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Biomedical subjects

C Miller

Publications and source records attributed to C Miller.

At least 127 records · Page 7Linked to original sources
PubMed2000

Injuries and risk factors in an 18-day Marine winter mountain training exercise.

OBJECTIVES: This study determined the incidence of and risk factors for injuries among 356 Marines during a winter mountain training exercise. METHODS: Marines received a podiatry screening and completed a questionnaire on race, education, tobacco use, height, weight, and fitness (4.8-km run, sit-ups, pull-ups). RESULTS: Forty-five Marines (12.6%) reported at least one injury each, 68.9% of which were traumatic injuries. Total injuries resulted in 114 days of limited duty time. A final foot examination (N = 141) revealed 118 injuries (82.2% blisters and abrasions, 11.9% frostnip). White ethnicity was a risk factor for overall injuries, and forefoot varus alignment was a risk factor for traumatic injuries. Lower education and rank and smokeless tobacco use were associated with foot injuries. The Marine ski-march leather boot and smoking were related to foot cold injuries. CONCLUSIONS: Military winter training is associated with injuries and lost training time. Risk factors were identified, suggesting that these injuries may be preventable.

Adult↗
PubMed2000

Working in tandem.

Explore the source record for details and available documents.

Cooperative Behavior↗
PubMed2000

The effect of intraislet somatostatin immunoneutralization on insulin secretion in the isolated perfused rat pancreas.

BACKGROUND: There is evidence of a local inhibitory effect of somatostatin on insulin secretion in the isolated human pancreas, but this has not been shown in a rat model. The possible phasic effect of somatostatin on insulin secretion has not been demonstrated. AIMS: This study was undertaken to determine if somatostatin has a local regulatory effect on phasic insulin secretion within a rat pancreas model. METHODS: The basal and glucose stimulated secretion of insulin was compared with and without immunoneutralization of somatostatin using a somatostatin antibody in an isolated perfused rat pancreas model. High concentration, high affinity monoclonal somatostatin antibody was perfused through isolated rat pancreata. Radioimmunoassay for insulin was performed on the portal effluent. RESULTS: Immunoneutralization of somatostatin during basal insulin secretion produced a rise in insulin secretion of 551 +/- 163% that approached significance. Immunoneutralization during glucose stimulated insulin secretion produced a significant rise in insulin secretion compared to the control group of 2,678 +/- 187% vs. 535 +/- 39% (p < 0.05). The phase I vs. the phase II response in the glucose stimulated pancreas was similar in the presence of control antibody, 867 +/- 351% vs. 900 +/- 398% (p = NS). With somatostatin immunoneutralization, the glucose stimulated pancreas had a significantly higher phase II response than phase I; 3,832 +/- 688% vs. 2,516 +/- 431% (p < 0.05). CONCLUSION: These data indicate that intraislet somatostatin is an inhibitor of insulin secretion in the isolated perfused rat pancreas. This effect occurs primarily in phase II of insulin secretion.

Animals↗
PubMed1999

Amitriptyline increases GABA-stimulated 36Cl- influx by recombinant (alpha 1 gamma 2) GABAA receptors.

WSS-1 cells expressing (alpha 1 gamma 2)GABAA receptors show an augmented 36Cl- response to GABA in the presence of amitriptyline that is increased by flumazenil, unlike augmentation by diazepam which is blocked by flumazenil. This amitriptyline effect is opposite to the inhibition of GABA-stimulated 36Cl influx manifested in membrane vesicles prepared from drug-naive rats or submissive rats (a model of depression) but is similar to that seen in tissue from amitriptyline-treated rats or dominant rats. The results suggest a novel mechanism of antidepressant drug action having a delayed onset.

Amitriptyline↗
PubMed1999

A comparison of eubacterial and archaeal structure-specific 5'-exonucleases.

The 5'-exonuclease domains of the DNA polymerase I proteins of Eubacteria and the FEN1 proteins of Eukarya and Archaea are members of a family of structure-specific 5'-exonucleases with similar function but limited sequence similarity. Their physiological role is to remove the displaced 5' strands created by DNA polymerase during displacement synthesis, thereby creating a substrate for DNA ligase. In this paper, we define the substrate requirements for the 5'-exonuclease enzymes from Thermus aquaticus, Thermus thermophilus, Archaeoglobus fulgidus, Pyrococcus furiosus, Methanococcus jannaschii, and Methanobacterium thermoautotrophicum. The optimal substrate of these enzymes resembles DNA undergoing strand displacement synthesis and consists of a bifurcated downstream duplex with a directly abutted upstream duplex that overlaps the downstream duplex by one base pair. That single base of overlap causes the enzymes to leave a nick after cleavage and to cleave several orders of magnitude faster than a substrate that lacks overlap. The downstream duplex needs to be 10 base pairs long or greater for most of the enzymes to cut efficiently. The upstream duplex needs to be only 2 or 3 base pairs long for most enzymes, and there appears to be interaction with the last base of the primer strand. Overall, the enzymes display very similar substrate specificities, despite their limited level of sequence similarity.

Archaea↗
PubMed1999

Anergy and cytokine-mediated suppression as distinct superantigen-induced tolerance mechanisms in vivo.

Recombinant-activating gene 2 (RAG-2-/-) T cell receptor-transgenic mice repeatedly injected with the superantigen staphylococcal enterotoxin A entered a tolerant state in which splenic CD4+ T cells produced little interleukin (IL)-2, interferon gamma, or IL-4. This state resulted from a combination of both clonal anergy and cytokine-mediated immunosuppression. The anergy persisted for at least 3 wk and could be distinguished from the suppression by a decrease in IL-2 production per cell, a block in the activation of early response kinases, and a failure to be reversed with anti-transforming growth factor (TGF)-beta. Full suppression lasted for only 1 wk and involved both IL-10 and TGF-beta, but required additional unknown molecules for optimal effect. These experiments show that complex in vivo interactions of multiple peripheral tolerance mechanisms can now be dissected at both the cellular and molecular levels.

Animals↗
PubMed1999

Meta-analysis of sentinel lymph node biopsy in breast cancer.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is a minimally invasive way to diagnose axillary lymph node (ALN) metastases in breast cancer. The most important features are ability to identify the SLN (I.D. rate), how often the SLN and ALN pathology match (concordance), and how often the SLN is negative for cancer when the ALNs are positive (false negative). Technique and patient criteria for SLNB vary among studies. This study performed meta-analysis of published studies to determine the I.D., concordance, and false negative rate (1) overall and for (2) both blue dye and radiocolloid, (3) the injection method, (3) palpable and nonpalpable ALNs, and (4) invasive and in situ disease. METHODS: Inclusion criteria were patients with breast cancer who had SLNB followed by ALN dissection with H&E staining. Meta-analysis was performed using analysis of variance with each observation weighted inversely to its variance. P < 0.05 was considered significant. RESULTS: Eleven studies (n = 912) met the inclusion criteria. Overall, 762 (84%) SLNs were identified, concordance was 747/762 (98%), and 15/296 (5%) were falsely negative. Highest I.D. rates (P < 0.05) were reported with albumin radiocolloid or dye + radiocolloid (97 and 94%, respectively), with injection around an intact tumor (96%), with invasive cancer (95%), and in the clinically negative axilla (96%). Concordance and false negative rates did not vary. CONCLUSIONS: The SLN can be identified in over 97% of patients if certain techniques and inclusion criteria are used. SLNB reflects the status of the axilla in 97% of cases and has a 5% false negative rate.

Adult↗
PubMed1999

Introduction to stem cell biology in vitro. Threshold to the future.

Transplantable hematopoietic cells with multilineage reconstituting ability can be quantitated in suspensions of human or murine cells using similar assay procedures. The incorporation into these assays of stringently defined functional endpoints ensures a high degree of specificity for the cells detected. Application of these assays to stem cell-containing suspensions after they have been stimulated for several days with defined cytokines in vitro, or by a mixture of defined and/or undefined factors in vivo, has shown that net amplifications in these populations can be obtained under both circumstances. Such studies have allowed cytokine conditions that support stem cell self-renewal divisions to be identified and have also provided evidence that stem cell regeneration can be manipulated both in vitro and in vivo by altering the molecular milieu of the responding cells. These observations pave the way to future delineation of mechanisms that control the normal behavior, pathology and future clinical exploitation of hematopoietic stem cell populations.

Animals↗
PubMed1999

Administration of oxytocin immediately after insemination does not improve pregnancy rates in mares bred by fertile or subfertile stallions.

It is probable that reduced pregnancy rates in mares bred to subfertile stallions is attributable, in part, to the reduced number of normal spermatozoa that colonize the oviduct. Administration of oxytocin stimulates both uterine and oviductal contractility. The hypothesis that oxytocin may enhance sperm transport to/into the oviducts, and thereby increase pregnancy rates, was tested in 2 trials. For both trials, fertile estrous mares with follicles > or = 35 mm in diameter were inseminated once at 24 h after administration of 1500 to 2000 U hCG. The inseminate dose was limited to 100 million spermatozoa in order to lower pregnancy rates and thus increase the chance of detecting a treatment effect. Pregnancy status was determined by transrectal ultrasound examination 14 to 16 d after insemination. In Trial 1, 49 mares were inseminated with 4 mL extended semen from 1 of 3 stallions (1 fertile and 2 subfertile males). Immediately after insemination, the mares were administered either 20 U oxytocin or 1 mL saline intravenously. In Trial 2, 51 mares were inseminated with 4 mL extended semen from 1 of 4 stallions (1 fertile and 1 subfertile male used in Trial 1, and 2 additional fertile males). Immediately after insemination, and again 30 min later, mares were administered either 5 U oxytocin or 0.25 mL saline intramuscularly. To test for effects of treatment with oxytocin and for the interaction between semen quality and treatment, a generalized linear mixed regression model was used that accounted for the split-plot design (treatment within stallions), the random effect of stallion, the fixed effect of semen quality, the binary outcome of a single breeding trial, and the varying number of trials per stallion/treatment groups. Three treatment protocols or regimens were used: placebo, 5 U oxytocin injected twice intramuscularly, and 20 units oxytocin injected twice intravenously. Semen was classified as high (fertile stallions) or low (subfertile stallions) quality. No interaction between semen quality and treatment was detected (P > 0.10). The pregnancy rate of mares treated with oxytocin immediately after insemination was 30% (15/50) compared with 50% (25/50) for mares treated with saline immediately after breeding. Administration of oxytocin did not affect pregnancy rates (P > 0.10).

Animals↗
PubMed1999

Simultaneous treatment of cytomegalovirus and varicella zoster infections in a renal transplant recipient with ganciclovir: use of viral load to monitor response to treatment.

Disseminated zoster occurring simultaneously with cytomegalovirus (CMV) disease in a renal transplant recipient is potentially life threatening. We describe the use of intravenous ganciclovir to treat both infections. The efficacy of treatment was assessed clinically and by the measurement of CMV viral load using the hybrid capture (Murex version 2) and varicella zoster (VZV) viral load using an in-house assay. Results from this case suggest that clinical resolution in severe viral infections such as described below may be related to early control of viraemia.

Adult↗
PubMed1999

Calphostin C induces AP1 synthesis and AP1-dependent c-jun transactivation in normal human chondrocytes independent of protein kinase C-alpha inhibition: possible role for c-jun N-terminal kinase.

Activator protein-1 (AP1) regulates the promoter activity of a large number of genes associated with developmental, proliferative, inflammatory, and homeostatic processes in human connective tissue cells. Some of these genes (e.g., cyclooxygenase-2) are regulated by the protein kinase C (PKC) inhibitor, calphostin C (CalC). We examined whether CalC could indeed induce AP1 and AP1 gene transactivation (c-jun) in human chondrocytes. Exploratory studies confirmed the anti-PKC effects of CalC, as equal molar concentrations of CalC blocked the PMA-induced translocation of PKC-alpha from the cytosolic to the membrane fraction. CalC induction of AP1, as judged by gel-shift analysis, using a consensus AP1 oligonucleotide, was biphasic with an initial increase (maximum 4 h), followed by a decline, reaching its nadir after 16 h, and finally a major upregulation phase at 24 h. Maximum induction of AP-1 was reached at a concentration of 250 nmol/L of CalC. CalC did not block PMA-induced AP1 synthesis. Gel-shift analysis in the presence of specific antibodies to c-Jun, JunB, JunD, c-Fos, and CREB/ATF showed that the AP1 complexes were probably c-Jun/c-Jun, c-Fos/c-Jun, c-Fos/JunB, or c-Jun/JunB dimers. Northern blot analysis confirmed that c-jun, junB, and c-Fos were the principal proto-oncogenes induced by CalC. To confirm that c-jun induction occurs at the transcriptional level and to examine the role of the AP1 site present in the c-jun promoter in the induction of c-jun by CalC, we performed transient transfections of c-jun promoter-CAT constructs harboring either wild-type (WT) AP1 regulatory element sites or mutant AP1 sites. CalC (250 nmol/L) induced a marked increase in CAT activity (i.e., promoter activation) with WT AP1 c-jun promoter-CAT plasmids, but the response was completely abrogated when using constructs where the AP1 site was mutated. PMA produced similar results, but the induction of the WT AP1 c-jun promoter-CAT plasmid was smaller. CalC (250 nmol/L) inhibited MAPK (p42/44) activity while stimulating c-Jun N-terminal kinase activity in a time-frame coincident with the activation of AP1. We conclude that CalC induces signaling pathways that activate AP1 and transactivate genes harboring AP1 enhancer sites independent of PKC-alpha.

Base Sequence↗
PubMed1999

Perceptions of the effect of an impending restaurant smoking ban on dining-out experience.

BACKGROUND: The introduction of bans on smoking in restaurants is frequently marred by claims that they will lead to a loss of business. METHODS: A representative sample of 3,019 South Australians age 15+ years were asked questions about dining-out frequency and perceived effects of the ban on their dining-out enjoyment and restaurant patronage. RESULTS: Sixty-one percent thought the ban would make dining out more enjoyable, 5% thought it would be less enjoyable, and 34% thought it would make no difference. Overall, 82% thought the ban would make no difference to their likelihood of dining out, 14% would be more likely to dine out, and 4% would be less likely. CONCLUSIONS: These data suggest that the public expects bans on smoking in restaurants to result in both increased enjoyment and increased patronage of restaurants.

Adolescent↗
PubMed1999

Leber's hereditary optic neuropathy mitochondrial DNA mutations in familial multiple sclerosis.

Leber's hereditary optic neuropathy (LHON) can be difficult to distinguish from optic neuritis due to multiple sclerosis (MS). For several decades an association of LHON and MS has been suspected, and within the past 7 years the LHON nucleotide (nt)-3460 and nt-11778 mtDNA mutations have been identified in several patients with MS-like phenotypes. To further study this association, we tested 42 index patients with clinically definite, familial MS for the LHON mtDNA mutations at nt-3460, nt-11778, and nt-14484. No patients had a pathogenic LHON mtDNA mutation; however, two MS patients with unilateral optic neuritis harbored the nt-15257 mtDNA polymorphism that was reported originally as a pathogenic LHON mutation. Several investigators have shown evidence that the nt-15257 mtDNA mutation is not primarily pathogenic. Therefore, we conclude that pathogenic LHON mtDNA mutations are absent or rare in unselected patients with familial, clinically definite MS (95% confidence intervals for each of the negative mutations 0-7.0%).

Adult↗
PubMed1999

Which copper is paramagnetic in the type 2/type 3 cluster of laccase?

Understanding the structure and function of the three copper atoms in the dioxygen reduction site of the blue oxidases such as laccase has been a long standing challenge. In the case of a widely studied derivative, known as type 2-depleted laccase, the removal of one copper from the cluster abolishes the EPR signal of the so-called type 2 copper. However, the present studies of isotopically enriched protein from Polyporus versicolor show that the readily replaceable copper is not active in the low-temperature EPR spectrum of fungal laccase or its difluoride adduct. The same is true for the difluoride adduct of the tree enzyme. Thus, in type 2-depleted laccase the pattern of antiferromagnetic coupling is quite different from that of the native protein or the difluoride adduct.

Copper↗
PubMed1999

Flow cytometric analysis of in vitro proinflammatory cytokine secretion in peripheral blood from multiple sclerosis patients.

The cytokines, interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and interleukin-2 (IL-2) are important endogenous proinflammatory proteins and have been linked to disease activity in multiple sclerosis. In this study, we use flow cytometric methodology to compare the secretion of IFN-gamma, IL-2, and TNF-alpha from peripheral blood-derived T cells of multiple sclerosis patients to the secretion in healthy controls. The percentages of IFN-gamma, IL-2, and TNF-alpha secreting cells are not significantly different between multiple sclerosis patients and controls. However, the TNF-alpha secreting CD3 cell percentage is correlated with the IFN-gamma and IL-2 secreting CD3 cell percentages in multiple sclerosis patients. In the controls, only the TNF-alpha secreting CD3 cell percentage is correlated with IFN-gamma. These findings show that correlated secretion of cytokines occurs in multiple sclerosis and suggest that concerted intercytokine interactions may play an important role in the disease.

Adolescent↗