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Biomedical subjects

M Nichols

Publications and source records attributed to M Nichols.

At least 37 records · Page 2Linked to original sources
PubMed1996

Interleukin-6-mediated hyperalgesia/allodynia and increased spinal IL-6 expression in a rat mononeuropathy model.

It has been suggested that neuroimmunologic mechanisms may be involved in the development and maintenance of neuropathic pain. To further address this concept, the immunoreactive spinal expression of the pro-inflammatory cytokine, interleukin-6 (IL-6), was determined in the mononeuropathy model in the rat, sciatic cryoneurolysis (SCN). This well-established animal model expresses behaviors suggestive of neuropathic pain in humans. Immunohistochemical localization in the spinal cord was determined at 3, 7, 14, 21, 35, and 120 days after SCN (n = 6 per time point). Immunoreactive IL-6 increased incrementally in the substantia gelatinosa and motoneurons over time following SCN as compared with normal rats. In an additional study, recombinant human IL-6 was administered intrathecally to normal and previously SCN-lesioned rats. Intrathecal IL-6 produced touch-evoked allodynia (increased sensitivity to a nonnoxious stimulus) in normal rats and thermal hyperalgesia (increased sensitivity to a noxious stimulus) in previously lesioned SCN rats. These results provide evidence that IL-6 may be involved in the cascade of events leading to the development and maintenance of behaviors suggestive of neuropathic pain following peripheral nerve injury.

Analysis of Variance↗
PubMed1995

Use of endoscopes for chronic ear surgery in children.

OBJECTIVE: To determine whether an endoscopic second-look examination of the mastoid and middle ear could replace an open second-look mastoidectomy. DESIGN: Patients were examined endoscopically. The findings were compared with a standard open mastoidectomy procedure during the same operation. The mastoid can be inspected through a small postauricular incision and the middle ear can be inspected through a myringotomy incision or tympanomeatal flap. PATIENTS: Ten patients aged 6 to 16 years. RESULTS: Endoscopic findings correlated exactly with open mastoidectomy findings in all cases. CONCLUSION: In light of this study an open second-look mastoidectomy may be avoided if minimal or no recurrent cholesteatoma is found during the endoscopic exploration. The use of the ridged endoscope has added another dimension to the standard microsurgical techniques used in pediatric otology. The indications, techniques, and findings of otoendoscopy in the management of chronic otitis media in children will be presented.

Adolescent↗
PubMed1994

Revision stapes surgery with and without laser: a comparison.

In this study, the results of 76 revision stapes surgeries performed from 1974 to 1992 were reviewed. Either the KTP or the argon laser was used in 40 operations. Prosthesis problems were the most common cause for revision (63%) followed by eroded/necrotic incus (29%) and adhesions (29%). Overall "success" in air-bone gap closure (air-bone gap < or = 10 dB) was 46% for first revisions and 33% for second or greater revisions. The "improvement" rate (air-bone gap < or = 20 dB) was 65% for first revisions and 53% for second or greater revisions. There was no statistically significant difference in hearing results between laser surgery and conventional technique. However, an absence of adhesions was noted when the laser had been used in the primary procedure.

Adolescent↗
PubMed1994

Patient management in a tobacco-cessation program in the dental practice.

Smoking and smokeless tobacco can cause significant damage to the oral cavity, including life-threatening cancers. Consequently, dentists and their office staffs should and can play an influential role in advising their patients to quit using tobacco. The National Cancer Institute has developed the "Four A's" approach to tobacco-cessation counseling: (1) ask about tobacco use; (2) advise to quit; (3) assist with quitting; and (4) arrange for follow-up. With minimal expenditures of treatment time, the dentist and office staff can encourage patients to quit using tobacco through nonconfrontational messages that point out the clinical damage caused by smoking and smokeless tobacco. Besides behavior modification, dentists can prescribe several Food and Drug Administration-approved pharmaceutical agents as adjuncts to a tobacco-cessation program. Nicotine polacrilex (gum) and nicotine transdermal systems have proven very useful in helping tobacco users quit their habit.

Administration, Cutaneous↗
PubMed1994

Curriculum change in an obstetrics-gynecology residency program and its impact on pregnancy in residency.

OBJECTIVE: Our purpose was to determine whether pregnancy was better tolerated by the individual female resident and the program as a whole after changes in the curriculum. STUDY DESIGN: The 1983 through 1992 graduates of an obstetrics-gynecology residency program were questioned to assess the stress experienced by all residents and by the pregnant female residents. The level of agreement to statements expressing support and resentment for pregnancy in residency was measured. RESULTS: Resentment among residents toward their pregnant colleagues was significantly greater in 1983 through 1987 than in 1988 through 1992. Male residents expressed more resentment toward pregnancy in their colleagues than did female residents, but they were perceived by the pregnant female residents as equally supportive as female residents. The level of stress experienced by the 1983 through 1987 graduates was greater than by those from 1988 through 1992. CONCLUSION: Reducing the workload in training programs is associated with a decrease in the resentment of the residents toward pregnant residents and in the overall stress of the program.

Adult↗
PubMed1993

Characterization of the nuclear proteins binding the CACCC element of a glucocorticoid-responsive enhancer in the tyrosine aminotransferase gene.

The nuclear proteins which act synergistically with the glucocorticoid receptor to induce transcription of the tyrosine aminotransferase gene include factors recognizing the CACCC element. We have purified and characterized the proteins from rat liver nuclei which bind to the CACCC motif in the glucocorticoid-inducible enhancer of the gene. Three protein-DNA complexes (C1, C2, and C3) were detected in band-shift assays. The protein component of complex C1 also binds a GC motif (a Sp1 binding site) and is recognized by anti-Sp1 antiserum. The proteins forming complexes C2 and C3 have been purified by DNA-affinity chromatography and their molecular masses (75-80 kDa and 35-40 kDa, respectively) have been determined by ultraviolet cross-linking to radio-labelled DNA and SDS/PAGE. The DNA-affinity-purified C2 and C3 activities do not bind significantly to the GC motif and are not recognized by anti-Sp1 antiserum. Methylation interference analysis indicates that the nucleotides of the CACCC element bound by the C2 and C3 proteins correspond to those of the glucocorticoid-responsive enhancer which are contacted in vivo following glucocorticoid administration. Our data suggest that these proteins contribute to glucocorticoid-induced transcription of the tyrosine aminotransferase gene.

Animals↗
PubMed1993

Effect of four combined oral contraceptives on blood pressure in the pill-free interval.

OBJECTIVE: To evaluate blood pressure changes in the pill-free interval and from baseline among women taking four different low-dose monophasic oral contraceptives. DESIGN: 131 women were randomized to four different oral contraceptives. Pressures were obtained at baseline, at the end of treatment cycles and at the end of the 7 pill-free days, during 6 months of treatment. Pressures were obtained at 4 and 8 weeks after discontinuation. Group 1 received norethisterone acetate 1000 micrograms, group 2 received levonorgestrel 150 micrograms, group 3 received desogestrel 150 micrograms, and group 4 received gestodene 75 micrograms, all combined with ethinyloestradiol 30 micrograms. RESULTS: All four groups showed an increase in pressure during treatment, with return to baseline levels four weeks after treatment. At the end of the pill-free interval, the readings did not differ significantly from on treatment except for women in Group 4, who experienced an increase in diastolic pressure. CONCLUSIONS: Use of the four oral contraceptives was associated with a small increase in systolic and diastolic pressure. Whatever mechanism causes the increase is not entirely reversible by 7 days without treatment.

Adolescent↗
PubMed1992

Phosphorylation of CREB affects its binding to high and low affinity sites: implications for cAMP induced gene transcription.

Cyclic AMP treatment of hepatoma cells leads to increased protein binding at the cyclic AMP response element (CRE) of the tyrosine aminotransferase (TAT) gene in vivo, as revealed by genomic footprinting, whereas no increase is observed at the CRE of the phosphoenolpyruvate carboxykinase (PEPCK) gene. Several criteria establish that the 43 kDa CREB protein is interacting with both of these sites. Two classes of CRE with different affinity for CREB are described. One class, including the TATCRE, is characterized by asymmetric and weak binding sites (CGTCA), whereas the second class containing symmetrical TGACGTCA sites shows a much higher binding affinity for CREB. Both classes show an increase in binding after phosphorylation of CREB by protein kinase A (PKA). An in vivo phosphorylation-dependent change in binding of CREB increases the occupancy of weak binding sites used for transactivation, such as the TATCRE, while high affinity sites may have constitutive binding of transcriptionally active and inactive CREB dimers, as demonstrated by in vivo footprinting at the PEPCK CRE. Thus, lower basal level and higher relative stimulation of transcription by cyclic AMP through low affinity CREs should result, allowing finely tuned control of gene activation.

Amino Acid Sequence↗
PubMed1992

Maternal origin of deletion 15q11-13 in 25/25 cases of Angelman syndrome.

About half of the cases of Angelman syndrome arise from deletions of chromosome band 15q12. In 25 cases we have been able to determine the parental origin of the deletion and, in line with other reported cases, we have found the deletion to be of maternal origin. There were no exceptions. The parental origin was determined using cytogenetic markers in 13 of the cases, in nine by using the pattern of inheritance of restriction fragment length polymorphisms, and in three using both techniques.

Abnormalities, Multiple↗
PubMed1991

The tissue-specific extinguisher locus TSE1 encodes a regulatory subunit of cAMP-dependent protein kinase.

The tissue-specific extinguisher locus TSE1, a dominant negative regulator of transcription in somatic cell hybrids, acts via a cAMP response element (CRE) to repress activity of a hepatocyte-specific enhancer. Guided by the antagonism between TSE1 and cAMP-mediated signal transduction, we identified the regulatory subunit RI alpha of protein kinase A (PKA) as the product of the TSE1 locus. The evidence derives from concordant expression of RI alpha mRNA and TSE1 genetic activity, high resolution mapping of the RI alpha gene and TSE1 on human chromosome 17, and the ability of a transfected RI alpha cDNA to generate a phenocopy of TSE1-mediated extinction. The mechanism of TSE1/RI alpha-mediated extinction involves repression of basal PKA activity, reduced phosphorylation of CREB at Ser-133, and a corresponding reduction of in vivo protein binding at the target CRE.

Animals↗
PubMed1991

Uniparental paternal disomy in Angelman's syndrome.

Angelman's syndrome and Prader-Willi syndrome are both causes of mental retardation with recognisable, but quite different, clinical phenotypes. Both are associated with deletions of chromosome 15q11-13, of maternal origin in Angelman's and paternal in Prader-Willi. Prader-Willi can arise by inheritance of two chromosomes 15 from the mother and none from the father (uniparental maternal disomy). In 2 patients with Angelman's syndrome we found evidence of uniparental paternal disomy. The phenotypic effects of maternal and paternal disomy of chromosome 15 are very different and inheritance of two normal 15s from one parent does not lead to normal development--strong evidence in man for genomic imprinting, in which the same gene has different effects dependent upon its parental origin.

Alleles↗
PubMed1990

Shirodkar cerclage in a multifactorial approach to the patient with advanced cervical changes.

Patients with a markedly effaced or dilated cervix and protruding membranes between 21 and 26 weeks' gestation were managed by Shirodkar cervical cerclage, perioperative tocolysis, broad-spectrum antibiotic therapy, and, in selected cases, inhibition of prostaglandin synthesis with indomethacin. The average duration of pregnancy after cerclage in nine patients was 11.8 weeks (range, 1 to 18 weeks). The mean birth weight was 2456 gm (range, 810 to 4341 gm). Eight of the nine pregnancies resulted in live infants (fetal survival rate, 89%); six patients (66%) were delivered at or near term. Preterm delivery occurred at 28 and 35 weeks' gestation in two patients and premature rupture of the membranes occurred in another at 25 weeks, 5 days after cerclage. There was no maternal postoperative or postpartum morbidity. A multifactorial approach to the patient with advanced cervical changes and protruding membranes in the second trimester resulted in a high rate of fetal survival and prolongation of pregnancy until term in the majority of patients. The Shirodkar cerclage holds a distensible cervix closed while the adjunctive medical therapy restores homeostasis.

Anti-Bacterial Agents↗
PubMed1989

Interaction of yeast transcription factor IIIC with dimeric Schizosaccharomyces pombe tRNA(Ser)-tRNA(Met) genes.

A unique tRNA(Ser)-tRNA(Met) tandem gene arrangement was characterized previously from Schizosaccharomyces pombe. Three alleles exist in which a tRNA(Ser) gene is separated by 7 base pairs from an initiator tRNA(Met) gene. Promotion of transcription occurs only within the tRNA(Ser) gene, yielding a dimeric precursor transcript. Using nuclease protection and gel retardation assays, we have analyzed how the Saccharomyces cerevisiae RNA polymerase III transcription factor C (TFIIIC) interacts with this dimeric gene template. The primary interaction site of TFIIIC with the tRNA(Ser) gene is at the 3'-internal control region (ICR), which can be distinguished kinetically from its weaker interaction with the 5'-ICR of the gene. We examined a variety of point mutations and double mutations within the tRNA(Ser) gene which reduce transcription. We found that changes in highly conserved nucleotides within the ICRs reduce TFIIIC binding up to 7-fold compared with the parent suppressor gene. The interaction of TFIIIC with the tRNA(Ser) gene does not sterically prevent stable binding of TFIIIC to the 3'-ICR of the tRNA(Met) gene. However, the affinity of binding of TFIIIC to the dimeric template is 7-fold higher than to the tRNA(Met) gene, alone, demonstrating that the tRNA(Met) gene contains intrinsically weak promoter elements. This may contribute to the inability of the tRNA(Met) gene to independently direct transcription from its ICR elements.

Alleles↗
PubMed1989

Multiple mutations of the first gene of a dimeric tRNA gene abolish in vitro tRNA gene transcription.

Eukaryotic tRNA expression initiates with transcription by RNA polymerase III and requires two additional protein factors and two regions within the tRNA gene (the 5'-internal control region (ICR) or A-box and the 3'-ICR or B-box). Using a reconstituted Saccharomyces cerevisiae RNA polymerase III system, the transcription of various 5'-ICR, 3'-ICR, and double mutation alleles of the Schizosaccharomyces pombe sup3-e dimeric tRNA gene were studied. The sup3-e tRNA locus consists of an upstream serine tRNA gene and a downstream initiator methionine tRNA gene which are transcribed as a dimeric precursor and processed to give two tRNAs. Only the ICRs of the tRNA(Ser) gene are active in directing dimeric gene transcription. Mutations in the 3'-ICR of the tRNA(Ser) gene reduce transcription of the dimer more than those in the 5'-ICR. Mutations in the 5'-ICR were found which greatly increased or decreased transcription of the dimer, while base changes in the 3'-ICR were only found to decrease transcription. This suggests a modulatory role for the 5'-ICR in transcription regulation. Mutation of the methionine tRNA gene ICR has little effect on sup3-e transcription, and no detectable transcripts initiate from the methionine tRNA gene when the tRNA(Ser) gene promoter is inactivated by mutation. Comparison with transcription studies of other mutant tRNA genes suggests that nucleotides sites within the ICRs, such as nucleotides 8, 10, 13, 18, and 19 in the 5'-ICR and 48, 53, 56, 57, and 58 in the 3'-ICR, appear to have evolved universal importance for RNA polymerase III transcription in eukaryotes. Thus these ICR sequences may play a critical role in regulation of tRNA expression.

Cloning, Molecular↗