with the appearance of morphological signs of apoptosis. E6 expression did not override the differentiation-associated G1 arrest or prevent the induction of squamous differentiation-specific markers, transglutaminase 1 and involucrin. E6 expression led, however, to a significant reduction in cell stratification and cell death by apoptosis, which correlated with prolonged expression of Bcl-2 and reduced elevation of Bax levels that occurred concomitant with a complete loss of p53. The data argue that E6 inhibits terminal differentiation of foreskin PHKs through inhibition of their differentiation-induced apoptotic program.

3T3 Cells↗