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Biomedical subjects

D Rowe

Publications and source records attributed to D Rowe.

At least 55 records · Page 3Linked to original sources

Females vastly outnumber males in basal cell carcinoma of the upper lip. A peculiar subset of high risk young females is described.

BACKGROUND: It was noted that females, particularly young females, outnumbered males with basal cell carcinoma (BCC) of the upper lip among patients treated by Mohs micrographic surgery in Vancouver, British Columbia. OBJECTIVE: To investigate female-to-male ratios for BCC of the upper lip at the Vancouver Mohs micrographic surgery service, and to compare this with data from the provincial-wide registry as well as with worldwide data in the literature. METHODS: The female-to-male ratios by age group were determined for 136 upper lip lesions treated at the Mohs service from 1983 to 1992. Similar data were obtained from 731 perioral BCCs recorded at the provincial-wide registry from 1982 to 1989. The literature was reviewed for comparative data worldwide. RESULTS: At the Mohs service females outnumber males 3.5:1 for upper lip BCCs. Young females 30-39 years old outnumber males 16:1. Regional data from the British Columbia Cancer Registry confirm that females outnumber males 2:1 for the lip region (including upper lip, lower lip, nasolabial fold). This is significant when compared with all BCCs diagnosed in the province (ie, all sites), in which males outnumber females 1.3:1. Data from the literature worldwide confirm this relationship. CONCLUSION: BCC of the upper lip is a female-predominated disease. Young females are at a much higher risk for this disease than young males.

Adult↗

Characterisation of non-concordance in the T-cell receptor gamma chain genes at presentation and clinical relapse in acute lymphoblastic leukemia.

We have analysed the structure of the T-cell receptor gamma chain (TCRG) genes in a panel of biopsies taken from 24 patients with acute lymphoblastic leukemia (ALL) (13 cALL, one pre-B ALL, two null ALL and eight T-ALL) at presentation and at clinical relapse. In the majority of cases (18/24) the structure of these genes was concordant, but in a significant minority of cases (6/24) the TCRG genes were in a different conformation at different clinical stages. In three of these patients (one null ALL, two T-ALL) the clonal TCRG rearrangements detected at presentation were absent at relapse possibly as a result of clonal regression. In one other patient (cALL), the TCRG locus at relapse was rearranged to V genes which are located downstream of the V genes found in the presentation rearrangement. This indicates that the relapse leukemic clone is probably the result of clonal evolution. In two patients (one cALL, one T-ALL) there were no clonally dominant rearrangements of the TCRG genes at presentation, but evidence for clonal rearrangements at relapse, possibly as a result of clonal progression. The structure of the IgH genes were determined in four of the six patients with clonal changes in the TCRG genes and were found to be concordant. The changes in TCRG gene structure were not restricted to ALL of any one particular age group, phenotype or duration of first remission. These data indicate that the assignment of clonal specific markers based upon the sequence of TCRG rearrangements at presentation may not always be useful in the detection of minimal residual disease in ALL.

Adolescent↗

Assessment of neurological injury due to circulatory arrest during profound hypothermia. An experimental study in vertebrates.

To investigate brain changes in induced deep core hypothermia (15 degrees C) with circulatory arrest, five groups of neonatal pigs were subjected to cardiopulmonary bypass (CPB), with circulatory arrest (CA) periods varying from 70-120 min. The parameters analysed were: 1. Histology and electron microscopy of the brain six hours post-CPB, 2. Creatinophosphokinase (CPK) from cerebrospinal fluid (CSF), 3. Vasointestinal neuropeptide (VIP) and 7B2 specific neuropeptide both in plasma and brain tissue. The earliest morphological changes were seen after 90 min CA and were highly significant after 120 min arrest. These changes involved mainly the Purkinje cells of the interior half of the cerebellum with vacuolation in their cytoplasm. A rise in CPK in CSF occurred in all piglet-groups. The differences among the various groups were highly significant at 2 and 5 h post-CPB. (P < 0.05). Statistically significant differences were not exhibited among the various groups both in serum and brain tissue total mean values of VIP and 7B2 neuropeptides. We suggest that 1. The cerebellar region is the most sensitive where ischemic lesions attain their maximal severity and extent; the frequency and pattern of selective vulnerability of the cerebellum may be related primarily to its pattern of blood supply 2. The maximum time of CA without histopathological sequelae should not exceed 70 min.

Anesthesia, General↗

An interstitial deletion in the rearranged T-cell receptor gamma chain locus in a case of T-cell acute lymphoblastic leukaemia.

This report describes the cloning and sequencing of the breakpoint of a deletion of approximately 166 bp in the 5' region of a rearranged T-cell receptor gamma (TCRG) V gamma 2 gene from the disease cells of a patient with T-cell ALL. This abnormal rearrangement was not detected in a biopsy taken during clinical remission. Sequence analysis indicated that the deletion breakpoint occurred at a position immediately upstream of sequences found in the germline V gamma 2 gene that are closely related to known heptamer and nonamer recombination signal sequences. Furthermore, the rearrangement was found to have non-germline nucleotides (N-region) in between otherwise intact V and J segments. These data indicate that this structure may be the result of an aberrant rearrangement event in common with the frequently occurring chromosomal abnormalities found in T-cell ALL. This event could either be one directly associated with the leukaemic transformation or one occurring during normal lymphocyte development but which is coincidental with leukaemic transformation. This represents the first molecular genetic evidence for an abnormality specifically involving the TCRG locus in ALL.

Base Sequence↗

A mutation of the glucocorticoid receptor in primary cortisol resistance.

The precise molecular abnormalities that cause primary cortisol resistance have not been completely described. In a subject with primary cortisol resistance we have observed glucocorticoid receptors (hGR) with a decreased affinity for dexamethasone. We hypothesize that a mutation of the hGR glucocorticoid-binding domain is the cause of cortisol resistance. Total RNA isolated from the index subject's mononuclear leukocytes was used to produce first strand hGR cDNAs, and the entire hGR cDNA was amplified in segments and sequenced. At nucleotide 2,317 we identified a homozygous A for G point mutation that predicts an isoleucine (ATT) for valine (GTT) substitution at amino acid 729. When the wild-type hGR and hGR-Ile 729 were expressed in COS-1 cells and assayed for [3H]-Dexamethasone binding, the dissociation constants were 0.799 +/- 0.068 and 1.54 +/- 0.06 nM (mean +/- SEM) (P < 0.01), respectively. When the wild-type hGR and hGR-Ile 729 were expressed in CV-1 cells that were cotransfected with the mouse mammary tumor virus long terminal repeat fused to the chloramphenicol acetyl transferase (CAT) gene, the hGR-Ile 729 conferred a fourfold decrease in apparent potency on dexamethasone stimulation of CAT activity. The isoleucine for valine substitution at amino acid 729 impairs the function of the hGR and is the likely cause of primary cortisol resistance in this subject.

Adult↗

EEG monitoring during angiographic balloon test carotid occlusion: experience in sixteen cases.

Ipsilateral hemispheric ischaemia related to permanent or temporary arterial occlusion at the time of operation is a potential risk of surgery upon some aneurysms or tumours which involve the internal carotid artery. Presurgical evaluation of the risks of temporary or permanent internal carotid artery occlusion may help predict patients in these circumstances at risk of stroke. Balloon test occlusion studies involve the elective preoperative occlusion of the internal carotid artery by a deflatable balloon inserted into the cerebral circulation under angiographic control. We have performed 16 balloon test occlusion studies; 2 subjects developed clinical and electroencephalographic changes when the carotid artery was temporarily occluded, and these changes reverted to normal when the balloon was deflated. The results of the test occlusion studies helped in planning the surgical management of all the subjects involved.

Adolescent↗

Complications from intra-aortic balloon counterpulsation: a review of 303 cardiac surgical patients.

From January 1980 to January 1990 all patients undergoing cardiac surgery at the Royal North Shore Hospital, Sydney, and requiring intra-aortic balloon counterpulsation (IABCP) were retrospectively reviewed. A total of 99 patients (32.6%) developed complications. Vascular/haemorrhagic complications occurred in 46 patients (15.2%); 79 patients (26%) required platelet transfusions. We have found that only a history of hypertension was predictive of an increased incidence of developing vascular complications. Surgical intervention was required in 17 patients (5.6%), or 47% of the patients who developed a vascular complication. The mortality among patients requiring IABCP was 36.6%. Intra-aortic balloon pump-related deaths occurred in 6 patients (2%). Use of the intra-aortic balloon pump can be a life-saving procedure, but it carries a significant morbidity and mortality rate. This makes it imperative to temper our indications to those patients who demonstrate a need for it.

Adult↗

Burkitt lymphoma cell lines are prone to recombination in the switch region of the Ig mu heavy chain locus.

Different recombinations have been found at the Ig heavy chain gene loci in a number of sublines of the Burkitt lymphoma (BL) cell line Namalwa, following prolonged in vitro culture. The Namalwa sublines examined are DNA fingerprint-identical and derived from a monoclonal source. Recombinant DNA clones were used to map the Ig heavy chain gene mutations to a region between the VDJ and C mu segment of the locus. This region is associated with Ig heavy chain class switching in normal B cells. Of 24 clones established from one subline, three were found to have additional VDJ-C mu region mutations, indicating a high frequency of mutation at this locus.

B-Lymphocytes↗

Detection of T-cell receptor gamma chain V gene rearrangements using the polymerase chain reaction: application to the study of clonal disease cells in acute lymphoblastic leukemia.

This report describes the development and characterization of a method for the amplification of rearranged V-J segments of the human T-cell receptor gamma chain (TCRG) locus using an adaptation of the polymerase chain reaction (PCR) technique. The technique uses a single pair of 'consensus' primers to amplify rearrangements involving the V gamma I subgroup genes, which are common in malignant cells from acute lymphoblastic leukemia (ALL) patients. Using this method we were able to detect rearrangements in the TCRG locus in disease cells from patients with T-cell ALL (12 of 12), common ALL (10 of 14), and Null cell ALL (2 of 2) at presentation. Monoallelic and biallelic rearrangements involving V gamma I subgroup genes were identified by restriction analysis of PCR products from DNA samples from a T-cell leukemic cell line, T-cell clones, and disease cells from patients with ALL of T-and B-cell lineage at presentation. These results confirmed the presence of cell clones within the presentation samples and, in one case, confirmed the persistence of the original malignant cell clone at relapse. This is a rapid and specific method for the detection and characterization of rearrangements of the TCRG locus without recourse to Southern blotting. Therefore, the PCR technique described herein can provide the basis for the study of clonal evolution and minimal residual disease on a high proportion of patients with ALL.

Alleles↗

CT and MR imaging of CNS lymphomatoid granulomatosis.

The clinical CT and MR imaging features of a pathologically confirmed case of lymphomatoid granulomatosis are presented. The disease was clinically confined to the central nervous system and the diagnosis was only made after brain biopsy had been performed. MR imaging revealed extensive non-confluent regions of white matter abnormality. Although uncommon, lymphomatoid granulomatosis should be included in the differential diagnosis of causes of periventricular and deep white matter lesions, even in the absence of pulmonary lesions. Specific therapy may produce clinical regression of disease.

Adult↗

Comparison of image analysis and flow cytometric determination of cellular DNA content.

A good correlation (r = 0.94) was obtained between the DNA indices (DI) using flow cytometry and image analysis of nuclei cytospins extracted from paraffin wax embedded tumour sections. Some of the limitations and problems associated with image analysis which came to light included an unacceptably high coefficient of variation (CV) and a "left-shift" in the DI in most DNA histograms obtained when using image analysis of 5 microns sections. In contrast, the DNA histograms generated using image analysis of cytospun nuclei from paraffin wax blocks were of good quality and similar to those obtained using flow cytometry. Variability in Feulgen staining was common and an important source of error despite rigorous control of the staining technique. This could be overcome by using internal controls such as fibroblasts rather than external controls (rat hepatocytes) to determine the diploid DI with image analysis. A thorough understanding and appreciation of the methodological problems associated with image analysis and flow cytometric determination of DNA content is required before these methods find widespread clinical application.

Adrenal Gland Neoplasms↗

Fusion of Rous-sarcoma-virus-transformed rat cells to morphologically normal human or rat cells results in transcriptional suppression of the provirus that depends on its chromosomal integration site.

The fusion of a Rous sarcoma virus (RSV)-transformed rat fibroblast clone to at least 2 different human cell types reproducibly produces phenotypically normal hybrids. Analysis of such hybrids reveals that proviral silence is the result of transcriptional down-regulation, presumably by a trans-acting human molecule. Furthermore, this phenomenon seems to be strongly influenced by the proviral chromosomal integration site and its imposition may entail a mechanism that is required only transiently.

Animals↗

Detection of mutations in human type I collagen mRNA in osteogenesis imperfecta by indirect RNase protection.

A method for detecting a wide variety of mutations within type I collagen has been developed and evaluated on a series of patients with osteogenesis imperfecta. RNA, extracted from the nuclear and cytoplasmic compartment of cultured fibroblasts from affected individuals, is hybridized with antisense single-stranded cDNA to the alpha 1(I) mRNA. The hybrid is digested with RNase A and T1 under varying degrees of stringency. The resistant RNA bands are separated by electrophoresis in agarose, transferred to nitrocellulose, and hybridized with antisense cRNA colinear with the protecting probe. This approach is capable of detecting previously defined mutations such as 252-base pair deletion and a 1-base pair mismatch within the alpha 1(I) mRNA. The method appears to be particularly useful in detecting abnormalities of RNA processing that behave as an insert or deletion within the mature mRNA. The procedure should be generally applicable for the identification and localization of any mutation within an entire gene if the gene is expressed as an RNA and a complete cDNA for the mRNA is available.

Chromosome Deletion↗

Insulin-like growth factor I regulates type I procollagen messenger ribonucleic acid steady state levels in bone of rats.

RNA extracted from parietal bones of rats was analyzed for the abundance of type I procollagen mRNA by a dot hybridization assay using specific cDNA probes. Hypophysectomized rats, deficient in IGF I, have 4.1-fold lower steady state levels of mRNA encoding the alpha 1 chain of type I collagen when compared to normal rats of the same weight (120 g). Administration of recombinant human insulin-like growth factor I (IGF I) for 6 days restores bone collagen mRNA levels to normal, and a single sc injection of 100 micrograms IGF I results in a 1.9-fold increase of both alpha 1(I) and alpha 2 (I)chain mRNAs after 8 h. Studies with calvaria cells in primary culture and with a bone-derived cell line, PyMS, yielded similar results: IGF I treatment of these osteoblast-like cells for 24 h increased steady state levels of type I procollagen mRNAs. Thus, IGF I appears to contribute to osteoblast mRNA expression for both chains of type I collagen.

Animals↗