PubMed Health⌕ Search

Biomedical subjects

D Dexter

Publications and source records attributed to D Dexter.

36 records · Page 2Linked to original sources
PubMed1990

Subcellular distribution and characterization of GTP-binding proteins in human neutrophils.

The subcellular distribution of GTP binding proteins in human neutrophils and their functional coupling to the N-formylmethionylleucylphenylalanine (FMLP) receptor was characterized to provide insight into mechanisms of cellular activation. Human neutrophils were nitrogen cavitated and fractionated on discontinuous Percoll gradients. Four subcellular fractions were obtained: cytosol, light membranes enriched for plasma membranes, specific granules and azurophilic granules. ADP-ribosylation catalyzed by pertussis toxin (PT) revealed a major substrate of 40 kDa only in plasma membrane and cytosol, and antiserum specific for Gi alpha confirmed the presence of neutrophil Gi alpha in plasma membrane and cytosol and its absence from specific granules. The cytosolic PT substrate was shown to be mostly in monomeric form by molecular sieve chromatography. The rate of the ribosyltransferase reaction was several-fold lower in cytosol compared to plasma membranes, and the extent of ADP-ribosylation was greatly augmented by supplementation with beta gamma subunits in cytosol. ADP-ribosylation catalyzed by cholera toxin (CT) revealed substrates of 52, 43 and 40 kDa in plasma membrane alone. FMLP receptors in plasma membrane were shown to be coupled to the 40 kDa substrate for CT by ligand-modulation of ADP-ribosylation, while FMLP added to specific granules did not induce ribosylation of this substrate even though FMLP receptors were found in high density in this compartment. Both 24 and 26 kDa [32P]GTP binding proteins were found to codistribute with FMLP receptors in specific granules and plasma membranes. Functional evidence for the coupling of GTP binding proteins to the FMLP receptor in specific granules was obtained by modulating [3H]FMLP binding with GTP gamma S, and by accelerating [35S]GTP gamma S binding with FMLP.

Cell Membrane↗
PubMed1990

Mitochondrial complex I deficiency in Parkinson's disease.

The structure and function of mitochondrial respiratory-chain enzyme proteins were studied postmortem in the substantia nigra of nine patients with Parkinson's disease and nine matched controls. Total protein and mitochondrial mass were similar in the two groups. NADH-ubiquinone reductase (Complex I) and NADH cytochrome c reductase activities were significantly reduced, whereas succinate cytochrome c reductase activity was normal. These results indicated a specific defect of Complex I activity in the substantia nigra of patients with Parkinson's disease. This biochemical defect is the same as that produced in animal models of parkinsonism by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and adds further support to the proposition that Parkinson's disease may be due to an environmental toxin with action(s) similar to those of MPTP.

Electron Transport Complex II↗
PubMed1990

Anatomic and disease specificity of NADH CoQ1 reductase (complex I) deficiency in Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is thought to produce parkinsonism in humans and other primates through its inhibition of complex I. The recent discovery of mitochondrial complex I deficiency in the substantia nigra of patients with Parkinson's disease has provided a remarkable link between the idiopathic disease and the action of the neurotoxin MPTP. This article shows that complex I deficiency in Parkinson's disease is anatomically specific for the substantia nigra, and is not present in another neurodegenerative disorder involving the substantia nigra. Evidence is also provided to show that there is no correlation between L-3,4-dihydroxyphenylalanine therapy and complex I deficiency. These results suggest that complex I deficiency may be the underlying cause of dopaminergic cell death in Parkinson's disease.

Citrate (si)-Synthase↗
PubMed1989

A selective increase in particulate superoxide dismutase activity in parkinsonian substantia nigra.

The total activity of superoxide dismutase (SOD) and cytosolic and particulate activity of SOD in human substantia nigra and cerebellum were measured by a spectrophotometric method based on the ability of SOD to inhibit the autoxidation of adrenaline. The cytosolic and particulate isoenzymes of SOD were differentiated by the inclusion of potassium cyanide which selectively inhibits cytosolic copper/zinc-dependent SOD activity. In autopsied human brains, there was no difference in total SOD activity, or the activity of SOD in cytosol in substantia nigra of patients dying with Parkinson's disease compared to age-matched controls. However, the activity of the particulate form of SOD was higher in the parkinsonian substantia nigra compared to control tissue. In the cerebellum there was no difference in the total, cytosolic, or particulate activity of SOD between parkinsonian patients and age-matched controls. Increased activity of SOD in particulate fraction may be a protective response to elevated levels of toxic free radicals in the parkinsonian substantia nigra. Alternatively, increased SOD activity may induce cell death through the accumulation of hydrogen peroxide.

Aged↗
PubMed1988

Smokeless tobacco use and attitudes toward smokeless tobacco among Native Americans and other adolescents in the northwest.

A survey of 1,180 sixth, ninth, and eleventh graders in three school districts in the State of Washington found that 34 per cent of male Native Americans, 24 per cent of female Native Americans, 20 per cent of male non-natives and 4 per cent of female non-natives are current users of smokeless tobacco products. In all areas and groups, the best predictor of whether an adolescent is a user is the use pattern of friends.

Adolescent↗
PubMed1987

Isolation and characterization of an undifferentiated human colon carcinoma cell line (MIP-101).

An undifferentiated human colon carcinoma cell line was established from tumor tissue obtained from metastasis to the liver of colonic adenocarcinoma in a patient with fulminant Dukes D colorectal carcinoma. Histological analysis of the tumor biopsy from the liver confirmed the hospital pathology report of poorly differentiated colonic adenocarcinoma. Explants of this tumor tissue xenografted into a nude mouse were used to establish an epithelioid-like cell culture line, MIP-101. The cell line formed tumors in nude mice that histologically appeared undifferentiated and did not stain for carcinoembryonic antigen (CEA). No CEA was present either by radioimmunoassay (RIA) of the culture supernatant or by immunoperoxidase staining of the tumors or monolayers. MIP-101 appears to be one of the most undifferentiated human colon carcinoma cells lines available. It should prove useful in the search for markers of undifferentiated colonic cancer and in studies of colonic cancer differentiation.

Adenocarcinoma↗
PubMed1985

Spontaneous and induced primary oncogenesis in natural killer (NK)-cell-deficient beige mutant mice.

Spontaneous tumor development and primary oncogenesis were compared in a large number of NK4-deficient, homozygous C57Bl/6-bg/bg mice and their NK normal, heterozygous +/bg littermate controls. In a group of 167 retired breeders followed for spontaneous tumors, the probability of survival for mice eventually dying with a tumor was greater for the NK-competent, +/bg than for the NK-deficient, homozygous C57BL/6-bg/bg mice (p = 0.0019), although the higher overall incidence of tumors in the bg/bg group (48%) was not significantly different from that in the +/bg group (37%). In the bg/bg group the incidence of tumor death appeared to increase relatively sharply in the 25- to 29-month age bracket compared to the fairly regular increase in incidence observed in the +/bg group. All the spontaneous tumors except 2 (discovered in +/bg mice) were classified histologically as widely disseminated malignant lymphomas. The other two were one squamous-cell carcinoma and one sarcoma. A total of 73 bg/bg mice injected s.c. with benzo[alpha]pyrene (BP) had a higher overall incidence of tumors (81%) (rhabdomyosarcomas) than 138 +/bg mice (64%) and in the largest group (0.3 mg, n = 85) the bg/bg group developed tumors, at a higher incidence (p = 0.01) and with a shorter latency (p = 0.025) than the +/bg group. On the other hand, mice injected with dimethylbenzanthracene or given 4 weekly doses of 160 rads of gamma irradiation showed no difference in overall tumor incidence. In addition, mice injected with various doses of DMBA-induced murine leukemia virus (DMBA-LV) also showed no significant difference in tumor incidence. Others have reported that some of these treatments (DMBA, split-dose irradiation) cause profound NK suppression, thereby reducing NK differences between the two groups of mice. These results suggest that a partial NK impairment in beige mutant mice early in life may lead to significantly greater rates of death with spontaneous malignant tumors late in life. Some primary oncogenesis treatments (BP) but not others (DMBA, split-dose irradiation, leukemia viruses) cause tumors with a greater incidence and shorter latency in beige mice. The results suggest, but do not prove, that NK cells play a role in surveillance against spontaneously arising, and possibly some types of carcinogen-induced, tumors.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1984

A model of human cancer metastasis: extensive spontaneous and artificial metastasis of a human pigmented melanoma and derived variant sublines in nude mice.

The extensive metastatic capacities in nude mice of variants of a human melanoma line, MeWo, were studied. BALB/c nude mice received subcutaneous implants of lung cubes impregnated in vitro with small numbers (less than 1,000) of MeWo cells as a result of previous in vitro coincubation. Such implants always resulted in lethal tumors, despite the fact that injection of dispersed 3 X 10(5) MeWo cells was normally required to obtain a tumor take. A BALB/c nude mouse that had received a MeWo lung cube implant was found to have numerous, large lung nodules 6 months after implantation. Transfer of the metastatic lung nodules to new recipients also led to the appearance of lung metastases. Cell lines established from such metastases, or from primary tumors that arose in nude mice implanted with MeWo-infiltrated cubes, showed a remarkable ability to colonize the lungs after iv injection, in contrast to the parent MeWo cells: Lungs were found to be engorged with hundreds of nodules, many, but not all, being melanotic. Widespread extrapulmonary metastases were also observed, but only after iv injection of MeWo sublines established from metastases. Karyotype analysis revealed that lung colonies established by iv cell injection had a near diploid (i.e., wild type) number of human chromosomes (mode: 44), whereas cell lines from spontaneous metastases possessed a near tetraploid number, a possible consequence of either selection or tumor progression in vivo. The results indicate that human tumor variants with unusually aggressive metastatic capabilities can be obtained in adult nude mice, similar in nature to some highly metastatic variants derived from mouse tumors (e.g., the B16 melanoma). The availability of such variants should be a valuable aid to study aspects of tumor cell heterogeneity, progression, and metastasis from a human cancer cell perspective.

Animals↗
PubMed1983

A comparative analysis of the phenotypic characteristics of available fusion partners for the construction of human hybridomas.

Of several human fusion partners available for the production of monoclonal antibodies, only SKO-007 and RPMI 8226 have phenotypic features characteristic for myeloma cells. Cells from both lines exhibited abundant rough endoplasmic reticulum (RER) with a prominent Golgi apparatus, few free ribosomes, condensed nuclear chromatin, and absence of the Epstein-Barr virus determined nuclear antigen (EBNA). However, following prolonged passage of these lines, the amount of immunoglobulin (Ig) production has declined. The other cell lines, GM 1500 6TG-A11, KR-4, B6, HS-Sultan, and Raji possessed the phenotypic characteristics of B-lymphoblastoid cell lines (LCLs) and B-lymphomas including surface Ig expression, sparse RER, free polyribosomes, a poorly developed Golgi apparatus and strong EBNA expression. Accordingly, they secreted little (nanograms) or no Ig. However, hybrids constructed with two LCLs secrete very large amounts of Ig despite their expressed morphologic similarity to the parental lines. These data indicate that morphology can still be used as an important consideration in choosing a human fusion partner but other parameters such as fusion frequency, cloning efficiencies, and growth rates may be equally important.

Antibodies, Monoclonal↗
PubMed1979

Endodermal sinus (yolk sac) tumors in infants and children.

Endodermal sinus tumors, as a specific entity, were first proposed and described by Teilum on the basis of morphological and histogenetic features. Recent work utilizing tumor markers (alpha-fetoprotein), immunofluorescent and electron microscopic studies have supported Teilum's original concept as to the origin of these tumors. Five typical presentations of endodermal sinus tumors seen in the pediatric age group were reviewed with reference to the original presentation, the utilization of tumor markers (alpha-fetoprotein) and the prognostic implications of this neoplasm.

Child↗
PubMed1966

Pulmonary oil deposition in patients subjected to lymphography: Detection by thoracic photoscan and sputum examination.

During clinical trials of intralymphatic therapy with radioiodinated ethiodized oil (Lipiodol Ultra-Fluid; Ethiodol) [LUF-I(131)] for malignant disease involving lymph nodes, significant pulmonary deposition of radioactive material was demonstrated by thoracic scan in each of five cases treated. Radioactivity was detected in sputum obtained from two cases. Induced sputum specimens were subsequently obtained from patients undergoing lymphography. Fat demonstrated in sputum was confirmed as Lipiodol in one of six patients tested. Sputum examination and use of tracer doses of LUF-I(131) plus photoscanning are suggested as sensitive methods of assessing the incidence of oil deposition in the lungs of patients undergoing lymphography. Despite limitation of the volume of oil injected, monitoring of the infusion, and absence of radiographic evidence of contrast medium in the lungs, some degree of pulmonary oil deposition appears to be an inevitable result of lymphography. Further study of lung dosimetry is being undertaken by the authors before clinical usage of endolymphatic radioisotope therapy is expanded.

Ethiodized Oil↗
PubMedDate not supplied

The in vivo clearance of Ha-ras transformants by natural killer cells.

The experiments in this study were designed to test the hypothesis that natural killer (NK) cells play a role in host surveillance against early neoplastic changes in the malignant process. C3H 10T1/2 mouse fibroblasts were transfected with a pSV2-neo plasmid vector which contains EJ, the mutated c-Ha-ras, regulated by its own promoter. Control cells were transfected with pSV2-neo alone and did not contain the ras gene. Oncogene-transfected cells were compared with control cells for lung colony formation following tail vein injection into C3H mice. Intravenous injection of ras-transfected 10T1/2 cells induced marked lung colony formation in vivo, whereas C3H 10T1/2 parental lines or 10T1/2 cells transfected with pSV2-neo alone induced no lung colonies in C3H mice. The colonising potential of ras transfectants could be decreased by augmentation of NK activity by injection of polyinosinic cytidylic acid and increased by depletion of NK effectors with anti-asialo GM1. Experiments with beige mice demonstrated that the mortality of syngeneic, NK-deficient C3H-bg/bg mice injected with ras tranfectants was significantly greater than similarly treated NK-normal C3H(-)+/bg littermate controls. The results support the view that NK cells are capable in vivo of recognizing early defined stages in the neoplastic process initiated by oncogenes.

Animals↗