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At least 793 records · Page 44Linked to original sources
PubMed2003

Mutations within the cyclooxygenase-1 gene in aspirin non-responders with recurrence of stroke.

INTRODUCTION: Aspirin is a common antiplatelet drug used in the prevention of ischemic stroke due to its inhibitory effect on platelet cyclooxygenase-1 (Cox-1). Patients can be categorized as either aspirin 'responders' or 'non-responders' depending on whether they are protected against a secondary stroke event or not. In this study, we have searched for variants of the Cox-1 gene that could possibly result in an unblocked and thus, aspirin-resistant Cox-1 enzyme and phenotype. MATERIALS AND METHODS: The Cox-1 gene was sequenced in 68 patients with recurrent ischemic stroke despite taking aspirin. The genotype distribution of identified variants was determined and compared with healthy control subjects. Mutations that involved amino acid substitutions of the mature Cox-1 molecule were analysed by molecular modelling and functional analysis using whole blood aggregometry. RESULTS: Fourteen variants of the Cox-1 gene were identified. Seven of the variants involved amino acid substitutions of the Cox-1 molecule. None of the mutations were located near the catalytic site as judged from a three-dimensional model of the human Cox-1. Carriers and non-carriers of one of the mutations behaved similarly when aggregation and granule content release function were studied using collagen, ADP and arachidonic acid as agonists. CONCLUSION: The results do not support the hypothesis that common variants of the Cox-1 gene results in unblocked Cox-1 molecules in aspirin non-responders.

Aged↗
PubMed2004

Combined 5-fluorouracil and Er:YAG laser treatment in a case of recurrent giant keratoacanthoma of the lower leg.

BACKGROUND: Keratoacanthomas are fast-growing squamous tumors, which usually show spontaneous regression. The development of giant variants with an aggressive behavior has been described. Although surgical excision remains the treatment of choice for very large keratoacanthomas, other therapeutic options including laser surgery and topical chemotherapy may be superior in special situations. OBJECTIVE: The objective was to evaluate the efficacy of Er:YAG laser surgery combined with topical 5-fluorouracil treatment in a case of recurrent giant keratoacanthoma. METHODS: A 64-year-old woman presented for evaluation and treatment of recurrent tumors in her face and extremities. Despite repeated invasive surgical removal of these lesions, recurrence of fast-growing giant keratoacanthomas developed in the pretibial region of her left lower leg. Owing to recurrence after conventional surgery and the tumor size, a novel treatment method using ablative Er:YAG laser combined with topical 5-fluorouracil was performed. RESULTS: After four treatments with excellent patient compliance, histologic analysis of punch biopsies revealed tumor-free ulcerations. Complete epithelization was obtained after 9 weeks. Six months after the treatment, no recurrence was observed. CONCLUSION: The combined use of ablative Er:YAG laser and topical 5-fluorouracil chemotherapy may be considered as an effective treatment option in cases of giant keratoacanthoma when conventional surgery is not indicated.

Administration, Cutaneous↗
PubMed2005

Cutaneous carcinoma with mixed histology: a potential etiology for skin cancer recurrence and an indication for Mohs microscopically controlled surgical excision.

Cutaneous carcinomas with mixed histology describe nonmelanoma skin cancers which have more than one histologic subtype. These include basal cell carcinomas with concurrent aggressive growth patterns (such as sclerosing, infiltrating, micronodular, keratinizing, and tumors with perineural involvement) and nonaggressive growth patterns (such as superficial, nodular, and follicular) and squamous cell carcinomas with concurrent poorly differentiated and well-differentiated components. One mechanism of recurrence of nonmelanoma skin cancer may very well result from the inadequate initial treatment of cutaneous tumors with mixed histology. If the aggressive histologic subtype of the original tumor is initially not suspected based upon the pathology observed from a superficial biopsy specimen, the clinician may initiate therapy that would be appropriate for the less aggressive variant that was diagnosed. Subsequently, the more aggressive tumor may persist and eventually manifest as a clinical recurrence of the cancer. This is particularly important when there is perineural tumor involvement. We describe two patients whose skin cancers had more than one histologic subtype to demonstrate the histologic features of cutaneous malignancies with more than one pathologic pattern and to emphasize how inaccurate a single diagnostic biopsy can be. We also suggest that clinicians consider Mohs surgical excision of nonmelanoma skin cancers since this technique incorporates microscopically controlled removal of the tumor with complete pathologic evaluation of all surgical margins for any residual cancer.

Aged↗
PubMed1988

Botryoid odontogenic cyst: clinicopathologic analysis of ten cases with three recurrences.

The botryoid odontogenic cyst (BOC) is a rare cyst of odontogenic origin originally described in 1973 by Weathers and Waldron as a variant of the lateral periodontal cyst. Ten examples of this rare lesion were studied by light and electron microscopy and the clinical and radiographic findings were analyzed. Eight of ten lesions were located in the mandible; the anterior mandible being the dominant site. Five of the ten lesions were unilocular, the largest measuring 4.5 X 1.2 cm. Only two of the ten botryoid odontogenic cysts were radiographically multilocular. Three lesions represented recurrences 8, 10, and 10 years after previous surgical intervention. All patients were white with an average age of 46 years. Perhaps the most significant information gained from this investigation of botryoid odontogenic cysts is the fact three of ten lesions recurred after initial surgical removal. It is important that practitioners take note of the fact that: 1) a recurrence potential may exist for the botryoid odontogenic cyst that has gone unrecognized, 2) recurrence may not occur until a decade after initial surgery, and 3) lesions may occasionally become destructive.

Adult↗
PubMed2001

[Diagnosis and treatment of persistent or recurrent hyperthyroidism].

Reasons for postoperative persistence of primary hyperparathyroidism (pHPT) are missed parathyroid adenoma, incomplete removal of multiple altered pararthyroid glands, and rare variants of localisation. A reoperation is indicated in symptomatic patients if calcium serum levels are elevated above 2.9 mmol/l. Preoperatively, cervical sonography and 99mTc sestamibi scintigraphy should be carried out. Additionally, selective venous blood sampling and nuclear magnetic resonance tomography can be of use. After successful localization, a unilateral approach is advisable. If position remains unclear, bilateral exploration is required. In secondary hyperparathyroidism (sHPT), renal function is crucial for development of recurrence. For postoperative persistence, identification of less than four pararthyroid glands or leaving of the thymus are the main reasons. Before reoperation it has to be clarified if parathyroid hyperfunction is caused by persisting cervical or mediastinal tissue, or if hyperfunction of autotransplanted tissue in the forearm is evident. Diagnostic and operative procedures are similar to those used in pHPT.

Adenoma↗
PubMed2026

Expanding the Genomic Spectrum of NHLRC2-Associated FINCA Disease: Integrated Bioinformatic Characterization of a Novel Deep Intronic Variant Predicted to Activate a Pseudoexon.

NHLRC2-associated FINCA disease is an ultra-rare autosomal recessive multisystem disorder caused by biallelic pathogenic variants in NHLRC2. Its mutational spectrum and genotype-phenotype correlations remain incompletely defined, and the contribution of non-coding variants is poorly understood. Here, we report a male infant with a severe FINCA-like phenotype, including early-onset hemolytic anemia, pulmonary involvement, neurodevelopmental impairment, growth failure, recurrent infections, and fatal progression at 8.5 months. Whole-genome sequencing identified a compound heterozygous NHLRC2 genotype comprising the previously reported pathogenic missense variant c.442G>T (p.Asp148Tyr) and a novel deep intronic variant, c.331+6863A>G. Segregation analysis confirmed inheritance from different parents. Integrated genomic and splicing analysis predicted that c.331+6863A>G creates a strong cryptic donor splice site and supports pseudoexon inclusion. Reconstruction of the predicted aberrant transcript indicated premature termination and potential susceptibility to nonsense-mediated mRNA decay. To our knowledge, this is the first reported deep intronic NHLRC2 variant predicted to activate pseudoexon inclusion. Although experimental validation was unavailable, convergent clinical, segregation, population, and computational evidence supports c.331+6863A>G as the most plausible second disease-associated allele. This case expands the genomic spectrum of NHLRC2-associated FINCA disease and highlights the diagnostic value of phenotype-driven whole-genome sequencing.

Humans↗
PubMed1994

Evolution and replacement of Candida albicans strains during recurrent vaginitis demonstrated by DNA fingerprinting.

Southern blot hybridization with the Ca3 probe and the C fragment of the Ca3 probe was used to assess the genetic relatedness of Candida albicans strains from one patient with recurrent C. albicans infection in whom the same strain was maintained, one patient in whom the infecting strain was replaced, and their male sexual partners. In the patient in whom the infecting strain was maintained, the infecting strain exhibited a minor genetic change in each successive episode of Candida vaginitis. These genetic changes occurred in the C-fragment bands of the Ca3 hybridization pattern. In the patient in whom the infecting strain was replaced by another infecting strain, a transition infection involved a genetically mixed infecting population, and the replacement strain appeared to have originated from the oral cavity of the male partner. The results demonstrate that the infecting strains of recurrent Candida vaginitis are not genetically stable, that drug treatment can result in the selection of variants of the previously infecting strain or replacement by a genetically unrelated strain, and that the male partner can be the source of a replacement strain.

Adult↗
PubMed2002

Bipolar disorder.

Bipolar, or manic-depressive, disorder is a frequent, severe, mostly recurrent mood disorder associated with great morbidity. The lifetime prevalence of bipolar disorder is 1.3 to 1.6%. The mortality rate of the disease is two to three times higher than that of the general population. About 10-20% of individuals with bipolar disorder take their own life, and nearly one third of patients admit to at least one suicide attempt. The clinical manifestations of the disease are exceptionally diverse. They range from mild hypomania or mild depression to severe forms of mania or depression accompanied by profound psychosis. Bipolar disorder is equally prevalent across sexes, with the exception of rapid cycling, a severe and difficult to treat variant of the disorder, which arises mostly in women. Because of the high risk of recurrence and suicide, long-term prophylactic pharmacological treatment is indicated. Lithium salts are the first choice long-term preventive treatment for bipolar disorder. They also possess well documented antisuicidal effects. Second choice prophylactic treatments are carbamazepine and valproate, although evidence of their effectiveness is weaker.

Anticonvulsants↗
PubMed2003

Chordoma of the skull base: predictors of tumor recurrence.

OBJECT: Chordomas of the skull base are generally regarded as slow-growing tumors; however, approximately 20% of these lesions have been shown to recur as early as 1 year postsurgery. The classic pathological paradigms are poor predictors of outcome, and additional markers are needed to identify patients at risk for early tumor recurrence. In this study the authors describe such a marker. METHODS: In a series of 26 patients with chordomas of the skull base, the authors investigated the relationship between the biological behavior of the tumor, which was determined according to the interval for its recurrence and volume doubling time, and several pathological and molecular features, which included the histological variant, proliferative activity, mutation of p53 protein, expression of human telomerase reverse transcriptase (hTERT) messenger (m)RNA, loss of heterozygosity (LOH), and microsatellite instability. The major finding in this study was that hTERT mRNA expression in chordoma cells identifies those tumors that exhibit unusually fast rates of growth. The expression of hTERT mRNA was frequently associated with mutation of p53 protein, indicating that telomerase dysfunction combines with abnormal p53 function to initiate the unrestrained clonal expansion of the tumor cells. In cases in which the tumor was partially removed, mutation of p53 protein and expression of hTERT mRNA predicted increased doubling time for residual tumor as well as the probability of tumor recurrence. Cell proliferation, as investigated using the Ki-67 method, was significantly related to the tumor doubling time; however, the authors found that the pattern of cell proliferation was not homogeneous throughout the chordoma tissue, and that the proliferative index might change by a factor as high as 8 among different regions of the same tumor. The LOH and microsatellite instability do not seem to affect the prognosis of skull base chordomas. CONCLUSIONS: Reactivation of telomerase in chordomas is a reliable predictor of outcome. The ability to predict the biological behavior of chordomas might have immediate implications in the management of this disease in patients who undergo surgery.

Adult↗
PubMed1997

Expression of CD44 standard form and variant isoforms in non-small cell lung carcinomas.

CD44, a cell adhesion molecule, has been implicated in tumor invasion and metastasis in certain malignancies. We studied the expression of CD44 standard (CD44s) and variant isoforms (CD44v) in 98 non-small cell lung carcinomas (NSCLCs) by immunohistochemistry and correlated the observations with clinical outcome. Formalin-fixed, paraffin-embedded archival tissues from 49 squamous cell carcinomas (SCCs) and 49 adenocarcinomas (ACs) were immunostained after microwave irradiation with monoclonal antibodies against CD44s and CD44v3, v4/5, v6, v7/8, and v10, and the results were correlated with histological tumor type, tumor stage, recurrence, and survival rates. SCCs of the lung showed strong membranous expression of each of the CD44s, v3, v4/5, v6, and v10 proteins in comparison with ACs (P < .0001). Staining for CD44 v4/5 was overwhelmingly positive in SCCs (72%) as compared with ACs (2.2%). Intense immunoreactivity for CD44v6 was present in 19 of 20 (95%) metastatic lung carcinomas. The bronchiolar basal cells and alveolar pneumocytes were positive for CD44s, v3, and v6. CD44s and variant isoform expression did not correlate with tumor stage, recurrence, and survival rates. In conclusion, there is significant immunopositivity of CD44s and variant isoforms in SCCs over ACs of the lung. Expression of CD44v6 may suggest an increased risk for local lymph node metastasis in NSCLCs. CD44v4/5 reactivity may be useful to discriminate squamoid differentiation in poorly differentiated NSCLCs.

Adult↗
PubMed2026

Histone variant H2A.J is an epigenetic regulator of metastasis in lung adenocarcinoma.

Metastasis is a major contributor to poor patient survival in lung adenocarcinoma (LUAD); however, the underlying mechanisms remain incompletely understood. Unlike tumorigenesis-associated mutations, recurrent genetic alterations specifically linked to metastasis have not been identified, suggesting that epigenetic mechanisms may play a key role. In this study, we report that histone H2A variant H2A.J expression is significantly down-regulated in LUAD, and that low H2A.J levels are associated with unfavorable survival outcomes. Functional assays revealed that H2A.J overexpression suppresses cancer cell invasion and metastatic potential by modulating the expression of metastasis-associated genes, including TMEM158. Mechanistically, H2A.J is deposited in the promoter region of TMEM158, where it alters the local chromatin status to suppress transcriptional activity. Taken together, our findings suggest that H2A.J functions as an epigenetic suppressor of metastasis in LUAD and highlights its potential as both a prognostic biomarker and a therapeutic target to metastatic progression.

Humans↗
PubMed1989

Surgical treatment of bronchopulmonary carcinoid tumours.

Based on histopathological characteristics bronchopulmonary carcinoid tumours can be divided into a typical and an atypical variant. Atypical carcinoid tumours often have regional lymph node metastases. A differentiation between the two types of tumours cannot be made preoperatively. A total of 23 patients underwent resectional therapy for carcinoid tumours of the lung. Eleven underwent pneumonectomy, eight patients lobectomy and three patients had bilobectomy. Segmental resection was performed in one patient. One patient died in the postoperative period. During the follow-up period, ranging from 5 to 22 years (median 11 years), neither local recurrences nor metastatic spread was observed. In eight patients the tumour was classified as the atypical variant. There was no correlation between the size of the tumour and the presence of regional lymph node metastases. All tumours with lymph node metastases were classified as atypical carcinoids. As in other studies, our data suggest that treatment based on standard resectional procedures is to be preferred for bronchopulmonary carcinoids since a preoperative distinction between the typical and atypical variants is as yet not possible.

Adult↗
PubMed2005

Association of genetic variation in tamoxifen-metabolizing enzymes with overall survival and recurrence of disease in breast cancer patients.

Tamoxifen has been a mainstay of adjuvant therapy for breast cancer for many years. We sought to determine if genetic variability in the tamoxifen metabolic pathway influenced overall survival in breast cancer patients treated with tamoxifen. We examined functional polymorphisms in CYP2D6, the P450 catalyzing the formation of active tamoxifen metabolites, and UGT2B15, a Phase II enzyme facilitating the elimination of active metabolite in a retrospective study of breast cancer patients. We also examined whether the combination of variant alleles in SULT1A1 and UGT2B15 had more of an impact on overall survival in tamoxifen-treated patients than when the genes were examined separately. We conducted a retrospective study using archived paraffin blocks for DNA extraction and data from pathology reports and hospital tumor registry data for information on clinical characteristics, treatment, and outcomes (162 patients receiving tamoxifen and 175 who did not). Genotypes for CYP2D6 and UGT2B15 were obtained and Cox proportional hazards modeling was performed. After adjusting for age, race, stage of disease at diagnosis, and hormone receptor status, we found no significant association between CYP2D6 genotype and overall survival in either group of breast cancer patients. Tamoxifen-treated patients with UGT2B15 high activity genotypes had increased risk of recurrence and poorer survival. When UGT2B15 and SULT1A1 'at-risk' alleles were combined, women with two variant alleles had significantly greater risk of recurrence and poorer survival than those with common alleles. These studies indicate that genetic variation in Phase II conjugating enzymes can influence the efficacy of tamoxifen therapy for breast cancer.

Antineoplastic Agents, Hormonal↗
PubMed2005

Bilateral variant contributions in the formation of median nerve.

Bilateral variations in the formation of median nerve (Mn) and the recurrent course of its communications with musculocutaneous nerve (MCn) are very rare. These bilateral anomalies were observed during a routine dissection of the upper limbs of an adult male cadaver in the Department of Anatomy, PGIMER, Chandigarh. On both the sides, Mn was formed by the union of three roots. There was an additional lateral root on both sides. On the right side it was a contribution from the lateral cord and on the left it arose from the anterior division of the middle trunk. On the left side the lateral cord was formed distal than usual in relation to the second part of the axillary artery. On the right side a communicating branch arising from the additional lateral root followed a recurrent course and divided into two to unite separately with medial root of median, while on the left side a single communicating branch from an additional lateral root united with the medial root of median. Recurrent course of the communicating branch between lateral root of median and medial root of median has not been reported earlier. On the right side the MCn after piercing the coracobrachialis gave another communicating branch, which joined the Mn at the level of insertion of deltoid.

Adult↗
PubMed1998

Electrospray ionization mass spectrometry identification of fibrinogen Banks Peninsula (gamma280Tyr-->Cys): a new variant with defective polymerization.

Fibrinogen Banks Peninsula was identified in the mother of a patient referred for investigation following recurrent epistaxis. Coagulation tests revealed prolonged thrombin and reptilase times and a decreased functional fibrinogen level. Thrombin-catalysed release of fibrinopeptides A and B was normal, and no abnormalities were detected by DNA sequencing of the regions encoding the thrombin cleavage sites in the Aalpha and Bbeta genes. Reducing SDS-PAGE and reverse-phase HPLC analysis of purified fibrinogen chains were normal, as was electrospray ionization mass spectrometry (ESI-MS) analysis of isolated Aalpha and Bbeta chains. However ESI-MS revealed a mass of 48345 D for the isolated gamma chains, 31 D less than the measured mass of control chains (48376 D). Since normal and abnormal gamma chains were not resolved, this implies a 60-62 D mass decrease in 50% of the molecules. A 60 D decrease was confirmed when DNA sequencing indicated heterozygosity for a mutation of Tyr-->Cys at codon 280 of the gamma chain gene. Fibrin monomer polymerization revealed a delayed lag phase and reduced final turbidity and although factor XIIIa crosslinking of fibrinogen was normal, it is likely that this delay is due to impaired D:D self association. Recent crystallographic studies show residues gamma280 and gamma275 make contact across the D:D interface, suggesting a similar mechanism for the polymerization defects in fibrinogens Banks Peninsula and Tokyo II (gamma275Arg-->Cys).

Afibrinogenemia↗
PubMed1989

[Verrucous elephantiasis: a maximum variant of lymphedema].

Verrucous elephantiasis is a special form of stage III lymphedema. Extensive deformation may cause immobility, and recurrent infections may be dangerous to life. Even in serious cases, conservative treatment (complex physiotherapy) may prove to be very successful. Surgery is not indicated as a treatment of first choice, but it may be very helpful in addition to physiotherapy.

Aged↗
PubMed1988

[Recurrent hypersomnia].

Recurring hypersomnias are described according to 3 etiological groups: 1) idiopathic - the Kleine Levin syndrome and its clinical variants - 2) organic and 3) psychiatric. The typical form of the Kleine Levin syndrome is remarkable for the association of recurring episodes of sleep, overeating and temporary mental disturbances lasting from a few hours to several days. Its diagnosis is mainly based on clinical data Laboratory investigations have so far failed to document specific features. Emphasis is laid on circumstances at onset and pathological studies which could be in favour of a viral origin. Some clinical aspects and polysomnographic features are reminiscent of endogenous depression. The treatments of hypersomniac episodes based on stimulants are often disappointing. On the other hand, the prevention of the hypersomniac episodes of the Kleine Levin syndrome with lithium carbonate has been successful in several well-documented cases as well as the prevention of the hypersomniac episodes of the menstruation related hypersomnia with ovulatory inhibitors. Organic and psychiatric forms of recurring hypersomnias are not well known. Their clinical features are described and their various possible etiologies indicated.

Adolescent↗
PubMed2000

A signal-flow-graph approach to on-line gradient calculation.

A large class of nonlinear dynamic adaptive systems such as dynamic recurrent neural networks can be effectively represented by signal flow graphs (SFGs). By this method, complex systems are described as a general connection of many simple components, each of them implementing a simple one-input, one-output transformation, as in an electrical circuit. Even if graph representations are popular in the neural network community, they are often used for qualitative description rather than for rigorous representation and computational purposes. In this article, a method for both on-line and batch-backward gradient computation of a system output or cost function with respect to system parameters is derived by the SFG representation theory and its known properties. The system can be any causal, in general nonlinear and time-variant, dynamic system represented by an SFG, in particular any feedforward, time-delay, or recurrent neural network. In this work, we use discrete-time notation, but the same theory holds for the continuous-time case. The gradient is obtained in a straightforward way by the analysis of two SFGs, the original one and its adjoint (obtained from the first by simple transformations), without the complex chain rule expansions of derivatives usually employed. This method can be used for sensitivity analysis and for learning both off-line and on-line. On-line learning is particularly important since it is required by many real applications, such as digital signal processing, system identification and control, channel equalization, and predistortion.

Algorithms↗