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D Bassett

Publications and source records attributed to D Bassett.

At least 19 recordsLinked to original sources

Novel membrane-bound GM-CSF vaccines for the treatment of cancer: generation and evaluation of mbGM-CSF mouse B16F10 melanoma cell vaccine.

Cancer vaccines composed of tumor cells engineered to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF) are currently being clinically evaluated. To enhance the immunogenicity of GM-CSF-secreting tumor cell vaccines, a novel approach expressing GM-CSF as a membrane-bound form (mbGM-CSF) on the tumor cell surface was investigated. The intent was to enhance antigen presentation by increasing interactions between the tumor cell lines in the vaccine and GM-CSF receptor positive antigen presenting cells (APC), notably the patient's Langerhans cells residing within the intradermal injection site. B16.F10 cells engineered to express either membrane-bound or secreted GM-CSF were compared in the B16.F10 mouse melanoma model. We observed that mbGM-CSF on the tumor cell surface retarded growth and induced protective immunity to subsequent wild-type tumor challenge more effectively than tumor cells secreting GM-CSF. Vaccination with irradiated mbGM-CSF B16.F10 also provided strong protection from wild-type tumor challenge, improved therapeutic effects against established tumors, and retarded lung metastases. These results demonstrate that mbGM-CSF B16.F10 cells can induce strong systemic immunity that protects against and therapeutically treats B16.F10 melanoma more effectively than analogous vaccines containing only secreted GM-CSF. These data warrant further development and clinical testing of mbGM-CSF tumor cell vaccines.

Animals↗

Inflammatory cell availability affects ozone-induced lung damage.

Identifying whether or not neutrophils have a role to play in the early stages of acute lung epithelial injury brought about by inhalation of reactive substances continues to be a major area of investigation. In this study, the availability of circulating neutrophils was manipulated by treatment with either cyclophosphamide or rabbit antiserum against rat neutrophils, prior to exposures to air, a single high ozone exposure of 1 or 2 ppm for 3 h, or a continuous exposure to 0.8-1.0 ppm for up to 48 h. Although cyclophosphamide treatment resulted in undetectable levels of neutrophils in the blood, the recovery of tissue marginated-interstitial neutrophils of 1 x 10(6) cells by collagenase tissue digestion was not significantly diminished at the onset of air and ozone exposures. Cyclophosphamide treatment alone did not cause any permeability damage to air-exposed rat lungs, but did ameliorate ozone-induced increases in bronchoalveolar lavage (BAL) neutrophil and albumin recoveries after both short-term and 1 d of continuous ozone exposure. In contrast to cyclophosphamide, antiserum treatment resulted in greater than a 90% decrease in neutrophil recoveries from both blood and lung tissue at the onset of air and ozone exposures. Antiserum treatment also abrogated ozone-induced neutrophil accumulations in lung lavageable spaces following both single and continuous ozone exposures, but did not significantly affect ozone-associated lung permeability damage indicated by unaltered BAL fluid albumin recoveries. These data demonstrated that under experimental conditions when neutrophils remain within lung tissue marginated and interstitial pools, reduction in circulating blood neutrophil availability is associated with a concomitant decrease in ozone-induced lung damage.

Animals↗

Fish are rising.

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Animals↗

XREFdb: cross-referencing the genetics and genes of mammals and model organisms.

XREFdb supports the investigation of protein function in the context of information available through work in multiple organisms. In addition to facilitating the association of functional data among known genes from multiple organisms, XREFdb has developed strategies that provide access to information associated with as-yet unstudied genes. The database organizes protein similarity and genetic map positional information from diverse sources in the public domain to facilitate investigator evaluation of potential functional significance. XREFdb is found at URL www.ncbi.nlm.nih.gov/XREFdb

Animals↗

Detecting patterns of protein distribution and gene expression in silico.

Most biological information is contained within gene and genome sequences. However, current methods for analyzing these data are limited primarily to the prediction of coding regions and identification of sequence similarities. We have developed a computer algorithm, CoSMoS (for context sensitive motif searches), which adds context sensitivity to sequence motif searches. CoSMoS was challenged to identify genes encoding peroxisome-associated and oleate-induced genes in the yeast Saccharomyces cerevisiae. Specifically, we searched for genes capable of encoding proteins with a type 1 or type 2 peroxisomal targeting signal and for genes containing the oleate-response element, a cis-acting element common to fatty acid-regulated genes. CoSMoS successfully identified 7 of 8 known PTS-containing peroxisomal proteins and 13 of 14 known oleate-regulated genes. More importantly, CoSMoS identified an additional 18 candidate peroxisomal proteins and 300 candidate oleate-regulated genes. Preliminary localization studies suggest that these include at least 10 previously unknown peroxisomal proteins. Phenotypic studies of selected gene disruption mutants suggests that several of these new peroxisomal proteins play roles in growth on fatty acids, one is involved in peroxisome biogenesis and at least two are required for synthesis of lysine, a heretofore unrecognized role for peroxisomes. These results expand our understanding of peroxisome content and function, demonstrate the utility of CoSMoS for context-sensitive motif scanning, and point to the benefits of improved in silico genome analysis.

Gene Expression Regulation, Fungal↗

Establishing acute flaccid paralysis surveillance under difficult circumstances: lessons learned in Cambodia.

The implementation of the World Health Organization's recommended strategies for polio eradication, particularly acute flaccid paralysis (AFP) surveillance, can be limited by difficult circumstances beyond the control of immunization personnel. In Cambodia, however, obstacles to establishing AFP surveillance were rapidly overcome using a strategy that improved reporting through active surveillance in a geographically limited area before gradually expanding to include the whole country. The success of the strategy was ensured by the timely provision of the resources that were needed to establish, expand, and monitor surveillance activities.

Cambodia↗

Definition of the minimal MEN1 candidate area based on a 5-Mb integrated map of proximal 11q13. The European Consortium on Men1, (GENEM 1; Groupe d'Etude des Néoplasies Endocriniennes Multiples de type 1).

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder with a high penetrance characterized by tumors of the parathyroid glands, the endocrine pancreas, and the anterior pituitary. The MEN1 gene, a putative tumor suppressor gene, has been mapped to a 3- to 8-cM region in chromosome 11q13 but it remains elusive as yet. We have combined the efforts and resources from four laboratories to form the European Consortium on MEN1 with the aims of establishing the genetic and the physical maps of 11q13 and of further narrowing the MEN1 region. A 5-Mb integrated map of the region was established by fluorescence in situ hybridization on both metaphase chromosomes and DNA fibers, by hybridization to DNA from somatic cell hybrids containing various parts of human chromosome 11, by long-range restriction mapping, and by characterization of YACs and cosmids. Polymorphic markers were positioned and ordered by physical mapping and genetic linkage in 86 MEN1 families with 452 affected individuals. Two critical recombinants identified in two affected cases placed the MEN1 gene in an approximately 2-Mb region around PYGM, flanked by D11S1883 and D11S449.

Animals↗

Definition of the Minimal MEN1 Candidate Area Based on a 5-Mb Integrated Map of Proximal 11q13

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder with a high penetrance characterized by tumors of the parathyroid glands, the endocrine pancreas, and the anterior pituitary. The MEN1 gene, a putative tumor suppressor gene, has been mapped to a 3- to 8-cM region in chromosome 11q13 but it remains elusive as yet. We have combined the efforts and resources from four laboratories to form the European Consortium on MEN1 with the aims of establishing the genetic and the physical maps of 11q13 and of further narrowing the MEN1 region. A 5-Mb integrated map of the region was established by fluorescence in situ hybridization on both metaphase chromosomes and DNA fibers, by hybridization to DNA from somatic cell hybrids containing various parts of human chromosome 11, by long-range restriction mapping, and by characterization of YACs and cosmids. Polymorphic markers were positioned and ordered by physical mapping and genetic linkage in 86 MEN1 families with 452 affected individuals. Two critical recombinants identified in two affected cases placed the MEN1 gene in an approximately 2-Mb region around PYGM, flanked by D11S1883 and D11S449.

Journal Article↗

Reduced cholesteryl ester transfer in plasma of patients with lipoprotein lipase deficiency.

The net mass transfer of cholesteryl ester (CE) from high density lipoprotein (HDL) to the apolipoprotein (apo) B-containing lipoproteins, very low density lipoprotein (VLDL) and low density lipoprotein (LDL) in plasma (cholesteryl ester transfer (CET)) from three patients lacking lipoprotein lipase (LpL) activity was significantly lower (P < 0.001) than in plasma from fasting control subjects with comparable triglyceride levels. Chylomicrons isolated from LpL-deficient fasting plasma showed the same low level of CET activity as observed in the intact plasma when combined with HDL and cholesteryl ester transfer protein (CETP)-containing d 1.063 g/ml bottom fractions from control subjects. Preincubation of chylomicrons and large triglyceride-rich lipoproteins (Sf > 400) from LpL-deficient plasma with milk LpL, however, stimulated the capacity to engage in CET 4- to 5-fold to the same level as chylomicrons and VLDL from control subjects after a fat load. Consistent with these measurements of CET activity in plasma, chylomicrons obtained from the LpL-deficient subjects after a 14-h fast had higher TG/CE ratios than chylomicrons from controls 3 h after ingesting a fat load (LpL-deficient 26.3 +/- 9.0 vs. controls 6.9 +/- 2.1; mean +/- SD). The mass of CETP did not differ in LpL-deficient and control subjects (LpL-deficient 1.03 +/- 0.22 micrograms/ml vs. controls 1.58 +/- 0.58 micrograms/ml). These studies are consistent with earlier in vitro studies showing that the actions of lipoprotein lipase and its lipolytic products are essential, for maximal cholesteryl ester transfer protein activity.

Cholesterol Esters↗

Inpatient suicide in a general hospital psychiatric unit. A consequence of inadequate resources?

The incidence of suicide and high lethality attempted suicide in the 20-bed inpatient psychiatric unit of a general hospital was reviewed over a 10-year period. Although locating accurate records was difficult, a trend suggestive of increasing incidence was identified. We noted that this observation corresponded with an increase in the number of patients being treated by staff on the ward, reduced length of stay, and an increase in the proportion of severely disordered patients. Although the ward was accepting a greater number of patients, the available facilities (both physical resources and personnel) were not changed until the early results of this study were known (late 1991). We suggest that the clinical demands placed upon a psychiatric facility may affect the incidence of suicide and attempted suicide. This has particular significance in the general hospital setting where resources may be limited by competing requirements from other units and the current trend to close large mental hospitals places more demand upon them.

Australia↗

A simple method for the release of islets by controlled collagenase digestion of the human pancreas.

A simple technique for the controlled collagenase digestion of the human pancreas is described. The pancreas is distended with collagenase, and a biopsy taken and divided into 5 pieces that are placed in Universals containing minimal essential medium and dithizone at 39 degrees C. The pancreas itself is incubated in MEM at 39 degrees C. Starting at 5 min and at intervals thereafter, a Universal is removed from the water bath, shaken for 30 sec, and the contents examined by microscopy. As soon as free cleaved islets are seen, the pancreas is placed into one compartment of a kidney-bowl divided in half by a 1-mm mesh. The pancreas is gently teased apart and fluid digest in the empty half of the bowl aspirated and passed through a 500-micron mesh into ice-cold MEM containing 20% newborn calf serum. This process is repeated until the digestion process has ceased. Using this technique on 20 consecutive pancreata, median wt. (range) 53.9 (45.2-72.9) g, we have counted 131,672 (43,516-400,000) islets in the digest, equivalent to 2394 (715-8000) islets/g pancreas. The volume of islet tissue in the digest was 299 (26-1341) mm3 equivalent to 5.81 (0.36-26.81) mm3/g pancreas. In conclusion, we have found this simple technique to be an effective method for the controlled collagenase digestion of the human pancreas.

Adolescent↗

The influence of hypercholesterolaemia on the adrenal uptake and metabolic handling of 131I-6 beta-iodomethyl-19-norcholesterol (NP-59).

The biodistribution of 131I-6 beta-iodomethyl-19-norcholesterol (NP-59) was assessed in hypercholesterolaemic patients and in a rabbit model of HC to examine the alterations in the relative distribution of NP-59 and its metabolites and to explain the changes in the patterns of adrenal cortical imaging in patients with expanded cholesterol pools. Rabbits were rendered hypercholesterolaemic with a diet supplemented with 2% cholesterol for 2 weeks prior to the intravenous administration of 240 to 570 microCi of NP-59. Adrenal, bile and serum samples were obtained from four hypercholesterolaemic rabbits at 48 h following NP-59 administration, and the distribution of 131I radioactivity was compared to that of seven rabbits maintained on a standard laboratory diet. Serum cholesterol levels were 1940 +/- 248 mg dl-1 in the hypercholesterolaemic rabbits as compared to 268 +/- 62 mg dl-1 in the controls. Adrenal cortical uptake of NP-59 was decreased in HC rabbits but no significant differences were observed in the relative proportions of NP-59 or its metabolites in the bile and adrenal tissues of hypercholesterolaemic versus control animals. Hypercholesterolaemic animals did exhibit an increase in NP-59 esters in serum as compared to controls. In three of five patients with hypercholesterolaemia, adrenal uptake of NP-59 was enhanced after successful lowering of serum cholesterol levels, while the remaining two patients who responded inadequately to cholesterol-lowering therapy showed a slight drop in NP-59 uptake.

19-Iodocholesterol↗

Effects of dietary sodium on body and muscle potassium content during heat acclimation.

It has been suggested that renal conversion of sodium (Na+) during training in hot environments results in potassium (K+) deficiencies. This investigation examined the influence of two levels of dietary Na+ intake (399 vs 98 mmol X d-1) on intramuscular, urinary, sweat, and whole body K+ homeostasis. Nine unacclimated, untrained males underwent heat acclimation during two 8 day dietary-exercise regimens (40.1 +/- 0.1 degrees C, 23.5 +/- 0.4% RH). Both diets resulted in depressed urinary K+ excretion. Sweat K+ and muscle K+ concentrations were not altered by diets or acclimation. The whole body stores of Na+ increased 31.1% (+916.8 mmol) during the high Na+ diet and decreased 7.8% (-230.4 mmol) during the low Na+ diet; whole body stores of K+ increased 4.1% (+137.6 mmol) during the high Na+ diet and increased 3.4% (+113.6 mmol) during the low Na+ diet. This dietary-acclimation protocol did not result in whole-body or intramuscular K+ deficits and offers no evidence to support previous claims that dietary sodium levels affect K+ balance.

Acclimatization↗

The relative importance of rotavirus and other pathogens in the etiology of gastroenteritis in Trinidadian children.

Over a 2-year period, 300 infants less than 3 years old with gastroenteritis admitted to hospitals in Trinidad were investigated for the presence of certain microorganisms in the feces, along with an equal number of age- and sex-matched controls. Rotavirus was detected in 23% of cases and 1% of controls; Salmonella in 7% of cases and in 1% of controls; Shigella in 4% of cases and in no controls and two serotypes of enteropathogenic E. coli in 7% of cases and in 2% of controls. Campylobacter fetus subspecies jejuni was cultured from 7 out of 60 cases and from 1 of 60 controls. Enterotoxigenic E. coli, most strains of enteropathogenic E. coli, cytopathic enteroviruses and adenoviruses and fecal parasites were not significantly associated with diarrhea. Rotaviruses were detected throughout the year but were more prevalent in the dry than in the rainy season. They were found less often in children younger than 6 months than in those aged 6 to 35 months and were present in 6 of the 20 children who died.

Adenoviridae↗

Salmonella in wildlife from Trinidad and Grenada, W.I.

Forty-four of 219 animals from Trinidad and Grenada, W.I., yielded 20 serotypes of Salmonella, 16 of which are known to have been associated with human infection in the United States in recent years. Toads (Bufo marinus) provided the greatest number of isolates. Other carriers were mammals, vultures, lizards, a tree-frog and a cave cockroach.

Animal Population Groups↗

The Mallory-Weiss lesion: a five-year experience.

A retrospective survey has been made of patients with the Mallory-Weiss lesion who presented with upper gastrointestinal tract bleeding during the period 1972 to 1976. The lesion was diagnosed endoscopically in 78 cases, representing 7.7% of the total number of patients admitted with upper gastrointestinal tract bleeding. Patients ranged in age from 18 to 86 years (mean 43 years). The male-female ratio was 3:1. A history of retching and vomiting clearly preceded the bleeding in 60 patients. Significant alcohol intake within 48 hours of bleeding was reported in 53% of patients. Other upper gastrointestinal tract conditions, or migraine, may have induced vomiting in some instances. Previously known Mallory-Weiss lesions were rare (two patients), but 21% of patients had well documented past upper gastrointestinal tract bleeding from other causes. The tears were situated at the cardio-oesophageal junction in 47% of patients and were entirely gastric in 30%; 23% were oesophageal. Blood replacement was required in 31 patients (40%), and 16 of these were transfused with five or more units. Of those patients requiring transfusion, half had other significant pathological lesions. The mean hospital stay was four days and prolonged stay in hospital was usually necessary only in the presence of other disease. In no instance was surgery required primarily to control bleeding from mucosal tears. This study suggests that the Mallory-Weiss lesion is a relatively common cause of upper gastrointestinal tract bleeding, but that it is usually a benign condition, unless it complicates some other disorder.

Adolescent↗