Common variants in DLG1 locus are associated with non-syndromic cleft lip with or without cleft palate.

Non-syndromic cleft lip with or without cleft palate (nsCL/P) is a common craniofacial anomaly with a complex and heterogeneous aetiology. Knowledge regarding specific genetic factors underlying this birth defect is still not well understood. Therefore, we conducted an independent replication analysis for the top-associated variants located within the DLG1 locus at chromosome 3q29, which was identified as a novel cleft-susceptibility locus in our genome-wide association study (GWAS). Mega-analysis of the pooled individual data from the GWAS and replication study confirmed that common DLG1 variants are associated with the risk of nsCL/P. Two single nucleotide polymorphisms (SNPs), rs338217 and rs7649443, were statistically significant even at the genome-wide level (Ptrend = 9.70E-10 and Ptrend = 8.96E-09, respectively). Three other SNPs, rs9826379, rs6805920 and rs6583202, reached a suggestive genome-wide significance threshold (Ptrend < 1.00E-05). The location of the strongest individual SNP in the intronic sequence of the gene encoding DLG1 antisense RNA suggests that the true causal variant implicated in the risk of nsCL/P may affect the DLG1 gene expression level rather than structure of the encoded protein. In conclusion, we identified a novel cleft-susceptibility locus at chromosome 3q29 with a DLG1 as a novel candidate gene for this common craniofacial anomaly.

Validity of Peripheral Arterial Disease Diagnoses in the Danish National Patient Registry.

OBJECTIVES/BACKGROUND: The objective was to validate the diagnoses of peripheral arterial disease (PAD) in the legs, obtained from national registers in Denmark. METHODS: In total, 1435 registered cases of PAD were identified in the Danish National Patient Registry among 57,053 middle aged participants from the Danish Diet, Cancer and Health cohort study. Validation was performed by reviewing all medical records using pre-specified criteria for a diagnosis of PAD. RESULTS: The overall positive predictive value (PPV) of PAD diagnoses was 69.4% [95% confidence interval (CI) 67.0-71.7]. The PPV of diagnoses given in departments of vascular surgery was significantly higher than diagnoses given in other departments: 71.9% (95% CI 69.2-74.4) versus 58.3% (95% CI 52.2-64.2), respectively. In a sub-study, 141 potential cases of PAD also registered in the Danish National Vascular Registry were evaluated, and a PPV of 87.9% (95% CI 81.4-92.4) was found for these diagnoses. CONCLUSION: More than 30% of the diagnoses of PAD notified in the Danish National Patient Registry were not valid, stressing the importance of validation when using register information for research purposes. In contrast, diagnoses obtained from the Danish National Vascular Registry had a high validity ready for use without further validation.

A convenient route to optically pure α-alkyl-ß-(sec-amino)alanines.

The cyclization of N-Boc-α-alkylserines to corresponding ß-lactones under Mitsunobu reaction conditions and the ring opening with heterocyclic amines (pyrrolidine, piperidine, morpholine and thiomorpholine) produced N-Boc-α-alkyl-ß-(sec-amino)alanines. The removal of the Boc group gives di-hydrochlorides of non-protein amino acids.

Experimental osteoporosis--different methods of ovariectomy in female white rats.

UNLABELLED: Rats are currently principal laboratory animals, used to investigate osteoporosis. The aim of the study was to present and compare two operative methods of inducing osteoporosis in rats. MATERIALS AND METHODS: Ten 3 months old female Wistar rats were divided into two groups with five animals in each group. In the first group, ovariectomy was preceded by a mid-line dorsal skin incision, 3 cm long. After removing the ovary, the previous incision of the muscle required suturing. In the second group, ovariectomy was performed by two dorso-lateral incisions, approximately 1 cm long above the ovaries. With the use of a sharp dissecting scissors, the skin was cut almost together with the dorsal muscles and the peritoneal cavity was accessed. There was no need of muscle suturing. CONCLUSION: The operation, performed in the second group, was technically easier, less time consuming and less harmful for the used female white rats.

[Endocrinologic and metabolic complications of Alagille syndrome]. / Endokrinologische und metabolische Komplikationen des Alagille-Syndroms.

BACKGROUND: Patients with gastrointestinal and hepatobiliary disorders, either congenital or acquired early in childhood, are at high risk for various endocrine and metabolic abnormalities. CASE REPORT: A 27-year-old woman with Alagille's syndrome presented with progressive jaundice and gait disturbances following surgery and ingestion of oral contraceptives. On physical examination, short stature, facial dysmorphism and neuromuscular symptoms such as polyneuropathy and spinocerebellar ataxia were noted. Serum concentrations of total bilirubin (54 mg/dl) and alkaline phosphatase were markedly increased, whereas serum levels of haptoglobin, zinc, vitamin D and E were decreased. Although prehepatic or intrahepatic etiologies of jaundice were more likely in this patient, posthepatic etiologies were ruled out by abdominal ultrasound and endoscopic retrograde cholangio-pancreaticography. Based on a working diagnosis of acute drug-induced cholestasis, treatment with high doses of lipid-soluble vitamins and ursodeoxycholic acid was initiated. In response to therapy, her abnormal laboratory results normalized and her neurologic symptoms markedly improved. CONCLUSION: This clinicopathological conference of a patient with Alagille's syndrome illustrates the clinical presentation and therapy of metabolic and endocrine complications in chronic cholestasis.

[Familial sarcoidosis. Report of 2 cases in brothers]. / Rodzinne wystepowanie sarkoidozy. Opis 2 przypadków u braci.

For many years a genetic predisposition to sarcoidosis has been considered likely, however no convincing evidence have ever been found. We report histologically proven cases of sarcoidosis in two brothers. Initially, the case of sarcoidosis was diagnosed in a 36-year-old male patient (II stage of radiological lesions) and 4 years later the case of sarcoidosis was diagnosed in 28-year-old younger brother of the first patient (III stage). The brothers did not live together but, in the same neighbourhood. We evaluated the active evolution of a disease by clinical, radiological, including high resolution computed tomography and functional methods as well as by evaluating cellular and soluble components of bronchoalveolar lavage fluid (angiotensin converting enzyme, protein, phospholipids). The above constitutes the first report on familial sarcoidosis recorded in Poland.

[Concentration of sialic acid in bronchoalveolar lavage fluid in selected interstitial pulmonary diseases]. / Stezenie kwasu sialowego w plynie z plukania oskrzelowo-pecherzykowego w wybranych chorobach sródmiazszowych pluc.

Sialic acid is a component of cell membranes and it can take part in immunological processes with lymphocytes and neutrophiles. In the present work the concentration of sialic acid in BALF in selected interstitial pulmonary disease was studied (in sarcoidosis, pulmonary fibrosis, avian fanciers lung) and compared with the control group of healthy persons. The investigations were repeated during the observations. The patients were divided into active and inactive groups. The analysis included the results in 187 patients divided into 9 groups. Sialic acid was measured with colorimetric method with the use of Ehrlich's reagent. The growth of sialic acid concentration in supernatant of BALF was observed in the studied diseases. The increase of sialic acid occurs in inflammatory processes especially those with neutrophiles. The correlation of acid concentration with the percentage or the total number of lymphocytes in BALF was observed. It is specific that the concentration of sialic acid in BALF in patients with avian fanciers lung keeps growing even after the contact with the antigen was discontinued.

Stability properties of proliferatively coupled cell replication models.

To address the possibility that proliferative disorders may originate from interactions between multiple populations of proliferating and maturing cells, we formulate a model for this process as a set of coupled nonlinear first order partial differential equations. Using recent results for the asymptotic behaviour of the solutions to this model, we demonstrate that there exists a region of coupling coefficients, maturation rates, and proliferation rates that will guarantee the stable coexistence of coupled cellular populations. The analysis shows that increases in the coupling between populations may ultimately lead to a loss of stability. Furthermore, the analysis indicates that increases (decreases) in the maturation and/or proliferation rates above (below) critical levels will lead either to instability in the populations or the destruction of one population and the persistence of the other.

[Transthoracic lung biopsy (TBP)]. / Transtorakalna biopsja pluca (TBP).

The results of transthoracic lung biopsy using the Nordenströms method are discussed. Basing on this technique lung biopsies were performed in 138 patients suspected of pulmonary malignancy. High diagnostic efficacy, simplicity of this method and low incidence of side effects characterize this method.

[Usefulness of bronchoalveolar lavage for diagnosis of pulmonary tuberculosis. Case report]. / Przydatnosc plukania oskrzelowo-pecherzykowego w rozpoznawaniu gruzlicy pluc. Opis przypadku.

The case of a 57 year old male with Wegener's granulomatosis is reported in whom the course of cyclophosphamide and prednisone treatment a subacute mycobacterial tuberculosis pneumonia evolved. The diagnosis was based on culture of Mycobacterium tuberculosis organisms from the bronchoalveolar lavage fluid. The authors discuss the role of bronchoscopy and bronchoalveolar lavage in the diagnosis of pulmonary tuberculosis.

[Lavage of the whole lung in a patient with pulmonary alveolar lipoproteinosis]. / Plukanie calego pluca u chorego z lipoproteinoza pecherzyków plucnych.

The first in Poland procedure of whole lung lavage is reported. The patient had intravitally diagnosed pulmonary alveolar lipoproteinosis. Difficulties in an effective and safe performance of the procedure are discussed. Modernized methods of lung lavage in patients with severe respiratory failure due to pulmonary alveolar lipoproteinosis are described.

[Lipid proteinosis of the pulmonary alveoli--diagnostic difficulties]. / Lipoproteinoza pecherzyków plucnych--trudnosci diagnostyczne.

It is the first polish case of diagnosis of alveolar lipid proteinosis diagnosed during life is described. The diagnosis was based on biochemical analysis and morphological assessment in electron microscope of the fluid obtained in bronchoalveolar large in a patient aged 18 years with disseminated radiological pulmonary changes. Diagnostic difficulties are discussed comparing them with the cases of this disease reported as yet in Poland. The importance of bronchoalveolar lavage for the diagnosis is emphasized.

Globally asymptotic properties of proliferating cell populations.

This paper presents a general model for the cell division cycle in a population of cells. Three hypotheses are used: (1) There is a substance (mitogen) produced by cells which is necessary for mitosis; (2) The probability of mitosis is a function of mitogen levels; and (3) At mitosis each daughter cell receives exactly one-half of the mitogen present in the mother cell. With these hypotheses we derive expressions for the alpha and beta curves, the distributions of mitogen and cell cycle times, and the correlation coefficients between mother-daughter (rho md) and sister-sister (rho ss) cell cycle times. The distribution of mitogen levels is shown to be given by the solution to an integral equation, and under very mild assumptions we prove that this distribution is globally asymptotically stable. We further show that the limiting logarithmic slopes of alpha (t) and beta (t) are equal and constant, and that rho md less than or equal to while rho ss greater than or equal to 0. These results are in accord with the experimental results in many different cell lines. Further, the transition probability model of the cell cycle is shown to be a simple special case of the model presented here.

Minimizing therapeutically induced anemia.

A model for erythroid production based on a continuous maturation-proliferation scheme is developed. The model includes a simple control mechanism operating at the proliferating cell level, and analytic solutions for the time dependent response of the model are derived. Using this model, the response of the erythron to a massive depletion of the proliferating cell compartment (due for example to cytostatic drugs or radiation) is calculated. It is demonstrated that a therapeutic measure designed to decrease the erythroid precursor maturation velocity may considerably ameliorated the deleterious effects of proliferating cell destruction. One way to decrease the erythroid cell maturation rate would be by having the patient breathe in an oxygen enriched atmosphere.

The extinction of slowly evolving dynamical systems.

The time evolution of slowly evolving discrete dynamical systems xi + 1 = T(ri, xi), defined on an interval [0, L], where a parameter ri changes slowly with respect to i is considered. For certain transformations T, once ri reaches a critical value the system faces a non-zero probability of extinction because some xj psi [0, L]. Recent ergodic theory results of Ruelle, Pianigiani, and Lasota and Yorke are used to derive a simple expression for the probability of survival of these systems. The extinction process is illustrated with two examples. One is the quadratic map, T (r, x) = rx (1 - x), and the second is a simple model for the growth of a cellular population. The survival statistics for chronic myelogenous leukemia patients are discussed in light of these extinction processes. Two other dynamical processes of biological importance, to which our results are applicable, are mentioned.