Search PubMed⌕ Search

Biomedical subjects

C Morris

Publications and source records attributed to C Morris.

At least 181 records · Page 10Linked to original sources

A complex chromosome rearrangement forms the BCR-ABL fusion gene in leukemic cells with a normal karyotype.

Chromosome in situ hybridization studies showed that the normal karyotype of leukemic cells from a patient with Ph1-negative, BCR-positive chronic myeloid leukemia (CML) concealed a complex t(9;22;20)(q34;q11;p13). The close association of 5'-BCR and 3'-ABL was demonstrated by field inversion gel electrophoresis, and in situ hybridization showed that BCR-ABL was located on the short arm of chromosome 20. Our findings further indicate that chromosome rearrangement is the cause of BCR-ABL gene fusion in leukemic cells that show a normal karyotype. Results from in situ hybridization studies were consistent with formation of the t(9;22;20) by a two step chromosomal rearrangement, but field inversion gel electrophoresis results indicated a more complex rearrangement.

Aged↗

Non-ulcer dyspepsia.

This paper discusses the definition of non-ulcer dyspepsia and its relationship to other functional bowel disorders. The research on the prevalence, outcome, aetiology and management of this condition is reviewed with particular emphasis on its multifactorial nature. Future research will need to concentrate on the inter-relationship of physical and psychosocial factors including the health beliefs of the individual patient.

Dyspepsia↗

Laterality and 5HT2 receptors in human brain.

Serotonin2 (5HT2) receptors were investigated in left and right frontal cortex of clinically and neuropathologically assessed controls. No significant difference in receptor binding between hemispheres was seen.

Aged↗

Extrathymic tolerance of mature T cells: clonal elimination as a consequence of immunity.

The mechanism by which T lymphocytes are tolerized to self or foreign antigens is still controversial. Clonal deletion is the major mechanism of tolerance for immature thymocytes; for mature T cells, tolerance is considered to reflect anergy rather than deletion, and to be a consequence of defective presentation of antigen. This paper documents a novel form of tolerance resulting when mature T cells encounter antigen in immunogenic form. Evidence is presented that exposure of mature T cells to Mlsa antigens in vivo leads to specific tolerance and disappearance of Mlsa-reactive V beta 6+ T cells. Surprisingly, the clonal elimination of V beta 6+ cells is preceded by marked expansion of these cells. Thus, tolerance induction can be the end result of a powerful immune response. These data raise important questions concerning the relationship of tolerance and memory.

Animals↗

Rearrangement of the human ABL oncogene in a glioblastoma.

A number of protooncogenes have been implicated in human tumorigenesis. The ABL oncogene is consistently rearranged and activated as a consequence of the translocation t(9;22) that gives rise to the Philadelphia chromosome in chronic myeloid leukemia and in some cases of acute lymphoblastic leukemia. Here we describe rearrangement of ABL in a different type of malignancy. The glioblastoma cell line A172 lacks germline alleles of ABL. A recombination event, presumably followed by a duplication, has created two ABL alleles in which exon 11 is joined to chromosome 16 sequences. Although the main body of ABL exons was still present, two considerably shortened ABL mRNAs of 3.8 and 2.8 kilobases were detected; the 3.8-kilobase mRNA hybridized exclusively to an exon IB probe. Neither mRNA hybridized to an ABL probe encompassing part of the tyrosine kinase domain. Thus, the cell line A172 is able to survive in the absence of a functional ABL gene product, indicating that the role of ABL is unlikely to be "housekeeping."

Base Sequence↗

Poly(anhydride) administration in high doses in vivo: studies of biocompatibility and toxicology.

Poly(anhydrides) proposed for use as vehicles for controlled drug delivery were administered subcutaneously in Sprague-Dawley rats at two dosage levels (800 mg/kg rat and 2400 mg/kg rat) for a period of eight weeks. Biocompatibility was assessed using a number of methods. Thirty-six clinical chemistry and hematology parameters were monitored throughout the study. Blood values were statistically analyzed for any possible effects due to the implanted polymer. After 8 weeks, rats were sacrificed and complete necropsies were performed. Histological evaluations of 33 organ sites including heart, lung, liver, kidney, and brain were performed. In addition, subcutaneous implant sites were excised and examined both grossly and microscopically. Results from evaluations of blood chemistry and hematology data, organ analyses and local implant site analyses overall demonstrated that the poly(anhydride) biomaterial possessed excellent in vivo biocompatibility.

Animals↗

Fibroblast growth factor stimulates protein kinase C in quiescent 3T3 cells without Ca2+ mobilization or inositol phosphate accumulation.

To elucidate the transmembrane signalling processes initiated by fibroblast growth factor (FGF), we have studied the effect of recombinant basic FGF (bFGF) on various early events associated with mitogenesis in Swiss 3T3 fibroblasts. bFGF, at mitogenic concentrations, neither induced Ca2+ mobilization from intracellular stores nor increased the accumulation of inositol phosphates. In contrast, bFGF stimulated the phosphorylation of the Mr 80,000 (80K) cellular protein which is a major substrate of protein kinase C. This effect was potentiated by the diacylglycerol kinase inhibitor R59022. Two-dimensional polyacrylamide gel electrophoresis and phosphopeptide mapping showed that the 80K phosphoproteins generated in response to bFGF, bombesin, and phorbol 12,13-dibutyrate were indistinguishable. Down-regulation of protein kinase C prevented bFGF stimulation of 80K phosphorylation. Other protein kinase C-dependent early events such as transmodulation of the epidermal growth factor receptor, cytoplasmic alkalinization, inhibition of vasopressin induced increase in cytosolic [Ca2+], and enhancement of cAMP accumulation in response to forskolin were also induced by bFGF. Similar results were obtained when bFGF was added to quiescent cultures of tertiary mouse embryo fibroblasts. We conclude that bFGF stimulates protein kinase C through a signal transduction pathway distinct from inositol phospholipid turnover and Ca2+ mobilization.

Animals↗

Low-level lead exposure, blood pressure, and calcium metabolism.

Previous research has shown an association of both blood lead and dietary calcium with blood pressure (BP) in populations. We examined the relationship between blood levels and BP, the effect of calcium supplementation on blood lead, and whether the reported antihypertensive effect of calcium supplementation was related to any observed change in blood lead. BP was measured on four occasions, 1 week apart in 251 subjects. During this period, blood lead and erythrocyte protoporphyrin (EPP) levels were measured, as well as markers of calcium metabolism. In an intervention period, 142 patients were assigned to receive 1 g of calcium per day as calcium carbonate for 12 weeks; at the end of this period, blood lead and EPP were remeasured. In males, blood lead levels were significantly, directly related to BP; a 0.48 mumol/dL (10 micrograms/dL) increase in blood lead concentration was associated with a 5 mm Hg increase in systolic pressure. There was no relationship of blood lead levels to BP in females. EPP was unrelated to BP. Similarly, there was no relationship of blood lead levels to markers of calcium metabolism. With calcium supplementation, blood lead and EPP levels did not change significantly. We conclude that it is unlikely that modification of lead status explains any effects of calcium supplementation on BP.

Adult↗

Transsphenoidal surgery for Cushing's disease: does what is removed determine the endocrine outcome?

Fifty-seven patients with pituitary-dependent Cushing's syndrome and eight with Nelson's syndrome underwent transsphenoidal pituitary exploration, with removal of macroscopically abnormal tissue in 64 patients and detailed histology of this in 63. The cure rate by stringent criteria 1 month later was 48 (83%) of the 58 with assessable data, who were followed for 225 patient-years. Two patients relapsed later, a rate of one per 112 patient-years of follow-up. In 27% of patients, the macroscopically abnormal tissue removed was histologically indistinguishable from normal pituitary gland but the cure rate was 82%, and a quarter of the patients in this group assessable for recovery of normal ACTH function gained it. Another 53% of biopsies showed corticotroph adenomas, and the cure rate in these was 89% though rather more (69%) recovered normal ACTH function. The remaining 20% of biopsies were consistent with corticotroph hyperplasia. The cure rate varied little whether the lesion was diffuse or localized, whether or not it was in the invasion zone/interlobar cleft, whether or not there was pituitary enlargement, or whether the surgery was radical or selective. Six patients, of whom three are cured, showed surgical or radiological evidence of invasion outside the pituitary fossa. The data are consistent with the idea that pituitary adenoma is merely the end stage of some other process in the corticotrophs, and cure often follows removal of a lesion other than adenoma. Of patients who were permanently cured, 47% regained normal ACTH function within 3 years of operation (none later), 53% remaining ACTH-deficient at 3 years or more. Of all patients 48% acquired gonadotrophin deficiency, 28% have TSH deficiency and 25% permanent diabetes insipidus. All these pituitary function deficits were more common after radical surgery and in patients with normal histology, The literature contains so little objective data on these functions that we cannot say whether the endocrine damage in our patients is exceptional or not.

Adenoma↗

Epicardial mapping: how to measure local activation?

UNLABELLED: Epicardial ventricular mapping was performed in 5 dogs during sinus rhythm with a sock array containing 41 electrodes. Maps were generated with a computer-assisted mapping system using four different definitions of local epicardial activation: (1) maximal negative slope (intrinsic deflection) of the unipolar electrogram, (2) maximal slope of the bipolar electrogram, (3) maximal amplitude of the bipolar electrogram, and (4) first onset by 45 degrees from the baseline of the bipolar electrogram. The site of earliest and latest epicardial activation was identical with maximal negative slope in the unipolar electrogram and maximal slope and maximal amplitude of the bipolar electrogram in all five animals. Times of earliest and latest epicardial activation calculated with maximal amplitude of the bipolar electrogram were most similar to those evaluated with maximal negative slope of the unipolar electrogram. Using onset of the bipolar electrogram, activation times were measured 10 to 12 msec earlier than with each of the other three definitions of local activation, and in two of the five animals, first epicardial breakthrough was mapped to a different site than with the three other methods. CONCLUSIONS: (1) Maximal amplitude of the bipolar electrogram coincided with maximal negative slope of the unipolar electrogram; (2) Using onset of the bipolar electrogram, timing and location of earliest epicardial activation may be misinterpreted.

Animals↗

The human tyrosine kinase gene (FER) maps to chromosome 5 and is deleted in myeloid leukemias with a del(5q).

A novel member of the SRC tyrosine kinase gene family was recently isolated and characterized (Hao et al., 1989). This FES/FPS-related gene, named FER, lacks the transmembrane and extracellular domains which characterize tyrosine kinases with receptor function. Expression of FER in a wide range of cell types indicates a general role in intracellular signalling or differentiation processes. We have now mapped FER to chromosome 5q14----q23 using in situ hybridization techniques and suggest a more precise location within bands 5q21----q22. This region lies adjacent to a complex domain of growth factors and receptors, many involved in regulation of haematopoiesis. FER maps within a critical segment frequently deleted from chromosome 5 in patients with acute myeloid leukemia or myelodysplastic syndromes and was shown to be deleted in two such patients. It also maps close to the familial polyposis coli locus at 5q22.

Chromosome Deletion↗

Infection of chimpanzees with the Uganda I/CDC strain of Plasmodium malariae.

Nine splenectomized chimpanzees were infected with the Uganda I/CDC strain of Plasmodium malariae. Two had no history of previous malarial infection, whereas 6 had been infected with P. vivax and 1 with P. vivax and P. ovale. The animals with no previous infection had maximum parasitemias of 8,740 and 10,800/mm3. The other animals had maximum parasite counts of 930-75,700/mm3. Anopheles freeborni, An. stephensi, An. dirus, An. maculatus, An. quadrimaculatus, An. culicifacies, An. arabiensis, and An. gambiae were readily infected by feeding through membranes on heparinized blood from these animals.

Animals↗

Multiple synergistic signal transduction pathways regulate c-fos expression in Swiss 3T3 cells: the role of cyclic AMP.

The promoter region of the c-fos gene contains several upstream enhancer elements which dictate the transcriptional response to specific intracellular signals. Among these is the cyclic AMP (cAMP)-responsive element, which is required for c-fos expression by cAMP in vitro. However, we have previously shown that cAMP-elevating agents cause only a slight increase in c-fos mRNA levels in intact Swiss 3T3 cells. Here, we show that cAMP can potentiate the induction of c-fos by other second messengers. A combination of forskolin and either phorbol-12,13-dibutyrate or epidermal growth factor leads to an increase in c-fos mRNA levels comparable to those induced by bombesin or serum. Furthermore, cAMP-elevating agents can act in synergy with calcium ionophores (which alone do not induce c-fos) to increase c-fos expression by up to 60% of the bombesin response, although, in parallel cultures, this combination does not stimulate the phosphorylation of 80K, an Mr 80,000 protein, which is a major substrate for protein kinase C. These results suggest that, in intact cells, cAMP acts synergistically with distinct intracellular signals to stimulate c-fos transcription through protein kinase C-dependent and -independent pathways.

1-Methyl-3-isobutylxanthine↗