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Biomedical subjects

S Bruce

Publications and source records attributed to S Bruce.

At least 19 recordsLinked to original sources

Crystallization and preliminary X-ray analysis of ocr, the product of gene 0.3 of bacteriophage T7.

Ocr, the product of gene 0.3 of bacteriophage T7, prevents the action of restriction endonucleases of the host bacteria. The amino-acid sequence of ocr has less than 20% similarity to any protein of known three-dimensional structure. Ocr has been crystallized in a number of different crystal forms and X-ray data for the seleno-L-methionine-substituted form has been collected to a resolution of 1.8 A. The presence of caesium was found to be required for good crystal growth. Anomalous X-ray data was used to identify possible positions for Se and Cs atoms in the unit cell.

Amino Acid Sequence↗

Angiotensin-I converting enzyme genotype-dependent benefit from hormone replacement therapy in isometric muscle strength and bone mineral density.

Low bone mineral density (BMD) and muscle weakness are major risk factors for postmenopausal osteoporotic fracture. Hormone replacement therapy (HRT) reverses the menopausal decline in maximum voluntary force of the adductor pollicis and reduces serum angiotensin-I converting enzyme (ACE) levels. The insertion (I) allele of the ACE gene polymorphism is associated with lower ACE activity and improved muscle efficiency in response to physical training. Therefore, we examined whether the presence of the I allele in postmenopausal women would affect the muscle response to HRT. Those taking HRT showed a significant gain in normalized muscle maximum voluntary force slope, the rate of which was strongly influenced by ACE genotype (16.0 +/- 1.53%, 14.3 +/- 2.67%, and 7.76 +/- 4.13%, mean +/- SEM for II, ID, and DD genotype, respectively; P = 0.017 for gene effect, P = 0.004 for I allele effect). There was also a significant ACE gene effect in the response of BMD to HRT in Ward's triangle (P = 0.03) and a significant I allele effect in the spine (P = 0.03), but not in the neck of femur or total hip. These data suggests that low ACE activity associated with the I allele confers an improved muscle and BMD response in postmenopausal women treated with HRT.

Bone Density↗

The relationship between comorbid personality disorders and treatment received in patients with anxiety disorders.

Few studies have addressed the relationship between the presence of a comorbid personality disorder and the amount of psychiatric treatment received by patients with an Axis I disorder. This issue has not been studied in patients with anxiety disorders. In a prospective, naturalistic, longitudinal study of anxiety disorders, 526 subjects were assessed with the Personality Disorder Examination, and types of treatment received in 1991 and 1996 were identified. In 1991, compared to subjects without a personality disorder, subjects with a personality disorder were as likely to receive medication and they received a greater number of medications. Subjects with borderline personality disorder were more likely to receive heterocyclic antidepressants and interventions characteristic of psychodynamic psychotherapy and cognitive therapy; they also reported receiving a greater number of medications and types of psychosocial treatment than other subjects. In 1996, subjects with borderline personality disorder were more likely to receive psychodynamic interventions. These findings suggest that in patients with an anxiety disorder, the presence of a comorbid personality disorder is associated with receiving a greater number of medications but not with a greater likelihood of receiving pharmacologic or psychosocial treatment. However, the presence of borderline personality disorder is associated with a greater likelihood of receiving, and receiving a greater number of, certain types of somatic and psychosocial treatments.

Adult↗

Cardiac sympathetic denervation in Parkinson disease.

BACKGROUND: In Parkinson disease, orthostatic hypotension can result from L-dopa treatment or from sympathetic neurocirculatory failure. The latter is detected by abnormal blood pressure responses to the Valsalva maneuver and can be associated with loss of functional cardiac sympathetic nerve terminals. OBJECTIVE: To determine the frequency of cardiac sympathetic denervation in Parkinson disease, with or without sympathetic neurocirculatory failure, and its association with disease duration, severity, and L-dopa treatment DESIGN: Intergroup comparisons in resting patients. SETTING: National Institutes of Health Clinical Center, Bethesda, Maryland. PATIENTS: 29 patients with Parkinson disease (9 with sympathetic neurocirculatory failure, 10 who had stopped receiving or had never been treated with L-dopa), 24 patients with multiple-system atrophy (17 with sympathetic neurocirculatory failure, 8 receiving L-dopa), 7 patients with pure autonomic failure, 33 controls with episodic or persistent orthostatic intolerance without sympathetic neurocirculatory failure, and 19 normal volunteers. MEASUREMENTS: Beat-to-beat blood pressure responses to the Valsalva maneuver, interventricular septal 6-[18F]fluorodopamine-derived radioactivity, cardiac extraction fraction of [3H]norepinephrine, appearance rate of norepinephrine in coronary sinus plasma (cardiac norepinephrine spillover) and venous-arterial differences in levels of dihydroxyphenylglycol (DHPG) and endogenous L-dopa. RESULTS: Of the 29 patients with Parkinson disease, 9 with sympathetic neurocirculatory failure and 11 without had low septal 6-[18F]fluorodopamine-derived radioactivity (2861 +/- 453 Bq/mL per MBq/kg and 5217 +/- 525 Bq/mL per MBq/kg, respectively). All 6 patients with Parkinson disease and decreased 6-[18F]fluorodopamine-derived radioactivity who underwent right-heart catheterization had a decreased cardiac extraction fraction of [3H]norepinephrine and virtually no cardiac norepinephrine spillover or venous-arterial increments in plasma levels of DHPG and L-dopa. Sympathetic neurocirculatory failure and decreased 6-[18F]fluorodopamine-derived radioactivity were unrelated to disease duration, disease severity, or L-dopa treatment CONCLUSIONS: Many patients with Parkinson disease-including all those with sympathetic neurocirculatory failure-have evidence of cardiac sympathetic denervation. This suggests that loss of catecholamine innervation in Parkinson disease occurs in the nigrostriatal system in the brain and in the sympathetic nervous system in the heart

Adult↗

Armadillo exposure and Hansen's disease: an epidemiologic survey in southern Texas.

BACKGROUND: Naturally occurring leprosy has been demonstrated in wild nine-banded armadillos (Dasypus novemcinctus ). This suggests a possible mode of transmission of human leprosy in regions where armadillo contact is prevalent. OBJECTIVE: Our purpose was to study the possible relationship between armadillo exposure and Hansen's disease. METHOD: One hundred one patients (67 men, 34 women) with established Hansen's disease seen in the Hansen's Disease Clinic in Houston, Texas, were questioned about their exposure to armadillos. These patients were divided into two groups: Asian (n = 32) and non-Asian (n = 69). RESULTS: Seventy-one percent of the non-Asian patients surveyed reported either direct or indirect armadillo exposure. None of the Asian patients reported armadillo exposure (P <.001). Of the non-Asian patients, 75.4% had lepromatous disease versus 50.0% of the Asian patients (P <.001). The average age at diagnosis for the non-Asian group with Hansen's disease in this study was 51 versus 38 years for the Asian group (P <.001). CONCLUSION: Although it is yet to be determined whether direct transmission from the armadillo to human occurs, it is likely based on the high incidence of armadillo exposure in non-Asian patients with Hansen's disease in our study population that this animal acts as a reservoir for human disease. However, the Asian patients reporting no known armadillo exposure likely obtained the disease from person-to-person contact in their respective countries of origin where Hansen's disease has a much higher prevalence.

Adolescent↗

Informed consent.

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Clinical Competence↗

Cutaneous sarcoidosis in a patient with Philadelphia-positive chronic myelogenous leukemia treated with interferon-alpha.

A patient with Philadelphia-positive (Ph+) chronic myelogenous leukemia (CML) was diagnosed with cutaneous sarcoidosis after treatment with interferon-alpha (IFN-alpha). Following IFN-alpha dose reduction, the skin lesions disappeared. Few cases of sarcoidosis associated with IFN treatment have been reported, and only in one patient with pre-existing CML. Our patient was unique in that (1) the sarcoidosis was induced by the IFN-alpha treatment alone, (2) it developed de novo, and (3) it was confined to the skin.

Female↗

A randomized phase II study comparing four different interferon therapies in patients with recalcitrant condylomata acuminata.

BACKGROUND: Interferon (IFN) alpha and IFN gamma have synergistic in vitro and in vivo effects and have each been used in the treatment of anogenital condylomata acuminata. STUDY GOALS: To compare the efficacy and safety of regional 3 x 10(6) U IFN alpha (Group A), 3 x 10(6) U IFN gamma (Group B), 1.5 x 10(6) U IFN alpha plus 1.5 x 10(6) U IFN gamma (Group C), and 3 x 10(6) U IFN alpha plus 1.5 x 10(6) U IFN gamma (Group D) in the treatment of recalcitrant anogenital condylomata acuminata. STUDY DESIGN: Six-week courses of regional IFNs were administered in a randomized, double-blind, multicenter study. Response was assessed as change in the total area affected by condylomata. RESULTS: The treatments of Groups A, B, and C were similarly effective (complete response in 13.6%, 18.5%, and 16.0%, respectively). Group D had the lowest rate of complete response (3.8%), but this combination was the most effective when partial and complete responses were combined (73.0%). CONCLUSION: Regional IFN is a moderately effective and safe treatment in patients with recalcitrant anogenital condylomata acuminata. Combinations of IFNs alpha and gamma were not superior to IFN monotherapy.

Condylomata Acuminata↗

Use of Voigt lineshape for quantification of in vivo 1H spectra.

Quantification of NMR visible metabolites by spectral modeling usually assumes a Lorentzian or Gaussian lineshape, despite the fact that experimental lineshapes are neither. To minimize systematic fitting errors, a mixed Lorentzian-Gaussian (Voigt) lineshape model was developed. When tested with synthetic FIDs, the Voigt lineshape model gave more accurate results (maximum error 2%) than either Lorentzian (maximum error 20%) or Gaussian models (maximum error 12%). The three lineshape models gave substantially different peak areas in an in vitro experiment, with the Voigt model having a much lower chi2 (2.1 compared with 5.2 for the Lorentzian model and 6.2 for the Gaussian model). In a group of 10 healthy volunteers, fitting of 1H spectra from cerebral white matter gave significantly different peak areas between the methods. Even when area ratios were taken, the Lorentzian model gave higher values (+5% for NAA/choline and +2% for NAA/creatine) than the Voigt lineshape model, whereas the Gaussian model gave lower values (-2% and -1%, respectively).

Brain Chemistry↗

High-level expression of recombinant human fibrinogen in the milk of transgenic mice.

Fibrinogen is a complex plasma protein composed of two each of three different polypeptide chains. We have targeted expression of r-human fibrinogen to the mammary gland of transgenic mice. Three expression cassettes, each containing the genomic sequence for one of the three human fibrinogen chains controlled by sheep whey protein beta-lactoglobulin promoter sequences, were coinjected into fertile mouse eggs. Southern blot analysis demonstrated that more than 80% of the transgenic founders contained all three fibrinogen genes. Reducing sodium dodecyl sulfate polyacrylamide gel electrophoresis of milk from the highest producing founder animal demonstrated the presence of human fibrinogen subunits at concentrations of 2000 micrograms/ml. In several animals with a balanced ratio of the individual fibrinogen subunits, up to 100% of the protein was incorporated into fully assembled fibrinogen hexamers. Incubation of the transgenic milk with thrombin and factor XIII resulted in a cross-linked fibrin clot, indicating that a major portion of the secreted fibrinogen was functional. These studies represent the first report of high-level biosynthesis and secretion of a functional, complex, hexameric protein in the milk of a transgenic animal.

Animals↗

Evidence that a low-fat diet reduces the occurrence of non-melanoma skin cancer.

The effect of a low-fat diet on occurrence of non-melanoma skin cancer was examined in a 2-year dietary intervention trial. A total of 101 skin-cancer patients were randomized either to a control group that consumed, on average, 38% of caloric intake as fat, and in which no changes in dietary habits were introduced, or to a low-fat dietary-intervention group, in which patients were instructed to limit their calories from fat to 20% of total caloric intake. Patients were examined at 4-month intervals by dermatologists blinded to their dietary assignments. Nutrient analyses, conducted at each of the 4-month follow-up visits, indicated that the % calories of fat consumed in the intervention group had been reduced to 21% at 4 months and remained below this level throughout the 2-year period. There were no significant differences in total calories consumed, or in mean body weights, between the control and the intervention groups. Nor were there significant group differences in P/S ratios until month 24. Numbers of new skin cancers treated at each examination were analyzed in 8-month periods of the 2-year study. Comparisons of skin-cancer occurrences revealed no significant changes in the control group from baseline values. However, cancer occurrence in the low-fat intervention group declined after the first 8-month period and reached statistical significance by the last 8-month period. Patients in this group had significantly fewer cancers in the last 8-month period than did patients in the control group. In addition, there was a significant reduction in the number of patients developing skin cancer in the last 8-month period, as compared with the first 8-month period, within the low-fat intervention group. There were no significant changes in the control group. These data indicate that a low-fat diet can significantly reduce occurrence of a highly prevalent form of cancer.

Carcinoma↗

Herpesvirus-like DNA sequences in non-Kaposi's sarcoma skin lesions of transplant patients.

Herpesvirus-like DNA sequences (KSHV) have been reported to be associated with various forms of Kaposi's sarcoma (KS). To determine if KSHV was associated with other proliferative skin lesions from non-AIDS immunocompromised patients, 33 skin lesions (basal cell carcinomas, squamous cell carcinomas, actinic keratoses, verruca vulgaris, atypical squamous proliferations, and seborrhoeic keratosis) from 4 organ-transplant patients receiving immunosuppressive therapy were tested for KSHV by PCR. KSHV sequences were detected in 82% of these skin lesions. Our results suggest that KSHV is associated with lesions other than KS in non-AIDS immunocompromised patients, and may also be involved in the pathogenesis of the various forms of proliferative skin lesions from organ-transplant patients.

Base Sequence↗

Cetirizine and astemizole therapy for chronic idiopathic urticaria: a double-blind, placebo-controlled, comparative trial.

BACKGROUND: Cetirizine and astemizole have been shown to be safe and effective in the treatment of patients with chronic idiopathic urticaria. Cetirizine brings about clinical benefit more rapidly. OBJECTIVE: The purpose of this study was to compare the efficacy of single daily doses of cetirizine and astemizole in relieving the symptoms of chronic idiopathic urticaria, with particular emphasis on the commencement of action. METHODS: Patients with chronic idiopathic urticaria were randomly assigned to relieve either 10 mg of cetirizine, 10 mg of astemizole, or placebo for 4 weeks in a multicenter double-blind trial. Patients rated symptom severity each night, and investigators rated symptoms weekly. RESULTS: One hundred eighty-seven patients were enrolled in the trial; 180 were included in the safety analysis and 177 were included in at least one efficacy analysis. Both cetirizine and astemizole were significantly superior to placebo in relieving symptoms of chronic idiopathic urticaria. Both patients' and investigators' ratings indicated that cetirizine acted more rapidly. Both active treatments were well tolerated, and the incidence of somnolence did not differ statistically between cetirizine (14.5%) and astemizole (10.3%). CONCLUSION: Both cetirizine and astemizole provide effective relief of the symptoms of chronic idiopathic urticaria with similar side-effect profiles. However, clinical benefit occurs significantly more rapidly with cetirizine.

Adult↗

Chronic cutaneous lupus erythematosus mimicking mycosis fungoides.

Mycosis fungoides, which is characterized by a malignant infiltrate of T lymphocytes involving the epidermis, can be confused with other inflammatory skin diseases. We report the case of a patient with skin lesions containing an infiltrate of atypical lymphocytes with epidermotropism. This patient's condition was initially diagnosed as mycosis fungoides. Repeated biopsy samples had the histologic features of chronic cutaneous lupus erythematosus. The patient had a strongly positive antinuclear antibody response and the clinical lesions responded to hydroxychloroquine, however, and these findings led to an altered diagnosis. Other disorders that either clinically or histologically mimic mycosis fungoides are reviewed, and the diagnostic evaluation of patients in whom mycosis fungoides is suspected is summarized. Chronic cutaneous lupus erythematosus should be added to the list of diseases that can mimic mycosis fungoides.

Antibodies, Antinuclear↗

Computer analysis of the early diastolic notch in Doppler sonograms of the uterine arteries.

This article describes a set of processing and analysis techniques for automated identification and quantification of the early diastolic notch (EDN), a feature of Doppler sonograms from the uterine arteries which has been associated with adverse pregnancy outcomes such as preeclampsia and intrauterine growth retardation. Examples covering different sonogram types are provided to illustrate the effectiveness and reproducibility of the processing/analysis tools. Also, a receiver-operating characteristic-based evaluation of the EDN quantification and pulsatility indexes is presented, which examines the ability to predict hypertension and/or intrauterine growth retardation, using a set of uterine Doppler sonograms from 92 patients acquired at 18 weeks of gestation. In summary, the ROC results confirm the link between the EDN and abnormal pregnancy outcomes, and suggest that EDN quantification has a higher diagnostic accuracy than the pulsatility index, which characterises the flow waveform in a global manner and therefore does not take explicitly into account the localised nature of the EDN. Quantification of the EDN at 18 weeks of gestation appears to best predict the most severely abnormal pregnancy outcomes.

Arteries↗

Basal cell carcinoma on the scalp of an Indian patient.

BACKGROUND: Basal cell carcinoma (BCC) is the most common malignancy in whites, but it rarely occurs in dark persons. OBJECTIVE: To report a BCC on the hairy scalp of an Asian Indian female with no obvious risk factors except previous scalp trauma. METHODS: We review the English literature concerning BCC in Indians, and compare this with data for North American blacks and whites; and reports of BCC arising in areas of prior trauma. RESULTS/CONCLUSION: Skin cancer accounts for 1-2% of malignancies in blacks and Indians, compared with one-third of neoplasms in whites. BCC comprises 75% of skin cancers in whites, but squamous cell carcinoma represents 60-65% of skin cancers in blacks and Indians. Although most BCCs occur in sun-exposed areas in whites, blacks, and Indians, a significant percentage also develop in photoprotected areas. Trauma may be a significant risk factor for BCC, either with actinic damage or alone, as in our case.

Black People↗