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Biomedical subjects

J Chiles

Publications and source records attributed to J Chiles.

10 recordsLinked to original sources
PubMed2001

SR48692 is a neurotensin receptor antagonist which inhibits the growth of small cell lung cancer cells.

Neurotensin (NT) is an autocrine growth factor for some small cell lung cancer (SCLC) cells. In this communication, the effects of a non-peptide NT receptor antagonist, SR48692, were investigated using SCLC cells. (3)H-SR48692 bound with high affinity (IC(50) = 20 nM) to NCI-H209 cells. Also, NT and SR48692 inhibited specific (125)I-NT binding with high affinity (IC(50) values of 2 and 200 nM). In contrast, the NT(2) receptor agonist, levocabastine, had little effect on specific (125)I-NT binding, second messenger production and proliferation using NCI-H209 cells. SR48692 (5 microM) antagonized the ability of NT (10 nM) to cause elevated cytosolic Ca2+ in Fura-2 AM loaded NCI-H209 cells. SR48692 antagonized the ability of NT to cause elevation of c-fos mRNA in these cells. Using a MTT proliferation assay, SR48692 inhibited NCI-H209 and H345 proliferation in a concentration-dependent manner. Using a clonogenic assay, 1 microM SR48692, reduced NCI-H209 colony number. Also, SR48692 (0.4 mg/kg per day) inhibited NCI-H209 xenograft proliferation in nude mice. These results suggest that SR48692 is a NT(1) receptor antagonist which inhibits SCLC growth.

Animals↗
PubMed1999

Mosquito-Plasmodium interactions in response to immune activation of the vector.

During the development of Plasmodium sp. within the mosquito midgut, the parasite undergoes a series of developmental changes. The elongated ookinete migrates through the layers of the midgut where it forms the oocyst under the basal lamina. We demonstrate here that if Aedes aegypti or Anopheles gambiae, normally susceptible to Plasmodium gallinaceum and P. berghei, respectively, are immune activated by the injection of bacteria into the hemocoel, and subsequently are fed on an infectious bloodmeal, there is a significant reduction in the prevalence and mean intensity of infection of oocysts on the midgut. Only those mosquitoes immune activated prior to, or immediately after, parasite ingestion exhibit this reduction in parasite development. Mosquitoes immune activated 2-5 days after bloodfeeding show no differences in parasite burdens compared with naive controls. Northern analyses reveal that transcriptional activity for mosquito defensins is not detected in the whole bodies of Ae. aegypti from 4 h to 10 days after ingesting P. gallinaceum, suggesting that parasite ingestion, passage from the food bolus through the midgut, oocyst formation, and subsequent release of sporozoites into the hemolymph do not induce the production of defensin. However, reverse transcriptase-PCR of RNA isolated solely from the midguts of Ae. aegypti indicates that transcription of mosquito defensins occurs in the midguts of naive mosquitoes and those ingesting an infectious or noninfectious bloodmeal. Bacteria-challenged Ae. aegypti showed high levels of mature defensin in the hemolymph that correlate with a lower prevalence and mean intensity of infection with oocysts. Because few oocysts were found on the midgut of immune-activated mosquitoes, the data suggest that some factor, induced by bacterial challenge, kills the parasite at a preoocyst stage.

Aedes↗
PubMed1998

Biochemical analysis of a blood meal-induced Aedes aegypti glutamine synthetase gene.

Glutamine synthetase (GS) in the mosquito, Aedes aegypti, is induced in the midgut following a blood meal. Mosquito GS message is detected as soon as 1 h post-blood feeding and remains stable for 18 h. Using a PCR product encoding mosquito GS, a lambda gt10 adult female mosquito cDNA library was screened. A cDNA clone, pCl5A2, encoding the full translation product of mosquito GS was isolated and sequence analyses performed. Mosquito GS cDNA is 2.5 kb in length and its putative translation product shares all the conserved regions characteristic of the GS gene family, including the presumed ATP biding site. Glutamine synthetase activity in the mosquito midgut is highest at 18 h post-blood feeding. Activity can be detected over a broad pH range, from 6.0 to 7.5. Unlike other cellular GS enzymes, mosquito GS is not active in the presence of ATP. Very low dosages (0.05 mM) of L-methionine S-sulfoximine are sufficient to partially inhibit mosquito GS activity. Inhibition of GS disrupts the normal formation of the midgut peritrophic matrix, suggesting that GS enzyme might be involved in the initial pathway of chitin synthesis. The unique expression pattern and inducible nature of the mosquito GS gene make it an interesting candidate for studying promoter function. Additionally, the blood meal activation of the GS gene makes this a potentially valuable tool in mosquito transformation studies.

Aedes↗
PubMed1991

Tardive dyskinesia in the mentally retarded: comparison of prevalence, risk factors and topography with a schizophrenic population.

Thirty mentally retarded patients treated with neuroleptics for aberrant behavior were compared with 30 neuroleptic-treated schizophrenics for the presence, topography and risk factors associated with tardive dyskinesia (TD). In the total sample (n = 60), female sex, schizophrenic diagnosis and increasing age were associated with TD. The length of neuroleptic treatment and current neuroleptic dose were not significantly associated with TD. The only topographical difference in TD presentation was that the mentally retarded group had significantly more tongue involvement.

Adult↗
PubMed1990

Weight gain associated with clozapine.

Six of seven patients treated with clozapine gained 6-69 lb. Because of clozapine's anticipated availability in the United States, clinicians should be aware of this possible side effect, which, to the authors' knowledge, has not been reported previously.

Adult↗
PubMed1984

The pharmacotherapy-psychotherapy triangle: psychiatrist, nonmedical psychotherapist, and patient.

Members of the Washington State Psychiatric Association (N = 387) were sent a questionnaire asking about their experience with providing adjunctive medicinal treatment to patients in psychotherapy with someone else. Of the 202 respondents, 63% acknowledged such "therapeutic triangles." Younger psychiatrists, psychiatrists working in clinic and/or public settings, and non-psychoanalytic psychiatrists were more likely to participate in such arrangements. It is estimated that between 7200 and 21,000 U.S. psychiatrists participate in such arrangements, with 72,000-210,000 patients seen each month. More extensive study of all aspects of this phenomenon is urged.

Adult↗
PubMed1978

Diagnostic significance of persistent colonic gallium activity: scintigraphic patterns.

One hundred and forty-eight gallium scans were reviewed to determine the diagnostic significance of colonic gallium activity and its relationship to colonic disease. Location or intensity of the activity was unchanged during the course of the radionuclide study in 25 patients imaged more than once. Of those patients who had colonic gallium activity that did not change in location or intensity during the study, 9 had proved colonic disease. The patterns of colonic activity were either focal or diffuse. These distinct patterns, however, cannot distinguish benign from malignant disease.

Adult↗
PubMed1978

Hyperactivity: diagnostic confusion.

Histories of hyperactive symptoms were evaluated for two samples of young men and women under treatment for drug or psychiatric disorders. More than one in five had shown hyperactivity but almost all of these developed pictures of other psychiatric problems, frequently the antisocial personality, by late adolescence. This picture is felt to reflect inaccurate use of hyperactive labels in difficult-to-handle children. The potential consequences of these practices are discussed.

Adolescent↗