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At least 1,315 records · Page 73Linked to original sources
PubMed1997

A Cys634Gly substitution of the RET proto-oncogene in a family with recurrence of multiple endocrine neoplasia type 2A and cutaneous lichen amyloidosis.

Germ-line mutations of the RET proto-oncogene, involving five cysteine residues at codons 609, 611, 618, 620 and 634, are associated with two variants of the inherited cancer syndrome multiple endocrine neoplasia type 2: type 2A and familial medullary thyroid carcinoma. The association of multiple endocrine neoplasia type 2A with the dermatological disorder cutaneous lichen amyloidosis has already been reported, and mutations in the Cys634 have been identified in different families. We describe here an additional pedigree in which multiple endocrine neoplasia type 2A and cutaneous lichen amyloidosis cosegregate. A Cys634Gly was identified by direct sequencing of the RET proto-oncogene exon 11 in the affected individuals. The mutation creates a new HaeIII site, and restriction analysis performed on all family members rules out the presence of the altered allele in two children and consequently the risk of developing thyroid tumors. These results emphasize the role of molecular analysis of the RET proto-oncogene in diagnosing presymptomatically those individuals at risk of inheriting the disease allele.

Adolescent↗
PubMed2005

Increased expression and activity of CDC25C phosphatase and an alternatively spliced variant in prostate cancer.

Alterations in the control of cell cycle progression have been implicated in a wide variety of malignant neoplasms, including prostate cancer. CDC25 phosphatases belong to the tyrosine phosphatase family and play a critical role in regulating cell cycle progression by dephosphorylating cyclin-dependent kinases at inhibitory residues. CDC25C plays an important role in the G2-M transition by activating Cdc2/Cyclin B1 complexes. To determine whether CDC25C activity is altered in prostate cancer, we have examined the expression of CDC25C and an alternatively spliced variant in human prostate cancer samples and cell lines. CDC25C protein is up-regulated in prostate cancer in comparison with normal prostate tissue and is present almost exclusively in its active dephosphorylated form. Expression of a biologically active alternatively spliced CDC25C isoform is also increased in prostate cancer and expression of alternatively spliced CDC25C is correlated to occurrence of biochemical (prostate-specific antigen) recurrence. We have also developed a quantitative reverse transcriptase-PCR analysis of Ki-67 expression as a method of measuring proliferative activity in prostate cancer from RNA samples. Based on this analysis of Ki67 expression, some but not all of this increase in CDC25C and its alternatively spliced variants is correlated with increased proliferation in prostate cancer. This data suggests that CDC25C might play an important role in prostate cancer progression and could be used to monitor and predict the aggressiveness of this disease.

Alternative Splicing↗
PubMed1997

Strategy for identification of sequence variants in COL7A1 and a novel 2-bp deletion mutation in recessive dystrophic epidermolysis bullosa.

The diagnostic hallmark of the dystrophic forms of epidermolysis bullosa (DEB), a group of heritable blistering skin diseases, is abnormalities in the anchoring fibrils at the dermal-epidermal basement membrane zone. Since type VII collagen is the major, if not the exclusive, component of the anchoring fibrils, the corresponding gene (COL7A1) is the candidate gene in DEB. Recent cloning of the type VII collagen cDNA and elucidation of the exon-intron organization of the gene have provided the basis for us to develop a novel strategy for identification of sequence variants in COL7A1. Optimization of 72 balanced primer pairs corresponding to flanking intronic sequences allowed PCR amplification of all 118 exons directly from genomic DNA. The PCR products were examined by heteroduplex analysis followed by comparative nucleotide sequencing. More than 100 sequence variants have been identified thus far in COL7A1 using this method, some of which are single base pair polymorphisms and many of which are pathogenetic mutations contributing to the blistering phenotype in DEB. The comprehensive method described is useful for rapid, reliable, and sensitive detection of sequence variants in COL7A1. We demonstrate the utility of this novel strategy in mutation detection and prenatal exclusion of RDEB in a consanguineous family at risk for recurrence.

Collagen↗
PubMed2004

[Intra-articular myxofibrosarcoma of the hip in a 10-year-old child].

We report a case of intra-articular myxofibrosarcoma with acetabular involvement observed in a 10-Year-old boy. Myxofibrosarcoma is a frequent soft tIssue sarcoma usually observed in elderly subjects. It is extremely rare in children and has not been reported previously before the age of 22 Years. Myxofibrosarcoma is a specific type of soft tIssue tumor. Discussion continues concerning its relation with the myxoid variant of malignant fibrous histiocytoma. The myxoid matrix harbors fibroblastic cells with a curvilinear vessel configuration. Prognosis is good after complete resection and careful surveillance. Local recurrence may occur generally with progression of the tumor stage and risk of later metastasis. This is the first report of an intra-articular localization. We discuss the therapeutic options.

Child↗
PubMed2000

Low grade fibromyxoid sarcoma. a further low-grade soft tissue malignancy characterized by a ring chromosome.

Supernumerary rings in the context of a simple karyotype characterize several low-grade malignant tumors of soft tissue and bone. Low-grade fibromyxoid sarcoma is an uncommon low-grade sarcoma, the cytogenetics of which has not yet been reported. Here we describe the first molecular-cytogenetic characterization of a pulmonary metastasis of low-grade fibromyxoid sarcoma. The histology of the primary and recurrent tumors was consistent with the diagnosis of low-grade fibromyxoid sarcoma of the usual type, whereas the pulmonary metastasis was of the "giant rosettes" variant. Cytogenetic analysis revealed a ring chromosome. Because gain of material of chromosomes 7 and 16 was detected by CGH, the ring chromosome is assumed to be composed of material from these respective chromosomes.

Adult↗
PubMed2003

Persistence of TEL-AML1 transcript in acute lymphoblastic leukemia in long-term remission.

BACKGROUND: It has recently been shown that t (12;21) (p13;q 22) is the most common molecular genetic abnormality in childhood acute lymphoblastic leukemia (ALL). We have analyzed this translocation in an attempt to evaluate its incidence and to monitor minimal residual disease (MRD) with t (12; 21) rearrangement by detection of TEL-AML1 transcript in patients with childhood ALL. PROCEDURE: All cryopreserved bone marrow samples were analyzed using a nested reverse transcription-polymerase chain reaction (RT-PCR) method. TEL-AML1 transcripts were searched for in 34 ALL patients, including six in relapse consecutively diagnosed at our institution between 1991 and 1997. RESULTS: TEL-AML1 transcripts were found in five (19%) of 27 patients with B precursor ALL. The patients with BCR-ABL, chromosome 11q23 rearrangement and T-ALL patients did not express TEL-AML1 transcripts. Moreover, MRD in five patients with TEL-AML1 transcripts were analyzed in serial samples. Although TEL-AML1 transcripts disappeared soon after the beginning of chemotherapy in three of the five patients, one patient continued to express them for up to 21 months without recurrence and remained in continuous complete remission for seven years after the cessation of chemotherapy. The remaining patient was admitted to our hospital after the second relapse but died following a failure to induce complete remission. CONCLUSION: For most patients, the presence of TEL-AML1 transcripts suggests excellent chemosensitivity and a favorable prognosis, but some patients with these transcripts have a different outcome. The present study suggests the possibility that a persistence of MRD is not necessarily related to a relapse of ALL with TEL-AML1 fusion. The prognostic significance of TEL-AML1 transcript remains controversial. Further studies are needed to evaluate the relation between the TEL-AML1 transcript and prognosis.

Child↗
PubMed1985

Combined IgG2, IgG4 and IgA deficiency: low C1q concentrations and the presence of excess C1r and C1s in an adult patient with recurrent pneumococcal infections.

The complement (C) profile was investigated in an adult patient with combined IgG2, IgG4 and IgA deficiency and recurrent pneumococcal infections. The analysis revealed no gross impairment of the classic and alternative pathways of C activation. However, the concentrations of circulating C1q were persistently decreased, and the sera contained an excess of C1r-C1s complexes, resembling the C1 aberrations previously found in children with recurrent acute otitis media. The concentrations of C4 in the patient were persistently low. This could be ascribed to partial C4 deficiency with lack of C4A variants. The patient's IgG and IgM antibody responses to pneumococcal capsular polysaccharides and to other bacterial carbohydrate antigens were very poor. Interestingly, pneumococcal C-polysaccharide (CPS) could be detected in serum obtained during infection-free periods. Since CPS has been shown to bind C1q without causing C1 activation, the possibility was considered that the C1 aberrations in serum were due to circulating CPS. After administration of intramuscular gammaglobulin to the patient, the serum C1q levels were observed to return to normal.

Adolescent↗
PubMed2026

Why Specialized Metabolism Recurrently Emerges in Plants: Chemical and Genomic Biases in Metabolic Diversification.

Specialized metabolism plays a central role in mediating ecological interactions and adaptive responses in plants, while leaving enduring signatures in genome structure and evolution. Here, we synthesize advances in genomics, biochemistry, and evolutionary biology into a metabolite-driven genetic diversification (MGD) framework, in which metabolite chemistry biases the generation, retention, and reuse of genetic variation. When metabolic flux produces reactive, inhibitory, or otherwise costly intermediates, pathways handling these liabilities recurrently recruit gene dosage changes, duplication, and divergence at catalytic and regulatory choke points. These biases do not impose deterministic outcomes; instead, they shape which genomic variants are preferentially sampled and retained under selection, giving rise to predictable patterns of genomic change. Genome multiplication-through whole-genome duplication, allopolyploidy, and cell type-specific endoreduplication-amplifies these effects by altering dosage balance, regulatory context, and retention trajectories. Integrating MGD with genome-scale dosage dynamics explains why specialized metabolism repeatedly converges on similar solutions across plant lineages, even amid extensive genomic turnover and chemical diversity.

Journal Article↗
PubMed1982

Multifocal neuropathy and vocal cord paralysis in relapsing fever.

A 19-year-old soldier developed multifocal neuropathy following an infection with tick-borne Borrelia. He suffered from involvement of the right accessory nerve, the right brachial plexus and the left recurrent laryngeal nerve. As was expected, all these complications were reversible. In contrast to louse-borne relapsing fever, neurological manifestations in the tick-borne variants are not common. To the best of our knowledge, vocal cord paralysis has never been described before.

Adult↗
PubMed2006

Genomic alterations in Hodgkin's lymphoma.

Cytogenetic analysis of Hodgkin's lymphoma (HL) is hampered by the scarcity of neoplastic cells within a sea of reactive cells. There is accumulating evidence that HL represents 2 disease entities, classic HL (cHL) with its morphologic variants and nodular lymphocyte predominant HL (NLPHL). This subdivision, initially worked out in morphologic and immunohistochemical studies, has been further substantiated by molecular cytogenetic investigations. Two recurrent chromosomal aberrations, namely gains of 2p13-p16 and 9p24, have been found by comparative genomic hybridization analysis in microdissected cells from cHL patients as well as in cHL cell lines, but not in NLPHL cells. The available cHL cell lines are remarkably heterogeneous in their karyotypes, suggesting profound genomic instability leading to numeric chromosomal aberration and multiple chromosomal breaks and translocations. In this article, we review genomic aberrations that may contribute to the development and maintenance of the morphologic and clinical presentation of these beta-cell lymphoma entities. Furthermore, we delineate current data on the genomic changes observed in the neoplastic cells of HL that are created by epigenetic mechanisms, which are alternative mechanisms that regulate the expression of relevant genes.

Chromosome Aberrations↗
PubMedDate not supplied

Advanced adenosquamous carcinoma of the gallbladder with bilio-biliary fistula: an uncommon case treated by hepatopancreatoduodenectomy.

A 70 year-old female, who presented with jaundice and abdominal pain, was found to have an advanced gallbladder cancer involving the liver parenchyma, duodenum, and transverse colon. This was complicated by a bilio-biliary fistula between the gallbladder and both the right and left hepatic ducts. After obtaining an accurate pre-operative diagnosis, the patient underwent hepatopancreatoduodenectomy (HPD) with lymph node dissection around the hepatic pedicle, celiac trunk, aorta, and inferior vena cava. Histologic examination revealed adenosquamous carcinoma. This rare variant accounts for 3.5% of gallbladder cancers, and is associated with a worse prognosis than adenocarcinoma. The patient is in good condition without any signs of recurrence 42 months after the HPD. In this case report, we discuss the histological type and internal biliary fistula with regard to the literature, and the usefulness of an aggressive surgical procedure such as HPD with extended lymph node dissection which can improve survival and quality of life in selected patients.

Aged↗
PubMedDate not supplied

[The clinical and diagnostic characteristics of perforations in acutely bleeding gastroduodenal ulcers].

Over the period 1982-1996 a total of 8822 patients with ulcerorrhagias were treated in a clinical setting. In 122 (1.4%) patients different variants of association of perforation of the bleeding ulcers (PBU) were recordable. Features of development, course, diagnosis and treatment of PBU patients were studied. Two variants of PBU development were identified: concurrently emerging perforation with ulcer bleeding--in 34 (27.9%) patients; when perforation of the ulcer emerged in 88 (72.1%) in--patients one to seven days following a bleeding event, presenting in 48 (54.5%) with bleeding recurrence, and in 40 (45.5%) patients without the above recurrence against the background of varying degrees gravity of loss of blood. As to PBU localization, 92 (75.4%) patients had the same site (in the stomach--18 subjects, pyloroduodenal region--74 ones), 30 (24.6%) patients developed simultaneously one perforating gastric or duodenal ulcer and some other ulcer bleeding. Analysis of symptoms in PBU and in 474 patients presenting with perforating ulcers without bleeding revealed varying degrees atypicalness of PBU course depending on variants of combination. A symptom complex of lesser PBU sign has been singled out, an algorithm proposed for procedures that might be helpful in making early diagnosis and planning surgical treatment to be done in a timely fashion. The suggested approach enabled the postoperative mortality to be reduced 3.5-fold (from 25% to as low as 7.1%).

Acute Disease↗
PubMed1999

Spindle cell thymic carcinoma: clinicopathologic and immunohistochemical study of a distinctive variant of primary thymic epithelial neoplasm.

We report 16 cases of a distinctive variant of primary thymic epithelial neoplasm characterized by prominent spindling of the tumor cells. The patients were seven women and nine men aged 23 to 82 years (mean, 54 years). The lesions presented as anterior mediastinal masses without clinical or radiographic evidence of tumor elsewhere. Most patients had chest pain, dyspnea, and cough; in five patients, the tumors were asymptomatic and were discovered on routine clinical examination. Grossly, the lesions were firm, well-circumscribed, and locally infiltrative, and had a firm cut surface with foci of hemorrhage, necrosis, and cystic changes. Most of the tumors were treated by complete surgical excision. Histologically, they were characterized by a spindle cell proliferation showing varying degrees of atypia and mitotic activity. In 12 cases, transitions could be seen with areas that showed the features of conventional spindle cell thymoma. In two cases, areas showing features of poorly differentiated (lymphoepitheliomalike) carcinoma and anaplastic carcinoma could also be observed. Immunohistochemical studies in 10 cases showed strong positivity of the spindle tumor cells for CAM5.2 cytokeratin, and negative staining for a panel of antibodies including epithelial membrane antigen, carcinoembryonic antigen, actin, desmin, vimentin, S-100 protein, HMB45, CD34, CD5, and CD99. Clinical follow-up of eight patients showed an aggressive biologic behavior with recurrence, metastasis, and death by tumor in five of them 2 to 5 years after diagnosis. Based on these findings, the present tumors are interpreted as an unusual spindle cell variant of thymic carcinoma. The close association of these cases with areas showing the features of spindle cell thymoma within the same tumor mass suggests that some of these lesions may arise as a result of malignant transformation in a preexisting spindle cell thymoma.

Adult↗
PubMed1990

Diffuse sclerosing variant of papillary carcinoma of the thyroid. Report of three cases.

Three cases of an unusual diffuse sclerosing variant of papillary carcinoma were found among 370 consecutive malignant tumors of the thyroid gland retained in the surgical pathology files of Kanazawa University Hospital over the last 10 years. The tumors were characterized by diffuse involvement of one or both lobes of the thyroid, dense fibrosis, papillary carcinoma with marked squamous metaplasia and abundant psammoma bodies, heavy lymphocytic infiltration and extensive lymphatic permeation. In two cases, the neoplasms showed more aggressive regional lymph node metastases and local invasion; the patient in the first case underwent surgery three times after initial radical surgery because of regional lymph node recurrences, and the second case showed direct invasion of the thyroid tumor to the larynx and distant metastasis to the lungs. Although the number of examined cases was small, the findings suggest that the diffuse sclerosing variant type has a less favorable prognosis and should be differentiated from papillary carcinomas with excellent prognosis.

Adult↗
PubMedDate not supplied

Clear cell meningioma variant and clinical aggressiveness.

The few reports about clear cell meningiomas (CCM) point to an inordinate clinical aggressiveness despite their histological benignity. We studied 5 CCM aiming to assess their clinicopathological, cytometric, and ultrastructural features. Two patients were females and 3 males, with a mean age of 36 years. Two tumors were spinal, one of the cerebral convexity, one of the tentorium-clinoid region, and one of the base of the skull. The first 3 were totally removed and have not recurred for a mean follow-up time of 40 months. The tentorium-clinoid and the skull base tumors had radical subtotal and partial resections, and recurred after 16 and 1.5 months, respectively. All tumors but one, a non-recurrent one, presented no signs of histological anaplasia. The proliferative capacity, as assessed by MIB-1 staining index (SI), of recurrent tumors was slightly higher than that of those tumors that did not recur. All cases showed DNA diploid pattern. Amianthoid-type fibers were disclosed on ultrastructural study. CCM arose in patients younger than those with other variants of meningioma, the spinal canal and the posterior fossa were the common sites. Finally, intracranial tumors were linked to an aggressive behavior.

Adult↗
PubMed1993

Osteofibrous dysplasia: clinicopathologic study of 80 cases.

A thorough review of the clinical, radiologic, and histologic features of 80 cases of long bone osteofibrous dysplasia is presented. Of the six cases of osteofibrous dysplasia immunostained with a cytokeratin antibody, two were cytokeratin positive; however, the five cases of fibrous dysplasia that were stained were all negative. Follow-up (mean, 5.4 years; range, 1 month to 31 years) data were available for 41 cases (51%). From the consultation series nine of the 18 patients studied had recurrences, regardless of the different treatment regimens. The average recurrence interval in these patients was 2.7 years. Two patients had incomplete excision and six had biopsy only. All eight of these patients had residual tumors. Among the 16 Mayo Clinic patients, one had recurrence 5 years after the initial treatment. In two cases, 7-year-old and 6-year-old boys, histologic maturation to fibrous dysplasia was observed 4 and 10 years later, respectively. Adamantinoma has not developed in any of the 41 cases of osteofibrous dysplasia for which we have follow-up information. It seems clear that osteofibrous dysplasia does not progress to adamantinoma. Our study suggests that osteofibrous dysplasia is probably a variant of fibrous dysplasia, as demonstrated by the maturation of two lesions of osteofibrous dysplasia to fibrous dysplasia. Surgical treatment may be appropriate in cases with an extensive lesion, pseudoarthrosis, and accentuated tibial bowing. The overall prognosis is good, even with recurrence.

Adolescent↗
PubMed2006

An association between a common variant (G972R) in the IRS-1 gene and sex hormone levels in post-menopausal breast cancer survivors.

Insulin receptor substrate-1 (IRS-1) is a key downstream signaling molecule common to both the insulin and IGF signaling pathways that can interact with the estrogen pathway to regulate breast cell growth. We investigated whether a putative functional variant for IRS-1 (G972R) influences circulating levels of sex hormones, sex hormone binding globulin (SHBG), C-peptide, and insulin-like growth factor 1 (IGF-1) levels among post-menopausal African-American and non-Hispanic white breast cancer patients enrolled in the Health, Eating, Activity, and Lifestyle (HEAL) Study. Circulating levels of sex hormones and growth factors can influence breast cancer recurrence and survival. Serum estrone, estradiol, testosterone, SHBG, IGF-1 and C-peptide were measured in 468 patients at 30+ months post diagnosis. Non-protein bound hormone levels (free estradiol, free testosterone) were calculated. In African-American patients, the IRS-1 variant was associated with increased serum levels of estrone (p = 0.02), free estradiol (p = 0.04), total testosterone (p = 0.04), free testosterone (p = 0.006) and decreased levels of sex hormone-binding globulin (p = 0.02). No association was present for white patients. Our findings provide suggestive evidence that IRS-1 G972R variant may be associated with circulating levels of sex hormones and SHBG in African American breast cancer survivors.

Black or African American↗