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Biomedical subjects

S Miller

Publications and source records attributed to S Miller.

At least 19 recordsLinked to original sources

Peptide-induced conformational changes in class I heavy chains alter major histocompatibility complex recognition.

Small peptides, derived from endogenous proteins bind within the antigen binding groove created by the beta-pleated sheets and alpha helices of the alpha 1 and alpha 2 domains of the class I molecule of the major histocompatibility complex (MHC). However, the precise role of peptide in class I MHC conformation remains unclear. Here, we have shown that, in at least some instances, changes induced in the MHC molecule by the binding of distinct peptides can be identified as specific alterations in serological epitopes expressed on the class I protein. The nature of specific peptides expressed by class I-bearing cells may, therefore, have a dramatic influence on T cell development, self-tolerance, and alloreactivity.

Amino Acid Sequence

Insertion of SMRV-H viral DNA at the c-myc gene locus of a BL cell line and presence in established cell lines.

Mutation of the c-myc gene locus has occurred during in vitro culture of the Burkitt lymphoma cell line Namalwa. Gene cloning and sequencing of this c-myc gene locus has revealed the insertion of incomplete copies of the Squirrel Monkey Retrovirus-Human (SMRV-H) proviral genome. Insertions of the SMRV-H genome were seen in all Namalwa cell lines tested, with multiple insertions being seen in some sublines. Viral particles with the morphology of type-D retrovirus, budding from these cells, were seen by transmission EM. New insertions of the genome were produced spontaneously in these cells. The origins of the type-D retrovirus and its implications for workers in the field are discussed.

Base Sequence

Role of hypothalamic paraventricular nucleus alpha- and beta-adrenergic receptors in regulation of blood glucose, free fatty acids and corticosterone.

The potential roles of adrenergic and noradrenergic terminals in the hypothalamic paraventricular nucleus in the regulation of blood glucose and free fatty acids, the two major metabolic fuels, were examined. Corticosterone was also measured, both to assess the specificity of any effects for metabolic fuels, and because endogenous catecholamines in this site have previously been implicated in corticosterone regulation. In the first experiment adult male albino rats having chronically implanted guide cannulae aimed at the hypothalamic paraventricular nucleus or the caudate nucleus received microinjections of the agonists methoxamine (alpha 1), clonidine (alpha 2), and isoproterenol (beta) (0, 10, 30, 100 nmol/500 nl), and blood samples were taken from the tail tip. In the second experiment a different set of rats received 30 nmol clonidine or vehicle subcutaneously instead of brain microinjections. Intracranial clonidine and isoproterenol produced marked and moderate hyperglycemia, respectively; methoxamine did not alter glucose. For neither clonidine nor isoproterenol was there any difference in hyperglycemia as a function of microinjection site; also, subcutaneous clonidine injections produced the same peak glucose response as was found after both paraventricular and caudate nucleus microinjections of the same dose. Free fatty acid levels were increased by clonidine and isoproterenol, but slightly suppressed by methoxamine; the alpha agonist effects, but not the beta agonist effect, were greater after paraventricular microinjections than after caudate microinjections. Corticosterone was increased by both alpha agonists after paraventricular but not after caudate nucleus microinjections; beta agonist microinjections into the paraventricular and caudate nuclei produced equivalent corticosterone elevations. These results suggest that most, if not all, of the hyperglycemic effects of alpha and beta adrenergic agonist microinjection into the paraventricular nucleus can be ascribed to leakage of the material into the vasculature, with subsequent action at a distant site. In contrast, all 3 agonists seem capable of acting within the brain to alter free fatty acid levels. The effects on corticosterone of both the alpha 1 and alpha 2 agonists, but not the beta agonist, also appear due, at least in part, to actions within the brain. Previous suggestions that catecholamine terminals in the hypothalamic paraventricular nucleus are directly and strongly involved in metabolic fuel regulation may require reconsideration.

Animals

Reproducibility of electrophysiologic testing during antiarrhythmic therapy for ventricular arrhythmias secondary to coronary artery disease.

Although electrophysiologic studies are often used to assess antiarrhythmic drug efficacy in patients with ventricular tachycardia (VT), the reproducibility of these studies during therapy has not been definitively established. Confirmation studies were performed during drug therapy in 64 patients (51 men, mean age 63 years) with sustained ventricular arrhythmias induced during initial study to assess the reproducibility of drug effect. All patients had coronary artery disease. The stimulation protocol used included the serial introduction of up to 3 premature ventricular stimuli during sinus rhythm and with ventricular pacing at 2 pacing rates. Rapid ventricular pacing techniques were also used. Antiarrhythmic drug efficacy was confirmed in 77% of patients. Sustained VT was induced at repeat electrophysiologic study in 19% of patients during antiarrhythmic therapy that was previously thought to be effective. In summary, electrophysiologic study results during antiarrhythmic therapy exhibit significant day-to-day variability. Sustained VT can be induced during antiarrhythmic therapy that was previously defined as effective by programmed stimulation in a substantial number of patients.

Adult

Enhanced unscheduled DNA synthesis by secondary cultures of lung cells established from calorically restricted aged rats.

Unscheduled DNA synthesis (UDS) induced by two exposure levels of ultraviolet light (UV) or two concentrations of methyl methane sulfonate (MMS) was evaluated in secondary cultures of lung fibroblasts established from weanling, 11-month-old and 31-month-old female Fischer 344 rats fed ad libitum (AL) or calorically restricted (CR) diets. [3H]Thymidine incorporation as a function of UDS was highest for weanling-derived cells treated with either UV or MMS, declining consistently with increased age between cells from weanling, 11-month-old and 31-month-old animals. [3H]Thymidine incorporation as a function of UDS in cells from 11-month-old AL vs. CR rats differed only at the highest UV exposure level. In contrast, cells derived from 31-month-old CR rats exhibited UDS levels which were at least twice as high at each UV treatment level as UDS levels of cells derived from the same age AL rats. Cells from both old AL and old CR rats were shown to initiate DNA excision repair at about the same rate. Cells from CR rats, however, repaired DNA damage at an accelerated rate and completed excision repair while repair in cells from AL animals was slower and apparently did not proceed to completion. Data from this study indicate that cells from young and old AL and CR animals initiate excision repair, but demonstrate an age-related loss of UV- or MMS-stimulated [3H]thymidine incorporation in cells derived from AL animals. Cells derived from CR animals did not exhibit that age-related loss of UDS activity; rather, they showed an enhanced UDS response to DNA damage and appeared to complete ligation as the final step in excision repair. The data suggest that caloric restriction of a cell donor animal not only delays the age-associated decrease in in vitro DNA excision repair capacity in cells from that animal, but may actually enhance repair capacity.

Aging

Carbonate inhibition of leukotriene D4-dipeptidase in human serum.

Human serum contains an inhibitor of leukotriene D4 (LTD4) dipeptidase which was separated from the enzyme by ultrafiltration (Amicon, YM-10). Removal of the inhibitor resulted in a 3- to 5-fold increase in total LTD4-dipeptidase activity in the material retained by the filter. Inhibitor activity (which was assayed with a partially purified LTD4-dipeptidase) was recovered in the filtrate. Ultrafiltration of serum using YM-3, YM-1, and YC-05 membranes suggested an inhibitor molecular weight of less than 500. Elution of inhibitor activity from a Bio Gel P2 gel filtration column was identical to the elution pattern of pure carbonate. The inhibitor was heat stable (95 degrees C, 30 min), stable in 0.1 N NaOH, but rapidly inactivated by 0.1 N HCl at both 4 degrees C and 30 degrees C. Partially purified LTD4-dipeptidase was inhibited by carbonate and phosphate but not by nitrate, sulfate, or chloride. Based on these observations it was concluded that the inhibitor of LTD4-dipeptidase in human serum either was carbonate or required carbonate. The relative concentrations of LTC4, LTD4, and LTE4 appear to be important parameters in determining the duration and intensity of LT mediated reactions. The relative concentration of carbonate in serum or extracellular fluids might, therefore, be a factor in modulating localized LT mediated responses.

Carbonates

The relationship between communication attitude, anxiety, and depression in stutterers and nonstutterers.

People who stutter are frequently viewed as more anxious than nonstutterers and as being depressed. Further, a strong and pervasive stereotype is held by nonstutterers that people who stutter are guarded, nervous, and tense. This study examined self-perceptions of general state and trait anxiety, depression, and communication attitude in matched groups of stutterers and nonstutterers. Results refute the assertion that people who stutter are more anxious or depressed than those who do not. Anxiety and depression are not related to self-ratings of stuttering severity. Communication attitude is negative for this group of people who stutter and becomes increasingly negative as self-ratings of stuttering become more severe. People who stutter, grouped by severity rating, differed in the strength of the relation between measures of communication attitude, anxiety, and depression. Findings suggest that the anxiety of people who stutter is restricted to their attitude towards communication situations and that it is a rational response to negative communication experiences.

Adolescent

A new look at mandibular growth--a preliminary report.

Cephalometric radiographs of 42 growth study subjects (21 males, 21 females) were the basis of an investigation into the longitudinal growth of the mandible from 5 to 20 years using a digitizer program capable of generating curved outlines through groups of four points. In this presentation mean plots for all subjects at 5, 10, 15, and 20 years of age, variously superimposed, confirmed the previous theories of Björk and Skieller (1983) with regard to mandibular rotation and provide a visual representation of the processes of mandibular growth.

Adolescent

Total laryngectomy with primary voice restoration.

Forty-three patients were prospectively studied following tracheo-oesophageal puncture at the time of laryngectomy (primary voice restoration). Blom-Singer voice prostheses were used. The surgery was regarded as successful if a patient continued to use the voice prosthesis as the major means of communication with clear intelligibility 4 months after the operation. Using this criterion, the success in this series was 70%. No attempt was made to assess the quality of speech. Complications and causes of failure are discussed.

Esophagostomy

1-Aminocyclopentane-trans-1,3-dicarboxylic acid induces glutamine synthetase activity in cultured astrocytes.

In this study we have investigated the effect of excitatory amino acids on the activity of glutamine synthetase, a glial-specific enzyme that plays a key role in the regulation of glutamate concentration in the CNS. We found that of L-glutamate, N-methyl-D-aspartate, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate, kainate, and 1-aminocyclopentane-trans-1,3-dicarboxylic acid (trans-ACPD), only the metabotropic glutamate receptor agonist trans-ACPD had an effect on glutamine synthetase specific activity in cultures of rat type I cortical astrocytes. Exposure of astrocytes to 1.0 mM trans-ACPD for 24 h resulted in an increase in glutamine synthetase activity to 149 +/- 11% of that in control cultures. This effect was concentration dependent, stereoselective, and blocked by cycloheximide. In addition, the increase in glutamine synthetase activity occurred at lower concentrations of trans-ACPD that did not produce morphological alterations or lysis of the astrocytes as measured by the lactate dehydrogenase content. These findings are consistent with the hypothesis that activation of the metabotropic excitatory amino acid receptor in astrocytes is coupled to the regulation of an enzyme essential to the metabolism and recycling of the excitatory transmitter L-glutamate.

Amino Acids

A clinical evaluation of trichomoniasis in San Jose, Costa Rica using the InPouch TV test.

OBJECTIVE: to determine the prevalence of trichomoniasis in San Jose, Costa Rica, comparing two methods, the InPouch TV test and the saline wet mount. METHODS: One hundred symptomatic and asymptomatic female patients at two hospitals and at a sexually transmitted disease (STD) clinic were evaluated. Vaginal discharge was the most prevalent genitourinary abnormality among symptomatic patients. The patients were between 18 and 70 years old. Fifty-seven were from the STD clinic, 43 from the two hospitals. A saline wet mount and a culture were taken from each patient. The culture employed a new procedure for diagnosis of trichomonads, the InPouch TV test (BioMed Diagnostics, San Jose, CA). RESULTS: Thirteen of the 100 patients were culture positive, two of whom were wet mount positive. No wet mount positives were culture negative. Eleven of the positive tests were from the STD clinic and two were from the hospitals. CONCLUSIONS: The results of this initial epidemiologic study indicate a prevalence of 19% for trichomoniasis in the STD clinic population and 4.6% in the hospitals group. Trichomonas vaginalis was not diagnosed by laboratory methods prior to this study. The InPouch TV test has a selective fungicidal and bactericidal, enriched proteose-peptone medium which provides a sensitivity of 4 organisms per ml and a 1 year shelf life at room temperature. This in vitro culture test demonstrated unique capabilities as a transport and culture medium. Its procedure offers simplicity in application and an excellent visualisation of trichomonads.

Adult

Class III malocclusion: surgery or orthodontics?

The pre-treatment lateral cephalograms of two groups of 20 subjects with severe Class III malocclusions were compared. One group had been considered suitable for orthodontic correction by the diagnosing clinician and the other offered orthognathic surgery. The most significant differences between the groups were in angle ANB, M/M ratio (P less than 0.001), lower incisor inclination and Holdaway angle (P less than 0.01). Threshold values for angle ANB and lower incisor angulation below which surgery was almost always carried out were--4 and 83 degrees, respectively.

Adolescent

Telephone counseling improves adherence to colposcopy among lower-income minority women.

PURPOSE: A randomized trial was conducted to evaluate the impact of a telephone counseling intervention to improve patient adherence to colposcopic examination for suspected cervical intraepithelial neoplasia (CIN). METHODS: Subjects were lower-income, minority women who missed a scheduled initial appointment for colposcopy at an urban medical clinic. Patients were randomly assigned to either a control condition (n = 42) or a telephone counseling condition (n = 48). The 15-minute, structured telephone counseling intervention protocol addressed educational, psychosocial, and practical barriers to colposcopy adherence. RESULTS: The most common patient-reported barriers to colposcopy adherence included a lack of understanding of the purpose of colposcopy (50%), worry about or fear of cancer (25%), and forgetting (23%). Telephone counseling was found to be highly effective in addressing these barriers and improving adherence to diagnostic follow-up and treatment. Of patients in the control condition, 43% complied with a rescheduled colposcopy appointment, compared with 67% in the telephone counseling condition. Logistic regression analysis indicated that the effect of telephone counseling was independent of sociodemographic confounder variables (odds ratio = 2.6; P less than .003). Additionally, 74% of patients who received the initial telephone counseling adhered to recommended treatment, compared with 53% of patients in the control condition. CONCLUSION: Brief, structured telephone contact may be a cost-effective mechanism for improving adherence to diagnostic follow-up and treatment for a variety of cancer screening tests.

Adolescent

Screening for multiple endocrine neoplasia type 2A with DNA-polymorphism analysis.

Nine chromosome 10 DNA markers (FNRB, D10S34, D10Z1, MEN203, D10S94, RBP3, D10S15, MBP [48.11], D10S22) were typed in two large Canadian pedigrees with multiple endocrine neoplasia type 2A (MEN 2A). These markers and the gene for MEN 2A (MEN2A) are believed to be in one linkage group spanning approximately 15 cM (male). MEN203 and D10S94 were informative and tightly linked to MEN2A with no recombinants observed in 26 meiotic events. D10S15 (MCK2), widely used in DNA genotyping predictions, demonstrated two recombinants in these two families. The use of multiple flanking markers increases both the likelihood of informativeness and the accuracy of risk assessments for predictive testing. We were able to assign a risk estimate for all 10 at-risk individuals.

Female