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Biomedical subjects

T F Beals

Publications and source records attributed to T F Beals.

At least 19 recordsLinked to original sources
PubMed2001

Histology of herniations through the body wall and cuticle of zooplankton from the Laurentian Great Lakes.

Zooplankton of the Laurentian Great Lakes developed hernial protrusions whose gross appearance matches those on zooplankton described elsewhere in the world. We have carried out a histologic and cytologic analysis of the protrusions and found that they are composed of apparently degenerating or necrotic tissue(s) that has been expressed from the organism through the process of herniation. At their base the protrusions are continuous with viable tissue(s) within the organism through a fissure in the exoskeleton. Our observations lead us to suspect that these hernial protrusions are lethal. The development of such protrusions in zooplankton may be a worldwide phenomenon, but the cause of the herniation remains a mystery.

Animals↗
PubMed2001

Primary diagnosis of whipple disease manifesting as lymphadenopathy: use of polymerase chain reaction for detection of Tropheryma whippelii.

Whipple disease is a rare, chronic multisystem disease associated with the recently characterized organism Tropheryma whippelii. Extraintestinal manifestation involving the central nervous system, heart, and joints occasionally occurs. Involvement of the abdominal lymph nodes, especially the mesenteric and periaortic nodes, is not uncommon. However, peripheral lymphadenopathy as the sole clinical manifestation of Whipple disease is rare. We describe 2 patients with Whipple disease whose initial manifestation was lymphadenopathy. Lymph nodes from both patients showed infiltration of the sinuses by macrophages containing periodic acid-Schiff-positive, diastase-resistant, sickle-like structures. Electron microscopic evaluation confirmed the presence of rod-like organisms. DNA from each sample was amplified by the polymerase chain reaction using a specific set of oligonucleotide primers developed against the 16S ribosomal RNA coding sequence of T. whippelii. The histopathologic features and differential diagnosis of lipogranulomatous lymphadenopathy secondary to Whipple disease, as well as use of molecular-based assays, are discussed.

Actinobacteria↗
PubMed1999

Predictive markers for response to chemotherapy, organ preservation, and survival in patients with advanced laryngeal carcinoma.

OBJECTIVE: A systematic retrospective study of the largest randomized trial of induction chemotherapy and radiation for advanced laryngeal cancer was undertaken to determine whether specific tumor or biologic factors were predictive of chemotherapy response, organ preservation, or survival. METHODS: The variables analyzed included clinical and histologic factors, immunohistochemical expression of proliferating cell nuclear antigen and p53, and adjusted DNA index measurements. Variables were evaluated for correlation with outcomes of tumor response, organ preservation, and survival. RESULTS: Multivariate analysis revealed that the best predictor of complete response to induction chemotherapy was low T class. The full multivariate model for predicting larynx preservation in patients treated with induction chemotherapy plus radiation shows that T class, p53 overexpression, and elevated proliferating cell nuclear antigen index were independent predictors of successful organ preservation. CONCLUSIONS: These predictive markers should be included in future clinical trials of advanced laryngeal cancer to determine their usefulness prospectively.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Lung lymphocyte elimination by apoptosis in the murine response to intratracheal particulate antigen.

Pulmonary immune responses are suited to determine mechanisms of lymphocyte elimination, as lung inflammation must be regulated tightly to preserve gas exchange. The self-terminating response of primed C57BL/6 mice to intratracheal challenge with the T cell-dependent Ag sheep erythrocytes (SRBC) was used to test the importance of lung lymphocyte apoptosis in pulmonary immunoregulation. Apoptosis of alveolar and interstitial lymphocytes was demonstrated morphologically, by three independent methods to detect DNA fragmentation, and by surface expression of phosphatidylserine. Apoptotic lymphocytes were exclusively CD4-, CD8-, B220-, but many were CD3+ and Thy 1+. Inhibiting apoptosis by in vivo cyclosporine treatment prolonged lung lymphocyte accumulation following SRBC challenge. Experiments using mice homozygous for the lpr or gld mutations showed that pulmonary lymphocyte apoptosis depended on expression of Fas (CD95) and its ligand (Fas-L). Pulmonary inflammation increased on repeated intratracheal SRBC challenge of lpr/lpr mice, in contrast to the waning response in normal mice. These results confirm that in situ lymphocyte apoptosis contributes to termination of immune responses in nonlymphoid organs, probably because of activation-induced cell death, and may be important in inducing tolerance to repeated antigen exposure.

Animals↗
PubMed1997

p53 mutation as a prognostic marker in advanced laryngeal carcinoma. Department of Veterans Affairs Laryngeal Cancer Cooperative Study Group.

OBJECTIVE: To determine the relationship of p53 mutations in advanced laryngeal carcinomas to p53 immunohistochemistry, organ preservation, and patient survival. DESIGN: Paraffin-embedded tumor specimens were obtained from patients enrolled in the Department of Veterans Affairs Laryngeal Cancer Cooperative Study, a multi-institutional randomized clinical trial comparing induction chemotherapy (cisplatin and fluorouracil) plus radiation therapy surgery plus postoperative radiation therapy. Tumor specimens were analyzed for p53 mutations in exons 5 through 8 by using single-strand conformational polymorphism (SSCP) analysis followed by DNA sequencing of all variants. Five-year follow-up data were available for all patients studied. SUBJECTS: Forty-four patients enrolled in the Department of Veterans Affairs Laryngeal Cancer Cooperative Study from whom paraffin-embedded tumor specimens were readily available. RESULTS: p53 immunostaining did not correlate with p53 SSCP and DNA sequencing results. More than half (62% [16/26]) of the tumors that overexpressed p53 immunohistochemically did not have a detectable p53 gene mutation. Similarly, 39% (7/18) of tumors that did not overexpress p53 did have a p53 gene mutation. p53 mutations were present in 39% of tumors tested. Mutations within exon 5 made up 41% of p53 gene mutations in laryngeal carcinomas. Transitions were the most common type of mutation in this study (92% of mutations). CONCLUSIONS: The presence of a p53 mutation as detected by SSCP is associated with decreased patient survival. Further study is required to confirm this relationship and to determine whether specific p53 mutations predict organ preservation.

Carcinoma, Squamous Cell↗
PubMed1997

Frequent loss of heterozygosity on chromosome arm 18q in squamous cell carcinomas. Identification of 2 regions of loss--18q11.1-q12.3 and 18q21.1-q23.

OBJECTIVES: To determine the frequency and regions of loss on chromosome arm 18q in uncultured head and neck squamous cell carcinomas. DESIGN: Polymerase chain reaction amplification of DNA extracted from 18 tumor specimens (1 patient had 2 tumors) and blood samples from 17 patients with head and neck squamous cell carcinoma was performed using primers flanking 16 microsatellite repeat polymorphisms spanning most of chromosome 18q. DNA was extracted only from specimens with greater than 70% tumor nuclei. SETTING: Research university. PATIENTS: Seventeen individuals with newly diagnosed head and neck cancer. MAIN OUTCOME MEASURE: Loss of heterozygosity (LOH). RESULTS: There was LOH at more than 1 locus in 52% (9/ 17) of the tumors; 3 tumors had LOH at all informative markers. Four had loss at only 1 locus, raising the total with loss to 12 (75%) of 16. Loss of 18q11.1-q12.3 in 4 tumors without distal loss defines a proximal region of loss. Loss of heterozygosity affecting 18q21.1 in 1 tumor, without proximal loss and LOH for 18q21.1, 18q22, or 18q23 in 9 (52%) of 17 tumors defines a distal region of loss. CONCLUSIONS: Loss of heterozygosity on chromosome arm 18q is not an artifact of in vitro culture. The finding of 18q LOH in 50% to 70% tumors makes 18q an important region for study. Regions 18q11.1-q12.3 and 18q21.1-q23 are common regions of loss, indicating that there may be more than one 18q tumor suppressor gene involved in the genesis and progression of head and neck squamous cell carcinomas.

Carcinoma, Squamous Cell↗
PubMed1997

Identifying genetic changes associated with tumor progression in squamous cell carcinoma.

Tumor behavior is the result of specific genetic changes that alter gene expression. From our cytogenetic studies chromosome 18 loss emerged as a common genetic change in squamous carcinoma cell lines. In this report we summarize data that link loss of 18 to tumor progression and reduced survival, indicating that one or more tumor suppressor gene(s) are located on this chromosome. Tumors grown in vitro were karyotyped either as short-term or permanent cultures. Loss of chromosome 18 was measured by karyotype, decreased frequency of heterozygosity at the DCC locus, and loss of heterozygosity (LOH) for microsatellite repeat polymorphisms (MSRP). Loss of any part of chromosome 18 was observed in approximately 63% of cultured tumors. Primary and secondary tumors from the same individuals sometimes differed in loss of 18 indicating that this genetic change is associated with tumor progression. Heterozygosity for DCC was present in only 3/19 cultured SCC (16%), compared with 68% (11/16) of blood samples from unrelated donors, which is consistent with LOH in roughly one half of the cases. Of 4 informative cases with normal and tumor tissue, LOH was observed in 2. Microsatellite analysis also shows loss of 18q in 55% of fresh tumors. Analysis of tumor tissue and cell lines from the same patient gave identical results. There was an excess of deaths from cancer in the group with 18 loss (20/25) when compared with the group without (5/15). Loss of chromosome 18 appears to be a marker of tumor progression in SCC. It is likely that mutation affecting DCC or another gene on 18 affects tumor growth or spread, leading to more rapid progression and reduced survival.

Carcinoma, Squamous Cell↗
PubMed1995

Modulation of adhesive properties of DEAE-dextran with laminin.

Human squamous epithelial cells produce lower amounts of laminin and fibronectin when cultured on DEAE-dextran than when cultured on gelatin-coated polystyrene (Biotechnol. Bioeng., 33:1235). The epithelial cells also spread much more slowly on DEAE-dextran than they do on gelatin-coated polystyrene. To determine if the low level of matrix production by cells grown on DEAE-dextran contributed to the slowness of cell spreading on this substrate, microcarriers made from DEAE-dextran were treated with exogenous laminin (10 micrograms/cm2 of surface area) and then examined for ability to support cell adhesion. Squamous epithelial cells spread as rapidly on the laminin-treated DEAE-dextran as they did on gelatin-coated polystyrene (much more rapidly than on untreated DEAE-dextran). This indicates 1) that laminin can bind to DEAE-dextran in a fashion that is biologically usable by anchorage-dependent cells, and 2) that when laminin is bound to DEAE-dextran, the failure of squamous epithelial cells to rapidly spread is overcome. These data support the hypothesis that failure of the cells to synthesize an intact extracellular matrix on DEAE-dextran is responsible, at least in part, for the slowness with which cells spread on this substrate.

Adhesives↗
PubMed1994

Neuroblastoma-like neurilemoma.

We report three cases of neurilemoma occurring in the superficial soft tissue of the palm, posterior neck, and flank that closely resembled neuroblastoma by virtue of a predominance of small, round hyperchromatic schwann cells with scant cytoplasm which, in one case formed perivascular rosettes and, in the others, giant rosettes with central collagen cores. Although the diagnosis of neuroblastic tumor was seriously entertained in all cases, the diagnosis of a schwannoma was substantiated by the finding of focal areas of conventional schwannoma and by the typical immunophenotypic profile. All tumors strongly and diffusely expressed S-100 protein but lacked neurofilament protein, protein gene product (PGP), and synaptophysin. Ultrastructurally the cells contained slender cytoplasmic processes invested with basal lamina, but no dense core granules. All were excised conservatively, and none has recurred during the 2, 12, and 27 month follow-up periods.

Abdominal Neoplasms↗
PubMed1994

DNA content and regional metastases in patients with advanced laryngeal squamous carcinoma. Department of Veterans Affairs Laryngeal Study Group.

Abnormal DNA content of cancer cells in a primary tumor is thought to reflect the altered proliferative capacity of that cancer and overall patient prognosis. Recently, increased DNA content has been associated with early tumor recurrence in patients with advanced laryngeal cancer. To determine if DNA content correlates with a tumor's metastatic behavior, 94 previously untreated patients with stage III (n = 54) or stage IV (n = 40) squamous carcinoma of the larynx were prospectively studied. The adjusted DNA index (aDI) of the primary tumor was measured by computerized cytomorphometry, and correlations with regional metastases, number of positive nodes, extracapsular spread, and pattern of relapse were determined. Median follow-up was 35 months. Of 94 patients, 73 underwent neck dissection. Positive nodes were found in 51 patients (70%) and three or more positive nodes were found in 31 patients (42%). High aDI (> .024) was significantly associated with the presence and number of histologically positive nodes (P = .016). Among patients with high aDI, 19 (50%) of 38 had three or more nodes positive compared to 12 (21%) of 56 of those with low aDI. Median aDI levels in patients with three or more nodes were significantly higher than in patients with 1 or 2 nodes (P = .003). Time to recurrence was shorter in patients with high aDI (P = .0078). These findings provide further evidence that increased DNA content is associated with more aggressive laryngeal cancers having high rates of multiple lymph node metastases and worse overall prognosis.

Carcinoma, Squamous Cell↗
PubMed1993

A cellular model of oxidant-mediated neuronal injury.

Oxidants derived from the partial reduction of oxygen are thought to play a significant role in neuronal injury. We present here a cellular model of neuronal injury mediated by hydrogen peroxide (H2O2) using the PC 12 rat pheochromocytoma cell line. The organization of microtubules and microfilaments within neurites of PC 12 cells differentiated by exposure to nerve growth factor was examined after H2O2 injury using fluorescence microscopy. Concentrations of H2O2 as low as 100 microM produced an initial periodic pattern of microtubule depolymerization over 3-4 h which later progressed to complete depolymerization. Neuritic microspikes containing actin filaments were relatively more resistant to injury by H2O2 than microtubules. Blebbing of PC 12 cell bodies and neurites also was seen after H2O2 injury and the blebs appeared to contain microtubules. The destructive changes affecting neuritic structure preceded but were not essential for PC 12 cell lysis. Exposure of the cells to the Ca2+ ionophore, ionomycin (25 microM) also produced the same pattern of microtubule depolymerization in PC 12 neurites as was seen after H2O2 injury suggesting that H2O2 may mediate its destructive effect on the neurites via elevation of intracellular Ca2+.

Actin Cytoskeleton↗
PubMed1993

ATP depletion induces an increase in the assembly of a labile pool of polymerized actin in endothelial cells.

Depletion of cellular ATP is associated with profound effects on the cytoskeleton, particularly disruption of microfilaments. We examined this process in bovine pulmonary artery endothelial cells by inducing differential reductions of cellular ATP using mitochondrial inhibition and variable amounts of glucose. Reduction of cellular ATP to levels < 40% of control produced discrete stages in the visible disruption of microfilaments. Using the deoxyribonuclease I assay, a reversible 11% decrease in monomeric (G) actin occurred in conjunction with microfilament disruption. Polyacrylamide gel electrophoretic (PAGE) analysis of the detergent-insoluble cytoskeleton did not reveal any differences in actin content between normal or ATP-depleted cells. Image analysis of adherent endothelial cells that had been fixed and stained with N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)-phallacidin revealed that an increase of F-actin of approximately 20% occurred in cells depleted of ATP. If the cells were lysed with detergent before fixation, the increase in F-actin was lost. PAGE analysis and electron microscopy of detergent-soluble material from the cells obtained by ultracentrifugation directly demonstrated the presence of a labile pool of F-actin within the cells, which increased with ATP loss. These observations suggest that ATP may play an important role in the organization and remodeling of microfilaments within cells.

Actin Cytoskeleton↗
PubMed1992

Scanning electron microscopy of body fluids.

Scanning Electron Microscopic (SEM) examination of body fluid specimens submitted for cytopathological diagnosis is technically easy and can be accomplished within hours. Specimens refrigerated for as long as 72 hr show no significant structural alterations that would interfere with recognition of diagnostically significant cells. SEM is particularly well suited for these specimens because the cells are free floating, and even cells in clusters have "natural" surfaces. Clinical uses of SEM on body fluids include the identification of ambiguous cells, distinction of reactive (benign) mesothelial cells from metastatic adenocarcinoma, and distinction of lymphoid cells from small cell carcinoma of the lung. In addition, SEM of these fluids assists cytologists to better understand the cellular features and associations seen in the light microscope. Ultrastructural analysis can be an important component of the Quality Assurance Plan for those cytodiagnostic laboratories that have access to an electron microscopy facility.

Body Fluids↗
PubMed1991

Actin polymerization in cellular oxidant injury.

Microfilaments undergo an ATP-dependent disruption into shortened bundles following cellular exposure to oxidants. This phenomenon does not require a net change in the amount of polymerized actin. However, increased amounts of polymerized actin have been detected in oxidant-injured cells and it was the purpose of this study to determine the conditions under which the actin polymerization may occur. Utilizing the formation of oxidized glutathione (GSSG) as an indicator of cellular sulfhydryl oxidation, conditions were chosen to accentuate sulfhydryl oxidation within the target P388D1 cell line following exposure to the oxidants, H2O2 and diamide. Using the DNase I and flow cytometric assays of actin polymerization, significant polymerization of actin was detected only under conditions in which sulfhydryl oxidation occurred after exposure to the two oxidizing agents. Greater sulfhydryl oxidation early in the course of injury was associated with a greater rate and extent of actin polymerization in the injured cells. Experiments with cells depleted of glutathione (GSH) demonstrated that neither loss of GSH nor absolute levels of GSSG formed during oxidant exposure were responsible for the polymerization of actin. The data presented are consistent with the hypothesis that oxidizing conditions which induce significant sulfhydryl oxidation in target cells are correlated with assembly of polymerized actin and that this represents a process which is distinct and separate from the ATP-dependent gross disruption of microfilaments.

Actins↗
PubMed1991

Marijuana exposure and pulmonary alterations in primates.

As part of a large multidisciplinary study, we examined lungs from 24 periadolescent male rhesus monkeys that were sacrificed seven months after daily marijuana smoke inhalation of 12 months duration. Animals were divided into four exposure groups: A) high-dose (one marijuana cigarette 7 days/week), B) low-dose (one marijuana cigarette 2 days/week and sham smoke 5 days/week), C) placebo (one extracted marijuana cigarette 7 days/week), and D) sham (sham smoke 7 days/week). Lungs, removed intact, were formalin inflated, sectioned and examined. Several pathological alterations, including alveolitis, alveolar cell hyperplasia and granulomatous inflammation, were found with higher frequency in all cigarette-smoking groups. Other alterations, such as bronchiolitis, bronchiolar squamous metaplasia and interstitial fibrosis, were found most frequently in the marijuana-smoking groups. Alveolar cell hyperplasia with focal atypia was seen only in the marijuana-smoking animals. These changes represent mostly early alterations of small airways. Additional follow-up studies are needed to determine their long-term prognostic significance.

Animals↗