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M Crone

Publications and source records attributed to M Crone.

At least 19 recordsLinked to original sources
PubMed2003

Genetic and functional analyses of FH mutations in multiple cutaneous and uterine leiomyomatosis, hereditary leiomyomatosis and renal cancer, and fumarate hydratase deficiency.

Germline mutations of the fumarate hydratase (FH, fumarase) gene are found in the recessive FH deficiency syndrome and in dominantly inherited susceptibility to multiple cutaneous and uterine leiomyomatosis (MCUL). We have previously reported a number of germline FH mutations from MCUL patients. In this study, we report additional FH mutations in MCUL and FH deficiency patients. Mutations can readily be found in about 75% of MCUL cases and most cases of FH deficiency. Some of the more common FH mutations are probably derived from founding individuals. Protein-truncating FH mutations are functionally null alleles. Disease-associated missense FH changes map to highly conserved residues, mostly in or around the enzyme's active site or activation site; we predict that these mutations severely compromise enzyme function. The mutation spectra in FH deficiency and MCUL are similar, although in the latter mutations tend to occur earlier in the gene and, perhaps, are more likely to result in a truncated or absent protein. We have found that not all mutation-carrier parents of FH deficiency children have a strong predisposition to leiomyomata. We have confirmed that renal carcinoma is sometimes part of MCUL, as part of the variant hereditary leiomyomatosis and renal cancer (HLRCC) syndrome, and have shown that these cancers may have either type II papillary or collecting duct morphology. We have found no association between the type or site of FH mutation and any aspect of the MCUL phenotype. Biochemical assay for reduced FH functional activity in the germline of MCUL patients can indicate carriers of FH mutations with high sensitivity and specificity, and can detect reduced FH activity in some patients without detectable FH mutations. We conclude that MCUL is probably a genetically homogeneous tumour predisposition syndrome, primarily resulting from absent or severely reduced fumarase activity, with currently unknown functional consequences for the smooth muscle or kidney cell.

Amino Acid Metabolism, Inborn Errors↗
PubMed2000

Prevalence of the Chiari/hydrosyringomyelia complex in adults with spina bifida: preliminary results.

AIM: To establish the prevalence of Chiari malformations and hydrocephalus (HS) in adults with spina bifida (SB). INTRODUCTION: Adults with SB have recently been shown to be at risk from significant deterioration arising from the C/HS complex. Little is known about the prevalence of these malformations in adulthood, their natural history, risk factors for deterioration and optimum management. MATERIALS AND METHODS: Patients are recruited from a clinic for adults with SB and hydrocephalus, routinely questioned about recent changes in neurological symptoms and a full neurological examination performed. Functional assessments include: Barthel Index; Nottingham EADL; Nine Hole Peg Test; 10 metre timed walk test. Sagittal T1 and TSE (turbo spin-echo) magnetic resonance images (MRI) of the cranio-cervical junction and spinal cord are obtained using a 1.0-T MRI system with a phased-array surface coil. Scans are reported blindly. RESULTS: 76 patients have been assessed, 40 female, 36 male, mean age 27.5 years. Of these, 48 (63.2%) have symptoms +/- signs compatible with C/HS, but only 18 (23.7%) have reported new, potentially relevant, neurological symptoms over the previous 12 months. Of 25 patients undergoing MRI so far, 19 (76%) have had Chiari malformations and 12 (48%) have had HS. None of those with a negative scan have had signs/symptoms suggestive of the C/HS complex but a negative clinical evaluation has been unable to exclude such pathology. CONCLUSIONS: These early results suggest that the prevalence of the C/HS complex is high in adults with SB and cannot be predicted by neurological examination alone. Given past experience, the need for continued neurological follow up in a large proportion of the SB population throughout adulthood is likely to be essential.

Activities of Daily Living↗
PubMed1999

Left leg paralysis in a renal transplant.

The postoperative course of renal transplant patients is often complicated by opportunistic infection. Up to 4% of posttransplant infections are caused by Nocardia species. We present an unusual case of a nocardial spinal cord abscess that caused left leg paralysis.

Abscess↗
PubMed1999

Group therapy for spouses of aphasic patients.

The setting, course, and results of a counseling and a therapeutic group for relatives of chronic aphasic patients are reviewed. Generally, providing and discussing information on the illness, its consequences, and medical and social services are greatly appreciated by group members. Counseling and group psychotherapy, as conducted by us, did not result in measurable improvements of relatives' perceptions of personal, social, and familial burdens. We assume, however, that group therapy does lead to more realistic attitudes toward burdensome and severely straining situations and may help with coping. Further research into psychotherapeutic strategies for relatives of disabled persons, who themselves suffer from psychological and social handicaps, is needed.

Adaptation, Psychological↗
PubMed1996

Engelmann's disease: a 45-year follow-up.

We report a 45-year follow-up of a patient with Engelmann's disease previously described in 1950, showing progression of the disease with unique involvement of the femoral capital epiphyses. The case is compared with others to add some information about the later stages of a disease which is not fully understood.

Aged↗
PubMed1989

Nonrandom abnormalities of chromosome 9p in childhood acute lymphoblastic leukemia: association with high-risk clinical features.

To assess the frequency and significance of nonrandom abnormalities of chromosome 9p in childhood acute lymphoblastic leukemia (ALL), we analyzed our experience with 398 consecutive cases with completely banded karyotypes. Forty cases (10%) with abnormalities of 9p were identified: 26 with deletions, nine with unbalanced translocations resulting in the loss of 9p material, and five with apparently balanced reciprocal translocations. As compared with children with ALL lacking 9p abnormalities, these 40 cases were significantly older, had higher initial circulating WBC counts, more "lymphomatous" disease characteristics (including presence of a mediastinal mass in 15%. T-cell phenotype in 26%, splenomegaly greater than 8 cm in 25%), an increased failure rate in the first 2 to 3 years after diagnosis, and a higher incidence of extramedullary relapse. Conversely, lymphomatous ALL cases were twice as likely (19% v 8%) to have an abnormality of chromosome 9p than ALL cases lacking lymphomatous features (P = .01). The finding of an abnormal chromosome 9p, however, was not specific for lymphomatous ALL or T-cell lineage, because most cases were neither lymphomatous nor T-cell, and the overall Kaplan-Meier distribution of treatment failures for abnormal 9p cases was not statistically significantly different from control ALL cases receiving the same treatment who lacked abnormalities of 9p (P = .06, by log-rank test). We conclude that nonrandom abnormalities of chromosome 9p, especially a breakpoint in 9p21-22, occur with increased frequency in childhood ALL in association with some high-risk clinical features. Despite this association, the chromosome anomaly is nonspecific in its syndrome delineation and confers no major adverse consequence on long-term survival of childhood ALL treated with modern therapy. However, due to an apparently increased hazard of involvement of the CNS (eight of 17 failures), it may be inadvisable to lessen the intensity of CNS preventive therapy for this group of patients.

Child↗
PubMed1988

Synovial chondromatosis.

We reviewed 53 cases of synovial chondromatosis and compared their clinical, radiological and pathological features. A radiological diagnosis is possible with increasing frequency as the disease progresses; in the early phase arthrography is helpful. Radiologically the disease may be classified as either extra-articular, or intra-articular; the intra-articular variety may be localised or generalised. Recurrence after operation was seen in 11.5% and was much the same after either synovectomy or simple removal of loose bodies. A protocol for treatment is proposed.

Adolescent↗
PubMed1987

The chicken erythrocyte-specific MHC antigen. Characterization and purification of the B-G antigen by monoclonal antibodies.

Mouse monoclonal antibodies with B-G antigen (major histocompatibility complex class IV) specificity were obtained after immunization with erythrocytes or partially purified B-G antigen. The specificities of the hybridoma antibodies were determined by precipitation of B-G antigens from 125I-labeled chicken erythrocyte membranes (CEM) followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and autoradiography. The B-G antigen had an approximate molecular mass of 46-48 kd in reduced samples, depending on the haplotype, and in unreduced samples contained either dimers (85 kd), when labeled erythrocytes were the antigen source, or trimers (130 kd), when B-G was purified and precipitated from CEM. The B-G antigen was unglycosylated as studied by in vitro synthesis in the presence or absence of tunicamycin, binding experiments with lectin from Phaseolus limensis, and treatment of purified B-G antigen with Endoglycosidase-F or trifluoromethanesulfonic acid. Two-way sequential immunoprecipitation studies of erythrocyte membrane extracts with anti-B-G alloantisera and monoclonal antibodies revealed only one population of B-G molecules. Pulse-chase experiments have shown B-G to be synthesized as a monomer, with dimerization taking place after 20-30 min. No change in the monomer's molecular mass due to posttranslational modifications was revealed. The antigen was purified from detergent extract of CEM by affinity chromatography with a monoclonal antibody, and then reduced and alkylated and affinity-purified once more. Finally, reverse-phase chromatography resulted in a pure product. The B-G antigen was identified in the various fractions by rocket immunoelectrophoresis. The final product was more than 99% pure, as estimated by SDS-PAGE analysis followed by silver stain of proteins. The yield from the affinity chromatography step was 3-4 micrograms B-G/ml blood, calculated from Coomassie-stained SDS-PAGE of B-G using ovalbumin standards. The monoclonal antibodies were also used to identify the B-G (class IV) precipitation arc in crossed immunoelectrophoresis. No common precipitate with the B-F (class I) antigen was observed.

Animals↗
PubMed1987

Dosimetry in phototherapy cabinets.

Many skin diseases can be treated with phototherapy. The dose of ultraviolet radiation received at the skin surface should be recorded to guide subsequent treatment doses as well as to monitor cumulative dose. In order to see if a single reading from an electric dosimeter accurately reflected the dose of ultraviolet radiation received at the skin surface, 212 photoresponsive dosimeter badges were affixed at various sites to the skin of one side of a female volunteer. The volunteer was then exposed to ultraviolet A (UVA) radiation in a UVA light treatment cabinet. The monitors were then removed and the received dose recorded. Portions of the body facing the lights directly received the most irradiation. Areas inclined to the plane of the lamps, shaded areas, and anatomic areas near the top and bottom of the cabinet received the least. Dosimetry as recorded by an electronic monitor in the center of the cabinet decreased when a subject stood next to it. Evidently a single measurement of dose by an electronic monitor in an empty treatment cabinet does not necessarily reflect the amount of ultraviolet radiation received at any given anatomic site by a patient undergoing phototherapy.

Equipment Safety↗
PubMed1986

Isolation and characterization of chicken and turkey beta 2-microglobulin.

Chicken and turkey beta 2-m were isolated from citrated plasma in sequential use of three chromatographic steps: affinity chromatography, gel filtration chromatography and anion-exchange chromatography. The purified protein was identified as beta 2-m by reaction with a beta 2-m specific monoclonal antibody and by the ability to recombine with the chicken MHC class I heavy chain. The purity was estimated by SDS-PAGE and IEF. The pI was between 5.1 and 5.3 for chicken beta 2-m and 4.7 and 4.8 for turkey beta 2-m, which fact is reflected in their different electrophoretic mobilities in agarose gel (turkey migrates in the alpha and chicken migrates in the beta region). The mol. wt of both chicken and turkey beta 2-m was 14,500 estimated by SDS-PAGE whereas calculations based on the amino acid compositions gave mol. wts of 11,000. EM280 was 15.9 for chicken beta 2-m and 16.4 for turkey beta 2-m. The amino acid compositions and sequences of the two avian beta 2-m molecules have been compared with earlier data from the literature. The sequence of the 23 N-terminal amino acids was found to be identical in our preparations from both chicken and turkey, namely DLTPKVQVYSRFPASAGTKNVLN, and is incompatible with a previously published sequence also thought to be from turkey beta 2-m. Reasons for our opinion that the molecules isolated and sequenced in this paper are the correct ones are given.

Amino Acid Sequence↗
PubMed1985

Analysis of chickens for recombination within the MHC (B-complex).

In an attempt to further map the chicken MHC (the B complex), a systematic search for genetic recombinants within the B complex was performed by serotyping the progeny from F2 crosses of chickens by means of specific anti-class I, anti-class II, and anti-class IV alloantisera. Two recombinant B-haplotypes (B21r and B15r) were found by analysing 2,656 F2 chickens representing 5,312 informative typings. In either case, the B-G (class IV) allele was recombined with both the B-F and B-L alleles of the opposite haplotype. MLC typings, tests for direct compatibility by GVH reactions, and absorption analyses confirmed the original serological typing of the two recombinant B haplotypes. No recombination between B-F (class I) and B-L (class II) loci was found. This very low frequency of recombination within the B complex as compared with recombination frequencies found in mammalian MHC's is discussed.

Animals↗
PubMed1982

The MHC haplotypes of the chicken.

The major histocompatibility complex (MHC) of Gallus gallus is the B complex of which three classes of cell-membrane antigens have been clearly defined by serological, histogenetic, and biochemical methods. Two of these classes are homologous to classes I and II of mammals (B-F and B-L, respectively), while the third (B-G) is a differentiation antigen of the erythroid cell-line; the mammalian homologue of this class is still undefined. The B haplotypes comprise at least one gene of each class that displays linkage disequilibrium of a remarkable strength. The present work is the first systematic comparison by serological and histogenetic methods of the allelic products (allomorphs) of 15 haplotypes, including all of the 11 that were accepted as "standard" B haplotypes at the recent international Workshop on the chicken MHC in Innsbruck, Austria. The analysis has revealed many similarities, but only four pairs of probable identities: G2 and G12, F4 and F13, L4 and L13, L12 and L19. It appears therefore that the B-G locus is comparable in its degree of polymorphism to the class I (B-F) locus. The "standard" haplotypes are almost all of White Leghorn derivation, and preliminary typings of other breeds of chickens, and of wild chickens, indicate the existence of a much wider spectrum of allomorphs.

Alleles↗