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Biomedical subjects

S Cohen

Publications and source records attributed to S Cohen.

At least 379 records · Page 21Linked to original sources

A treatment need index: a pilot study.

The traditional caries index, DMF, provides inadequate information to assess dental treatment needs of a community. Dental health planners are often called upon to estimate the treatment needs, costs, time and personnel required for a proposed programme. A treatment needs index (TNI) is presented which provides important data for dental health planning. The index defines seven basic levels of treatment: (0) no treatment needed; (1) preventive treatment; (2) fissure sealants; (3) initial conservative restorations; (4) moderate conservative restorations; (5) advanced conservative restorations; and (6) radical treatment, including pulp therapy, prosthetic restorations and extractions. A pilot study and an example comparing data of both DMF and TNI demonstrates the values of the latter index. The Treatment Needs Index provides a more accurate description of caries severity and extent than does the traditional DMF index, and can be used to estimate the time required to treat a community.

Adolescent↗

Inter-relationships between bone mineral content measures. Dual energy radiography (DER) and bitewing radiographs (BWX).

In vitro periodontal alveolar bone mineral content (BMC) measurements obtained with dual-energy radiography (DER) were compared with assessments based on bitewing radiographs (BWX). In addition, in patients, the relationship between bitewing and several postcranial dual-energy-radiographic measures were evaluated. Dual-energy-radiographic and bitewing measurements were made on 2 cadaver mandibles initially and after 2 incremental bone reductions at 4 sites. Rank-order correlations between dual-energy-radiographic and bitewing measures for the 4 sites ranged from 0.7 to 1.00. Bitewing measures indicated true bone loss with a sensitivity of 1.00. For patients, correlations between bitewing measures and dual-energy-radiographic scans suggested the strongest relationships were in the distal sections of the radius and ulna and in the intertrochanteric and Ward's areas of the femur. Correlations, in the 0.5-0.6 range, were not statistically significant (p > 0.05), but were quite robust considering the small sample size and preliminary nature of this investigation. Results suggest that the bitewing measure is sufficiently sensitive to detect clinically meaningful (5% or greater) changes in alveolar BMC and, further, that alveolar bone mineral content may reflect postcranial BMC. The implications of postcranial bone mineral changes being reflected in alveolar bone would enhance both our understanding and treatment of alveolar bone loss. The use of bitewing measures to facilitate identification of patients with postcranial bone loss is discussed.

Absorptiometry, Photon↗

Laryngeal brain stem evoked response in the porcine model.

Exaggeration of normally protective laryngeal reflexes is thought to play a role in several disorders, including the sudden infant death syndrome. An analysis of brain stem neural activity following laryngeal stimulation may provide insight into the pathophysiology of pathologic laryngeal reflexes and help to identify individuals at risk for these disorders. The purpose of this study was to define the far-field brain stem activity following laryngeal stimulation in the porcine model. This activity has been termed the laryngeal brain stem evoked response and may represent a potentially useful and objective measure of the neuronal activity in the laryngeal reflex pathway. Electrical stimulation of the superior laryngeal nerve was performed in 14 mixed-breed piglets under a variety of physiologic conditions. A total of six positive and six negative discrete waves were detected, with mean latencies ranging from 1.24 to 7.16 milliseconds. Stimulations performed during hypoxic, hypercapneic, or hypocapneic conditions resulted in no significant differences in waveform latencies. There appears to be a reproducible, but somewhat variable, brain stem response elicited by superior laryngeal nerve stimulation that can be recorded via a far-field technique in the porcine model.

Animals↗

Correlation between the laryngeal brain stem evoked response and the laryngeal chemoreflex in the porcine model.

The laryngeal brain stem evoked response (LBR) represents the neural activity involved in laryngeal reflex pathways. The laryngeal chemoreflex (LCR) is a centrally mediated response consisting of apnea and hemodynamic changes that result from laryngeal stimulation. The purpose of this study is to determine the characteristics of the LBR that are predictive of LCR severity in the porcine model. The duration of apnea resulting from stimulation of the supraglottic larynx defined LCR severity. The LBR tracings were recorded from electrodes flanking the brain stem following direct electrical stimulation of the superior laryngeal nerve. The LBR peak latencies from piglets demonstrating prolonged LCR apnea were compared to those without an exaggerated LCR response. Two LBR peak latencies demonstrated a statistically significant difference between the two piglet groups. These peak latencies appear to be indicators of susceptibility to exaggerated laryngeal reflex sensitivity. Thus, the LBR may prove useful in identifying and evaluating subjects predisposed to conditions associated with dysfunctional laryngeal reflex activity.

Animals↗

Smoking, alcohol consumption, and susceptibility to the common cold.

OBJECTIVES: This study was conducted to test the supposition that both smoking and consuming alcohol suppress host resistance to viral infections. METHODS: The relations between smoking, alcohol consumption, and the incidence of documented clinical colds were prospectively studied among 391 subjects intentionally exposed to one of five respiratory viruses and 26 subjects given saline. Clinical colds were defined as clinical symptoms verified by the isolation of virus or by an increase in virus-specific antibody titer. Analyses included control variables for demographics; body weight; virus; and environmental, immunological and psychological factors. RESULTS: Smokers were at greater risk for developing colds than nonsmokers because smokers were more likely both to develop infections and to develop illness following infection. Greater numbers of alcoholic drinks (up to three or four per day) were associated with decreased risk for developing colds because drinking was associated with decreased illness following infection. However, the benefits of drinking occurred only among nonsmokers. CONCLUSIONS: Susceptibility to colds was increased by smoking. Although alcohol consumption did not influence risk of clinical illness for smokers, moderate alcohol consumption was associated with decreased risk for nonsmokers.

Adult↗

An audit of thrombolytic therapy in a rural hospital.

OBJECTIVE: To ascertain the complications from the use of streptokinase in a hospital remote from specialist support. DESIGN: A retrospective analysis from record files of patients treated with streptokinase thrombolysis following myocardial infarction. SETTING: Busselton District Hospital, Busselton, Western Australia. METHOD: The medical records of all patients admitted to Busselton District Hospital, from 1986 to 1991 with diagnoses of chest pain, angina or myocardial infarction were studied retrospectively and those admitted in 1992 who were given streptokinase were studied prospectively. RESULTS: Thirty-one patients received streptokinase. Two patients received this treatment twice. The drug was started a median of 30 minutes after arrival in casualty. Four deaths and one case of serious haemorrhage were recorded. CONCLUSION: Thrombolytic therapy is simple to give. Early use of it should be encouraged in isolated hospitals.

Adult↗

Malignancy-induced secondary achalasia.

Secondary achalasia refers to the development of clinical, radiographic, and manometric findings of achalasia as a result of (i.e., secondary to) another underlying disorder. A variety of malignancies have been associated with secondary achalasia. Adenocarcinoma of the esophagogastric junction accounts for the majority of cases of malignancy-induced achalasia, however, noncontiguous tumors may also cause this disorder. Although rare, malignancy-induced achalasia will occasionally be encountered by gastroenterologists and gastrointestinal radiologists who see patients with dysphagia and/or achalasia. Since treatment is aimed at the underlying neoplasm, it is important to recognize this disorder. Three clinical features suggest the possibility of malignancy as a cause of achalasia: 1) short duration of dysphagia (< 1 year); 2) significant weight loss (> 15 pounds); and 3) age > 55 years. The presence of any of these should at least raise a suspicion of malignancy. Diagnosis may not be evident on routine esophagrams and endoscopy, and requires clinical suspicion for further evaluation with thoraco-abdominal CT scanning and endoscopic ultrasonography.

Esophageal Achalasia↗

Epidermal growth factor stimulates tyrosine phosphorylation in the neonatal mouse: association of a M(r) 55,000 substrate with the receptor.

Administration of epidermal growth factor (EGF) to neonatal mice resulted in rapid tyrosine phosphorylation of a number of specific substrates in liver, kidney, lung, bladder, skin, and brain as detected by Western blot analysis of tissue homogenates with anti-phosphotyrosine antibodies. In the liver, three prominent EGF-dependent substrates of M(r) approximately 170,000, 120,000, and 55,000 were detected. A number of less prominent EGF-dependent substrates also were noted. Maximal tyrosine phosphorylation of pp170, pp120, and pp55 occurred within 5 min of subcutaneous injection and the levels of these phosphoproteins remained elevated for at least 45 min. Direct hepatic injection of EGF resulted in the tyrosine phosphorylation of these substrates within 60 sec of treatment. Tyrosine-phosphorylated pp170 was identified as the EGF receptor (EGFR). The tyrosine-phosphorylated pp55 substrate appeared to be associated with EGFR; both pp55 and EGFR were adsorbed to EGF-Affi-Gel, wheat germ lectin-Sepharose, and anti-EGFR antibodies bound to protein A-Sepharose. pp55 was not immunoreactive with anti-EGFR antiserum by Western blot analysis, indicating that it was not a fragment of the receptor. These results were confirmed by repeating the liver experiments using 32P-labeled neonatal mice. Increased amounts of 32P-labeled pp170 and pp55 were detected in anti-EGFR immunoprecipitates from liver extracts of EGF-treated animals as compared with controls. Phospho amino acid analysis of the 32P-labeled phosphoproteins revealed that EGF stimulated both serine and tyrosine phosphorylation in pp55 as well as in EGFR. The neonatal mouse may be a useful model for the study of signal transduction mediated by a variety of growth factors.

Animals↗

Mutagenesis of human acetylcholinesterase. Identification of residues involved in catalytic activity and in polypeptide folding.

Evidence for the involvement of Ser-203, His-447, and Glu-334 in the catalytic triad of human acetylcholinesterase was provided by substitution of these amino acids by alanine residues. Of 20 amino acid positions mutated so far in human acetylcholinesterase (AChE), these three were unique in abolishing detectable enzymatic activity (less than 0.0003 of wild type), yet allowing proper production, folding, and secretion. This is the first biochemical evidence for the involvement of a glutamate in a hydrolase triad (Schrag, J.D., Li, Y., Wu, M., and Cygler, M. (1991) Nature 351, 761-764), supporting the x-ray crystal structure data of the Torpedo californica acetylcholinesterase (Sussman, J.L., Harel, M., Frolow, F., Oefner, C., Goldman, A., Toker, L. and Silman, I. (1991) Science 253, 872-879). Attempts to convert the AChE triad into a Cys-His-Glu or Ser-His-Asp configuration by site-directed mutagenesis did not yield effective AChE activity. Another type of substitution, that of Asp-74 by Gly or Asn, generated an active enzyme with increased resistance to succinylcholine and dibucaine; thus mimicking in an AChE molecule the phenotype of the atypical butyrylcholinesterase natural variant (D70G mutation). Mutations of other carboxylic residues Glu-84, Asp-95, Asp-333, and Asp-349, all conserved among cholinesterases, did not result in detectable alteration in the recombinant AChE, although polypeptide productivity of the D95N mutant was considerably lower. In contrast, complete absence of secreted human AChE polypeptide was observed when Asp-175 or Asp-404 were substituted by Asn. These two aspartates are conserved in the entire cholinesterase/thyroglobulin family and appear to play a role in generating and/or maintaining the folded state of the polypeptide. The x-ray structure of the Torpedo acetylcholinesterase supports this assumption by revealing the participation of these residues in salt bridges between neighboring secondary structure elements.

Acetylcholinesterase↗

Exercise tolerance in panic disorder patients.

Sixteen panic patients and fifteen normal controls performed submaximal exercise testing on a bicycle ergometer. Only one patient subject panicked. Biochemical, physiological, and psychological data showed similar exercise tolerance in both patients and controls. Exercise-induced distress and lactate increment do not appear to cause panic attacks.

Adult↗

Differential long-term effect of AF64A on [3H]ACh synthesis and release in rat hippocampal synaptosomes.

The activities of various presynaptic cholinergic parameters were determined in hippocampal synaptosomes of rats 29 weeks after intracerebroventricular injection of ethylcholine aziridinium (AF64A) (3 nmol/2 microliters/side) or vehicle (saline). Synaptosomes were preloaded with [3H]choline ([3H]Ch), treated with diisopropyl fluorophosphate to inhibit cholinesterase activity and then were assayed for their content of [3H]Ch and [3H]acetylcholine ([3H]ACh) and for their ability to synthesize and release [3H]ACh. In synaptosomes from AF64A-treated rats compared with synaptosomes from vehicle-treated rats we observed that: (i) specific uptake of [3H]Ch was reduced to 60% of control; (ii) residing [3H]ACh levels were 43% of control while residing [3H]Ch levels were 72% of control; (iii) basal and K(+)-induced [3H]ACh release were 77% and 73% of control, respectively; (iv) high K(+)-induced synthesis of [3H]ACh was only 9% of control; (v) but, choline acetyltransferase activity remained relatively high, being 80% of control. These results suggest that AF64A-induced cholinergic hypofunction is expressed by both loss of some cholinergic neurons and impairment in the functioning of the spared neurons.

Acetylcholine↗

Low density lipoprotein inhibits accumulation of nitrites in murine brain endothelial cell cultures.

Endothelial cells produce nitric oxide which is considered to serve as a major source of endothelial derived relaxing factor activity. It has been demonstrated that activation of mouse brain endothelium by TNF-alpha and IFN-gamma led to accumulation of nitrite which is presumably formed by oxidation of nitric oxide. A number of studies suggest that reactive oxygen species produced by cytokine-activated cells are involved in the conversion of nitric oxide to nitrites and nitrates. We investigated whether low density lipoprotein (LDL), acting as a radical scavenger, is able to inhibit nitrite accumulation in mouse brain endothelial cell cultures and in a cell-free system in which sodium nitroprusside was used as a source of nitric oxide. A comparison of these two models indicates the active involvement of LDL in suppressing nitrite accumulation in murine endothelial cultures.

Animals↗

Ultrastructural immunolocalization of rat oxytocin-neurophysin in transgenic mice expressing the rat oxytocin gene.

Cell-specific expression of the rat oxytocin (OT)-neurophysin transgene in mice was achieved using a construct containing both OT and vasopressin genes (Young III, W.S., Reynolds, K., Shepard, E.A., Gainer, H. and Castel, M., Cell-specific expression of the rat oxytocin gene in transgenic mice, J. Neuroendocrinol., 2 (1990) 1-9). The present study describes the distribution of the protein products of these genes in various regions of the cell, and determines whether the transgenic rat and endogenous mouse OT-neurophysins are colocalized within the same neurosecretory granules. Two monoclonal antibodies against OT-neurophysins were used: PS38 which can react with both rat and mouse OT-neurophysin (pan-specific), and PS67 which is specific for rat OT-neurophysin only. Various approaches to double immunolabeling at the ultrastructural level were employed; these included: (1) pre-embedding immunoperoxidase followed by post-embedding immunogold; (2) post-embedding immunolabeling using gold particles of different sizes; and (3) labeling of consecutive ultrathin sections with different antibodies. Results from each of these approaches showed that both in the transgenic mouse and in the rat (used as control), immunocytochemical labeling for both PS38 and PS67 occurred in the same OT-ergic neurosecretory granules. In the control mouse, only PS38 elicited labeling. Hence, it may be concluded that the protein and peptide products of the transgene and the endogenous gene for OT-neurophysin are being processed similarly in the cell and finally concentrated together in the same neurosecretory granules.

Animals↗