PubMed Health⌕ Search

Biomedical subjects

C Pal

Publications and source records attributed to C Pal.

12 recordsLinked to original sources

The molecular evolution of signal peptides.

Signal peptides direct mature peptides to their appropriate cellular location, after which they are cleaved off. Very many random alternatives can serve the same function. Of all coding sequences, therefore, signal peptides might come closest to being neutrally evolving. Here we consider this issue by examining the molecular evolution of 76 mouse-rat orthologues, each with defined signal peptides. Although they do evolve rapidly, they evolve about half as fast as neutral sequences. This indicates that a substantial proportion of mutations must be under stabilizing selection. A few putative signal sequences lack a hydrophobic core and these tend to be more slowly evolving than others, indicating even stronger stabilizing selection. However, closer scrutiny suggests that some of these represent mis-annotations in GenBank. It is also likely that some of the substitutions are not neutral. We find, for example, that the rate of protein evolution correlates with that of the mature peptide. This may be a result of compensatory evolution. We also find that signal peptides of immune genes tend to be faster evolving than the average, which suggests an association with antagonistic co-evolution. Previous reports also indicated that the signal peptide of the imprinted gene, Igf2r, is also unusually fast evolving. This, it was hypothesized, might also be indicative of antagonistic co-evolution. Comparison of Igf2r's signal peptide evolution shows that, although it is not an outlier, its rate of evolution is comparable to that of many of the faster evolving immune system signal sequences and 5/6 of the amino acid changes do not conserve hydrophobicity. This is at least suggestive that there is something unusual about Igf2r's signal sequence.

Amino Acid Substitution↗

Assessment of patellar maltracking using combined static and dynamic MRI.

Between January 1995 and Jul 1997, 474 patients with anterior knee pain resistant to conservative treatment were referred for MR of the knee. The MR examination consisted of routine sequences with an additional patellofemoral dynamic examination using a technique that has been developed at this institution. The dynamic study examines both knees simultaneously, with the patient supine and the quadriceps loaded. No gating or restraint apparatus is needed. Patellar subluxation or tilt was present in 188(40%) of cases, bilateral in 104 and unilateral in 84 cases (right 39, left 45). It was classified as mild in 51%, moderate in 39% and severe in 10%. Subluxation was more prevalent in females than males (42% vs. 37%) and this was most obvious in the severe group where 68% were female. In 90 knees selected at random, four measurements of patellofemoral morphology were obtained using reconstructed images from a volume gradient echo sequence. These measurements were correlated with the degree of subluxation or tilt. A tibial tubercle distance greater than 20 mm, a femoral sulcus angle greater than 150 degrees, sulcus depth less than 4 mm were specific for subluxation but no measurement proved to be sufficiently sensitive to preclude a tracking study. MRI can be used to define more precisely the anatomy of the extensor mechanism and its relationship to the femur and tibia, in both a static and dynamic setting. In this way, patients with anterior knee pain can be classified more accurately and the outcomes of treatment more reliably assessed.

Adult↗

Optimal tests for no contamination in reliability models.

Inferences on mixtures of probability distributions, in general, and of life distributions, in particular, are receiving considerable importance in recent years. The likelihood ratio procedure of testing for the null hypothesis of no contamination is often very cumbersome and lacks its usual asymptotic properties. Recently, SenGupta (1991) has introduced the notion of an 'L-optimal' test for such testing problems. The idea is to recast the original several parametric hypotheses representation of the null hypothesis in terms of only a single hypothesis involving an appropriately chosen parametric function. This approach is shown to be both mathematically elegant and operationally simple for a quite general class of mixture distributions which contains, in particular, all mixtures of the one-parameter exponential family and also a very rich subclass of mixtures useful in life-testing and reliability analysis. It is also illustrated through two examples--one based on real-life data and the other on a simulated sample.

Likelihood Functions↗

Luteolin, an abundant dietary component is a potent anti-leishmanial agent that acts by inducing topoisomerase II-mediated kinetoplast DNA cleavage leading to apoptosis.

BACKGROUND: Plant-derived flavonoids, which occur abundantly in our daily dietary intake, possess antitumor, antibacterial, and free radical scavenging properties. They form active constituents of a number of herbal and traditional medicines. Several flavonoids have been shown to exert their action by interacting with DNA topoisomerases and promoting site-specific DNA cleavage. Therefore, flavonoids are potential candidates in drug design. We report here that, although the flavonoids luteolin and quercetin are potent antileishmanial agents, luteolin has great promise for acting as a lead compound in the chemotherapy of leishmaniasis, a major concern in developing countries. MATERIALS AND METHODS: Kinetoplast DNA (kDNA) minicircle cleavage in drug-treated parasites was measured by electrophoresis of the total cellular DNA, followed by Southern hybridization using 32P labeled kDNA as a probe. Cell cycle progression and apoptosis were measured by flow cytometry using propidium iodide and fluorescein isothiocyanate (FITC)-labeled Annexin V. RESULTS: Luteolin and quercetin inhibited the growth of Leishmania donovani promastigotes and amastigotes in vitro, inhibited DNA synthesis in promastigotes, and promoted topoisomerase-II-mediated linearization of kDNA minicircles. The IC50 values of luteolin and quercetin were 12.5 microM and 45.5 microM, respectively. These compounds arrest cell cycle progression in L. donovani promastigotes, leading to apoptosis. Luteolin has no effect on normal human T-cell blasts. Both luteolin and quercetin reduced splenic parasite burden in animal models. CONCLUSION: Luteolin and quercetin are effective antileishmanial agents. Quercetin has nonspecific effects on normal human T cells, but luteolin appears nontoxic. So, luteolin can be a strong candidate for antileishmanial drug design.

Animals↗

The prevalence and implications of ocular hypertension and glaucoma in thyroid-associated orbitopathy.

PURPOSE: The authors determined the prevalence of ocular hypertension and its association with progression to glaucomatous damage in patients with thyroid-associated orbitopathy (TAO). METHODS: The charts of 500 consecutive patients with TAO seen at the Allegheny General Hospital (Pittsburgh, PA) between 1985 and 1995 were analyzed. The amount of proptosis, degree and duration of myopathy, exposure to corticosteroids, prior glaucoma treatment, and family history of glaucoma were evaluated. RESULTS: One hundred twenty (24%) patients with TAO were noted to have an intraocular pressure (IOP) greater than 22 mmHg but less than 30 mmHg. This ocular hypertensive group was composed of 34 men and 86 women with a mean age of 55 years and mean follow-up of 4 years. Seven patients were defined as glaucoma suspects, based on increased but nonprogressive cup-to-disc ratios or nonprogressive, atypical visual field changes in the presence of increased IOP. Two patients demonstrated progressive visual field abnormalities and cupping. Of the factors evaluated, only the duration of active orbital involvement was statistically associated with progression to glaucomatous damage. The mean duration of TAO was 3, 8, and 12 years for ocular hypertensives, glaucoma suspects, and glaucomatous damage, respectively. CONCLUSIONS: Only a prolonged duration of active TAO in association with ocular hypertension correlated with progression to glaucomatous damage. These patients with chronic TAO deserve special attention and close follow-up to prevent optic nerve damage.

Adolescent↗

Increased hepatic secretion of very-low-density lipoprotein apolipoprotein B-100 in obesity: a stable isotope study.

1. We measured the hepatic secretion of very-low-density lipoprotein apolipoprotein B-100 (VLDL apoB) using a stable-isotope gas chromatography-mass spectrometry method in six obese subjects [three males, three females, age 41.5 +/- 3.4 years (mean +/- SEM), weight 105.0 +/- 4.8 kg, plasma total cholesterol concentration 6.2 +/- 0.4 mmol/l, triacylglycerol 2.8 +/- 0.8 mmol/l, high-density lipoprotein cholesterol 1.0 +/- 0.2 mmol/l] and six lean control subjects (three males, three females, age 41.8 +/- 3.7 years, weight 68.2 +/- 4.9 kg, total cholesterol concentration 4.5 +/- 0.3 mmol/l, triacylglycerol 0.8 +/- 0.2 mmol/l, high-density lipoprotein cholesterol 1.3 +/- 0.1 mmol/l). 2. Plasma total cholesterol, triacylglycerol and mevalonic acid (an index of cholesterol synthesis in vivo) concentrations were significantly higher in the obese subjects than in control subjects (P = 0.02, P = 0.03, P = 0.04, respectively). VLDL apoB pool size and absolute secretion rate were significantly higher in the obese subjects than in control subjects (323.4 +/- 99.8 mg versus 53.6 +/- 17.1 mg, P = 0.004; and 42.3 +/- 13.8 mg kg fat-free mass-1 day-1 versus 10.7 +/- 0.4 mg kg fat-free mass-1 day-1, P = 0.01), but there was no significant difference in the fractional catabolic rate of VLDL apoB.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Inflammatory markers of lower respiratory tract infection in elderly people.

Bacterial infections of the respiratory tract are a major cause of morbidity and mortality in elderly people. The inflammatory response to such infection is an important protective process and has been suggested to be less effective in elderly patients. To investigate the inflammatory response in respiratory infections acquired in the community by elderly people we studied 52 consecutive patients who met the criteria for either a non-pneumonic chest infection or pneumonia. After exclusion, 41 patients were available for evaluation, with 25 fulfilling the criteria of pneumonia and 16 the criteria of chest infection. Pyrexia was a feature of the patients with pneumonia. Circulating levels of neutrophil elastase-alpha-1-antitrypsin complex and C-reactive protein were greater in the patients with pneumonia than in those with a chest infection and were reduced following antibiotic treatment. No changes occurred in the chest infection group for these markers of inflammation. In both groups, a further neutrophil granule protein, lactoferrin, was unaffected by antibiotic treatment. This study indicates that elderly patients with pneumonia can initiate an appropriate inflammatory response as demonstrated by clinical indicators and circulating mediators of the inflammatory response.

Age Factors↗

Antiphospholipid syndrome: five year follow up.

Nineteen patients out of 250 subjects with antiphospholipid antibodies, who had initially presented to the lupus clinic at St Thomas's Hospital, London five or more years ago with a history of venous/arterial occlusions, were entered into the study. The patients were divided into two main groups: I those who remained well without any further thromboembolic complications (n = 10); II those who developed recurrent thrombotic events in the five year period (n = 9). The patients were followed up to determine the relation between the level or the isotype of the anticardiolipin antibodies, or both, to the recurrent thromboembolic events, and the effect of a variety of treatments (corticosteroids, immunosuppression, anticoagulation) in the prevention of further vascular occlusions. Lupus activity over the five year period varied considerably between the two groups--those in group I tending to be relatively inactive compared with those in group II. For some patients in group II thromboembolic events seemed to occur at the time of lupus activity. Antiphospholipid antibodies remained positive in all patients, the levels remaining fairly constant. Levels fell in only one patient in group I and in two in group II. Patients in group II had more systemic lupus erythematosus related disease than those in group I; most were receiving concomitant steroid and immunosuppressive therapy, but this did not seem to protect against the development of further occlusions. All patients were given anticoagulation treatment (warfarin/heparin) or salicylates (low dose aspirin 75 mg daily), or both. Patients with deep vein thromboses developed more complications during anticoagulation therapy than those with cerebrovascular symptoms. Problems in anticoagulation control and recurrent thromboses consequent on warfarin withdrawal despite the administration of subcutaneous heparin were responsible for complications in most patients in group II.

Antibodies↗

Study of interaction between catechin and native and modified bovine serum albumin by physico-chemical methods.

The interaction of native and modified bovine serum albumin (BSA) with catechin, a flavanoid having vitamin P activity, has been studied using equilibrium dialysis, pH-metric, viscosity and spectrophotometric methods. The order of reactivity of catechin binding to proteins was found to be: esterified BSA greater than BSA greater than formylated BSA greater than acetylated BSA with log K values of 3.778, 3.879, 3.748 and 3.813 and free energy change equal to -5.11, -5.16, -5.07 and -5.15 kcal/mole, respectively.

Catechin↗

Histochemistry of mucins in the submaxillary salivary gland of buffalo (Bubalus bubalis).

The histochemistry of mucins in the submaxillary salivary gland has been studied in 10 buffaloes of different age groups. The acidic mucins exhibited moderate to intense reaction in new-born and young animals; in adult animals, these were noticed in patches. Neutral and non-sulphated mucins were observed in traces and in mild amounts, respectively, in the mucous secretory end-pieces of different age groups; sialomucins were seen in moderate to intense concentrations. The seromucous end-pieces revealed traces of neutral mucins in new-born buffalo calves and moderate to intense concentrations in young and adult animals. These structures showed mild concentration of acidic mucins, hyaluronic acid and sialomucins. Sulphated and non-sulphated mucins were observed in traces in the seromucous end-pieces. The apical border of the lining cells of the intra- and interlobular ducts contained moderate to intense concentrations of acidic mucins. In young and adult animals, the epithelial cells showed mild to moderate reaction for neutral mucins. Goblet cells of the interlobular ducts exhibited the presence of mild and intense concentrations of sialo- and sulphomucins, respectively.

Age Factors↗

Studies on healthy contacts of leprosy patients--a preliminary report.

91 healthy contacts of leprosy patients were studied for subclinical infection and possibly the pre-clinical stage of the disease using a battery of tests. It was observed that the test based on competitive inhibition of monoclonal antibody binding to the MY2 a determinant of M. leprae identifies a preclinical stage of the disease.

Adolescent↗