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Biomedical subjects

A C Cohen

Publications and source records attributed to A C Cohen.

At least 19 recordsLinked to original sources

Chronic gestational exposure to ethanol causes insulin and IGF resistance and impairs acetylcholine homeostasis in the brain.

In fetal alcohol syndrome (FAS), cerebellar hypoplasia is associated with impaired insulin-stimulated survival signaling. This study characterizes ethanol dose-effects on cerebellar development, expression of genes required for insulin and insulin-like growth factor (IGF) signaling, and the upstream mechanisms and downstream consequences of impaired signaling in relation to acetylcholine (ACh) homeostasis. Pregnant Long Evans rats were fed isocaloric liquid diets containing 0%, 2%, 4.5%, 6.5%, or 9.25% ethanol from gestation day 6. Ethanol caused dose-dependent increases in severity of cerebellar hypoplasia, neuronal loss, proliferation of astrocytes and microglia, and DNA damage. Ethanol also reduced insulin, IGF-I, and IGF-II receptor binding, insulin and IGF-I receptor tyrosine kinase activities, ATP, membrane cholesterol, and choline acetyltransferase (ChAT) expression. In vitro studies linked membrane cholesterol depletion to impaired insulin receptor binding and insulin-stimulated ChAT. In conclusion, cerebellar hypoplasia in FAS is mediated by insulin/IGF resistance with attendant impairments in energy production and ACh homeostasis.

Acetylcholine↗

Influence of antimicrobial agents on the spoilage of a meat-based entomophage diet.

The microbial decomposition of a meat-based entomophage diet presented in Parafilm packets was investigated. Considerable bacteria but not fungi were associated with components used to prepare the diet (i.e., hens' eggs, liver, and ground beef). At the initial sampling time, there were no differences among diet treatments in the size of bacterial or fungal populations. Bacterial populations in diets not containing antibacterial agents rapidly increased and reached an asymptote by 24 h (approximately 10(10) colony-forming units per gram). Bacterial populations also increased in diets containing antibacterial agents, but they were significantly smaller than in diets not containing antibacterial agents. The most prevalent bacteria isolated were Carnobacterium piscicola, Carnobacterium divergens, Lactobacillus curvatus, Lactobacillus sakei, Leuconostoc mesenteroides, and Enterococcus spp., regardless of the antibacterial treatment used. The proliferation of fungi was delayed relative to bacteria, but significant differences were observed among the diet treatments. Fungi were most inhibited by sorbic acid and propionic acid in the absence of antibacterial agents. The most common fungi isolated were the yeasts Candida zeylanoides, Torulaspora globosa, and Yarrowia lipolytica. The pH of diets not containing antibacterial agents decreased rapidly and was highly correlated with increases in bacteria but not fungi. The results of this study demonstrate that antimicrobial agents significantly inhibit spoilage microorganisms in a meat-based diet and that alternative management strategies to delay the decomposition of such diets presented in Parafilm packets should target lactic acid spoilage bacteria, particularly Carnobacterium and Lactobacillus species.

Animals↗

Demonstration of amylase from the zoophytophagous anthocorid Orius insidiosus.

To better understand facultative phytophagy in the zoophytophagous anthocorid, Orius insidiosus, tests for amylase were conducted and the enzyme was partially purified. Three activity bands were detected with polyacrylamide-starch gel electrophoretic analysis of amylase in O. insidiosus. The major amylase was found to have a mean isoelectric point (pI) of 4.53. The presence of amylase indicates the ability of O. insidiosus to use starch, a nutrient, derived from plants, either by direct ingestion or by ingestion of plant material from the digestive system of their prey. The presence of amylase suggests that these predators are more committed to plant feeding than other species of predators that lack this enzyme.

Amylases↗

Partial characterization of alpha-amylase in the salivary glands of Lygus hesperus and L. lineolaris.

The alpha-amylases in the salivary glands of Lygus hesperus Knight and L. lineolaris (Palisot de Beauvois) were isolated and purified by ion exchange chromatography, and by isoelectric focusing, respectively. The alpha-amylase from L. hesperus had an isoelectric point (pI) of 6.25, and a pH optimum of 6.5. The specific activity of alpha-amylases in the salivary glands of L. hesperus was 1.2 U/mg/ml. The alpha-amylase from L. lineolaris had a pI of 6.54, and a pH optimum of 6.5. The specific activity of alpha-amylase from L. lineolaris was 1.7 U/mg/ml. The activity of alpha-amylase in both species was significantly inhibited by alpha-amylase inhibitor from wheat and also by EDTA and SDS. Sodium chloride enhanced alpha-amylase activity for both species. The enzyme characteristics and relative activities are discussed in the context of differences phytophagous versus zoophagous habits in these two congeneric species.

Animals↗

Comparison of alpha-amylase and protease activities of a zoophytophagous and two phytozoophagous Heteroptera.

To better understand the nature of facultative phytophagy in the zoophytophagous Geocoris punctipes (Say), and facultative zoophagy in phytozoophagous Lygus hesperus (Knight) and Lygus lineolaris (Palisot de Beauvois), we compared the activities of both the starch digesting enzyme alpha-amylase and of general proteases in these species. The alpha-amylases and proteases were demonstrated in L. hesperus, L. lineolaris and G. punctipes. The presence of alpha-amylase in the salivary gland complexes of G. punctipes indicates a disposition of this species toward utilization of nutrients that can be derived only from plants, either directly from ingestion of plant macromolecules or from second-hand ingestion of plant material from the digestive system of their prey. The alpha-amylase activity in G. punctipes was much less than those of phytozoophagous L. hesperus and L. lineolaris. The relative importance of amylolytic activity and proteolytic activity is also discussed.

Adaptation, Physiological↗

Crystal structure of botulinum neurotoxin type A and implications for toxicity.

Botulinum neurotoxin type A (BoNT/A) is the potent disease agent in botulism, a potential biological weapon and an effective therapeutic drug for involuntary muscle disorders. The crystal structure of the entire 1,285 amino acid di-chain neurotoxin was determined at 3.3 A resolution. The structure reveals that the translocation domain contains a central pair of alpha-helices 105 A long and a approximately 50 residue loop or belt that wraps around the catalytic domain. This belt partially occludes a large channel leading to a buried, negative active site--a feature that calls for radically different inhibitor design strategies from those currently used. The fold of the translocation domain suggests a mechanism of pore formation different from other toxins. Lastly, the toxin appears as a hybrid of varied structural motifs and suggests a modular assembly of functional subunits to yield pathogenesis.

Binding Sites↗

Osseointegrated implants for single tooth replacement in general practice: a 1-year report from a multicentre prospective study.

The single tooth implant is a treatment option for the replacement of missing single teeth and in many cases is the treatment of choice. It is, however, an expensive treatment requiring a co-ordinated approach to the surgical and restorative aspects of treatment. In this study, a group of dentists in general and restorative dental practice and with no previous experience in implant surgery underwent an intensive training course in all aspects of implant treatment for single teeth. Using a system of simplified instrumentation with a strict adherence to protocol, the group installed and restored single tooth implants ad modum Brånemark in a wide range of clinical situations. At the one year follow-up period following crown insertion, the success rate of treatment compared favourably with results reported from centres using the specialist team approach to treatment. The results of this study indicate that further consideration should be given to the training of general dentists so that improved delivery of dental health care can be provided at a more economic level.

Adolescent↗

Alterations of fluid and electrolyte balance in thoroughbred racehorses following strenuous exercise during training.

Alterations of acid-base status, and fluid and electrolyte balance subsequent to exercise in Thoroughbred racehorses in North America have not been well-characterized. Des-cribed here are the results of an observational study conducted to characterize changes in fluid and electrolytes following strenuous exercise of 16 Thoroughbreds under routine training conditions. Changes following strenuous exercise were determined for the following variables: serum concentrations of sodium (Na), potassium (K), chloride (Cl) and protein; pH of blood; osmolality of plasma and urine; body weight; and, fractional urinary excretion (FE) of Na, K and Cl. The following changes occurred during exercise: increased concentration of Na in blood; increased FE of Na; decreased concentration of Cl in blood; decreased FE of Cl; increased urinary and plasmal osmolality; weight-loss; decreased pH of blood; and, increased concentration of lactic acid. The concurrent decreased concentration of chloride in plasma and acidemia in these horses differed from the hypochloremic, metabolic alkalosis previously described among endurance horses. Acidemia was attributed to production of lactic acid by anaerobic glycolysis.

Acid-Base Equilibrium↗

Low-dose preoperative irradiation, surgery, and elective postoperative radiation therapy for resectable rectum and rectosigmoid carcinoma.

A regimen of low-dose preoperative radiation therapy (RT), surgery, and elective postoperative RT for resectable carcinomas of the rectum and rectosigmoid is presented. Initial results in a group of 36 patients is discussed. In four patients clinically silent metastatic disease was discovered. Of 16 patients without indications for postoperative RT, only one died with disease. Indications for postoperative irradiation were found in 15 patients and four relapses (26%) subsequently occurred. Since the surgicopathologic stage of the tumor is the best prognostic predictor for rectal cancer, this regimen allows for the delivery of high-dose adjuvant irradiation only to those at high risk of local recurrence. Thus, this combination selects patients likely to benefit from postoperative RT while preserving the advantages of preoperative RT.

Female↗

Combined modality treatment of gastric cancer.

In a series of 46 patients with localized gastric cancer treated at Massachusetts General Hospital, problems with excessive acute or chronic toxicity due to combination treatment with irradiation (XRT) and chemotherapy (CT) were not seen. Forty of the 46 received combined treatment with 2 regimens: 1) Irradiation plus concomitant 3 days of 5-FU followed by maintenance 5-FU or combined drugs--26 patients; 2) In the other 14 patients, the sequence of irradiation and chemotherapy was altered. A single course of combined drug chemotherapy was given prior to irradiation and 5-6 additional courses were administered after completion of XRT (CT-XRT-CT). The drug combination was initially 5-FU-BCNU but this was changed to FAM (5-FU, Adriamycin, Mitomycin C). Irradiation was delivered to tightly contoured portals using shaped blocks to spare as much small bowel, kidney and marrow as possible while giving 4500-5200 rad in 25 to 29 fractions over 5 to 6 weeks. In this series, there were no cases of septicemia or any deaths related to treatment. A 3 year survival rate of about 20% was achieved for the total group of patients and 43% in the group with resection but at high risk for later failure. Our inability to improve these numbers is undoubtedly a result of dose limitations with external beam irradiation combined with a systemic failure problem. When irradiation is combined with surgical resection of all or a majority of tumor, both survival and local control appear to be better than in the unresected patient group. Only 4 of 29 patients (14%) with curative resection, or resection but residual disease, had later evidence of failure within the irradiation field as opposed to 6 of 9 or 66% in the group with unresectable disease.

Adenocarcinoma↗

Residual, unresectable, or recurrent colorectal cancer: external beam irradiation and intraoperative electron beam boost +/- resection.

While combinations of external beam radiation (XRT) and surgery decrease pelvic recurrence and improve survival in the subgroups with residual disease (postop XRT) or initially unresectable disease (preop XRT), local recurrence is still unacceptably high, and survival could be improved. In view of this, pilot studies were instituted at Massachusetts General Hospital in which 32 patients received the standard previous treatment of external beam irradiation and surgery but in addition had an intraoperative electron beam boost of 1000-1500 rad to the remaining tumor or tumor bed. For the 16 patients who presented with unresectable primary lesions, the addition of intraoperative radiotherapy has resulted in a total absence of local recurrence with a minimum 20 month follow-up, and survival rates are statistically better than for the previous group treated with only external beam irradiation and surgical resection. In the group with residual disease, again there have not been any local recurrences in the 7 patients who received all treatment modalities versus 54% and 26% for the group with gross and microscopic residual treated with only external beam techniques. The remaining 9 patients presented with recurrent unresectable lesions--3 are alive (2 NED) at greater than or equal to 3 years.

Colonic Neoplasms↗