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Biomedical subjects

S Mackenzie

Publications and source records attributed to S Mackenzie.

At least 19 recordsLinked to original sources
PubMed2003

Management of soft tissue sarcomas of the abdomen and pelvis.

OBJECTIVE: Soft tissue sarcomas of the abdomen or pelvis are rare tumours that usually arise in the retroperitoneum but may also arise from the gastrointestinal tract or other abdominal organs. The aim of this study was to assess patient outcome following treatment of these tumours at a tertiary referral centre. PATIENTS AND METHODS: Data on all patients with soft tissue tumours treated under the care of one surgeon between January 1990 and December 2000 was reviewed. RESULTS: Over the 11-year period 61 patients underwent 79 operations for a soft tissue sarcoma of the abdomen or pelvis. Macroscopic clearance of tumour at operation was achieved in 45 (74%) of the 61 patients, for primary tumours this was 97%, recurrent tumours 50% and metastases 33%. The median survival for those undergoing complete resection was 50 months (range 3-238 months, median follow-up 33 months). This compared with a median survival of only 6 months range (1-127 months) for those that had incomplete resection (P = 0.001). The 5-year survival for patients that had complete resection was 61.5%, however, over one-third of the 5-year survivors have since recurred. CONCLUSION: This study confirms that most primary soft tissue sarcomas of the abdomen or pelvis are resectable and the majority of patients will experience a long disease free interval following resection.

Abdominal Neoplasms↗
PubMed2003

Phase II study of oxaliplatin versus oxaliplatin combined with infusional 5-fluorouracil in hormone refractory metastatic prostate cancer patients.

BACKGROUND: A randomized, multicenter phase II study evaluating oxaliplatin alone (OXA) and oxaliplatin-5-fluorouracil combination (OXFU) in advanced hormone-refractory prostate cancer (HRPC) patients. PATIENTS AND METHODS: Metastatic, pathologically proven prostate carcinoma patients, progressing despite anti-androgen therapy, received intravenous OXA (130 mg/m(2 )over 2 h), alone or with 5-FU (1000 mg/m(2)/day, continuous intravenous infusion, days 1-4), every 3 weeks. OXA patients could receive OXFU after treatment failure. RESULTS: Fifty-four patients (26 OXA, 28 OXFU) from nine centers received 269 treatment cycles (106 OXA, 163 OXFU; median 3.5 OXA or 5 OXFU cycles per patient; range 1-10 or 1-14, respectively). Patient characteristics were similar in both arms. Three partial responses (PR) occurred in 21 evaluable OXA patients [14%; 95% confidence interval (CI) 1% to 30%], and in five of 26 evaluable OXFU patients (19%; 95% CI 7% to 39%). Clinical benefit response (pain, performance status and weight changes) was assessed in 20 OXA and 22 OXFU symptomatic patients, with more responders in the OXFU arm (39% compared with 12%). Median time to progression in the OXA and OXFU arms was 2.6 and 3.4 months, and median overall survival was 9.4 and 11.4 months, respectively. Hematotoxicity was common, but mostly mild to moderate. Neutropenia was more common in OXFU than OXA patients. After oxaliplatin failure, 12 patients received 46 cycles of OXFU and one of 11 evaluable patients had a PR. CONCLUSION: The objective response rate, palliation benefit, survival and manageable toxicity obtained in this heavily pretreated HRPC population with OXFU merit further study.

Adult↗
PubMed2002

Phase II study of oxaliplatin and fluorouracil in taxane- and anthracycline-pretreated breast cancer patients.

PURPOSE: Phase II study evaluating efficacy and safety of combined oxaliplatin/fluorouracil (5-FU) in taxane-pretreated advanced and metastatic breast cancer (ABC) patients. PATIENTS AND METHODS: Sixty-four taxane- and anthracycline-pretreated (within 6 months of study entry) women were treated with oxaliplatin 130 mg/m(2) (2-hour intravenous [IV] infusion), day 1, and 5-FU 1,000 mg/m(2)/d (continuous IV infusion) days 1 to 4, every 3 weeks. RESULTS: Median patient age was 51 years (range, 34 to 71 years), with a median of two involved organs (range, one to six organs), and metastases in the liver (70%), bone (47%), and lung (34%). Patients had a median of two prior chemotherapy regimens (range, one to six regimens), and 78% had previous hormonal therapy, with clinical taxane and anthracycline resistance in 53% and 34%, respectively. A total of 367 cycles were administered, with a median of six cycles/patient (range, one to 15 cycles). Sixty patients were assessable for response (World Health Organization criteria): 17 partial response, 26 stable disease, and 17 disease progression, giving an overall response rate of 27% (95% confidence interval, 16.3% to 39.1%), and 26% and 36% in taxane- and anthracycline-resistant populations, respectively, all responders having metastatic liver disease. Median time to progression was 4.8 months, and median overall survival was 11.9 months. Four treatment-related serious adverse events occurred, seven patients withdrew because of treatment-related toxicity. Hematotoxicity was prevalent but rarely severe, with grade 3-4 neutropenia, leukopenia, and thrombocytopenia in 34%, 19%, and 16% of patients, respectively, and a single episode of febrile neutropenia. One third of patients developed grade 2-3 peripheral neuropathy (oxaliplatin-specific scale), with grade 3 in only 8%. CONCLUSION: This oxaliplatin/5-FU combination is effective with an excellent safety profile in anthracycline/taxane-pretreated ABC patients, showing encouraging activity in patients with anthracycline/taxane-resistance or visceral disease.

Adult↗
PubMed2001

Tracing evolutionary and developmental implications of mitochondrial stoichiometric shifting in the common bean.

The recombination and copy number shifting activities of the plant mitochondrial genome are widely documented across plant genera, but these genome processes have not been as well examined with regard to their roles in plant evolution. Because of the extensive plant collections of Phaseolus spp and the degree to which cytoplasmic male sterility (cms) has been characterized in the common bean, this system would be valuable for investigating mitochondrial genome dynamics in natural populations. We have used the cms-associated sequence pvs-orf239 as a mitochondrial genetic marker for these studies and have demonstrated its universal presence throughout a diversity of undomesticated Phaseolus lines. Within these populations, the pvs-orf239 sequence is present in high copy number in approximately 10% of the lines, but substoichiometric in all others. This mitochondrial sequence, derived apparently by at least two recombination events, is well conserved with two point mutations identified that are both apparently silent with regard to the sterility phenotype. A putative progenitor sequence was identified in Phaseolus glabelus in substoichiometric levels, suggesting that the present-day pvs-orf239 sequence was likely introduced substoichiometrically. Copy number shifting within the mitochondrial genome results in a 1000- to 2000-fold change, so that substoichiometric forms are estimated at less than one copy per every 100 cells. On the basis of PCR analysis of root tips, we postulate that a mitochondrial "transmitted form" resides within the meristem to assure transmission of a complete genetic complement to progeny.

Cloning, Molecular↗
PubMed2001

Modulations in gene expression and mapping of genes associated with cyst nematode infection of soybean.

Infection of the soybean root by the soybean cyst nematode (SCN) (Heterodera glycines Ichinohe) induces a well-documented, yet poorly understood, response by the host plant. The plant response, involving the differentiation of a feeding structure, or "syncytium," facilitates the feeding and reproduction of the nematode to the detriment of the host. We used a genetic system involving a single dominant soybean gene conferring susceptibility to an inbred nematode strain, VL1, to characterize the nematode-host interaction in susceptible line PI 89008. The restriction fragment length polymorphism marker pB053, shown to map to a major SCN resistance locus, cosegregates with resistance among F2 progeny from the PI 89008 x PI 88287 cross. Cytological examination of the infection process confirmed that syncytium development in this genetic system is similar to that reported by others who used noninbred nematode lines. Our study of infected root tissue in the susceptible line PI 89008 revealed a number of genes enhanced in expression. Among these are catalase, cyclin, elongation factor 1alpha, beta-1,3-endoglucanase, hydroxy-methylglutaryl coenzyme A reductase, heat shock protein 70, late embryonic abundant protein 14, and formylglycinamidine ribonucleotide synthase, all of which we have genetically positioned on the public linkage map of soybean. Formylglycinamidine ribonucleotide synthase was found to be tightly linked with a major quantitative trait locus for SCN resistance. Our observations are consistent with the hypothesis proposed by others that feeding site development involves the dramatic modulation of gene expression relative to surrounding root cells.

Animals↗
PubMed1998

Migration of hypoglossal myoblast precursors.

The intrinsic hypoglossal musculature develops from precursor myoblasts which undergo long-range migration from the occipital somites to the tongue. Little detail is known about the precise spatiotemporal pathway taken by these cells or the factors controlling migration. In this study, chick/quail chimeras in which the occipital paraxial mesoderm is quail derived, reveal that the pathway taken by the tongue muscle progenitors is both complex and highly specific. Precursor myoblasts are Pax-3 positive cells which descend from the somite and migrate around the pharyngeal endoderm. They then course rostrally, following the base of the pharynx, remaining in a tight strand. We have examined a number of factors implicated in the control of migration of the hypoglossal precursors. Replacement of the occipital somites with those originating in the flank reveals that intrinsic differences do not exist between these somites with respect to their capacity to respond to migratory cues. The lack of high level HGF/SF expression along the pathway of the migrating hypoglossal precursors suggests that this factor is not involved in the actual process of migration of the hypoglossal precursors to the tongue. The pathway followed by the migrating precursors is identical to that of both the developing hypoglossal nerve and the circumpharyngeal crest--a subpopulation of the cranial neural crest, and importantly these populations utilize this pathway before the myoblast precursors. However, ablation neither of the hypoglossal nerve nor of the neural crest results in a perturbation in the ability of this Pax-3 positive population to migrate. This demonstrates that migration of the precursors is independent of both of these cell populations, and that it is controlled by the peripheral tissues.

Animals↗
PubMed1995

Pollen fertility restoration by nuclear gene Fr in CMS bean: nuclear-directed alteration of a mitochondrial population.

Two nuclear genes, Fr and Fr2, have been identified that restore pollen fertility to cytoplasmic male sterile (CMS) common bean (Phaseolus vulgaris L.) by apparently distinct mechanisms. Whereas Fr2 appears to suppress the expression of a male sterility associated mitochondrial sequence (designated pvs), Fr restores pollen fertility by causing the elimination of this unusual mitochondrial DNA-segment. To further investigate the mechanism of Fr action, Fr and Fr2 were cointroduced into the nucleus of a bean line containing the sterility inducing cytoplasm. When the effect of pvs was suppressed by Fr2, the presence of Fr no longer directed the elimination of the mitochondrial pvs sequence. This result suggests that the Fr function is dependent on proper expression of the pvs sequence. To evaluate the temporal and spatial patterns of Fr action, we undertook a polymerase chain reaction-based approach to trace the fate of the pvs sequence in different tissues of F2 and F3 fertile-restored plants derived from a genetic cross between a cytoplasmic male sterile line of common bean, CMS-Sprite (frfr), and fertility restorer line R351 (FrFr). We demonstrate that the Fr-directed disappearance of pvs sequence occurs during flower development. Elimination of the pvs sequence from developing megaspores results in permanent fertility restoration in the following generations. Genetic analysis demonstrated that permanent fertility restoration, that is, the complete elimination of pvs from reproductive tissues requires two doses of the Fr allele or the absence of fr in F2 individuals.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed1995

Surveying the organizational culture in an NHS trust.

Describes the methodology used to survey the organizational culture in four strategic business units of an NHS trust. Data were collected from selected organizational members on 19 different dimensions of culture using both qualitative and quantitative methods. Reports the findings from the culture survey in one of the four directorates in detail to demonstrate the quality of data to be collected using this methodology.

Attitude of Health Personnel↗
PubMed1994

Pneumatic reduction of intussusception: clinical experience and factors affecting outcome.

Between 1987 and 1992, 54 patients (32 male, 22 female) underwent 62 attempts at pneumatic reduction of intussusception. The mean age at presentation was 12.5 months (range 2.5 to 4 years 4 months). A retrospective review of all cases was performed to identify success rate and factors affecting it. Successful reduction was achieved in 46 cases (74%). One case was complicated by perforation and four cases (7%) by early recurrence. Patients with failed pneumatic reduction were more likely than those with successful reduction to have: (1) long duration of symptoms; (2) bleeding per rectum; (3) small bowel obstruction. Among the 16 cases of failed reduction, surgical findings were: five cases of ileo-ileo-colic intussusception, one with ileo-ileal, one with perforated ischaemic colon during air enema and one whose intussusception was found to be reduced at surgery. Three patients had lead points: Meckel's diverticula in two and a pinworm in one. Resection was required in three cases for non-viable bowel and in another two for the Meckel's diverticula. Pneumatic reduction of intussusception offers a high success rate with few complications. Performing an air enema earlier in the course of the disease may increase the chance of successful reduction.

Child, Preschool↗
PubMed1994

Isolation of a new species-specific repetitive sequence from Thinopyrum elongatum and its use in the studies of alien translocations.

A new repetitive sequence that is extremely abundant and well dispersed in the Thinopyrum elongatum genome but present in low-copy number in wheat (Triticum aestivum L.) has been isolated. This repeat and a Th. elongatum repeat isolated in another laboratory were used to identify cosmid genomic clones containing the repeats and, thus, putatively located on a Th. elongatum/T. aestivum translocation arm. Most of the selected cosmids contained single- or low-copy sequences, making them potentially useful in mapping studies. The repeats were used in deletion mapping to deduce gene order of three genes located on the Th. elongatum translocation arm. In situ hybridization studies suggested that this newly identified Th. elongatum repeat is well dispersed throughout the Thinopyrum genome but present at only one location in wheat. This raises some interesting questions about the role of such repetitive elements in the evolution of grass species.

Base Sequence↗
PubMed1993

Case report: primary intrathoracic rhabdomyosarcoma: a rare childhood malignancy.

Primary intrathoracic rhabdomyosarcoma is a rare tumour in childhood. Three cases are presented and the radiological findings and clinical course are reviewed. The radiological manifestations are varied but a rapidly growing soft tissue mass with compression of adjacent structures is the most common. A rare association with an underlying congenital pulmonary cyst is described. The prognosis is worse than for rhabdomyosarcoma at other sites, with a predisposition for cerebral metastases.

Brain Neoplasms↗
PubMed1992

A mitochondrial DNA sequence is associated with abnormal pollen development in cytoplasmic male sterile bean plants.

Cytoplasmic male sterility (CMS) in common bean is associated with the presence of a 3-kb unique mitochondrial sequence designated pvs. The pvs sequence encodes at least two open reading frames (297 and 720 bp in length) with portions derived from the chloroplast genome. Fertility restoration by the nuclear restorer gene Fr results in the loss of this transcriptionally active unique region. We examined the effect of CMS (pvs present) and fertility restoration by Fr (pvs absent) on the pattern of pollen development in bean. In the CMS line, pollen aborted in the tetrad stage late in microgametogenesis. Microspores maintained cytoplasmic connections throughout pollen development, indicating aberrant or incomplete cytokinesis. Pollen-specific events associated with pollen abortion and fertility restoration imply that a gametophytic factor or event may be involved in CMS. In situ hybridization experiments suggested that significant reduction or complete loss of the mitochondrial sterility-associated sequence occurred in fertile pollen of F2 populations segregating for fertility. These observations support a model of fertility restoration by the loss of a mitochondrial DNA sequence prior to or during microsporogenesis/gametogenesis.

Amino Acid Sequence↗