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Biomedical subjects

E Hammond

Publications and source records attributed to E Hammond.

At least 19 recordsLinked to original sources
PubMed2004

Viral gastroenteritis--a danger to the patient, a danger to the staff.

Viral gastroenteritis is usually a mild, self-limiting illness. We report a case of a previously well 74-year-old woman who suffered a grave complication of this common condition, and caused a significant outbreak of illness amongst staff involved in her care. This case highlights the risks of Hospital Acquired Infection and raises important infection control issues. It illustrates the hazards associated with exposure to potentially infectious secretions and presents a clear message to medical and nursing staff involved in the care of the acute surgical emergency.

Aged↗
PubMed2003

P105 as a prognostic indicator in patients irradiated for locally advanced head-and-neck cancer: a clinical/laboratory correlative analysis of RTOG-9003.

PURPOSE: In a previous retrospective study, p105 AD, a proliferation-associated nuclear antigen density (AD), was found to be an independent prognostic factor for patients irradiated for locally advanced head-and-neck cancer. We sought to confirm this finding by analyzing patients entered on RTOG 9003, a Phase III randomized trial of altered fractionation radiotherapy. METHODS AND MATERIALS: Paraffin blocks of pretreatment biopsies of the primary tumor of patients with Stage III or IV squamous cell carcinoma of the oral cavity, oropharynx, or supraglottic larynx, or Stage II squamous cell carcinoma of the hypopharynx or base of tongue entered on RTOG 9003 were prospectively collected at patient entry. From these paraffin blocks, areas of tumor were selected based on histologic examinations and sectioned. Nuclear suspensions were then prepared and processed for p105 antibody and DNA staining. Flow cytometric quantification of p105 labeling indices and DNA content were then performed for correlation with local-regional control and survival. RESULTS: Paraffin blocks of tumor biopsies from 457 of 1073 patients entered were available for p105 determination. There was no significant difference in pretreatment characteristics between patients who had paraffin blocks available or not available. The median (range) of p105 labeling index (LI-C), p105 labeling index of cells in S phase (p105 LI-S), and p105 AD were 56 (range: 6-99), 8.255 (range: 0.913-23), and 67 (range: 5-364), respectively. Multivariate analysis of prognostic factors showed that T stage, N stage, Karnofsky performance status, and fractionation schedule were significant for local-regional control (p < 0.0001, 0.0011, <0.0001, and 0.007, respectively) and T stage, N stage, Karnofsky performance status, and tumor grade were significant for survival (p = 0.018, 0.002, <0.0001, and 0.0058, respectively). Neither p105 LI-C nor p105 LI-S nor p105 AD nor DNA ploidy was significant for local-regional control or survival. CONCLUSION: p105 labeling indices, antigen density, and DNA ploidy do not predict the outcome of patients irradiated for advanced squamous cell carcinomas of the head and neck.

Antigens, Neoplasm↗
PubMed2003

Loss of p16 expression is of prognostic significance in locally advanced prostate cancer: an analysis from the Radiation Therapy Oncology Group protocol 86-10.

PURPOSE: The retinoblastoma (RB) cell cycle regulatory pathway is known to be deregulated in virtually all known human tumors. The protein product of the RB gene, pRB, and its upstream regulator, p16, are among the most commonly affected members of this pathway. We investigated the prognostic significance of both pRB and p16 expression in locally advanced prostate cancers, from patients treated on the Radiation Therapy Oncology Group (RTOG) protocol 86-10. MATERIALS AND METHODS: Sixty-seven cases from RTOG 86-10 had immunohistochemically stained slides, judged interpretable for both p16 and pRB, available for analysis. Median follow-up was 8.9 years (range, 6.0 to 11.8 years) for surviving patients. Staining for each marker was then correlated with overall survival, local progression, distant metastasis, and disease-specific survival. RESULTS: Loss of p16 expression, as defined by expression was significantly associated with reduced overall survival (P =.039), disease-specific survival (P =.006), and higher risk of local progression (P =.0007) and distant metastasis (P =.026) in the univariate analysis. In the multivariate analysis, loss of p16 was significantly associated with reduced disease-specific survival (P =.0078) and increased risk of local failure (P =.0035) and distant metastasis (P =.026). A borderline association with reduced overall survival (P =.07) was also evident. Loss of pRB was associated with improved disease-specific survival on univariate (P =.028) and multivariate analysis (P =.043), but carried no other significant outcome associations. CONCLUSION: Loss of p16 is significantly associated with adverse clinical outcome in cases of locally advanced prostate cancer.

Adult↗
PubMed2001

Regulation of p53 by hypoxia: dissociation of transcriptional repression and apoptosis from p53-dependent transactivation.

Hypoxic stress, like DNA damage, induces p53 protein accumulation and p53-dependent apoptosis in oncogenically transformed cells. Unlike DNA damage, hypoxia does not induce p53-dependent cell cycle arrest, suggesting that p53 activity is differentially regulated by these two stresses. Here we report that hypoxia induces p53 protein accumulation, but in contrast to DNA damage, hypoxia fails to induce endogenous downstream p53 effector mRNAs and proteins. Hypoxia does not inhibit the induction of p53 target genes by ionizing radiation, indicating that p53-dependent transactivation requires a DNA damage-inducible signal that is lacking under hypoxic treatment alone. At the molecular level, DNA damage induces the interaction of p53 with the transcriptional activator p300 as well as with the transcriptional corepressor mSin3A. In contrast, hypoxia primarily induces an interaction of p53 with mSin3A, but not with p300. Pretreatment of cells with an inhibitor of histone deacetylases that relieves transcriptional repression resulted in a significant reduction of p53-dependent transrepression and hypoxia-induced apoptosis. These results led us to propose a model in which different cellular pools of p53 can modulate transcriptional activity through interactions with transcriptional coactivators or corepressors. Genotoxic stress induces both kinds of interactions, whereas stresses that lack a DNA damage component as exemplified by hypoxia primarily induce interaction with corepressors. However, inhibition of either type of interaction can result in diminished apoptotic activity.

Acetylation↗
PubMed1998

Age- and gender-related elastin distribution changes in human vocal folds.

The composition of the lamina propria in human vocal folds has been shown to affect vocal performance. Elastin plays a significant role in the biomechanical effects of the lamina propria. We obtained 19 larynges from the state medical examiner from subjects whose cause of death was unrelated to the trachea and laryngeal regions. The sample contained male and female subjects in the infant, adult, and geriatric age groups. We stained the vocal folds for elastin with Verhoeff's elastic tissue stain and studied them with use of an image analysis system configured for light microscopy. Distributions of elastin were measured from superficial to deep within the lamina propria (from epithelium to vocal muscle). These elastin distributions were then compared with the use of statistical software. The data showed that there was an increase in elastin content from the infant through geriatric stages. No gender-related differences were found. Infant folds had about 23% of the elastin found in adults, and geriatric subjects had about 879% of the elastin found in adults. Both of these results were statistically significant (p < 0.05). The distributions were consistent with previous observations that the lamina propria is a layered structure with most of the elastin present in the intermediate layer. This layer was larger in geriatric subjects than in adult and pediatric subjects. We observed that the fiber diameter appeared to be larger in geriatric subjects (this observation is currently being verified with electron microscopy) whereas smaller, spiraled fibers appeared in pediatric subjects.

Actin Cytoskeleton↗
PubMed1998

Apoptosis-specific protein (ASP) identified in apoptotic Xenopus thymus tumor cells.

A novel apoptosis-specific protein (ASP) has recently been identified in the cytoplasm of apoptotic mammalian cells. This paper investigates whether ASP is found in Xenopus thymus tumor-derived lymphoid cell lines undergoing apoptosis and also in apoptotic, nontransformed splenocytes. Cultured Xenopus tumor lymphoid cells induced to undergo apoptosis by serum deprivation or treatment with the calcium ionophore, ionomycin, displayed altered morphology typical of apoptotic cells, as judged by flow cytometric light-scatter characteristics and by fluorescence microscopy of acridine-orange-stained cells. Flow cytometry of permeabilized cells and fluorescence microscopy of acetone-fixed cytospins revealed that apoptotic Xenopus tumor cells, especially those displaying loss or condensation of DNA, displayed increased expression of epitopes recognized by a rabbit polyclonal antibody against ASP. Flow cytometry confirmed that ASP is also expressed in splenocytes induced to apoptose by culture in ionomycin or following concanavalin A stimulation. No increased expression of ASP was seen when lymphoid tumor cells or splenocytes were induced into necrosis by overdose with the antifungal agent amphotericin B. Western blotting with antibody against ASP identified the emergence of several protein bands in cell lysates from apoptotic, but not necrotic, Xenopus tumor cells. The new and simple methodology for identifying apoptotic cells described here is likely to be of value to those studying immune system development and associated programmed cell death in Xenopus.

Amphotericin B↗
PubMed1998

Analysis of cellular location and concentration in vocal fold lamina propria.

Studies have shown that the lamina propria plays an important role in voice production. Recent studies have analyzed the presence of different proteins and quantified their extent in the lamina propria, but no similar study has yet been done on cellular makeup. The distribution of three different cell types in the lamina propria of 22 human vocal folds was studied. These types are fibroblasts, macrophages, and myofibroblasts. The roles of these cells in the extracellular matrix are described. Their distribution was quantified with use of an image-analysis system. We arbitrarily divided the lamina propria into five sections (each representing 20% of the lamina propria) and compared cell numbers among these sections. Gender comparisons were also made. From these studies it is evident that the cellular distribution in the lamina propria is not uniform. Fibroblasts were more abundant in the deepest 20% of the lamina propria (p < 0.008), myofibroblasts were more abundant in the most superficial 20% (p < 0.016), and in the 36% of our samples that contained macrophages in the lamina propria, there was a significantly higher number of macrophages in the first 20% of the lamina propria (p < 0.003). The only significant gender difference was that women had twice as many macrophages in the most superficial 20% of the lamina propria as men (p < 0.05). The higher myofibroblast activity in the first 20% could indicate that the superficial layer is a region of constant repair. The increased number of macrophages in the superficial layer likely indicates an inflammatory response to inhalants (because of the role of macrophages in the inflammatory response and the fact that only 36% of the patients showed any macrophage activity at all).

Actins↗
PubMed1997

Resting and stimulated states in functional imaging studies: evidence of differences in attentional and intentional set.

In a [99mTc]-hexamethylpropyleneamine oxime single photon emission computed tomography study of cerebral blood flow (CBF) in a visual activation paradigm (awake, eyes closed versus eyes open viewing a reversing checkerboard pattern), the authors systematically measured previously observed qualitative alterations in frontal blood flow associated with visual stimulation (experiment 1). They confirmed a trend toward reductions in CBF throughout precentral cortex that approached significance in areas 9 and 46, in conjunction with significant increases in CBF in postcentral cortices, including visual association area PO, and areas 3-1-2, 22, and 23. The authors posited that these changes may be related to differences in attentional and intentional state in the eyes-closed and eyes-open conditions. Such differences should be associated with alterations in motor preparedness, leading to changes in response times and to alterations in thalamocortical gating of somatosensory information, which in turn lead to changes in somatosensory-evoked potential amplitudes. In experiment 2, the authors measured simple motor response times to a 1500-Hz tone stimulus and early components of somatosensory-evoked potentials under the same experimental conditions. In the visual stimulation condition, there was a significant increase in the evoked potential amplitude (t = 2.686, p = 0.021), and a significant decrease in response time (t = -2.464, p = 0.031). These observations provided tentative support for their hypothesis. The authors also demonstrated the major effect of normalization assumptions on regional blood flow measurements.

Adolescent↗
PubMed1996

Immunocytochemical study of proteoglycans in vocal folds.

We evaluated the proteoglycan composition of normal vocal folds using immunocytochemical techniques. Frozen sections of 14 normal cadaveric vocal folds were obtained within 12 hours of death and sectioned immediately. Vocal fold sections were stained with antibodies against keratan sulfate, chondroitin sulfate, heparan sulfate proteoglycan (HSPG), decorin, and hyaluronate receptor. We found that the lamina propria has diffuse staining of fibrillar components with keratan sulfate and decorin. Intense staining was observed in the vocal ligament area with keratan sulfate. The HSPG was localized to be basement membrane zone. Chondroitin sulfate, HSPG, and hyaluronate receptor were detected in the cytoplasm of interstitial cells with immunocytochemical characteristics of macrophages. The keratan sulfate distribution suggests that fibromodulin may be significant in normal vocal folds. Production of HSPG and probably versican occurs in macrophages and fibroblasts in the lamina propria.

Chondroitin Sulfate Proteoglycans↗
PubMed1995

Cardiac beta-adrenergic neuroeffector systems in acute myocardial dysfunction related to brain injury. Evidence for catecholamine-mediated myocardial damage.

BACKGROUND: Ten percent to 20% of potential cardiac donors with brain injury and no previous cardiac history have myocardial dysfunction. We assessed components of the beta-receptor-G-protein-adenylyl cyclase complex as well as the contractile response in 10 explanted acutely failing human hearts (donor heart dysfunction [DHD]) and compared the results with 13 age-matched nonfailing (NF) organ donor controls. METHODS AND RESULTS: As measured by echocardiography, all DHD hearts exhibited a decreased shortening fraction (16 +/- 2%, mean +/- SEM). Although total and subpopulation beta-receptor densities measured by [125I]iodocyanopindolol (ICYP) were similar in the DHD and NF groups, DHD hearts exhibited a 30% decrease in maximum isoproterenol-stimulated adenylyl cyclase activity and a 50% decrease in the maximal response to zinterol. DHD hearts also exhibited decreases in adenylyl cyclase maximal stimulation by forskolin (211 +/- 25 [DHD] versus 295 +/- 23 [NF] pmol cAMP.min-1.mg-1, P < .05) and 5'-guanylylimidodiphosphate (12.5 +/- 1.8 [DHD] versus 19.6 +/- 3.2 [NF] pmol cAMP.min-1.mg-1, P < .05), but there was no significant decrease in adenylyl cyclase stimulation by Mn2+, a direct activator of adenylyl cyclase. Right ventricular trabeculae removed from DHD hearts exhibited a profound decrease in the contractile response to isoproterenol (8.7 +/- 1 [DHD] versus 22 +/- 2 [NF] mN, P < .001) as well as reduced calcium responses (7.2 +/- 1.6 [DHD] versus 14 +/- 3 [NF] mN, P = .03). Morphological examination of two hearts revealed some ultrastructural evidence suggestive of catecholamine-mediated injury, but there was no difference in tissue creatine kinase activity between the two groups. CONCLUSIONS: Compared with NF hearts, DHD hearts exhibit marked uncoupling of beta 1- and beta 2-adrenergic receptors from adenylyl cyclase and contractile response stimulation as well as decreased intrinsic systolic function. Thus, acute myocardial dysfunction accompanying brain injury is characterized by marked alterations in beta-adrenergic signal transduction as well as changes in the contractile apparatus, and this profile is markedly different from what occurs in the chronically failing human heart.

Adenylyl Cyclases↗