A collagenous sequence in a prokaryotic hyaluronidase.
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Amino Acid Sequence↗
Biomedical subjects
M Stern
Publications and source records attributed to M Stern.
A model for fetal cleft lip repair in lambs.
Fetal wounds heal without inflammation and scar formation. This phenomenon may, in the future, be applicable to human cleft lip and palate repair. However, extensive experimental work must first be done to document the benefits of in utero repair. We developed a large animal model for creation and repair of a complete cleft lip and alveolus using fetal lambs. The cleft lip and alveolus deformity was created in eight 75-day-gestation fetuses (term = 145 days) and either repaired in three layers or left unrepaired. There were four sham-operated fetuses, and all animals were alive at harvest. Repaired, unrepaired, and control fetuses were harvested at 7, 14, 21, and 70 days following surgery. The unrepaired fetuses demonstrated a complete cleft lip and alveolus with an oronasal fistula. The maxilla was asymmetrical, with the greater segment deviated toward the cleft and with decreased anterior maxillary width. In contrast, repaired cleft lip and alveolus animals showed no scar, normal thickness of the lip, and a symmetrical maxilla. Histologic analysis of the repaired wounds showed evidence of tissue regeneration without scar formation. The results of this preliminary study indicate that the fetal lamb cleft lip and alveolus model is technically feasible with an excellent survival rate. Healing occurs without scar formation. In the repaired animals, the maxilla was symmetrical. This model will be used to document facial growth following in utero repair of a cleft lip and alveolus.
Alveolar Process↗
Topical minoxidil in alopecia areata: no effect on the perifollicular lymphoid infiltration.
The therapeutic value of topical minoxidil in alopecia areata (AA) has been investigated in recent years, with variable results. Although the mechanism whereby minoxidil may stimulate hair regrowth in some cases of AA has not yet been elucidated, there have been reports of a decrease in the perifollicular infiltrates of mononuclear leukocytes (MNC)--particularly T lymphocytes--that characterize this condition, in patients "responding" to topical minoxidil. In a randomized and double-blind study, we have investigated the effect of 5% topical minoxidil versus placebo (vehicle alone) on the extent and composition of the perifollicular MNC infiltration in 20 patients having extensive AA (26-99% scalp hair loss). The proportions of hair follicles showing perifollicular infiltration by MNC and their main subsets were determined with histologic and immunohistochemical stainings of scalp biopsies obtained before treatment, after 12 weeks of randomized double-blind minoxidil versus placebo treatment, and after 12 additional weeks during which all patients received minoxidil. Six of the patients showed cosmetically acceptable hair regrowth (CAHR) at the end of the 24 weeks and this was associated with a significant decrease in the proportions of follicles infiltrated by total T and B lymphocytes, macrophages, and Langerhans cells at week 12, and by total T lymphocytes at week 24. However, no significant differences in the extent or composition of the perifollicular infiltrates were detected at week 12 between patients receiving minoxidil and placebo, or between the week-12 and week-24 biopsies of those patients who first received placebo and then minoxidil. These findings indicate that in AA the reduction in perifollicular T-cell infiltration associated with CAHR is not attributable to an effect of topical minoxidil.
Adolescent↗
Detection of mycobacterial DNA in pleural fluid from patients with tuberculous pleurisy by means of the polymerase chain reaction: comparison of two protocols.
BACKGROUND: The detection of mycobacterial DNA in clinical samples on the basis of the polymerase chain reaction is a promising approach for the rapid diagnosis of tuberculous infections. No consensus exists, however, about which protocols are most sensitive, and the usefulness of this approach in the diagnosis of tuberculous effusions has been assessed in few patients. METHODS: The sensitivity of two protocols was compared for the detection of DNA from Mycobacterium tuberculosis in samples containing known amounts of mycobacterial DNA and in DNA extracted from 15 tuberculous pleural effusions. The results obtained for pleural fluid have been compared with cytological findings and with results obtained by standard microbiological techniques. RESULTS: Mycobacteria could be detected by acid fast staining in none and by culture in three of the 15 pleural fluid samples. A protocol based on the detection of the IS6110 insertion element (which could detect one mycobacterial genome/sample reproducibly) gave a positive result in nine of the 15 tuberculous effusions, though some samples were only intermittently positive (p less than 0.05 compared with culture). In contrast, a protocol based on the detection of the gene coding for the 65 kD mycobacterial antigen (which could detect mycobacterial genomes only if there were at least 10/sample) gave a positive result in three of the 15 tuberculous effusions. Pleural fluid that was always positive with the amplification procedure detecting the IS6110 sequence contained more neutrophils (30% (SD 27%)) than samples that were intermittently positive or always negative (3% (3%)); mycobacterial DNA was never detected in the four samples containing less than 1% neutrophils. CONCLUSIONS: The amplification of the IS6110 insertion element represents a rapid and sensitive means of detecting M tuberculosis in tuberculous effusions. The enrichment of cells containing mycobacteria (possibly neutrophils) before DNA extraction may be required to improve the sensitivity of this approach.
DNA Transposable Elements↗
The metabolic profile of NIDDM is fully established in glucose-tolerant offspring of two Mexican-American NIDDM parents.
NIDDM patients with overt fasting hyperglycemia are characterized by multiple defects involving both insulin secretion and insulin action. At this point of the natural history of NIDDM, however, it is difficult to establish which defects are primary and which are acquired secondary to insulinopenia and chronic hyperglycemia. To address this question, we have studied the glucose-tolerant offspring (probands) of two Mexican-American NIDDM parents. Such individuals are at high risk for developing NIDDM later in life. The probands are characterized by hyperinsulinemia in the fasting state and in response to both oral and intravenous glucose. Insulin-mediated glucose disposal (insulin clamp technique), measured at two physiological levels of hyperinsulinemia (approximately 240 and 450 pM [approximately 40 and 75 microU/ml]), was reduced by 43 and 33%, respectively. During both the low- and high-dose insulin clamp steps, impaired nonoxidative glucose disposal, which primarily represents glycogen synthesis, was the major defect responsible for the insulin resistance. During the lower dose insulin clamp step only, a small decrease in glucose oxidation was observed. No defect in suppression of HGP by insulin was demonstrable. The ability of insulin to inhibit lipid oxidation (measured by indirect calorimetry) and plasma FFA concentration was impaired at both levels of hyperinsulinemia. These results indicate that the glucose-tolerant offspring of two NIDDM parents are characterized by hyperinsulinemia and manifest all of the metabolic abnormalities that characterize the fully established diabetic state, including insulin resistance, a major impairment in nonoxidative glucose disposal, a quantitatively less important defect in glucose oxidation, and a diminished insulin-mediated suppression of lipid oxidation and plasma FFA concentration.
Adult↗
Identification and characterization of inebriated, a gene affecting neuronal excitability in Drosophila.
On the basis of behavioral interactions with mutations in a potassium channel gene of Drosophila--Shaker (Sh)--we have isolated mutations in a new gene called inebriated (ine). In a wildtype background, ine mutants display no observable behavioral defects. However, in a Sh mutant background, ine mutations cause downturned wings and an indented thorax. This distinctive phenotype is also exhibited by flies of other genotypes that cause extreme neuronal hyperexcitability. We utilized the potassium channel blocking drugs quinidine and dideoxy forskolin (DDF) to test the effects of ine on synaptic transmission. DDF and ine mutations each potentiated the effects of quinidine on synaptic transmission, but neither had any observable effects in the absence of quinidine. Application of DDF to ine mutants had no effects either in the presence or absence of quinidine. We conclude that ine mutations increase neuronal membrane excitability and perhaps block a DDF-sensitive potassium channel.
Animals↗
Action potential response of the corneal nerves to irritants.
The cornea, in addition to its refractive function for the eye, and by way of its very dense sensory innervation, serves a very important protective function for the visual organ. The cornea receives mainly sensory innervation from the first division of the trigeminal ganglion and a sparse amount of sympathetic fibers. The sensory nerves carry out their protective function by responding to various types of stimuli in a way so that they are all perceived psychologically as painful. Neurophysiological data indicates that, despite the morphological similarity of free-nerve endings in the cornea, they are differentiated functionally. A concentration series, (0.005 to 10% solution in saline), of various potential irritants (phosphate detergent, baby shampoo, liquid chlorine bleach, herbal shampoo, onion juice, SDS, and sodium chloride) was applied directly to the cornea of the anesthetized rabbit. Neural activity was assessed from extra-cellular records of long ciliary nerve over a ten second application period, and for ten seconds following stimulus removal. Baby shampoo was non-stimulatory over the applied concentration range. Sodium chloride, on the other hand, exhibited linear response dynamics over the range of 0.01 to 5% (p < 0.001). SDS was highly stimulatory, but showed no predictable concentration or response relationship. All of the other irritants tested responded in a logarithmic fashion. This suggests that the application of neurophysiological techniques to assess the pain and potential inflammatory aspects of a substance for human use can be monitored in this fashion. Moreover, response profiles for various classes of compounds and homologous series, as well as pH and osmolality, can be established.
Action Potentials↗
[Single lung transplantation].
Thirteen single lung transplantations have been performed in our department for non-infected end-stage lung diseases. Two patients died after surgery; a female patient died of uterine carcinoma one year and six months after the operation. The remaining ten patients are alive; they have resumed an active life and often working. The number of single lung transplantation is rapidly growing in the world, whereas heart-lung transplantation is regressing considerably.
Adult↗
[IgA endomysium antibodies. Detection in children with celiac disease].
BACKGROUND: Epidemiology of coeliac disease gives rise to the search for a non-invasive, reliable screening test. METHODS: We looked for IgA anti-endomysial antibodies (IgA-EmA) in 103 sera of 90 children (age: 2 months-13.9 years) using an indirect immunofluorescence method on monkey oesophagus sections. In 44 patients, the diagnosis of coeliac disease was confirmed fulfilling new criteria of the European Society of Pediatric Gastroenterology and Nutrition. RESULTS: All 24 coeliac disease patients with an initial flat mucosa had IgA-EmA (sensitivity 100%). In 36% of coeliac disease patients adhering to a gluten-free diet we found IgA-EmA. None of 46 patients in whom coeliac disease had been excluded by jejunal biopsy had IgA-EmA (specificity 100%). The sera of 102 blood-donors were used as controls and showed a test specificity of 99%. In coeliac disease patients, the titer of IgA-EmA declined during gluten-free diet by 0.66 steps/month on average, and rose 1.76 steps/month during gluten challenge. CONCLUSIONS: These results confirm the diagnostic significance of IgA-EmA for patients with suspected coeliac disease and their value for monitoring treatment even in young children (below 2 years).
Adolescent↗
Unstable asthma and theophylline.
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Adult↗
Hyaluronidase levels in urine from Wilms' tumor patients.
The pathophysiology of Wilms' tumor is associated with major alterations in hyaluronic acid metabolism. Elevated levels of both hyaluronic acid and a hyaluronic acid-stimulating activity occur in the urine and serum of patients with this tumor. In the current study, we describe elevated levels of urinary hyaluronidase in five patients with Wilms' tumor. Following surgical removal of the tumor, enzyme levels decreased toward normal. Characterization of enzyme activity indicates that hyaluronidase may be produced by the tumor itself. Alternatively, normal renal tissue may also be producing enzyme in a compensatory response to the elevated hyaluronic acid levels in these patients. We suggest that urinary hyaluronidase can be used as an additional marker for Wilms' tumor.
Biomarkers, Tumor↗
Badges of the dental profession. The Chairman's Medallion of the London Chapter of the Alpha Omega Fraternity.
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Emblems and Insignia↗
The epidemiology of Parkinson's disease. A case-control study of young-onset and old-onset patients.
While the cause of Parkinson's disease (PD) remains unknown, recent evidence suggests that certain external factors, ie, environmental agents, may act as neurotoxins, initiating the chain of oxidative reactions that ultimately destroy neurons in the substantia nigra. Young-onset PD might result from greater exposure to a putative neurotoxin. This hypothesis has rekindled interest in the epidemiology of PD. We therefore conducted a detailed analysis of various environmental exposures and early life experiences in 80 patients with old-onset PD (at an age older than 60 years), 69 young-onset patients (younger than 40 years), and 149 age- and sex-matched control subjects. Contrary to previous reports, we were unable to implicate well water or exposure to herbicides, pesticides, or industrial toxins as significant PD risk factors. A residential history of rural living was reported by more patient cases than control subjects and was marginally significant. On the other hand, at least one episode of head trauma "severe enough to cause vertigo, dizziness, blurred or double vision, seizures or convulsions, transient memory loss, personality changes, or paralysis" occurred significantly more often prior to disease onset in patients with both young-onset and old-onset PD than in control subjects (odds ratio = 2.7). When adjusted for head trauma and rural living, smoking was inversely associated with PD, as has been previously reported (odds ratio = 0.5). There were no significant differences in early life experiences or environmental exposures between young-onset and old-onset patients. We suggest that the risk of developing PD is influenced by a variety of factors.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Pulmonary embolectomy: a 20-year experience at one center.
Between 1968 and 1988, 96 consecutive patients with acute massive pulmonary embolism underwent pulmonary embolectomy under cardiopulmonary bypass. The operative mortality rate was 37.5%. We analyzed 12 clinical and hemodynamic variables by univariate and multivariate analyses to assess the predictive factors of postoperative outcome. Multivariate analysis disclosed that cardiac arrest and associated cardiopulmonary disease were independent predictors of operative death. Long-term follow-up (range, 2 to 144 months; mean, 56 months) information was available for 55 of the 60 discharged patients: 6 had died, and 5 complained of persistent mild or severe exertional dyspnea (New York Heart Association class II). These results help assess the preoperative risk in patients undergoing pulmonary embolectomy. They also show that, in the few patients who do not benefit from optimal medical therapy, pulmonary embolectomy remains an acceptable procedure in view of the long-term results.
Adult↗
Suppression of splenic accessory cell function in mice exposed to gallium arsenide.
Acute exposure of mice to a single intratracheal dose of gallium arsenide (50, 100, and 200 mg/kg) depresses the primary IgM antibody response to the T-dependent antigen sheep red blood cells (SRBC) through alterations in the function of splenic accessory cells. To determine the mechanism by which GaAs exposure influences splenic accessory cells, the cells were isolated by adherence and their functional capability investigated 24 hr following GaAs exposure in the animal. Splenic adherent cells from GaAs-exposed mice were greatly impaired in their ability to process and present the particulate antigen SRBC to a SRBC-primed T-cell population. However, GaAs exposure did not inhibit phagocytosis of fluorescent covaspheres by these cells, nor did it inhibit in vivo phagocytosis of 51Cr-labeled SRBC, indicating that the findings reported here were not due to decreased uptake of antigen by the accessory cells. Furthermore, production of IL-1 by these cells from exposed mice was not different from control and addition of exogenous IL-1 to cultures did not reverse GaAs-induced inhibition of the primary antibody response. GaAs exposure did not affect the percentage of Ia positive macrophages (F4/80 positive cells), but the amount of cell surface IAk molecules expressed was significantly decreased as measured by flow cytometry. In contrast to the SRBC response, GaAs did not suppress the ability of adherent splenocytes to process and present the antigen pigeon cytochrome c to the helper/inducer T cell clone F1.A.2 or the antigen KLH (keyhole limpet hemocyanin) to KLH-primed T cells. Therefore, GaAs exposure interferes with the capacity of splenic macrophages to process and/or present the particulate antigen SRBC, but not the soluble protein antigens pigeon cytochrome c or KLH.
Animals↗
The use of percutaneous transcatheter embolization to control postoperative bleeding following Le Fort I osteotomy: report of three cases.
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Adult↗
Medical students' perceptions of children: modifying a childhood cancer stereotype.
To assess whether an educationally based intervention could mitigate the negative effects of a childhood cancer stereotype, 168 first-year and fourth-year medical students were randomly assigned to view a healthy child described with either a healthy label (HL) or an in remission from leukemia label (RLL). One half of the 1st-year students also were given information summarizing the psychosocial sequelae of child survivors of cancer and one half were not given information. MANOVAs revealed that medical students in the information condition did not evidence any biases toward RLL children. However, RLL children were rated more negatively than HL children on several dimensions by 1st- and 4th-year students who did not participate in the intervention. The results suggest that a childhood cancer stereotype can be eliminated; however, standard medical training does not reduce the negative expectations health care providers hold toward children diagnosed with cancer.
Adult↗
Studies in fetal wound healing. V. A prolonged presence of hyaluronic acid characterizes fetal wound fluid.
Midgestation fetal wound healing is characterized by healing without fibrosis or scar formation. The mechanisms that underlie this remarkable process are mediated in part through a fetal wound extracellular matrix rich in hyaluronic acid. In this study a newly developed assay was used to determine the hyaluronic acid levels in fetal and adult wound fluid. Adult wound fluid had a rapid increase in hyaluronic acid, which peaked at 3 days and decreased to 0 by 7 days. In contrast levels of hyaluronic acid in fetal wound fluid increased rapidly and remained significantly elevated for 3 weeks. This prolonged presence of hyaluronic acid in the matrix of fetal wounds creates a 'permissive' wound environment that promotes fetal fibroblast movement and proliferation and inhibits cytodifferentiation. Such a matrix environment promotes healing by regeneration rather than by scarring. This observation has therapeutic implications. The prolonged application of hyaluronic acid or hyaluronate protein complexes to wounds in children or adults may modulate healing in a manner that makes the wounds more fetal-like.
Animals↗