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J Prat

Publications and source records attributed to J Prat.

At least 55 records · Page 3Linked to original sources
PubMed1998

K-ras mutations in nonmucinous ovarian epithelial tumors: a molecular analysis and clinicopathologic study of 144 patients.

BACKGROUND: To assess the putative prognostic value of K-ras mutations in nonmucinous ovarian tumors, the authors looked for K-ras point mutations at codons 12 and 13 in 144 nonmucinous ovarian tumors. METHODS: A series of 144 consecutive, unselected, archival, nonmucinous ovarian tumors (35 benign, 12 borderline, and 97 malignant) were studied. K-ras mutations at codons 12 and 13 were determined by polymerase chain reaction using the restriction fragment length polymorphism method with mismatched nested primers. Extensive clinicopathologic and follow-up data on all patients were evaluated. RESULTS: The overall prevalence of K-ras mutations at codons 12 and 13 was 30.5% (44/144). In benign tumors, it was 20% (7/35); in borderline tumors, 25% (3/12); and in carcinomas, 35% (34/97). The presence of K-ras point mutations did not correlate with survival. Among the benign tumors, K-ras mutations were detected in three Brenner tumors with a mucinous component. CONCLUSIONS: These results indicate that K-ras mutations are not initial events in the pathogenesis of nonmucinous ovarian tumors and do not appear to be related to survival.

Adult↗
PubMed1998

Sustentacular cells occur frequently in the familial form of medullary thyroid carcinoma.

The presence and distribution of S-100-immunoreactive sustentacular cells were investigated by immunohistochemistry in 67 medullary thyroid carcinomas (MTCs). The familial or sporadic status of the tumours was assessed by clinical data and confirmed by the identification of RET germline mutations using the polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and restriction analysis. Sustentacular cells were detected in 19 tumours (28.3 per cent). They were found significantly more frequently in the familial (15/24, 62.5 per cent) than in the sporadic MTCs (4/43, 9.3 per cent). The results indicate that sustentacular cells are commonly found in familial MTC and their presence in any MTC may be regarded as an indirect indicator that the tumour might be of the familial type.

Carcinoma, Medullary↗
PubMed1998

Molecular pathology of ovarian carcinomas.

There is evidence that ovarian cancer may be derived from the progressive transformation of benign and/or borderline tumours. Mutations involving different oncogenes and tumour suppressor genes accumulate during the process of malignant transformation, and the alterations of genes involved in the pathogenesis of familial ovarian cancer are probably early events in ovarian tumorigenesis. BRCA-1 and BRCA-2 act as classical tumour suppressor genes in hereditary tumours, but their role in sporadic tumours remains controversial; however, a high frequency of allele losses in BRCA-1 (17q) and BRCA-2 (13q) loci has been observed in both familial and sporadic tumours. The possible role of mismatch repair genes and microsatellite instability is also controversial, but a role for them has been proposed in borderline tumours. Mutations in K-ras are specific for mucinous tumours and may be related to mucinous differentiation. Finally, a role in tumour progression has been proposed for both c-erb B-2 and p53, but their practical value in prognosis remains questionable.

BRCA2 Protein↗
PubMed1998

Microsatellite instability in endometrial carcinomas: clinicopathologic correlations in a series of 42 cases.

Instability at microsatellite repeat sequences (MI) has been observed in endometrial carcinomas (EC) arising sporadically or in association with the hereditary colon cancer syndrome. However, the clinical and pathological features of the EC with MI have not been characterized. DNA of 42 patients with EC was extracted from blood and from fresh-frozen and paraffin-embedded tumor tissue. Microsatellite loci on chromosomes 4, 5, 10, 12, 17, and 18 were amplified by polymerase chain reaction. MI was defined by a mobility shift in the tumor DNA as compared with normal DNA. Results were correlated with the clinical and pathological features of the tumors. MI at three or more loci was detected in 12 of 42 cases (28%). There were no significant differences between EC with and without MI with regard to age of presentation, stage, evidence of estrogenic stimulation, mucinous differentiation, estrogen receptor, c-erbB2, or p53 immunostaining. However, MI was more frequent in endometrioid (11/33, 33.3%) than in nonendometrioid (1/9, 11%) carcinomas. Only one papillary serous carcinomas showed MI. MI was found in one of two cases of endometrial hyperplasia adjacent to EC. It was concluded that MI is a common genetic abnormality of endometrial carcinoma and appears to be more frequent in endometrioid than in nonendometrioid tumors.

Adult↗
PubMed1998

Müllerian inhibiting substance, alpha-inhibin, and CD99 expression in sex cord-stromal tumors and endometrioid ovarian carcinomas resembling sex cord-stromal tumors.

Müllerian inhibiting substance (MIS), alpha-inhibin, and CD99 are expressed by normal and neoplastic sex cord and stromal gonadal derivatives. The expression of MIS, inhibin, and CD99 was evaluated by immunohistochemistry in a series of 19 sex cord-stromal tumors and seven ovarian endometrioid carcinomas resembling sex cord-stromal tumors. Normal ovaries and testes from patients with the androgen insensitivity syndrome were used as control. All three markers were detected in primordial ovarian follicles and immature seminiferous tubules. Both inhibin and MIS were expressed by all sex cord-stromal tumors, but inhibin immunostaining appeared stronger and more diffusely distributed. CD99 was expressed by all adult and juvenile granulosa cell tumors, but only focally by Sertoli-Leydig cell tumors. In Sertoli-Leydig cell tumors, the three markers were predominantly expressed by the Sertoli cells. None of the seven endometrioid carcinomas with a sex cord-stromal pattern was positive for MIS or inhibin; two of them reacted for CD99, but their staining patterns were not membranous. Inhibin immunoreactivity was also detected in foci of stromal luteinization, occasionally present in these tumors. MIS, inhibin, and CD99 are potentially useful markers in the differential diagnosis between sex cord-stromal tumors and endometrioid carcinomas resembling sex cord-stromal tumors.

12E7 Antigen↗
PubMed1998

Design and test of neural networks and statistical classifiers in computer-aided movement analysis: a case study on gait analysis.

OBJECTIVE: To describe the methods for designing and testing diagnostic systems in movement analysis and to verify the clinical usefulness of neural networks and statistical classifiers in a case study. DESIGN: Connectionist and statistical models trained and tested with measured data. BACKGROUND: A basic need in rehabilitation and related fields is to efficiently manage the vast information obtained from a movement analysis laboratory. Many studies have dealt with the interpretation of measured variables in order to correlate objective descriptors to the presence and/or severity of specific neuromusculoskeletal disorders or their consequences. This traditional analytical approach has been complemented in the last decade by new non-linear classification tools called neural networks. METHODS: A gait analysis study on 148 lower limb arthrosis patients and 88 age-matched control subjects. Pathological and healthy gait patterns obtained from force plates wer discriminated by means of multilayer perceptrons and statistical classifiers. RESULTS: Ten input features were enough to train a multilayer perceptron with six hidden neurons. The discrimination rate of the neural net was 80% after cross-validation, significantly higher (P<0.05) than the performance of a Bayes quadratic classifier (about 75%). A great variance due to a small cross-validation set could be demonstrated. CONCLUSIONS: Strict statistical requirements must be observed for designing a neural network. Although these models attain a better performance than conventional statistical approaches, the benefits they bring are sometimes not sufficient to justify their use. Furthermore, clinicians routinely involved in critical decisions may not consider such diagnostic systems reliable enough.

Journal Article↗
PubMed1998

Primary ovarian rhabdomyosarcoma: a report of 13 cases.

Primary ovarian rhabdomyosarcomas were found in 13 patients aged 7 to 79 (mean 37) years who had reported abdominal pain and swelling. Six tumors involved the right ovary, 3 involved the left, 1 involved both, and the laterality was unknown in 3 cases. Four tumors were stage I, 2 were stage II, 4 were stage III, and 2 were stage IV; the stage of 1 tumor is not known. The tumors ranged from 10 to 19.5 (average 16) cm in diameter and had solid sectioned surfaces that varied from yellow to white to pink and from gelatinous to hemorrhagic. Microscopically, 11 tumors were embryonal and 2 were alveolar rhabdomyosarcomas. Follow-up information, available for 11 patients, revealed that 7 died of disease 10 days to 26 months postoperatively; 2 of these patients had stage II disease, 3 had stage III, and 2 had stage IV. Four patients were alive 2 to 9 months postoperatively; 3 had stage I and 1 had stage III disease. These 13 tumors and an additional 10 from the English-language literature are reviewed and the differential diagnosis of ovarian rhabdomyosarcoma is discussed.

Abdominal Pain↗
PubMed1998

Malignant schwannoma of the uterine cervix: a study of three cases.

Pure sarcomas of the uterine cervix are rare; most of those reported have been leiomyosarcomas or rhabdomyosarcomas. Minimal data exists on malignant nerve sheath tumors in this site; only one typical example and one melanocytic example have been reported. We report three additional examples here in three patients 25, 65, and 73 years of age. The two older patients had vaginal bleeding and underwent hysterectomy as initial treatment. The youngest patient initially underwent only polypectomy. The tumors were 1.3, 4.4, and 5.0 cm in greatest dimension. The tumors were red-grey to white: two were polypoid and the third was ulcerated. The dominant microscopic appearance was that of cellular fascicles of spindle cells with hyperchromatic nuclei and eosinophilic cytoplasm. However, hypocellular areas were striking in each case; the hypocellular areas were fibromatous in two tumors and two had areas with a myxoid stroma (prominent in one). One tumor focally had cellular aggregates with a swirling pattern within a hypocellular background. Epithelioid foci in which tumor cells were rounded with conspicuous eosinophilic cytoplasm were focally prominent in one case. Mitoses were readily identified in each case. All three tumors were positive for S-100 protein and vimentin and negative for cytokeratin. HMB-45, and desmin. One case is recent and one patient had multiple metastases in the abdomen 2 years after hysterectomy. The patient treated initially by polypectomy underwent repeat local excision, followed by cone biopsy with positive margins, and then hysterectomy. She is clinically free of disease 15 months after diagnosis. Although the diagnosis of malignant schwannoma was suggested by the histologic features of the tumors, other diagnoses were entertained and immunohistochemistry was crucial in confirming the diagnosis. These tumors should be distinguished from other malignant spindle cell tumors of the cervix, such as leiomyosarcoma, endocervical "stromal sarcoma," and spindle cell melanoma, so their features, behavior, and optimal therapy can be further delineated.

Adult↗
PubMed1998

[Clinical manifestations of Stenotrophomas (Xanthomonas) maltophilia infection].

OBJECTIVE: Stenotrophomonas maltophilia (SM) is a gram-negative bacillus whose incidence like nosocomial pathogen has been incremented in the last years, especially in immunocompromised patients, subjected to invasive procedures and those receiving broad-spectrum antimicrobial therapy. METHOD: We report 15 isolations of SM between 1994-1996. RESULTS: The criteria for SM infection were fulfilled by 9 patients (60%), and 6 patients (40%) were colonized. The mean age of the patient was 60 +/- 12 years. Major predisposing factors in infections included venous catheterization (100%), prior surgery (86%), residence in ICU (80%), prior antibiotic therapy (80%) and intubation (66%). The most common underlying disease were heart disease (60%), treatment with immunosuppressors and/or steroids (46%) and chronic lung disease (46%). Ten cases (66%) had polymicrobial culture. The mortality rate was 40%. Risk factors associated with fatal outcome included the following: chronic lung disease (p = 0.043), nasogastric catheterization (p = 0.01), urinary tract catheterization (p = 0.02), intubation (p = 0.04) and the presence of pneumonia or sepsis by SM (p = 0.02). The most active agents were colistina (100%), cotrimoxazol (71%) and ceftazidima (53%). The isolates were highly resistant to first and second-generation cephalosporins (100%) tetracyclines (86%), aztreonam (91%) and imipenem (71%). CONCLUSION: SM cause a wide range of clinical syndromes and is more likely to cause infection or colonization in patients who have underlying disease. Due to its inherent multiple-antimicrobial resistance, it would appear its potential as a nosocomial pathogen will continue to increase. Therapy of patients should include cotrimoxazole.

Cross Infection↗
PubMed1998

Mitochondrial membrane peroxidizability index is inversely related to maximum life span in mammals.

The oxidative stress theory of aging predicts a low degree of fatty acid unsaturation in tissues of longevous animals, because membrane lipids increase their sensitivity to oxidative damage as a function of their unsaturation. Accordingly, the fatty acids analyses of liver mitochondria from eight mammals, ranging in maximum life span from 3.5 to 46 years, show that the total number of double bonds and the peroxidizability index are negatively correlated with maximum life span (r = -0. 88, P < 0.003; r = -0.87, P < 0.004, respectively). This is not due to a low content of unsaturated fatty acids in longevous animals, but mainly to a redistribution between kinds of the polyunsaturated n-3 fatty acids series, shifting from the highly unsaturated docosahexaenoic acid (r = -0.89, P < 0.003) to the less unsaturated linolenic acid (r = 0.97, P < 0.0001). This redistribution pattern strongly suggests the presence of a constitutively low delta6-desaturase activity in longevous animals (r = -0.96, P < 0.0001). Thus, it may be proposed that, during evolution, a low degree of fatty acid unsaturation in liver mitochondria may have been selected in longevous mammals in order to protect the tissues against oxidative damage, while maintaining an appropriate environment for membrane function.

Aging↗
PubMed1998

BAX somatic frameshift mutations in endometrioid adenocarcinomas of the endometrium: evidence for a tumor progression role in endometrial carcinomas with microsatellite instability.

Microsatellite instability (MI) has been observed in endometrioid adenocarcinomas of the endometrium, either arising sporadically or in association with the hereditary colon cancer syndrome. Genes known to contain mononucleotide short tracts in their coding sequence are regarded as targets for mutations in these tumors. BAX is a proapoptotic gene that contains a tract of eight consecutive deoxyguanosines in its third coding exon. DNA of 26 patients with endometrial carcinoma was extracted from blood and from fresh-frozen and paraffin-embedded tumor tissue. For MI analysis, microsatellite loci on chromosomes 3, 5, 10, 12, and 18 were amplified by PCR. Frameshift mutations in the (G)8 tract of BAX were detected by single-strand conformation polymorphism (SSCP) analysis. MI at three or more loci was detected in 13 cases. BAX frameshift mutations were detected in seven MI+ tumors (53.8%), but in none of the 13 MI- neoplasms. In two cases, identical BAX frameshift mutations were detected in different areas of the neoplasm, whereas in the other five cases, BAX mutations were heterogeneously distributed throughout the tumor. Immunostaining with antibodies against the carboxy terminus of BAX protein was very useful in assessing the heterogeneous distribution of BAX frameshift mutations in the neoplasms. The results suggest that BAX frameshift mutations are frequent in endometrial carcinomas with MI, probably playing a role in the process of tumor progression of these neoplasms.

Base Sequence↗
PubMed1997

K-ras mutations in mucinous ovarian tumors: a clinicopathologic and molecular study of 95 cases.

BACKGROUND: To assess the role of K-ras mutations in the pathogenesis of mucinous ovarian tumors, the authors looked for K-ras point mutations at codons 12 and 13 in 95 mucinous ovarian neoplasms. The results were subsequently correlated with the clinicopathologic data. METHODS: Benign, borderline, and malignant mucinous ovarian tumors were identified microscopically. DNA was extracted from formalin fixed, paraffin embedded tissue, and target sequences were amplified in vitro by polymerase chain reaction. Mutations were detected by the presence of restriction fragment length polymorphisms artificially introduced by the use of mutant amplimers. In tumors containing areas that exhibited different histologic grade, precise microdissection of each of these areas was performed. The results were correlated with the clinical data and the morphologic features of the neoplasms. RESULTS: The overall frequency of codon 12/13 ras gene mutations was 68%. Codon 12 point mutations were present in 63% of the cases (55.7% of mucinous cystadenomas, 73% of borderline tumors, and 85% of carcinomas). Codon 13 mutations were detected in 11.5% of the tumors (five cystadenomas, three borderline tumors, and three carcinomas). Eight tumors (three benign, two borderline, and three malignant) exhibited mutations at codons 12 and 13. In 12 of the 15 tumors with 2 areas showing different histologic grade, identical point mutations were detected separately in both areas. CONCLUSIONS: The results of this study confirm that K-ras mutations do occur in benign and particularly in malignant mucinous ovarian tumors. The authors' findings support the hypothesis that K-ras mutational activation is an early event in mucinous ovarian tumorigenesis.

Adolescent↗
PubMed1997

Urinary pyrraline as a biochemical marker of non-oxidative Maillard reactions in vivo.

The presence of pyrraline, a non-oxidative glucose-derived Maillard reaction product in plasma proteins has been established previously. In this study we have investigated the presence of pyrraline in human urine to determine whether pyrraline-containing proteins are metabolized or selectively retained. Pyrraline was detected by means of HPLC, and its presence was confirmed by UV and electrospray-mass spectrometry. The quantification of pyrraline in urine from healthy individuals showed 1.21 +/- 0.4 micrograms/mg creatinine. In urine from diabetic patients, pyrraline levels varied considerably, although the mean level was higher than in healthy subjects (1.37 +/- 0.6 micrograms/mg creatinine). These data further support the presence of a catabolic pathway for advanced non-oxidative Maillard reaction products in vivo and suggest their role in the pathogenesis of diabetes.

Adolescent↗
PubMed1997

Molecular diagnosis of von Hippel-Lindau disease in a kindred with a predominance of familial phaeochromocytoma.

OBJECTIVE: To study the presence of germline mutations in the von Hippel-Lindau gene (vhl) in a kindred with a predominance of familial phaeochromocytoma in order to confirm the diagnosis of von Hippel-Lindau disease (VHLD) as well as to identify asymptomatic members. DESIGN: DNA extracted from peripheral blood was amplified by the polymerase chain reaction using oligonucleotide primers corresponding to exon 3 of the vhl gene. Specific mutations in codon 238 were screened by restriction endonuclease digestion of PCR products with Msp I. The results were confirmed by DNA sequence analysis. PATIENTS: Two generations of a family consisting of 15 individuals were studied. RESULTS: A germline missense point mutation at codon 238 of the vhl gene (CGG-->TGG; Arg-->Trp) was detected in all patients with phaeochromocytoma and in only one of the asymptomatic family members. CONCLUSION: Mutational analysis of the vhl gene in patients with familial phaeochromocytoma may permit specific diagnosis of von Hippel-Lindau disease, and is a good method for the identification of asymptomatic individuals at risk of von Hippel-Lindau disease.

Adolescent↗
PubMed1997

Glycaemic control and in vivo non-oxidative Maillard reaction: urinary excretion of pyrraline in diabetes patients.

The presence of pyrraline in human urine has recently been described. Using reversed-phase high-performance liquid chromatography, we measured urinary pyrraline in 45 insulin-treated diabetic patients with preserved renal function and in 30 age- and sex-matched healthy subjects. The relationship between urinary pyrraline and metabolic control parameters in the diabetic population (glycaemia, fructosamine, haemoglobin A1c, and 1-year mean haemoglobin A1c) was evaluated. The mean urinary level of pyrraline in diabetic patients with poor glycaemic control (HbA1c > 9.5%) was higher than that in healthy subjects (1.12 +/- 0.35 vs. 0.75 +/- 0.2 mumol mmol-1 creatinine, P < 0.04), whereas in patients with good to moderate glycaemic control (HbA1c < 9.5) it was slightly but not significantly higher than in healthy subjects (0.80 +/- 0.3 mumol mmol-1 creatinine vs. 0.75 +/- 0.2 mumol mmol-1 creatinine). There is a significant correlation between urinary pyrraline level and glycaemia (P < 0.008), haemoglobin A1c (P < 0.01) and 1-year mean haemoglobin A1c values (P < 0.007), but not with fructosamine. The results of the present work prove, for the first time, that glycaemic status influences circulating levels of advanced Maillard reaction products.

Adolescent↗
PubMed1997

Granulocytic sarcoma of the female genital tract: a clinicopathologic study of 11 cases.

Eleven patients, 13 to 76 (mean, 40) years of age, had granulocytic sarcoma of the female genital tract (FGT) (ovary, seven cases; vagina, three cases; cervix, one case). In nine cases, the FGT involvement was the initial clinical presentation of the disease, and in the other two cases, the FGT involvement was discovered during a relapse of acute myeloid leukemia. The tumors ranged from 0.5 to 14 (mean, 7.5) cm in greatest dimension. Two ovarian tumors were bilateral, and three were green. Microscopic examination revealed a predominantly diffuse pattern of growth, but cords and pseudoacinar spaces were also present focally in several cases. Sclerosis was seen in five tumors and was prominent in one. Prominent myeloid differentiation was readily recognizable on routinely stained sections in three cases, whereas the neoplastic cells in the other cases were primitive with only rare eosinophilic myelocytes. All 11 tumors were positive for chloroacetate esterase, nine of nine were strongly and diffusely positive for lysozyme, eight of eight for myeloperoxidase, seven of seven for CD68, and six of six for CD43. Examination of bone marrow or peripheral blood performed after the diagnosis of FGT involvement revealed acute myeloid leukemia in three of five cases. Two of these patients died of disease, 1 and 16 months after the initial diagnosis, and the third, who received chemotherapy, is alive and free of disease 8 months after the initial diagnosis. One of the two patients with negative bone marrow had recurrent granulocytic sarcoma 30 months after diagnosis and died of sepsis 1 month later; no residual disease was noted at autopsy. The other patient is alive and free of disease 18 months after the diagnosis. One of the four remaining patients with primary FGT involvement who did not have a bone marrow biopsy died of leukemia 24 months later; no follow-up information is available for the other three patients. One of the two patients with a prior diagnosis of acute myeloid leukemia was alive with disease 26 months later; follow-up is not available for the second patient. The diagnosis was often difficult in these cases, the most common problem being distinction from malignant lymphoma, but carcinoma, granulosa cell tumor, and, rarely, other tumors were considered. Immunohistochemical and enzyme histochemical staining were useful in establishing the diagnosis, although suspicion of the diagnosis on examination of routinely stained sections was of paramount importance.

Adolescent↗