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Biomedical subjects

R Meeker

Publications and source records attributed to R Meeker.

At least 19 recordsLinked to original sources
PubMed2000

Inhibition of hippocampal kindling by metabotropic glutamate receptor antisense oligonucleotides.

Recent work has shown that metabotropic glutamate receptors (mGluRs) increase in response to seizure activity and can contribute significantly to the expression and progression of partial seizures. Using the kindling model of temporal lobe seizures, we evaluated the ability of local hippocampal injections of mGluR1 antisense or mGluR3 antisense oligonucleotides to suppress receptor expression and alter hippocampal kindling. Daily antisense injections in the hippocampus resulted in a significant decrease in mGluR1 or mGluR2/3 immunoreactivity. Rats injected with mGluR3 antisense showed a brief suppression of afterdischarge duration when compared to matched rats injected with a nonsense-oligonucleotide. Rats injected with a mGluR1 antisense oligonucleotide had a dramatic suppression of the rate of seizure progression with no significant effect on afterdischarge duration. Suppression of mGluR1 synthesis by local antisense inhibition may provide a new therapeutic approach for the control of epileptogenesis.

Animals↗
PubMed2000

Osmotic and glutamate receptor regulation of c-Jun NH(2)-terminal protein kinase in neuroendocrine cells.

Expression of a c-Jun NH(2)-terminal protein kinase (JNK), also known as stress-activated protein kinase (SAPK) in rodents, has been implicated in the ability of cells to respond to a variety of stressors. In nonmammalian cells, JNK participates in the regulation of cell volume in response to hyperosmotic stress. To explore the possibility that JNK may participate in the transduction of osmotic information in mammals, we evaluated the expression of JNK immunoreactivity in neuroendocrine cells of the supraoptic nucleus. Low basal expression of JNK-2 (SAPK-alpha) and JNK-3 (SAPK-beta) was seen in vivo and in vitro. During water deprivation, JNK-2 increased in the supraoptic nucleus but not in the cortex. Osmotic or glutamate receptor stimulation in vitro also resulted in an increase in JNK-2 that was tetrodotoxin (TTX) insensitive and paralleled by increased nuclear phospho-c-Jun immunoreactivity. A TTX-sensitive increase in JNK-3 was seen in smaller neurons. Thus different JNK pathways may mediate individual cellular responses to osmotic stress, with JNK-2 linked to osmotic and glutamate receptor stimulation in magnocellular neuroendocrine cells.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Clinical and biologic activity of an estrogenic herbal combination (PC-SPES) in prostate cancer.

BACKGROUND: Herbal mixtures are popular alternatives to demonstrated therapies. PC-SPES, a commercially available combination of eight herbs, is used as a nonestrogenic treatment for cancer of the prostate. Since other herbal medicines have estrogenic effects in vitro, we tested the estrogenic activity of PC-SPES in yeast and mice and in men with prostate cancer. METHODS: We measured the estrogenic activity of PC-SPES with transcriptional-activation assays in yeast and a biologic assay in mice. We assessed the clinical activity of PC-SPES in eight patients with hormone-sensitive prostate cancer by measuring serum prostate-specific antigen and testosterone concentrations during and after treatment. RESULTS: In complementary yeast assays, a 1:200 dilution of an ethanol extract of PC-SPES had estrogenic activity similar to that of 1 nM estradiol, and in ovariectomized CD-1 mice, the herbal mixture increased uterine weights substantially. In six of six men with prostate cancer, PC-SPES decreased serum testosterone concentrations (P<0.05), and in eight of eight patients it decreased serum concentrations of prostate-specific antigen. All eight patients had breast tenderness and loss of libido, and one had venous thrombosis. High-performance liquid chromatography, gas chromatography, and mass spectrometry showed that PC-SPES contains estrogenic organic compounds that are distinct from diethylstilbestrol, estrone, and estradiol. CONCLUSIONS: PC-SPES has potent estrogenic activity. The use of this unregulated mixture of herbs may confound the results of standard or experimental therapies and may produce clinically significant adverse effects.

Animals↗
PubMed1997

Persistent elevation of corticotrophin releasing factor and vasopressin but not oxytocin mRNA in the rat after kindled seizures.

Intractable temporal lobe epilepsy is a disabling disorder with far reaching effects on brain function, behavior and neuroendocrine function. Previous work in the kindled-seizure model for temporal lobe epilepsy has shown that these seizures cause vasopressin (VP) release, an increase in resting VP and lasting increases in VP mRNA in the supraoptic nucleus (SON) of the hypothalamus. In this study we used in situ hybridization to examine the effects of kindled seizures on the expression of two other functionally-related, neuroendocrine genes, oxytocin (OT) and corticotrophin releasing factor (CRF). Comparisons in kindled and sham-stimulated controls revealed an increase in VP mRNA but not OT mRNA in magnocellular neurons and an increase in CRF mRNA in parvocellular neurons of the paraventricular nucleus (PVN) of the hypothalamus 1 month after the last seizure. We conclude that kindled seizures induce selective changes in neuroendocrine gene expression in neuroendocrine systems, VP and CRF but not OT.

Animals↗
PubMed1995

Antisense vasopressin oligonucleotides: uptake, turnover, distribution, toxicity and behavioral effects.

The uptake, turnover, distribution, toxicity and behavioral effects of antisense vasopressin oligonucleotides were investigated to define how these compounds interact with neural tissue to inhibit translation of a target mRNA. Both phosphorothioate modified and unmodified oligonucleotides are rapidly taken up by mammalian neural tissue. Turnover of the unmodified oligonucleotide was found to be fast (t1/2 < 1 h) relative to the phosphorothioate modified oligonucleotide (t1/2 = 12 h). The phosphorothioate vasopressin antisense oligonucleotide suppressed vasopressin synthesis in vivo at concentrations below the toxic threshold of approximately 5 microM. Intracranial injections of phosphorothioate antisense oligonucleotide into the region of the SON in vivo, resulted in a small decrease in vasopressin mRNA and a compensatory drinking response within the first 24 h, consistent with a deficit in vasopressin translation with kinetics similar to those observed in vitro. Water intake returned to normal by the second day indicating relatively rapid clearance of the oligonucleotide and minimal side effects. Although the mechanisms of accumulation and details of the molecular interactions are still unknown, our observation of preferential uptake and/or retention of oligonucleotide within a subset of neurons in vitro suggests some process of selective targeting. Thus, low concentrations of oligonucleotides targeted to the untranslated 5' end of vasopressin mRNA can be effective for the acute and reversible control of vasopressin synthesis in mammalian CNS with relatively rapid onset of behavioral effects and minimal side effects.

Animals↗
PubMed1992

Subclinical central nervous system infection with JC virus in patients with AIDS.

Immunocompromised patients, particularly those with AIDS, develop progressive multifocal leukoencephalopathy (PML) due to central nervous system infection with JC virus (JCV). It is unknown whether JCV infection in the central nervous system can occur in the absence of PML symptoms. To address this question, autopsy specimens from patients with AIDS were examined. The brains of a group of patients without AIDS or central nervous system disease were also examined. JCV DNA was detected by the polymerase chain reaction in brain tissue from 4 (31%) of 13 human immunodeficiency virus (HIV)-positive patients. JCV was also detected in 1 elderly HIV-negative patient but not in the 11 other control brains. JCV was not detected in 22 myocardial specimens obtained at autopsy from HIV-negative patients nor 10 peripheral blood specimens from HIV-positive patients. The presence of JCV in brains of patients without clinically evident PML suggests that JCV may be present in the central nervous system without clinical disease.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Highly purified pea chloroplast RNA polymerase transcribes both rRNA and mRNA genes.

Pea chloroplast RNA polymerase has been obtained with about 2000-fold purification using DEAE-cellulose and phosphocellulose chromatography. The purified enzyme contained ten prominent polypeptides of 150, 130, 115, 110, 95, 85, 75, 48, 44 and 39 kDa and four other minor polypeptides of 90, 34, 32 and 27 kDa. Purification of this enzyme using chloroplast 16S rDNA promoter affinity column chromatography also yielded an enzyme with similar polypeptides. Purified polyclonal antibodies against the purified chloroplast RNA polymerase were found to recognize most of the polypeptides of the enzyme in Western blot experiments. Primary mobility shift of the 16S rRNA gene and ribulose-1,5-bisphosphate carboxylase large subunit (rbc-L) gene promoters observed with the chloroplast RNA polymerase was abolished by these antibodies. The specific in vitro transcription of these rRNA and mRNA genes was also inhibited by these antibodies. The transcription of the rRNA and mRNA genes was also abolished by tagetitoxin, a specific inhibitor of chloroplast RNA polymerase. The chloroplast RNA polymerase was found to bind specifically to the chloroplast 16S rRNA gene promoter region as visualized in electron microscopy. The presence of the polypeptides of 130, 110, 75-95 and 48 kDa in the DNA-enzyme complex was confirmed by a novel approach using immunogold labeling with the respective antibodies. The polypeptides of this purified RNA polymerase were found to be localized in chloroplasts by an indirect immunofluorescence.

Bacterial Toxins↗
PubMed1989

Kindling in spontaneous hypertensive rats.

Vasopressin is a neurohormone and neuromodulator with many effects on behavior. Rats lacking vasopressin have been found to develop kindled seizures more slowly with amygdala stimulation. In the present study the spontaneous hypertensive (SH) rat and rats from the parent strain, the Wistar-Kyoto (WKY) rat received amygdala and pyriform kindling. The SH rat has been reported to have increased plasma vasopressin and increased brain vasopressin release. Plasma vasopressin, osmolality and hematocrit were also measured in blood samples obtained through chronic, indwelling catheters implanted in SH, WKY normal and Sprague-Dawley rats. SH rats were found to kindle with fewer afterdischarges than WKY normal rats with both amygdala and pyriform cortex stimulation. The total afterdischarge duration required to reach each kindling stage was significantly shorter in the SH rat. Plasma osmolality and vasopressin were significantly higher in the SH rats compared to WKY normal rats and Sprague-Dawley rats. These findings provide additional evidence that vasopressin may influence the establishment of enduring behaviors such as kindled seizures.

Animals↗
PubMed1988

Localization of replication origins in pea chloroplast DNA.

The locations of the two replication origins in pea chloroplast DNA (ctDNA) have been mapped by electron microscopic analysis of restriction digests of supercoiled ctDNA cross-linked with trioxalen. Both origins of replication, identified as displacement loops (D-loops), were present in the 44-kilobase-pair (kbp) SalI A fragment. The first D-loop was located at 9.0 kbp from the closest SalI restriction site. The average size of this D-loop was about 0.7 kbp. The second D-loop started 14.2 kbp in from the same restriction site and ended at about 15.5 kbp, giving it a size of about 1.3 kbp. The orientation of these two D-loops on the restriction map of pea ctDNA was determined by analyzing SmaI, PstI, and SalI-SmaI restriction digests of pea ctDNA. One D-loop has been mapped in the spacer region between the 16S and 23S rRNA genes. The second D-loop was located downstream of the 23S rRNA gene. Denaturation mapping of recombinants pCP 12-7 and pCB 1-12, which contain both D-loops, confirmed the location of the D-loops in the restriction map of pea ctDNA. Denaturation-mapping studies also showed that the two D-loops had different base compositions; the one closest to a SalI restriction site denatured readily compared with the other D-loop. The recombinants pCP 12-7 and pCB 1-12 were found to be highly active in DNA synthesis when used as templates in a partially purified replication system from pea chloroplasts. Analysis of in vitro-synthesized DNA with either of these recombinants showed that full-length template DNA was synthesized. Recombinants from other regions of the pea chloroplast genome showed no significant DNA synthesis activity in vitro.

Chloroplasts↗
PubMed1985

The resolution of health problems in school children.

The resolution rates of health problems identified in school children by primary care, physical examination, or screenings were examined during a two-year period. The evaluation component of the National School Health Program involved a range of school health services provided in four states to more than 13,000 children. A school nurse practitioner-health aide team worked in collaboration with a community physician consultant to manage the resolution of identified problems. More than 95% of the problems were resolved or in process of resolution at the end of each school year. Resolution patterns were relatively consistent across problem severity levels. Factors contributing to the timely resolutions of health problems by nurse practitioners included their ability to manage and resolve more than 90% of the problems within the school-based practice with physician backup and their access to a medical support network for external referrals.

Child↗
PubMed1983

Achieving optimal immunization levels in school-age children.

In a school-based immunization program in four states, 70% of the students were fully immunized by the end of the first year and 85% by the end of the second year. Because of student turnover, 20% of the immunization levels achieved by the end of a school year were not sustained into the subsequent year. Levels reported by the state immunization officers were higher than those recorded by school personnel. Completed immunization series for students requiring immunizations were 33% to 40% higher for students enrolled at the start of the year than for students who entered during the school year. Students who were unimmunized at the beginning of the year had a better change (P less than 0.001) of being immunized by the end of the year than those whose immunization status was unknown. To maintain high levels, a program must be sustained and continuing, provide immunizations, and have careful administrative monitoring of child-specific population-based data. Schools are uniquely able to provide all of these elements, which can augment the efforts of private practitioners.

Child↗
PubMed1983

Comparative values of school physical examinations and mass screening tests.

In this study mass screenings identified more problems than did physical examinations, but more problems per 100 contacts were identified by physical examinations (51.6) than by screenings (4.7). When time necessary to accomplish the evaluation is considered, screenings are a more efficient way of identifying problems in the general diagnostic categories for which screenings can be provided, but most (85.8%) of the problems identified by physical examination were in categories for which screenings are not provided. Overall, 99.1% of the problems were identified without overlap between physical examinations and screenings. Eighty-three percent of the problems identified by physical examinations were previously unknown. By the end of the school year, 86.3% of the problems identified by physical examinations and 94.5% of those identified by screenings had been or were in the process of being resolved. The integration of physical examinations and screenings in a school setting, staffed by nurse practitioners supported by physicians, can maximize the identification and resolution of health problems.

Child↗
PubMed1982

Sequence organization of rat brain mitochondrial DNA.

The sequence organization of rat brain and liver mitochondrial (mt) DNA has been characterized using restriction endonucleases HindIII, BamHI, HhaI, and HaeIII. There is no evidence of heterogeneity on the base sequence of liver or brain mt DNA. The liver and brain mtDNAs were found to produce identical DNA fragments using these enzymes. Both the liver and brain mtDNA were analyzed by enzymatic digestions using HpaII/MspI. There was no evidence of the presence of methylated cytosine residues. Six different recombinant DNA molecules were analyzed by HindIII restriction digests and found to contain all of the 6 mtDNA fragments. Recombinant DNA molecules were analyzed for their molecular sizes by electron microscopy. The recombinant DNAs again showed the mtDNA fragments to have the right molecular weight. The molecular sizes of the recombinant DNA molecules were found to be 10.4, 7.4, 6.1, 5.7, 4.7 and 4.1 kilobase pairs (kbp). These molecular sizes reflect the insertion of 6.1, 3.8, 2.3, 1.9, 0.8 and 0.1 kbp HindIII mtDNA fragments in pBR322. The presence of mtDNA fragments in recombinant DNA molecules was also confirmed by hybridizing the nick translated brain mtDNA with Southern transfers of the recombinant DNA molecules.

Animals↗
PubMed1980

Transfer ribonucleic acid genes in the chloroplast deoxyribonucleic acid of pea leaves.

The saturation hybridization between pea ctDNA and 125I-labeled pea ct-tRNAs has shown that 1.2% of the peak ctDNA codes for tRNA genes. The observed level of hybridization has been found to result from specific base pairings between ctDNA and ct-RNA as shown by competition hybridization experiments and thermal stability studies on DNA-tRNA hybrids. The level of hybridization obtained in this study amounts to the presence of approximately 40 tRNA genes in pea ctDNA. The tRNAs from the cytoplasm of the pea leaves, Escherichia coli, yeast, and calf thymus did not compete with the pea ct-tRNAs for the common base sequences in pea ctDNA. The presence of 17 aminoacyl-tRNA synthetases and their corresponding tRNAs was demonstrated in chloroplast. The acylation of ct-tRNAs proceeds with the same rate whether the partially purified tRNA synthetases from chloroplasts of E. coli are used. The aminoacylation of the three amino acids glutamic acid, glutamine, and cysteine proceeded very slowly in chloroplasts. The individually labeled aminoacyl-tRNAs hybridized with pea ctDNA. The hybridization follows true saturation rates, and the melting profiles of aminoacyl-tRNA-ctDNA indicate the formation of specific base pairs between the ctDNA and tRNA. Seventeen aminoacyl-tRNA genes have been identified in the pea ctDNA.

Chloroplasts↗