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Biomedical subjects

R Lang

Publications and source records attributed to R Lang.

At least 163 records · Page 9Linked to original sources

Neuropeptide Y: identification of the binding site.

Based on the hypothetical 3D structure of neuropeptide Y (NPY), NPY 1-4-Aca-25-36, a 17 amino acid analogue, has been synthesized replacing the sequence NPY 5-24 by epsilon-aminocaproic acid (Aca). This low-molecular weight deletion analogue showed nearly comparable receptor affinity to NPY. In order to elucidate the structural requirements for receptor recognition each amino acid of 1-4-Aca-25-36 was exchanged by its D-enantiomer, glycine and L-alanine. In addition distinct amino acids were replaced by closely related residues. Multiple peptide synthesis was applied using Fmoc-strategy and BOP activation. Binding assay was performed on rabbit kidney membrane preparations. The results of structure affinity studies suggest that the C-terminal tetrapeptide NPY 33-36 is essential for receptor recognition.

Alanine↗

Does pulsed-Doppler ultrasound have mutagenic effects? Application of the Ames mutagenicity assay to test pulsed-Doppler equipment.

Measurement of fetal blood flow has been accepted using pulsed-Doppler ultrasound. Until recently, there has been a lack of investigations concerning the potential risks of this method. The possible mutagenic effect of a pulsed-Doppler system was examined in vitro by applying the Ames test. Tester strains of Salmonella typhimurium indicating point mutations were irradiated (TA 98, TA 100, TA 102, TA 1535, TA 1537, TA 1538). A commercially available duplex system was applied in the experiments emitting an ultrasound beam with a spatial-peak temporal-average of 5.2 mW/cm2 and a spatial-peak temporal-peak of 117 mW/cm2 at a frequency of 2 MHz. The tester strains were sonicated up to 60 minutes, the bacterial suspension being in direct contact with the transducer surface. The ultrasound-exposed bacterial suspensions were compared with nonexposed samples. Reference mutagens were used for checking the sensitivity of the system. The results do not indicate any mutagenic effects.

DNA Damage↗

[An estimation of the future demand in orthodontic needs and of the appropriate number of orthodontists for the period 1989-1999].

The present study is a repetition of two previous orthodontic Gallup polls (Gehrig et al. 1981 and Roh et al. 1986). It was conducted with the goal to reactualize the orthodontic workload in Switzerland in 1989 and to produce prognostic figures for 1994 and 1999. 1092 questionnaires have been sent out and 53.1% were returned duly completed. The number of orthodontic specialists, 79 in 1984, has increased to 104 in 1989. Despite this augmentation and the additional factor of an increase from 152 to 173 new cases per year per specialist, all specialists together treated only 29.5% of the newly started cases. This figure was 22.6% in 1984. The total of Switzerland's orthodontic needs is still not covered and it will therefore be necessary to train 29 new specialists until 1994 and 34 additional specialists in the period 1994 to 1999. This means that 4 to 5 new specialists have to be trained in Switzerland per year over the next ten years.

Forecasting↗

Ciprofloxacin treatment of malignant external otitis.

The Ear, Nose, and Throat department of the Meir Hospital treated 91 patients with malignant external otitis during the past 16 years. The last 23 patients with malignant external otitis were treated with ciprofloxacin 750 mg twice daily, combined with local excision of the aural lesion. The records of 61 of our previous 68 patients who underwent surgery and were hospitalized and treated with an intravenous extended-spectrum penicillin and gentamicin for six to eight weeks, were analyzed. Twenty-one of 23 patients treated with ciprofloxacin were cured; therapy failed in two patients. Treatment averaged 16.8 days of hospitalization, and bacteriologic eradication was achieved after an average of 7.04 days, as compared with 49 and 15.3 days, respectively, in the group of patients with the intravenous treatment. The mean peak concentrations of ciprofloxacin in serum varied between 2.5 and 3.7 micrograms/ml, and the drug concentrations in different ear tissues were 0.2 to 13 micrograms/g. The treatment with ciprofloxacin was well tolerated with no significant side effects, whereas serious side effects were noted in 45.9 percent of the previous intravenously treated group. The concentrations of the drug in serum and ear tissues were higher than the average minimal inhibitory concentration for Pseudomonas aeruginosa. Use of ciprofloxacin treatment, combined with local excision of the aural lesion, will bring about healing of malignant external otitis in the majority of cases. Ciprofloxacin can be given on an ambulatory basis after a relatively short period of hospitalization.

Aged↗

Tolerance induction in double specific T-cell receptor transgenic mice varies with antigen.

The crucial role of the thymus in immunological tolerance has been demonstrated by establishing that T cells are positively selected to express a specificity for self major histocompatibility complex (MHC), and that those T cells bearing receptors potentially reactive to self antigen fragments, presumably presented by thymic MHC, are selected against. The precise mechanism by which tolerance is induced and the stage of T-cell development at which it occurs are not known. We have now studied T-cell tolerance in transgenic mice expressing a T-cell receptor with double specificities for lymphocytic choriomeningitis virus (LCMV)-H-2Db and for the mixed-lymphocyte stimulatory (MIsa) antigen. We report that alpha beta TCR transgenic mice tolerant to LCMV have drastically reduced numbers of CD4+CD8+ thymocytes and of peripheral T cells carrying the CD8 antigen. By contrast, tolerance to MIsa antigen in the same alpha beta TCR transgenic MIsa mice leads to deletion of only mature thymocytes and peripheral T cells and does not affect CD4+CD8+ thymocytes. Thus the same transgenic TCR-expressing T cells may be tolerized at different stages of their maturation and at different locations in the thymus depending on the antigen involved.

Animals↗

Highly potent and small neuropeptide Y agonist obtained by linking NPY 1-4 via spacer to alpha-helical NPY 25-36.

Analogues of neuropeptide Y (NPY) containing small N- and C-terminal segments linked via flexible spacer arms were found to exhibit receptor binding affinity constants almost as high as NPY as well as post- and presynaptic NPY-agonistic activities. One of the most active analogues contains N-terminal NPY segment 1-4 linked via epsilon-aminocaproic acid (Aca) to the C-terminal partially alpha-helical peptide amide segment 25-36. NPY 1-4-Aca-25-36 is the first highly potent NPY agonist, which is of considerably reduced size in comparison to the native hormone. The analogues are accessible by solid-phase synthesis using Fmoc strategy.

Aminocaproic Acid↗

T cell tolerance to Mlsa encoded antigens in T cell receptor V beta 8.1 chain transgenic mice.

To study T cell tolerance, transgenic mice were generated that expressed the Mlsa-reactive T cell receptor (TCR) beta chain V beta 8.1 (cDNA) under the control of the H-2Kb promoter/immunoglobulin heavy chain enhancer on approximately 90% of peripheral T cells. In transgenic mice bearing Mlsa, thymocytes expressing the TCR at a high density were deleted and the percentage of Thy 1.2+ lymph node cells was reduced. The CD4/CD8 ratio of mature T cells was reversed in Mlsa and Mlsb transgenic mice independent of the H-2. RNA analysis and immunofluorescence with TCR V beta-specific antibodies revealed that expression of endogenous TCR beta genes was suppressed. Both Mlsa and Mlsb TCR beta chain transgenic mice mounted a T-cell-dependent IgG response against viral antigens, whereas the capacity to generate alloreactive and virus-specific cytotoxic T cells was impaired in TCR beta chain transgenic Mlsa, but not in transgenic Mlsb mice.

Animals↗

'There is no sea, only fish': effects of United States policy on the health of the displaced in El Salvador.

The poor health status of El Salvador's displaced is a direct result of government policy which defines civilians as legitimate military targets. The effects of this 'strategic hamlet' policy on health is vividly seen in five areas of concern: war related trauma, infectious diseases, malnutrition and insufficient health services due to the repression of health providers and lack of resources. This report documents the major causes of mortality and morbidity among the 500,000 displaced in El Salvador and discusses the efforts of government and private organizations to meet their health needs. Health services for the displaced are primarily provided by private voluntary organizations which base their work on active neutrality. However, neutrality has become almost as dangerous as active opposition. The active repression of health workers by government security forces has exacerbated the already severe shortage of health care services for the displaced.

Disasters↗

Natriuretic factors and lithium clearance in patients with the syndrome of inappropriate antidiuretic hormone (SIADH)

Because the syndrome of inappropriate antidiuretic hormone (SIADH) is a state of disturbed body fluid volume regulation and altered sodium balance we sought to determine if recently described volume regulatory factors were stimulated in SIADH. We measured atrial natriuretic peptide (ANP), endogenous digitalis-like natriuretic factor (EDNF) and urinary free dopamine in SIADH (n = 27). We also determined fractional clearance of lithium (FCLi). The data obtained in SIADH were compared with similar measurements performed in sodium retaining hyponatremias, such as those of heart failure (n = 26), liver cirrhosis (n = 19) and volume contraction (n = 28). We observed: ANP was 19.5 +/- 2.7 fM/ml in SIADH; it was significantly lower than ANP in cardiac failure, but no different from ANP in volume contraction. Urinary free dopamine was 2.2 +/- 0.8 microM/24 h in SIADH; this was significantly higher than in volume contraction and liver cirrhosis. EDNF (259 +/- 42 nM/24 h) and FCLi (21.4 +/- 2%) were both numerically higher in SIADH than in other hyponatremic disorders; however, the differences did not achieve significance. In conclusion, our observations did not establish a specific role of ANP in chronic stable SIADH. As to the importance of EDNF, dopamine and proximal tubular fluid reabsorption (FCLi) additional work using acute volume changes may demonstrate their participation in the renal sodium handling of SIADH more clearly than our study did.

Aged↗

ANP and sodium excretion during acute baroreflex hypertension in conscious dogs.

The influence of an acute baroreflex hypertension elicited by common carotid occlusion (CCO) on plasma atrial natriuretic peptide (ANP) and renal sodium excretion was investigated in chronically instrumented, conscious foxhounds receiving a normal-sodium diet. CCO (n = 6) significantly increased mean arterial pressure (from 102 +/- 5 to 144 +/- 3 mmHg; P less than 0.01) and sodium excretion (from 82 +/- 10 to 133 +/- 9 mumol/min; P less than 0.05). No changes in plasma ANP and right atrial pressure were observed during the acute hypertension. In contrast, an acute 20% volume expansion (n = 7) corresponding to 1.8% of body weight raised right atrial pressure (from 1.3 +/- 1.2 to 5.8 +/- 1.2 cmH2O; P less than 0.01) and induced a sustained elevation of plasma ANP (from 39 +/- 8 to 67 +/- 16 pg/ml; P less than 0.05). The natriuresis in response to CCO was eliminated when renal perfusion pressure was regulated at the control level by a renal arterial cuff (n = 4); under these conditions, sodium excretion even tended to decrease during CCO (from 81 +/- 17 to 46 +/- 13 mumol/min; P less than 0.05). In conclusion, an increase in renal perfusion pressure and not an elevated ANP level is important in mediating the natriuresis during CCO in conscious dogs. These results imply that changes in plasma ANP are not essential for the induction and maintenance of a pressure natriuresis.

Acute Disease↗

Peripheral hemodynamics, blood viscosity, and the renin-angiotensin system in hemodialysis patients under therapy with recombinant human erythropoietin.

Treatment of renal anemia with rhEPO (120 U/kg body weight/hemodialysis) in transfusion-dependent patients on maintenance hemodialysis led to an increase in blood pressure, regional peripheral resistance and whole blood viscosity. Our results are in agreement with earlier findings that partial correction of renal anemia results in hemodynamic changes characterized by a fall in cardiac output together with an increase in blood pressure due to increased vascular resistance. The increase in whole blood viscosity correlated with the increase in regional peripheral resistance but not with the increase in mean arterial blood pressure. Thus, other regulating factors of vascular resistance must be involved. Correction of renal anemia does not influence the reninangiotensin system. However, peripheral responsiveness of vascular smooth muscles may have changed due to improved tissue oxygenation and thus leading to an increase in vasoconstriction.

Adult↗

[Diagnostic efficacy of cephalometry for Class II/1].

The present paper reports on a sample of Angle Class II/1 patients with reference to 43 orthodontic computer-stored metric parameters. The simple pairwise (Pearson) correlations of these 43 variables have been computed, and some of them illustrated graphically by means of their associate contour ellipses. Inspection of the numerical correlation coefficients has made it possible to evaluate the diagnostic potentialities separately for each of the mentioned variables. Thus, as far as Angle Class II/1 patients are concerned, the ANB-angle qualifies as a cephalometric parameter quite suitable for measuring the posterior displacement of the maxilla. Also, its use as a criterion in deciding whether or not orthodontic treatment should be supported by the Swiss Invalidity Insurance (AI/IV) proves wholly justified.

Cephalometry↗

Right atrial dilatation increases inositol-(1,4,5)trisphosphate accumulation. Implications for the control of atrial natriuretic peptide release.

Stretching the right atrium of isolated perfused [3H]inositol-labelled rat hearts was shown to stimulate the phosphatidyl-inositol turnover pathway as demonstrated by the accumulation of [3H]inositol-(1,4,5)trisphosphate and its degradation products. Stimulation was detectable after 1 min with larger increases observed after 10 or 20 min. These findings demonstrate that the myocardium can respond to dilatation by an activation of the phosphatidylinositol turnover pathway. Such a mechanism has implications for the release of atrial natriuretic peptide following right atrial distention.

Animals↗

Psychosocial aspects of disease duration and control in young adults with type I diabetes.

Self-report questionnaires completed by young adults with Type I diabetes were examined to determine if individuals differing in recent metabolic control (Poor, Moderate or Very Good) or disease duration (Long, Short) also vary in either occurrence or type of life events during the past year or occurrence of recent emotional distress. Subjects in Poor control reported more positive and neutral life events during the past year, suggesting even those life changes individuals view benignly may be associated with metabolic control difficulties. Individuals in Poor control also reported more recent symptoms of depression, anxiety and hostility than did individuals in Moderate or Very Good control--symptomatology which may further impair their ability to adhere to a complex self-care regimen. Individuals with Long disease duration reported more positive and negative recent life experiences than did subjects with Short disease duration, but did not evidence concomitant disruptions in metabolic control. The role experience with a chronic disease may play in this finding was unclear, however. Although more research is required to clarify the exact relation of psychosocial variables and diabetic control, these findings suggest that clinically relevant subgroup parameters, subjects' perceptions of life change, and demographic variables may be important factors to assess.

Adolescent↗