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PubMedDate not supplied

[Development and utilization of the integral system of computer monitoring in anesthesiology in clinical obstetrics and gynecology].

An original computer monitoring system for preoperative monitoring was developed at the department of anesthesiology and intensive care of the Research Center for Obstetrics and Gynecology of the Russian Academy of Medical Sciences. The system includes a bedside monitor Athena (S&W + Artema, Denmark) and two special monitors ABM-100 (Datex, Finland) and NCCOM (Bomed, USA). The potentialities of the system are discussed; physiological parameters were monitored and estimated in the real time mode. Variants of graphic interface of the system are presented, including an original multisystem integral nomogram. Utilization of the system demonstrated the advantages of objective physiological information recorded by the system, a high informative values of integral estimated parameters in the real time mode. The use of the multisystem integral nomogram helps the anesthesiologist rapidly and unambiguously to interpret the clinical situation and essentially accelerates the decision-making on further treatment strategy. The work with the system does not require any special knowledge and skills, the system is simple and easy in use.

Anesthesia, Obstetrical↗
PubMed1999

Identification of a novel splice variant of C3G which shows tissue-specific expression.

C3G is a guanine nucleotide-releasing protein that binds to the Src homology 3 (SH3) domain of the adapter protein Crk. In this study, we isolated cDNAs coding for rat C3G. Northern blot analysis of RNA from various rat tissues and cell lines showed a major transcript of about 7 kb which was present at the highest level in testis. A comparison of the amino acid sequence (derived from the cDNA sequence) of rat C3G with the human form showed 87.3% sequence identity. The principal difference was the presence of an additional 51 amino acids in the rat C3G sequence after the fifth PXXP motif. This difference may be attributable to alternative splicing of the primary transcript. This interpretation was supported by reverse transcription-polymerase chain reaction (RT-PCR) assays, which resulted in two products differing by 153 bp. The RT-PCR analysis of RNA from various rat tissues showed that the relative expression levels of the two splice forms were variable. The form of C3G with the insertion of 51 amino acids (named C3G-2) was present in rat testis at a high level and, to a lesser extent, in brain, but it was not seen (or was present at a very low level) in other rat tissues and certain rat and mouse cell lines. This expression pattern of the C3G-2 form was confirmed by Northern blotting using the insert region as a probe. The C3G-1 form, without the insertion of 51 amino acids, was present in almost all rat tissues except testis and in cell lines of rat, mouse, or human origin. Thus, in rat cells, we have identified a novel splice variant of C3G. The expression pattern indicates that the form of C3G described here is likely to serve a tissue- or cell-specific physiological function.

Amino Acid Sequence↗
PubMed1998

Large granular lymphocytosis.

BACKGROUND AND OBJECTIVES: An increased number of granular lymphocytes (GL) has been reported in various clinical conditions and is currently interpreted as a reactive process to an underlying antigen stimulation. In recent years, a disease characterized by a definite increase in granular lymphocytes has been identified and recognized as lymphoproliferative disease of GL (LDGL). The aim of this study is to review the clinical, biological and pathogenetic mechanisms leading to this disorder. DESIGN AND METHODS: Criteria for the diagnosis, immunologic and molecular evaluation, clinical features and new therapeutic approaches are reviewed. RESULTS: More than 500 patients have been adequately reported in the literature. Immunologic classification of this disease distinguishes a CD3+ form which is more common, and a CD3- variant; this latter accounting for nearly 15% of LDGL cases. CD3+ LDGL is symptomatic in approximately 50% of cases, neutropenia, infections and anemia being the most frequent findings. Clonality of the T-cell receptor is usually documented in these patients. Cytokines such as IL-2, IL-12 and IL-15 have been claimed to play a role in this disorder. Symptomatic patients may benefit from combination therapy with low dose methotrexate and steroids. CD3- LDGL are usually associated with viral infection of GL: in particular, Epstein Barr and human T lymphotropic virus I/II have been claimed to play a role. Neutropenia is usually less pronounced than in CD3+ LDGL patients. Clonality has rarely been demonstrated; however, when present, it correlates with an aggressive clinical course. Spontaneous regression of lymphocytosis has been reported in both CD3+ and CD3- patients. INTERPRETATION AND CONCLUSIONS: Lymphoproliferative disease of granular lymphocytes is a well recognized disorder which encompasses a large spectrum of conditions, ranging from mild asymptomatic lymphocytosis to aggressive, usually fatal, disorders. Diagnosis of this disease is related to the demonstration that a discrete subset of GL is chronically expanded. Therapy should be delayed in asymptomatic patients; however, when needed, the combination of methotrexate or cytoxan and steroids represents the best approach.

Humans↗
PubMed1997

Manipulation of the vsg co-transposed region increases expression-site switching in Trypanosoma brucei.

Disruption of a region of DNA in Trypanosoma brucei immediately upstream of the expressed telomere-proximal variant surface glycoprotein gene (vsg), known as the co-transposed region (CTR), can cause a dramatic increase in the rate at which the active expression site (ES) is switched off and a new ES is switched on. Deletion of most of the CTR in two ESs caused a greater than 100-fold increase in the rate of ES switching, to about 1.3 x 10(-4) per generation. A more dramatic effect was observed when the entire CTR and the 5' coding region of the expressed vsg221 were deleted. In this case a new ES was activated within a few cell divisions. This switch also occurred in cell lines where a second vsg had been inserted into the ES, prior to CTR deletion. These cell lines, which stably co-expressed the inserted and endogenous Vsgs, in equal amounts, did not differ from the wild-type in growth rate or switching frequency, suggesting that simultaneous expression of two Vsgs has no intrinsic effect. CTR deletion did not disturb the inserted vsg117. We tentatively conclude that it was not the disruption of the vsg221 in itself that destabilized the ES. All of the observed switches occurred without additional detectable DNA rearrangements in the switched ES. Deletion of the 70-bp repeats and/or a vsg pseudogene upstream of the CTR did not affect ES stability. Several speculative interpretations of these observation are offered, the most intriguing of which is that the CTR plays some role in modulating chromatin conformation at an ES.

Animals↗
PubMed2001

Fine-needle aspiration biopsy of peripheral T-cell lymphomas. A cytologic and immunophenotypic study of 33 cases.

INTRODUCTION: Peripheral T-cell lymphoma (PTCL) accounts for 10-20% of all non-Hodgkin lymphomas in the United States. In this study, the authors reviewed the cytologic and immunophenotypic findings of 33 fine-needle aspirations (FNAs) of PTCL. METHODS: Thirty-three FNAs from 26 patients (12 females and 14 males) with PTCL were identified during 1991-1999. The patients' age ranged from 19 to 96 years. Immunophenotyping was performed in 24 cases by using either flow cytometry (FC; 21 cases) or immunocytochemistry (IC; 3 cases). Follow-up included review of prior or current histology and clinical records. RESULTS: Nine cases were associated with mycosis fungoides, three cases were classified as T-cell chronic lymphocytic leukemia, and two were angioimmunoblastic adenopathy (AILD)-like T-cell lymphoma. The remaining 19 were classified as PTCL, not otherwise specified. The latter consisted of eight mixed cell variant, eight large cell variant, and three anaplastic variant. One of the mixed cell variant and one of the large cell variants contained numerous epithelioid histiocytes (Lennert lymphoma). Thirty (91%) cases had a definitive diagnosis of malignant lymphoma. Twenty-two cases (2 IC and 20 FC) showed a predominant population of T lymphocytes without a monoclonal B-cell population. In addition, FC revealed an aberrant expression of T-cell markers in 13 cases. Two cases were interpreted as "atypical lymphoid population"; one case was an AILD-like T-cell lymphoma, and the other case was PTCL, large cell type. One case initially was interpreted as granulomatous lymphadenitis; subsequent biopsy revealed PTCL, Lennert type. CONCLUSIONS: Peripheral T-cell lymphoma is a heterogeneous group of lesions with diverse cytomorphology. Cytologic analysis and immunophenotyping is an accurate method of diagnosing peripheral T-cell lymphoma.

Adult↗
PubMed1995

[Rare keratoacanthoma variants].

Keratoacanthomas are made up of the same spinocellular differentiated cell material as squamous cell carcinomas, but they differ from the latter in origin and growth properties. The majority--in our series 98% of 741 examined cases--are of the "crateriform" type, which after rapid growth during the initial stage give way to spontaneous regression, mostly with complete restoration of the cutaneous structure. Less than 2% belong to the rare destructive variants with disturbed or absent regression and persistent invasive growth. Keratoacanthoma marginatum centrifugum, mutilating keratoacanthomas and aggregated keratoacanthomas can lead to extremely severe defects. None of the "conservative" treatment methods recommended in the literature up to now has proved effective, with the exception of surgery and radiotherapy with tumour ratio doses. Many publications are obviously based on uncritically interpreted individual observations.

Aged↗
PubMedDate not supplied

Cleidocranial dysplasia with neonatal death due to central nervous system injury in utero: case report and literature review.

Cleidocranial dysplasia (CCD), an uncommon disorder involving membranous bones, is rarely lethal in early life. The calvaria is defective and wormian bones are present. Abnormalities of the clavicles vary in severity from a minor unilateral defect to bilateral absence. This report concerns pre- and postmortem anatomical and radiological findings in a 15-day-old female neonate with CCD. Her postnatal course was characterized by seizures and recognition of hydrocephalus during the first day of life. The calvaria was hypoplastic with numerous wormian bones. A pseudofracture of the right clavicle was present. Hydrocephalus was present in the brachycephalic brain which had a severely thinned cerebral cortex. Hemosiderin in the ventricular lining and marked subependymal gliosis were interpreted as evidence of old intraventricular hemorrhage that had occurred in utero. A CCD-related condition, Yunis-Varon syndrome (YVS), is noted for early lethality and for developmental and secondary abnormalities of the central nervous system. The present case only partially matches the phenotype of YVS and might represent a part of a spectrum of phenotypic variants ranging from viable CCD to lethal YVS.

Adult↗
PubMedDate not supplied

MTD-PLS: A PLS-based variant of the MTD method. 2. Mapping ligand-receptor interactions. Enzymatic acetic acid esters hydrolysis.

The PLS variant of the MTD method (T. I. Oprea et al., SAR QSAR Environ. Res. 2001, 12, 75-92) was applied to a series of 25 acetylcholinesterase hydrolysis substrates. Statistically significant MTD-PLS models (q(2) between 0.7 and 0.8) are in agreement with previous MTD models, with the advantage that local contributions are understood beyond the occupancy/nonoccupancy interpretation in MTD. A "chemically intuitive" approach further forces MTD-PLS coefficients to assume only negative (or zero) values for fragmental volume descriptors and positive (or zero) values for fragmental hydrophobicity descriptors. This further separates the various kinds of local interactions at each vertex of the MTD hypermolecule, making this method suitable for medicinal chemistry synthesis planning.

Acetates↗
PubMed2005

Photochemical production and release of gaseous NO2 from nitrate-doped water ice.

Temperature-programmed NO2 emissions from frozen aqueous NaNO3 solutions irradiated at 313 nm were monitored as function of nitrate concentration and heating rate, H, above -30 degrees C. Emissions increase nonmonotonically with temperature, displaying transitions suggestive of underlying metamorphic transformations. Thus, NO2 emissions surge at ca. -8 degrees C in frozen [NO3-] > 200 microM samples warmed at H = 0.70 degrees C min(-1) under continuous irradiation, and also in the dark from samples that had been photolyzed at -30 degrees C. The amounts of NO2 released in individual thermograms, SigmaN, increase less than linearly with [NO3-] or the duration of experiments, revealing the significant loss of photogenerated NO2. The actual SigmaN proportional, variant [NO3-]1/2 dependence (at constant H) is consistent with NO2 hydrolysis: 2NO2 + H2O --> NO3- + NO2- + 2H+, overtaking NO2 desorption, even below the eutectic point (-18 degrees C for aqueous NaNO3). The increasingly larger NO2 losses detected in longer experiments (at constant [NO3-]) are ascribed to secondary photolysis of trapped NO2. The relevance of present results to the interpretation of polar NO2 measurements is briefly analyzed.

Journal Article↗
PubMed1984

Exposure of nondividing populations of primary human fibroblasts to UV (254 nm) radiation induces a transient enhancement in capacity to repair potentially lethal cellular damage.

Nondividing (arrested) populations of primary human fibroblasts from normal individuals exposed to an initial dose (1.5 or 3 J X m-2) of far-UV (254 nm) radiation and then incubated in medium containing low (0.5%) serum develop enhanced resistance to inactivation of cloning efficiency by a second (challenge) dose of UV. The resistance develops within 2-4 days, after which there is a decline. Resistance develops to a higher degree and more rapidly (1-2 days) in cells derived from patients with the variant form of xeroderma pigmentosum. Excision-deficient cells from xeroderma pigmentosum complementation group A individuals also develop UV resistance after a lower (0.2 J X m-2) exposure to UV. Enhanced UV resistance does not develop in UV-irradiated cell populations incubated with the protein synthesis inhibitor cycloheximide (5 microM). These observations are consistent with the interpretation that exposure of human fibroblasts to low doses of UV induces synthesis of a protein involved in a metabolic pathway that transiently enhances the capacity of cells to repair potentially lethal damage resulting from a subsequent dose of UV.

Cell Division↗
PubMed2025

A novel high-dimensional model for identifying regional DNA methylation QTLs.

Varying coefficient models offer the flexibility to learn the dynamic changes of regression coefficients. Despite their good interpretability and diverse applications, in high-dimensional settings, existing estimation methods for such models have important limitations. For example, we routinely encounter the need for variable selection when faced with a large collection of covariates with nonlinear/varying effects on outcomes, and no ideal solutions exist. One illustration of this situation could be identifying a subset of genetic variants with local influence on methylation levels in a regulatory region. To address this problem, we propose a composite sparse penalty that encourages both sparsity and smoothness for the varying coefficients. We present an efficient proximal gradient descent algorithm that scales to high-dimensional predictor spaces, providing sparse solutions for the varying coefficients. A comprehensive simulation study has been conducted to evaluate the performance of our approach in terms of estimation, prediction and selection accuracy. We show that the inclusion of smoothness control yields much better results over sparsity-only approaches. An adaptive version of the penalty offers additional performance gains. We further demonstrate the utility of our method in identifying regional mQTLs from asymptomatic samples in the CARTaGENE cohort. The methodology is implemented in the R package sparseSOMNiBUS, available on GitHub.

Humans↗
PubMed1981

Mucin histochemistry of the columnar epithelium of the oesophagus: a retrospective study.

Reflux oesophagitis may be accompanied by replacement of squamous epithelium by columnar epithelium (Barrett's oesophagus). The columnar epithelium may resemble either gastric or intestinal mucosa, though ultrastructural and histochemical studies indicate that the intestinal type does not necessarily resemble normal small intestine. Twenty-two malignant and 10 benign oesophageal specimens were examined histologically and by mucin histochemistry in an attempt to classify the various types of columnar epithelium. An incompletely differentiated variant of intestinal metaplasia secreting sulphomucins was associated with well but not poorly differentiated adenocarcinomas (p less than 0.02; Fisher's exact test). Similar findings have been described in the stomach and incomplete intestinal metaplasia may be related to disorders of growth and differentiation described in other sites such as the colon. These observations may help in the interpretation of oesophageal biopsies, possibly permitting identification of patients at risk of developing oesophageal adenocarcinoma.

Adenocarcinoma↗
PubMed2006

[Pharmacogenetics and tailored drug treatment in schizophrenia].

BACKGROUND: Medical treatment of psychiatric disorders is often characterised by trial and error. Psychotropic drugs show a large variation in response and side effects. Molecular genetic techniques seem to have a potential for identifying biological predictors of drug response and side effects, and help to establish tailored drug treatment. MATERIAL AND METHODS: Based on relevant literature and own research, this article gives a short overview of some pharmacogenetic aspects related to pharmacological treatment of schizophrenia. RESULTS: Antipsychotic and antidepressive drugs are metabolized by many different enzymes in the cytochrome P450 system. The rate of the drug-metabolism depends to some extent on genetic variants, and several gene-variants affect the serum level of the drugs, which may cause side effects or non-response. Several pharmacogenetic studies have indicated that both the therapeutic response and the level of motor and metabolic side effects of antipsychotic drug treatment of schizophrenia are related to polymorphisms in the serotonine and dopamine receptor genes, but there are conflicting findings. INTERPRETATION: However, most of these data remain preliminary, and so far pharmacogenetics has been of little practical help for clinical psychiatry. Due to the progress in molecular genetics and improved quality of clinical studies, there is a hope that a new generation of psychiatric pharmacogenetic studies will provide us with more useful information for drug treatment of schizophrenia and other psychiatric conditions.

Antidepressive Agents↗
PubMed1978

An analysis of phytohemagglutinin lymphoblastogenesis in whole blood.

A population of 80 defined normal people ranging in age from 20 to 62 years were used to define a dose response curve in whole blood phytohemagglutinin blastogenesis of lymphocytes. Maximum stimulation occurred at four days of incubation and 18 hours of pulse labeling with tritiated thymidine using 50 micrograms per milliliter of phytohemagglutinin and 1 microcurie of tritiated thymidine. An analysis of variants indicates a statistically significant trend of reduction of disintegrations per minute per milliliter with advancing age. Likewise, there was an extremely significant difference between measurements performed in the morning and late in the afternoon. Measurements referred to sex and sequential testing were not shown to be significant. Therefore, whole blood phytohemagglutinin blastogenesis may be meaningfully performed and interpreted using nonparametric statistics and the raw blastogenesis of a standard amount of peripheral whole blood, provided that the remainder of the test conditions are rigidly controlled.

Adult↗
PubMedDate not supplied

[Interpretation of the karyotype characteristics of patients with developmental defects of the urogenital system].

35 patients with unclassified urogenital malformations were subjected to clinical and cytogenetic examination. Chromosome aberrations of the mosaicism type were found in 3 women. They were as follows: 45,X/46,XX(2); 45, X/46, XX/47, XXX(1). Moreover, two patients had identical pericentric inversions of chromosome 9: 46, XX, inv. (9) (p13; q13) and 3 patients had microvariants of acrocentric chromosomes. Despite the presence of chromosome anomalies and morphological variants of chromosomes in the examined patients, the comparison of the clinical and cytogenetic data suggests the multifactorial nature of urogenital malformation.

Chromosome Aberrations↗
PubMed2002

Hand grip strength: a phenotype suitable for identifying genetic variants affecting mid- and late-life physical functioning.

Physical functioning late in life has been shown to be affected by genetic factors. Only a few genetic variants have been suggested to be associated with physical functioning, and this only in selected populations (e.g., young healthy males and elite athletes). Declining physical functioning late in life is a major problem in terms of prevalence, morbidity, functional limitations, and quality of life. It is therefore of interest to find a phenotype reflecting physical functioning which has a relatively high heritability and which can be measured in large samples. Hand grip strength is known to be associated with muscular functioning in other muscle groups and with activities of daily living (ADL) functioning, and it predicts incident disability. We studied 1,757 Danish twin pairs aged 45-96 years, and found that this phenotype has a heritability of 52% (95% confidence interval (CI), 48-55%). A powerful design to detect genes associated with a phenotype is obtained using the extreme discordant and concordant sib pairs, of whom 28 and 77 dizygotic twin pairs, respectively, were found in this study. Hence grip strength is a suitable phenotype for identifying genetic variants of importance to mid- and late-life physical functioning.

Activities of Daily Living↗
PubMed1995

Systematics of New World monkeys (Platyrrhini, Primates) based on 16S mitochondrial DNA sequences: a comparative analysis of different weighting methods in cladistic analysis.

In order to investigate the effects of different weighting methods on a phylogeny reconstruction based on DNA sequences and to evaluate the phylogenetic information content of various secondary structures, a fragment of the large ribosomal mitochondrial gene (16S) was sequenced from 13 species of New World monkeys, three species of catarrhines, and Tarsius. The data were analyzed cladistically without weighting characters or changes, and with different weighting methods: a priori differential weights for transitions and transversions, two variants of dynamic weighting for each kind and direction of change, and successive approximations, using both the character consistency index (CI) and the rescaled consistency index (RC). The results were compared with published trees constructed from nuclear sequences of E-globins and morphological characters by different authors. The result of the analysis of the mtDNA data set with successive approximations, using the RC as weighting function, was the closest to the topology on which all molecular and morphological trees concur. Other relationships were unique to this tree. "Loops" were the type of secondary structure that showed maximum variation in sequence length and sites with the lowest character CI and RC. A large number of sites within loops showed high values for these indices, however, which suggests that uniform downweighting of these regions represents a large loss of phylogenetic information. Successive weighting, which assigns a weight for each particular character, seems to be a desirable alternative to this practice. We propose a new variant of dynamic weighting, which we call homoplasy-correcting dynamic weighting, that like dynamic weighting, is applicable to any kind of sequence, coding or noncoding.

Animals↗
PubMed2002

Lack of association between HoxA1 and HoxB1 gene variants and autism in 110 multiplex families.

A recent report suggested that the HoxA1 and/or HoxB1 genes play a role in susceptibility to autism. To determine whether these findings could be confirmed, we screened these genes for DNA polymorphisms by sequencing all exons in 24 individuals with autism. We identified the same sequence variants in the genes that appeared in this report, which include one single-base substitution variant in HoxA1 and a common haplotype in HoxB1. We performed an association study by applying the transmission disequilibrium test to detect possible association of these variants to autism in 110 multiplex families. Our results demonstrated no deviation from the null hypothesis of no association. We have also separately examined transmissions within individual mating types, for paternal versus maternal alleles, to affected versus unaffected children, and for transmission to affected boys versus girls. None of these subsets revealed significant deviation from the null expectation. Our interpretation of these findings is that it is unlikely that HoxA1 and HoxB1 play a significant role in the genetic predisposition to autism.

Autistic Disorder↗