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J D Morris

Publications and source records attributed to J D Morris.

At least 19 recordsLinked to original sources
PubMed2006

Protein kinase WNK3 increases cell survival in a caspase-3-dependent pathway.

The subfamily of WNK (with no K= lysine) protein kinases has four human members and germline mutations in the WNK1 and WNK4 genes were recently found to cause pseudohypoaldosteronism type II, a familial hypertension disease. Here, we describe cloning and functional analysis of a further WNK member, human WNK3. Endogenous WNK3 protein is an active protein kinase when immunoprecipitated from cells and its overexpression increases the survival of HeLa cells by delaying the onset of apoptosis. Suppression of endogenous WNK3 protein by RNA interference accelerates the apoptotic response and promotes the activation of caspase-3. The mechanism of WNK3 action involves interaction with procaspase-3 and heat-shock protein 70. These results demonstrate a role for WNK3 in promoting cell survival and suggest a mechanism at the level of procaspase-3 activation.

Apoptosis↗
PubMed2000

PSK, a novel STE20-like kinase derived from prostatic carcinoma that activates the c-Jun N-terminal kinase mitogen-activated protein kinase pathway and regulates actin cytoskeletal organization.

Degenerate polymerase chain reaction against conserved kinase catalytic subdomains identified 15 tyrosine and serine-threonine kinases expressed in surgically removed prostatic carcinoma tissues, including six receptor kinases (PDGFBR, IGF1-R, VEGFR2, MET, RYK, and EPH-A1), six non-receptor kinases (ABL, JAK1, JAK2, TYK2, PLK-1, and EMK), and three novel kinases. Several of these kinases are oncogenic, and may function in the development of prostate cancer. One of the novel kinases is a new member of the sterile 20 (STE20) family of serine-threonine kinases which we have called prostate-derived STE20-like kinase (PSK) and characterized functionally. PSK encodes an open reading frame of 3705 nucleotides and contains an N-terminal kinase domain. Immunoprecipitated PSK phosphorylates myelin basic protein and transfected PSK stimulates MKK4 and MKK7 and activates the c-Jun N-terminal kinase mitogen-activated protein kinase pathway. Microinjection of PSK into cells results in localization of PSK to a vesicular compartment and causes a marked reduction in actin stress fibers. In contrast, C-terminally truncated PSK (1-349) did not localize to this compartment or induce a decrease in stress fibers demonstrating a requirement for the C terminus. Kinase-defective PSK (K57A) was unable to reduce stress fibers. PSK is the first member of the STE20 family lacking a Cdc42/Rac binding domain that has been shown to regulate both the c-Jun N-terminal kinase mitogen-activated protein kinase pathway and the actin cytoskeleton.

Actins↗
PubMed1998

Central nervous system relapse of treated stage IV neuroblastoma.

Neuroblastoma is the most common extracranial solid tumor in pediatrics. The long-term survival of patients with advanced-stage neuroblastoma has remarkably improved secondary to aggressive treatment protocols including autologous bone marrow transplant (BMT). As a result, a different natural history of this disease is being reported with unusual, late manifestations. The central nervous system (CNS), once a rare site of disease, is being involved with increasing frequency. Appropriate neuroimaging in these patients is important. Two cases of patients with treated stage IV neuroblastoma who developed isolated CNS metastases are presented. The proposed pathogenesis and neuroradiologic manifestations of this complication are reviewed.

Adrenal Gland Neoplasms↗
PubMed1998

Cholecystokinin receptors in human pancreatic cancer cell lines.

Recent studies have suggested that cholecystokinin (CCK) receptors may play a role in the development and growth of pancreatic cancers. We detected the expression of mRNA encoding CCK-A and CCK-B receptors in eight human pancreatic tumour cell lines using reverse transcription-polymerase chain reaction (RT-PCR), but not by RNase protection assays. The K-ras gene, which can be activated by G-coupled protein receptors such as CCK receptors, was mutated in codon 12 in five of the cell lines. In addition, Mia PaCa-2 pancreatic cancer cells did not respond to CCK or gastrin in cell proliferation or focal adhesion kinase (FAK) phosphorylation assays. In contrast, mouse NIH3T3 fibroblasts transfected with human CCK-B receptor (NIH3T3CCK-BR) showed increased proliferation and phosphorylation to the peptides. Also, radioligand binding studies indicated that Mia PaCa-2 cells had approximately 12.5-fold less CCK-B receptors than NIH3T3CCK-BR. Our results suggest that in Mia PaCa-2 cells, CCK receptors may not play a crucial role in supporting cell growth.

3T3 Cells↗
PubMed1997

Antithrombin-III for the treatment of chemotherapy-induced organ dysfunction following bone marrow transplantation.

A hypercoaguable state has been shown to follow high-dose chemotherapy for bone marrow transplantation (BMT). Deficiency of the natural anticoagulants, antithrombin III (AT-III), protein C and protein S correlate with organ dysfunction following BMT. We treated 10 patients with severe post-BMT organ dysfunction with AT-III concentrate. Indications for treatment included AT-III anticoagulant level less than 88% and life-threatening single or multiorgan dysfunction. All patients were loaded with 50 units/kg AT-III every 8 h for three doses followed by 50 units/kg/day each day for 3-12 days. Clinical improvement was seen within 1-5 days of start of therapy in all patients. Patients with veno-occlusive disease (VOD) showed a decrease in platelet consumption in nine of nine patients, resolution of hepatic tenderness in six of eight patients, and reduction of severe ascites and weight gain in four of five patients. The probability of death due to VOD and life-threatening organ dysfunction was significantly less in the AT-III-treated group when compared to a historical control group receiving the same preparative regimen (P = 0.047 and P = 0.034, respectively). Significant improvements in organ dysfunction following AT-III treatment in this small study supports a causal relationship between AT-III deficiency and post-BMT chemotherapy-induced organ dysfunction.

Adolescent↗
PubMed1995

Viral infection and cancer.

Infection with specific viruses has a role in the pathogenesis of some cancers in human beings. However, the incidence of such cancers is much lower than the frequency of virus infection, suggesting either that infection alone does not result in cancer and that cellular events in addition to the presence of the virus must occur, or that cancer occurs only if viral proteins are expressed in an appropriate cell type or in an immunocompromised host. Molecular analysis of viruses found in association with cancer has revealed that they function, at least in part, by encoding proteins which can associate with and subvert the function of host cell-encoded tumour suppressor proteins which regulate pathways of growth arrest and apoptosis. Better understanding of the mechanisms underlying this association will have diagnostic, prognostic, and therapeutic implications in the near future.

Humans↗
PubMed1995

Intraoperative identification of parathyroid gland pathology: a new approach.

Technetium 99m-sestamibi, a radiopharmaceutical used for the diagnostic imaging of abnormal parathyroid tissue, and the Neoprobe 1000, a hand-held, gamma-detecting probe, were used concurrently, during surgical exploration, in three children with hyperparathyroidism. This novel combination assisted with the identification of an ectopic mediastinal parathyroid adenoma and with the localization of multiple hyperplastic parathyroid glands. 99mTc-sestamibi combined with the Neoprobe 1000 may prove to be a useful adjunctive technique for the intraoperative localization of abnormal parathyroid tissue in selected patients.

Adenoma↗
PubMed1994

HPV16 E7 oncoprotein deregulates B-myb expression: correlation with targeting of p107/E2F complexes.

HPV16 is a human tumour virus encoding two principal oncoproteins, E6 and E7. Expression of E7 can induce DNA synthesis in quiescent cells and this property coincides with its ability to bind to the cell proteins pRb and p107. As these cell proteins are regulators of the transcription factor E2F, we have investigated whether the interaction with E7 could result in induction of cell cycle regulated genes. We show that B-myb, whose induction at the G1/S boundary is regulated by release from E2F mediated transcriptional repression, is a target for transcriptional activation by E7 and is the first E7 responsive cell gene to be identified. E7 transactivation leads to both inappropriate transcription of B-myb during G1 and constitutive over-expression in cycling cells. B-Myb plays an essential role in cell cycle progression, and activation by E7 is likely to contribute to the mitogenic activity of the viral oncoprotein. Regulation of the B-myb promoter in NIH3T3 cells correlates with binding of distinct p107-containing complexes at the E2F binding site, and analysis of E7 mutants confirms that B-myb transcription in these cells is regulated through interactions with p107 rather than pRb. These results provide the first example of a potentially specific role for p107 in the regulation of the cell cycle.

3T3 Cells↗
PubMed1993

Human papillomavirus type 16 E7 regulates E2F and contributes to mitogenic signalling.

We have produced human papillomavirus type 16 E7 protein in a bacterial expression system and examined the mitogenic activity of this protein in Swiss 3T3 cells after scrape loading. The ability of E7 to induce cellular DNA synthesis in quiescent mouse fibroblasts is strongly enhanced by the presence of a single growth factor such as insulin. Although only weakly mitogenic, introduction of E7 alone resulted in the rapid induction of the transcriptionally active form of E2F, which was not enhanced further by the addition of insulin. Mutant E7 proteins defective for RB binding failed to induce the active form of E2F or act synergistically with insulin to stimulate DNA synthesis. The ability of E7 to regulate E2F may therefore be necessary, but is not sufficient, for full induction of DNA synthesis.

3T3 Cells↗
PubMed1992

A social-psychological perspective of dietary quality in later adulthood.

Nutrition has been implicated in the quality of life of older adults, beyond proving essential nutrients and calories. Recent concern about malnutrition has prompted a broader social-psychological approach to nutrition and aging research. The present investigation examined the relationship of self-actualization and social support to dietary intake. Data from 100 community-dwelling adults, ages 60-83 years, revealed significant and positive associations between the predictor variables and vitamin A, B vitamin complex, iron, and dietary fiber. Specifically, the personality trait of being internally motivated and the presence of support from family, friends and neighbors were found to positively influence dietary quality.

Aged↗
PubMed1991

Bone mass in healthy children: measurement with quantitative DXA.

Dual-energy x-ray bone densitometry was used to study the lumbar vertebral bone mass in 218 healthy children (134 girls and 84 boys) aged 1-19 years. Vertebral bone mass increased with weight, age, and pubertal Tanner stage. Results of multiple regression analyses showed that Tanner stage and weight were the best predictive indicators of bone mass and bone mineral density. The influences of age, sex, race, physical activity, and diet were not significant when Tanner stage and weight were controlled. Two tables of predictive intervals for lumbar vertebral bone mineral density in healthy children (one based on Tanner stage and weight; the other, on age and weight) are presented. With normative data now available for use with this precise technique, clinicians can better detect abnormal bone mineral density in children and evaluate changes in mineralization over time.

Absorptiometry, Photon↗
PubMed1990

Fate of Ice Nucleation-Active Pseudomonas syringae Strains in Alpine Soils and Waters and in Synthetic Snow Samples.

The stability of the ice nucleation activity (INA) and viability of INA Pseudomonas syringae 31a, used as an ice nucleator in the manufacture of synthetic snow, was determined in snow. The viability of P. syringae 1-2b, a rifampin-resistant mutant selected from strain 31a to improve recovery from test samples, was determined in laboratory tests of three alpine soil and water samples from three different sources. Snow samples were exposed to environmental conditions or held in darkness at -20 degrees C. Samples of soil and water were maintained in darkness at 0, 7.5, or 15 degrees C. Parent strain 31a INA decreased significantly (>99.0%) in snow exposed to sunlight and freeze-thaw, while the INA of the cell population in snow held in darkness at -20 degrees C remained essentially unchanged. No viable strain 31a was detected in snow exposed to the environment after 7 days, while the viability of strain 31a in snow held in darkness at -20 degrees C decreased to <3% of the original inoculation at the test conclusion. Mutant strain 1-2b viability was undetectable or had decreased significantly 19 days postinoculation in soil samples held at 0 or 15 degrees C. In contrast, 1-2b viability remained detectable at low levels for the duration of the test in soils held at 7.5 degrees C. The 1-2b population demonstrated a significantly longer half-life in peatlike soil than in the loam soils tested. The rate of decrease in 1-2b viability was essentially the same in the three alpine water samples tested with respect to water temperature and sample location.

Journal Article↗
PubMed1989

Stimulation of phosphatidylcholine breakdown and diacylglycerol production by growth factors in Swiss-3T3 cells.

The effect of a number of growth factors on phosphatidylcholine (PtdCho) turnover in Swiss-3T3 cells was studied. Phorbol 12-myristate 13-acetate (PMA), bombesin, platelet-derived growth factor (PDGF) and vasopressin rapidly stimulated PtdCho hydrolysis, diacylglycerol (DAG) production, and PtdCho synthesis. Insulin and prostaglandin F2 alpha (PGF2 alpha) stimulated PtdCho synthesis, but not its breakdown, whereas epidermal growth factor (EGF) and bradykinin were without effect. Stimulation of PtdCho hydrolysis by the above ligands resulted in increased production of phosphocholine and DAG (due to phospholipase C activity) and significant amounts of choline, suggesting activation of a phospholipase D as well. CDP-choline and glycerophosphocholine levels were unchanged. Down-regulation of protein kinase C with PMA (400 nM, 40 h) abolished the stimulation of PtdCho hydrolysis and PtdCho synthesis by PMA, bombesin, PDGF and vasopressin, but not the stimulation of PtdCho synthesis by insulin and PGF2 alpha. PtdCho hydrolysis therefore occurs predominantly by activation of protein kinase C (either by PMA or PtdIns hydrolysis) leading to elevation of DAG levels derived from non-PtdIns(4,5)P2 sources. PtdCho synthesis occurs by both a protein kinase C-dependent pathway (stimulated by PMA, PDGF, bombesin and vasopressin) and a protein kinase C-independent pathway (stimulated by insulin and PGF2 alpha). DAG production from PtdCho hydrolysis is not the primary signal to activate protein kinase C, but may contribute to long-term activation of this kinase.

Animals↗
PubMed1989

Stimulation of phosphatidylcholine hydrolysis, diacylglycerol release, and arachidonic acid production by oncogenic ras is a consequence of protein kinase C activation.

Swiss-3T3 cells were scrape-loaded with oncogenically activated p21ras protein. 10-20 min after introducing Val12p21ras into the cell, diacylglycerol levels were increased, but levels of inositol phosphates were unaltered. However, cellular choline and phosphocholine levels were increased with a similar time course to that observed for diacylglycerol production, suggesting that ras increases phosphatidylcholine turnover but not phosphatidylinositol turnover. Down-regulation of protein kinase C (by prolonged exposure to phorbol esters prior to scrape loading) blocked the ability of ras protein to elevate the levels of diacylglycerol, choline, and phosphocholine. Oncogenic ras can, therefore, cause a substantial increase in diacylglycerol (which correlates with increased phosphatidylcholine breakdown) in a protein kinase C-dependent fashion. Val12p21ras also increased arachidonic acid release, which was also dependent on protein kinase C activation. Induction of DNA synthesis by oncogenic ras was unaffected by inhibitors of prostaglandin synthesis, indicating that conversion of the released arachidonic acid to various prostaglandins is not required for stimulation of DNA synthesis by ras. We suggest that ras rapidly activates protein kinase C, which in turn activates a number of cellular signalling systems, leading to a sustained increase in diacylglycerol levels. This elevation of diacylglycerol could sustain protein kinase C activation over the 12-15 h required for initiation of DNA synthesis.

Animals↗
PubMed1989

Scrape-loaded p21ras down-regulates agonist-stimulated inositol phosphate production by a mechanism involving protein kinase C.

The effect of scrape-loaded [Val-12]p21ras on agonist-stimulated phosphatidylinositol 4,5-bisphosphate (PIP2) turnover in Swiss-3T3 cells was studied. Previously [Morris, Price, Lloyd, Marshall & Hall (1989) Oncogene 4, 27-31] we demonstrated that [Val-12]p21ras activates protein kinase C within 10 min of scrape loading. Here, we show that [Val-12]p21ras inhibits bombesin and platelet-derived growth factor-stimulated PIP2 breakdown 1.5-4 h after scrape loading. This effect persisted for at least 18 h and could be mimicked in control cells by activation of protein kinase C with 12-O-tetradecanoyl 13-acetate (TPA) 15 min prior to ligand stimulation. When protein kinase C was down-regulated by chronic TPA treatment, [Val-12]p21ras was no longer able to inhibit agonist-stimulated inositol phosphate production. These results indicate that changes in inositol phosphate levels caused by ras protein are probably due to activation of protein kinase C and not to an interaction of ras with phospholipase C.

Animals↗
PubMed1989

Signal transduction by p21ras.

Experiments using the physical loading of purified recombinant p21 ras proteins into quiescent normal cells to analyze how the proteins stimulate DNA synthesis and morphological transformation are reviewed. The results indicate that oncogenic p21ras proteins rapidly activate a protein-kinase-C-dependent pathway and a protein-kinase-C-independent pathway. The activation of protein kinase C is absolutely required for p21ras to stimulate DNA synthesis but is not required for morphological transformation.

Animals↗
PubMed1989

p21H-ras-induced morphological transformation and increases in c-myc expression are independent of functional protein kinase C.

It has previously been demonstrated that efficient DNA synthesis by oncogenic p21H-ras only occurs in the presence of insulin and is absolutely dependent on functional protein kinase C. Here we show that morphological transformation induced by oncogenic p21H-ras does not require functional protein kinase C. The early phases of protein kinase C-independent morphological transformation do not require de novo protein synthesis. We have also demonstrated that the introduction of p21H-ras into quiescent Swiss 3T3 cells by scrape-loading leads to increased levels of c-myc mRNA similar to those seen following serum stimulation. The increases in c-myc mRNA levels induced by p21H-ras are also independent of functional protein kinase C. Both morphological transformation and the elevation of c-myc mRNA levels do not require insulin. These results demonstrate that p21H-ras is generating protein kinase C-dependent and -independent signals.

Animals↗