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Biomedical subjects

P Machin

Publications and source records attributed to P Machin.

12 recordsLinked to original sources
PubMed2002

Neurotoxic lesions of the rat perirhinal cortex fail to disrupt the acquisition or performance of tests of allocentric spatial memory.

Rats with neurotoxic lesions of the perirhinal cortex (n = 9) were compared with sham controls (n = 14) on a working memory task in the radial arm maze. Rats were trained under varying levels of proactive interference and with different retention intervals. Finally, performance was assessed when the maze was switched to a novel room. None of these manipulations differentially impaired rats with perirhinal lesions. Rats were next trained on delayed matching-to-place in the water maze. Even with retention delays of 30 min, there was no evidence of a deficit. Although interactions between the perirhinal cortex and hippocampus may be important for integrating object-place information, the perirhinal cortex is often not necessary for tasks that selectively tax allocentric spatial memory.

Animals↗
PubMed2001

Molecular pathology of endometrial hyperplasia and carcinoma.

Four different genetic abnormalities may occur in endometrioid adenocarcinomas of the endometrium (mircosatellite instability and mutations in the PTEN, k-RAS and beta-catenin genes), whereas nonendometrioid carcinomas of the endometrium often have p53 mutations and loss of heterozygosity on several chromosomes. Occasionally, a nonendometrioid carcinoma may develop as a result of dedifferentiation of a preexisting endometrioid carcinoma; in such a case, the tumor exhibits overlapping clinical, morphologic, immunohistochemical, and molecular features of the 2 types. The insaturation of microsatellite instability in endometrial carcinogenesis seems to occur late in the transition from complex hyperplasia to carcinoma, and it is preceded by progressive inactivation of MLH-1 by promoter hypermethylation. Moreover, the endometrioid adenocarcinomas that exhibit microsatellite instability show a stepwise progressive accumulation of secondary mutations in oncogenes and tumor suppressor genes that contain short-tandem repeats in their coding sequences. Mutations in the PTEN and k-RAS genes are also frequent in endometrioid adenocarcinomas of the endometrium, particularly in the tumors that exhibit microsatellite instability, whereas beta-catenin mutations do not seem to be associated with such a phenomenon.

Cytoskeletal Proteins↗
PubMed2001

Loss of heterozygosity at the RB-1 locus and pRB immunostaining in epithelial ovarian tumors: a molecular, immunohistochemical, and clinicopathologic study.

Alterations in the retinoblastoma gene (RB-1) are common in human neoplasia. The frequency of loss of heterozygosity (LOH) at the RB-1 locus on chromosome 13q14 was studied in a series of 51 epithelial ovarian tumors (10 benign, 7 borderline, and 34 malignant). LOH was scored by the absence or reduction of the signal to < 50% of one of the alleles in tumor DNA compared with normal DNA. LOH results were correlated with retinoblastoma protein (pRB) immunostaining. LOH at the RB-1 locus was observed in 9 tumors (17.6%), specifically in 1 of 7 borderline tumors and 8 of 34 ovarian carcinomas (23.5%). Among the malignant tumors, LOH occurred more frequently in carcinomas with serous differentiation (7/23; 30%). A heterogeneous (10% to 70% cells) or diffuse (> 70% cells) pRB immunostaining was less frequent in benign (1/10; 10%) and borderline (2/7; 28%) tumors than in ovarian carcinomas (15/34; 44%), an observation that correlated with the higher proliferative index in carcinomas than in benign and borderline tumors. However, lack or only focal (< 10% cells) pRB immunostaining occurred in the vast majority of tumors with LOH at the RB-1 locus (7/9; 77%), a finding that may suggest a tumor suppressor role for RB-1 in these tumors. The results suggest that RB-1 may play a role in a subset of ovarian carcinomas, particularly those exhibiting serous differentiation.

Adenocarcinoma, Clear Cell↗
PubMed2000

Frameshift mutations at coding mononucleotide repeat microsatellites in endometrial carcinoma with microsatellite instability.

BACKGROUND: Microsatellite instability (MI) is a frequent occurrence in endometrioid carcinoma of the endometrium (EC). Several genes known to contain mononucleotide short tracts in their coding sequences (TGF-beta RII, IGFIIR, BAX, hMSH6, and hMSH3) are likely targets for mutations in these tumors. METHODS: DNA from 24 patients with EC and MI was extracted from blood and from fresh-frozen and paraffin embedded tumor tissue. Seven of these patients were found to have metastatic spread to paraaortic lymph nodes. DNA also was studied from 10 patients with EC without MI. RESULTS: Frameshift mutations at coding mononucleotide repeats were detected by single strand conformation polymorphism analysis and DNA sequencing. Frameshift mutations were detected more frequently in BAX (11 of 24 MI positive (+) tumors; 45.8%) than in TGF-beta RII (0 of 24 tumors; 0%), IGFIIR (3 of 24 tumors; 12.5%), hMSH3 (6 of 24 tumors; 25%), or hMSH6 (0 of 24 tumors; 0%). The mutations frequently were distributed heterogeneously throughout the tumors. Overall, frameshift mutations at 1 or more of these mononucleotide repeat microsatellites were found in 17 of 24 MI+ tumors (70.8%) but in none of the 10 MI negative neoplasms. In the seven EC patients with lymph node metastases, mutations in IGFRII were found more commonly in those with metastatic (three of seven patients) rather than primary (one of seven) tumors. CONCLUSIONS: The results of the current study confirm that BAX is an important target gene in ECs with MI. The frequent detection of IGFRII frameshift mutations in lymph node metastases suggest that IGFRII may play a role in tumor progression in these patients.

Endometrial Neoplasms↗
PubMed2000

Loss of heterozygosity on chromosome 17q in epithelial ovarian tumors: association with carcinomas with serous differentiation.

Loss of heterozygosity (LOH) on chromosome 17q is frequent in epithelial ovarian tumors, but its clinicopathologic significance remains to be elucidated. DNA of 50 patients with epithelial ovarian tumors was extracted from blood and from fresh-frozen and paraffin-embedded tissue (14 benign, 7 borderline, and 29 malignant). Six microsatellite loci were amplified by PCR (D17S250, TRHA1, D17S800, D17S855, D17S579, D17S513). LOH was scored by the absence or reduction of the signal to less than 50% of one of the alleles in tumor DNA compared with normal DNA. LOH was identified on chromosome 17q in at least one locus in 12 tumors (24%), all of them carcinomas (12 of 29 tumors, 41.3%). It occurred more frequently among high-grade serous carcinomas (8 of 14 tumors, 57%) and mixed endometrioid-serous carcinomas (2 of 5, 40%). LOH was detected in all informative markers of 10 tumors, suggesting the complete loss of an entire chromosome 17 homologue. Patients with LOH-positive carcinomas were older than those with LOH-negative malignant tumors (mean ages 67 and 49). The results support the hypothesis that LOH on chromosome 17q may be associated with the development of ovarian cancers in elderly patients, particularly with high-grade serous or mixed endometrioid-serous carcinomas.

Adenocarcinoma, Clear Cell↗
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

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

Stiff upper lip: coping strategies of World War II veterans with phantom limb pain.

OBJECTIVE: Study of coping with phantom pain in nonclinical war veteran amputees. DESIGN: Semistructured interview with amputees in their home setting. SETTING: Residential home for war veteran amputees or respondents' own homes. PATIENTS: Amputee veterans of World War II with phantom pain. OUTCOME MEASURES: Pain (McGill Pain Questionnaire) and pain history, coping (daily coping; Stone and Neale, J Pers Soc Psychol 1984;46:892-906), size of social network, and quality of war memories. RESULTS: No differences in pain or coping were associated with place of residence (and prevalence of cues) or social networks; war memories appeared not to be associated with availability of cues, whether media coverage or other amputees. There was some association between the emotional tone of war memories and pain intensity. Veteran amputees were in general accepting of high levels of pain and made little use of medical resources, relating that to past experience of their pain being dismissed. CONCLUSION: Coping with phantom pain in war veteran amputees is predominantly silent acceptance of the pain, with little use of social support however available, and rare recourse to medical help, based on past unhelpful experience. Pain and mood appeared to be unrelated to specific war cues, but higher pain scores were reported by those with unhappier war memories.

Adaptation, Psychological↗
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↗
PubMed1988

X-ray Laue diffraction from crystals of xylose isomerase.

The Laue method (stationary crystal, polychromatic x-rays) was used to collect native and heavy-atom-derivative data on crystals of xylose isomerase (EC 5.3.1.5). These data were used to find the heavy-atom positions. The positions found by use of Laue data are the same as those found by use of monochromatic data collected on a diffractometer. These results confirm that Laue diffraction data sets, which can be obtained on a millisecond time scale, can be used to locate small molecules bound to protein active sites. The successful determination of heavy-atom positions also indicates that x-ray crystallographic data collected by the Laue method can be used to solve protein structures.

Aldose-Ketose Isomerases↗