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PubMed2003

Functional characterization of melanocortin-4 receptor mutations associated with childhood obesity.

The melanocortin-4 receptor (MC4R) is a member of the rhodopsin-like G protein-coupled receptor family. The binding of alpha-MSH to the MC4R leads to increased cAMP production. Recent pharmacological and genetic studies have provided compelling evidence that MC4R is an important regulator of food intake and energy homeostasis. Allelic variants of MC4R were reported in some children with early-onset severe obesity. However, few studies have been performed to confirm that these allelic variants result in an impairment of the receptor's function. In this study, we expressed wild-type and variant MC4Rs in HEK293 cells and systematically studied ligand binding, agonist-stimulated cAMP, and cell surface expression. Six of the 11 mutants examined had either decreased (S58C, N62S, Y157S, C271Y) or no (P78L, G98R) ligand binding, with proportional impairments in [Nle4, d-Phe7]-alpha-MSH-stimulated cAMP production. Confocal microscopy confirmed that the observed decreases in hormone binding by these mutants are associated with decreased cell surface expression due to intracellular retention of the mutants. The other five allelic variants (D37V, P48S, V50M, I170V, N274S) were found to be expressed at the cell surface and to bind agonist and respond with increased cAMP production normally. The data on these latter five variants raise the question as to whether they are indeed causative of the obesity or not and, if so, by what mechanism. Our data, therefore, stress the importance of characterizing the properties of MC4R variants associated with early-onset severe obesity. We further propose a classification scheme for mutant MC4Rs based upon their properties.

Alleles↗

PubMed1999

Distribution of HCV genotypes among different exposure categories in Brazil.

Hepatitis C virus (HCV) infection is widespread and responsible for more than 60% of chronic hepatitis cases. HCV presents a genetic variability which has led to viral classification into at least 6 genotypes and a series of subtypes. These variants present characteristic geographical distribution, but their association with different responses to treatment with interferon and severity of disease still remains controversial. The aim of this study was to investigate the patterns of distribution of HCV genotypes among different exposure categories in Brazil. Two hundred and fifty anti-HCV positive samples were submitted to HCV-RNA detection by RT-PCR and their genotype was determined by restriction fragment length polymorphism (RFLP) analysis. In addition, the genotype/subtype of 60 samples was also determined by a reverse hybridization assay. HCV 1 was the most prevalent (72.0%), followed by type 3 (25.3%), HCV 2 (2.0%) and HCV 4 (0.7%). The HCV genotype distribution varied among the different exposure categories, with HCV 1 being more frequent among blood donors, hemophiliacs and hemodialysis patients. A high frequency of HCV 3 was observed in cirrhotic patients, blood donors from the South of Brazil and injecting drug users (IDUs). The general distribution of the HCV genotype in Brazil is similar to that in other regions of the world.

Blood Donors↗

PubMed1990

Benign proliferative disorders of the breast.

Fibrocystic disease of the breast has been generally regarded as a disorder due to either excess hormonal stimulation or an exaggerated proliferative response by hypersensitive breast epithelium. The unique lobular lesion-adenosis- and its variants have been regarded as non-neoplastic and non-preneoplastic glandular hypertrophy and hyperplasia, and have different organoid patterns and origins. We have examined a total of 242 cases previously diagnosed as 'fibrocystic disease' at the Department of Pathology with the purpose of clarifying the variants of adenosis in detail and refining the infinitely large 'fibrocystic disease' classification as non-proliferative fibrocystic change and proliferative disorders, such as epitheliosis and atypical hyperplasia. In this study, 224 cases (92.5%) were nonproliferative disease, mostly adenosis (40.1%), and 18 cases (7.5%) were proliferative disease, which consisted of moderate to florid hyperplasia and epitheliosis.

Adult↗

PubMedDate not supplied

High-resolution DNA flow cytometry in oral verrucous carcinoma.

The classification of verrucous carcinoma as an entity unto itself or as a variant of well differentiated squamous cell carcinoma is controversial. To contribute new insights into the biological behavior of this rare tumor, we applied DNA flow cytometry to three node-negative verrucous carcinomas of the oral cavity. All tumors expressed a single aneuploid cell population. One of the patients experienced three courses with local recurrence. All secondary tumors retained the initially established aneuploid clone. The development of aneuploidy is thus a cytogenetic event common to both verrucous and squamous carcinoma of the oral cavity.

Aged↗

PubMed2000

[Nomenclature of drug forms--overview of development and the present state].

If the names used for dosage forms in pharmacopoeias and professional literature are examined, changes are found which are not always connected with extended knowledge about preparations, or the development of new variants of the dosage form. The same finding holds true for their classification into systematic groups. The problem has become particularly topical within the framework of international co-operation. The objective of the present paper is to inform about the steps aiming at standardisation of their nomenclature at least in Europe.

Czech Republic↗

PubMedDate not supplied

[Forensic-medical evaluation of the histologic structure of the hymen].

Variants of microscopic structure of the hymen are described and its histological classification based on the stromal component structure is offered. Hypotheses on the hymen histogenesis under different conditions are formulated. Histological analysis and histological classification of the hymen are needed for objective solution of questions arising during expert evaluation of virginity and its violation, probability or improbability of coitus without defloration.

Adolescent↗

PubMed2003

[Non-differentiated carcinoma with osteoclast-like giant cells of the pancreas].

We report the case of a 53-year-old man who presented a mass involving the head of the pancreas resulting in isolated jaundice. Histologically, the tumor was an undifferentiated carcinoma with osteoclast-like giant cells of the pancreas. This very rare neoplasm resembles giant cell tumor of bone. An epithelial origin is now established and this tumor has been recently considered as a variant of ductal adenocarcinoma of the pancreas in the last WHO histological classification. The diagnosis requires both morphology and immunohistochemistry. Although the prognosis of these tumors is reported to be poor, our case is unusual because of a favorable outcome without relapse after 2 years.

Carcinoma↗

PubMed2003

[New WHO classification of lymphoid neoplasms: understanding and consideration].

The latest version of new WHO classification of lymphoid neoplasms is a comprehensive and distinct opinion of lymphoid neoplasms, and maybe put an end to the controversy held in this field for a long time. The new classification defines the neoplasm categories according to the principle that the classification should be based on the real entities of diseases and should contain the morphology, immunophenotypes, genetic alterations and clinical features rather than simply emphasize the pure morphologic presentations. The new subtyping of lymphoid cancers provides a correct framework for malignant lymphoma, and also represents a new paradigm in disease classification. So far the accumulated experiences have demonstrated that the new classification is reproducible and practical. However, it remains to determine how the variants of lymphomas relate to their clinical prognostic factors, such as international prognostic index and individual difference, since the current treatment approach relays on the types of lymphomas. The diagnosis, treatment and researches of lymphomas in China are also discussed.

Humans↗

PubMed2003

[New guidelines of the Joint National Committee (USA) on Prevention, Diagnosis and Management of Hypertension. From JNC VI to JNC VII].

Need for update of guidelines of the Joint National Committee (USA) on Prevention, Diagnosis and Management of Hypertension was based on necessity to adopt changes based on results of recent studies as well as creation of more simple and convenient variant for practical physicians. Compared with JNC VI most important changes concerned classification of blood pressure (BP) levels and approaches to drug therapy. New category "prehypertension" was introduced and 2 stages of hypertension distinguished: stage I - systolic BP 140-159 mm Hg or diastolic 90-99 mm Hg, stage II - systolic BP 160 mm Hg or higher, diastolic BP 100 mm Hg or higher. Diuretics were recommended as drugs of first choice and wider use of drug combinations encouraged. Some statements of JNC VII report have been criticized by some hypertension authorities.

Antihypertensive Agents↗

PubMed1990

[Complete duplication of the urethra].

A case of complete urethral duplication in a child is presented. The malformation consisted of a normal urethra and another epispadial dorsal urethra ending at the dome of the bladder. This is a rare variant of this type of malformation. Incontinence was the surgical indication. The classification, embryology, diagnosis, indications for surgery and treatment of this anomaly are presented.

Epispadias↗

PubMed1977

[Problems of histogenesis and classification of nephroblastoma (Wilms' tumor) in children].

Nephroblastoma, a tumour of the kidney, is most often observed in children; it always includes the nephrogenous tissue in any variant of its differentiation. Histogenesis of this neoplasm is multiform and complex. Its development from very immature pluripotential (polypotent) cells (possibly, at the level of blastodermic vesicle) is not ruled out. The histological classification of nephroblastomas, offered by the author, is based on the principles of differentiation of the tumour tissue and on its histogenesis and opens new perspectives for further investigation of neoplasms and for clinico-anatomic collations.

Cell Differentiation↗

PubMed2003

Rheological properties of concentrated skim milk: influence of heat treatment and genetic variants on the changes in viscosity during storage.

Heat treatment during manufacturing of milk powder is one of the most important tools for manipulation of its functional properties, and it is the basis of the classification of these proteins into low-, medium-, and high-heat types. Slight differences in the sequences of the major proteins in milk (genetic variants) seem to have also a significant effect in milk powder processing (U.S. patent). Therefore, the effects of high-temperature storage and heat treatment on skim milk of defined genetic variants of beta-lactoglobulin (beta-LG) were measured. The samples had 45% total solids, the temperature of aging was 50 degrees C, and the heat treatment was 90 degrees C for 10 min prior to evaporation. Measurements on shear rate and on apparent viscosity were determined for each sample. During storage of the concentrated milk, the apparent viscosity and yield values increased markedly, and the age-dependent increase in viscosity in heat-treated concentrated skim milks was much more pronounced than in those prepared from unheated skim milks. The increase in apparent viscosity and yield value with storage time was notably different for milks containing different genetic variants. Unheated concentrated milks containing the B variant of beta-LG showed the most rapid increase in apparent viscosity with storage time, whereas the viscosity increase was slowest in the concentrate containing the A variant. In contrast, heat-treated concentrated milks containing the A variant of beta-LG showed the most rapid increase in viscosity with storage time, whereas the viscosity increase was slowest in the concentrate containing the AB variant. The changes in apparent viscosity of concentrated milk were largely reversible under high shear during the early stages of storage, but samples stored for a long time showed irreversible changes in apparent viscosity. Particle size analysis confirmed irreversible aggregation and fusion of casein particles during storage.

Animals↗

PubMed2004

Chronic myelomonocytic leukemia: myeloproliferative variant.

Chronic myelomonocytic leukemia (CMML) has been classified into a new category of myelodysplastic and myeloproliferative diseases by the last World Health Organization classification of myeloid malignancies. However, a large fraction of patients with CMML show unequivocal prevalence of proliferative features, often with conspicuous leukocytosis and organomegaly, making any distinction with atypical chronic myeloid leukemia problematic. Although transformation into acute myeloid leukemia does not seem to be more frequent, prognosis in the proliferative variant of CMML (MP-CMML) is generally worse compared to dysplastic CMML (MD-CMML). Occurrence of mutations in the NRAS and KRAS oncogenes is significantly higher in MP-CMML compared to MD-CMML, whereas cytogenetic abnormalities seem to be less frequent. Constitutively activated platelet-derived growth factor-b receptor tyrosine kinase caused by specific chromosomal aberrations have been documented in a very small proportion of patients with MP-CMML whose malignant cell proliferation have been shown to be inhibited by imatinib mesylate. Treatment of MP-CMML remains challenging, with no strategy proven effective in prolonging survival. While waiting for novel potential targets by further understanding of cell proliferation molecular pathways, new strategies, including stem cell transplant, should be considered in treating patients with MP-CMML.

Cell Division↗

PubMed2000

Dyshaemopoiesis in adults: a practical classification for diagnosis and management.

Dyshaemopoiesis is a heterogeneous disease that may be classified into non-clonal and clonal dyshaemopoiesis. Non-clonal dyshaemopoiesis comprises reversible disorders with DNA synthesis impairment in dividing cells of the bone marrow by avitaminosis through various mechanisms or direct DNA damage from multiple causes. Complete haematologic recovery is obtained after vitamin supplementation or suppression of a myelotoxic agent. On the contrary, clonal dyshaemopoiesis is a group of chronic and usually irreversible diseases that may culminate in acute leukaemia (AL). These so called myelodysplastic syndromes (MDS) and their variants may be classified as primary, secondary and other diseases with doubtful clonality. A detailed classification of dyshaemopoiesis in adults may offer partial help in the diagnosis and management of dyshaemopoiesis. Pathobiological studies in progress allow better understanding of MDS and consequently the establishment of new modalities of treatment.

Adult↗

PubMed1983

Acute myelomonocytic leukemia and the French-American-British classification.

39 patients suffering from different subtypes of monocytic (M 5) and myelomonocytic (M 4) leukemia were analyzed retrospectively. In 8 cases a 'transitional myelomonocytic variant' was diagnosed; the leukemic cell in these patients is marked by morphological and cytochemical signs of monocytic and granulocytic precursors. As the correct diagnosis of this special subtype may be difficult, its place within the French-American-British (FAB) classification will be discussed.

Acid Phosphatase↗

PubMed2004

Toward a molecular genetic classification of familial hemiplegic migraine.

The genetics of migraine is a fascinating and rapidly moving research area. Familial hemiplegic migraine, a rare subtype of migraine with a Mendelian pattern of inheritance, is caused by mutations in the chromosome 19 CACNA1A gene or in the chromosome 1 ATP1A2 gene. Familial migraine variants are classified on the basis of clinical, descriptive criteria, but this is insufficient. In the future, a diagnostic classification based on mutation-analysis is needed.

Humans↗

PubMed1996

[Formulating problems of ecological diseases. Approaches to etiopathogenesis, classification and diagnosis of ecological diseases due to chemicals].

Our long-standing clinical trials proved nonspecific and stress factors contributing into environmental diseases. The studies helped to define traumatic variant of biologic stress, to describe its trigger mechanisms. The authors analyzed physiologic mechanisms of stress-related diseases, role of autonomous nervous system in formation of environmental diseases. Clinical classification of acute and chronic environmental diseases is given, with consideration of their diagnosis.

Adaptation, Physiological↗

PubMed2001

Evaluation of diagnostic efficiency of computerized image analysis based quantitative nuclear parameters in papillary and follicular thyroid tumors using paraffin-embedded tissue sections.

Computerized image analysis (IA) system has emerged in recent years as a very powerful tool for objective and reproducible quantification of histological features. It has shown considerable potential for diagnostic application in diverse histological situations. The objectives of the present study were to evaluate the discriminatory diagnostic efficiency of computerized image analysis based quantitative subvisual nuclear parameters in papillary and follicular neoplasms of thyroid. A total of 60 cases were studied. Forty-four cases belonged to training set and 16 cases belonged to a test set. A minimum of 100 nuclei was analyzed in each case using uniform 5 m mm thick hematoxylin stained sections. The IA workstation comprised of an Olympus microscope, a 10 bit digital video camera, an image grabber card and a pentium 120 MHz computer. Optimas 5.2 software was utilized for data collection on 8 morphometric and 8 densitometric parameters. Multivariate stepwise discriminant statistical analysis of data was done with the help of BMDP statistical software release 7.0. Results from a training set revealed correct classification rates of 98.0%, 84.5% and 61.2% for the histological groups of hyperplastic papillae versus papillae of papillary carcinoma (group I), follicular variant of papillary carcinoma versus the broad category of follicular neoplasms consisting of both follicular adenoma and follicular carcinoma (group II) and follicular adenoma versus follicular carcinoma (group III), respectively. Results of test set revealed correct classification rates of 100%, 80% and 50% for groups I, II and III respectively. It was concluded that computerized nuclear IA parameters have potential usefulness for discriminating benign versus malignant papillary lesions of thyroid, follicular variant of papillary carcinoma versus follicular adenoma and/or follicular carcinoma but are of no value in discriminating between follicular adenoma and follicular carcinoma.

Adenocarcinoma, Follicular↗