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Biomedical subjects

G Price

Publications and source records attributed to G Price.

At least 19 recordsLinked to original sources
PubMed1995

Complete nucleotide sequence, expression, and chromosomal localisation of human mixed-lineage kinase 2.

Protein kinases play pivotal roles in the control of many cellular processes. In a search for protein kinases expressed in human epithelial tumour cells, we discovered two members of a novel protein kinase family [Dorow, D. S., Devereux, L., Dietzsch, E. & de Kretser, T. A. (1993) Eur. J. Biochem. 213, 701-710]. Due to the unique mixture of structural domains within their amino acid sequences, we named the family mixed-lineage kinases (MLK). We initially isolated clones encoding partial cDNAs of MLK1 and 2 from a human colonic cDNA library. The MLK2 cDNA was subsequently used to screen a human brain cDNA library and we have now cloned and sequenced a 3454-bp cDNA encoding the full-length MLK2 protein. The predicted MLK2 polypeptide has 954 amino acids and contains a src homology 3 (SH3) domain, a kinase catalytic domain, a double leucine zipper and basic domain, and a large C-terminal domain. The 22-amino-acid N-terminal region has four glutamic acid residues immediately following the initiator methionine. Beginning at amino acid 23, the 55-amino-acid SH3 domain contains a 5-amino-acid insert in a position corresponding to inserts of 6 and 15 residues in the SH3 domains of n-src and the phosphatidylinositol 3'-kinase. Adjacent to the SH3 domain is a kinase catalytic domain with conserved motifs associated with both serine/threonine and tyrosine specificity. Beginning nine residues C-terminal to the catalytic domain, there are two leucine/isoleucine zippers separated by a 13-amino-acid spacer sequence and followed by a stretch of basic residues. The polybasic sequence contains a motif that is similar to nuclear localisation signals from several proteins. The C-terminal domain is composed of 491 amino acids of which 17% are serine or threonine and 16% are proline. This domain also has a biased ratio of basic to acidic amino acids with a calculated pI of 9.38. When used as a probe to examine mRNA expression in human tissues, a MLK2 cDNA hybridised to a species of 3.8 kb that was expressed at highest levels in RNA from brain and skeletal muscle. The 3454-bp cDNA was also used for fluorescence in situ hybridisation to localise the MLK2 gene to human chromosome 19 q13.2.

Amino Acid Sequence↗
PubMed1995

The lymph node pathology of Omenn's syndrome.

Omenn's syndrome is a rare, usually fatal immunologic disorder of infancy characterized by recurrent infections, skin lesion, lymphadenopathy, peripheral blood lymphocytosis, and eosinophilia. Histologic evaluation of a lymph node revealed total effacement of the microscopic architecture resulting from a diffuse proliferation of interdigitating reticulum cells and a depletion of B lymphocytes. The lymph node lacked a distinct cortex and had no follicle formation. The most striking feature was a diffuse hyperplasia of S-100-protein-positive nonphagocytic reticulum cells with large, pale Langerhans-like nuclei. Ultrastructural examination identified these cells to be interdigitating reticulum cells. The lymphocytes were small and predominantly of the CD8 cytotoxic/suppressor cell type.

Antigens, CD↗
PubMed1994

A reproducible method for identification of human genomic DNA autonomously replicating sequences.

We demonstrate a method for the isolation of autonomously replicating sequences from pools of clones obtained from genomic DNA libraries constructed using affinity purification of cruciform DNA. The selection of autonomously replicating sequences was based on their differential ability to replicate as episomes after transfection of pools of plasmid clones into human HeLa cells. Two separate libraries containing affinity-purified cruciform DNA were used, one prepared from DNA of log phase primary human genital fibroblasts and the other prepared from DNA of log phase SW48 colon adenocarcinoma cells. Representative samples of the entire phage libraries were converted to phagemid clones by filamentous helper phage-mediated mass excision to produce pBluescript libraries in Escherichia coli. Clones were grown up individually and the bacteria pooled into groups of 48 for recovery of plasmid DNA. Plasmid pools of 48 independent clones (120 micrograms total) were then transfected by calcium phosphate coprecipitation onto log phase HeLa cells, which were allowed to grow for 3 days before recovery of plasmid by Hirt lysis. The recovery of plasmid from each transfection was estimated to range from 10 to 60 ng. DpnI digestion was then used to digest plasmids which had not been replicated and therefore retained a bacterial methylation pattern which was sensitive to digestion. We estimated from agarose electrophoresis gels that 40-200 pg of recovered plasmid DNA per transfected pool of DNA was resistant to DpnI and therefore was capable of transforming competent E. coli cells. The DpnI-resistant fraction yielded from one to seven independent clones from each pool, with genomic DNA inserts ranging in size from 0.35 to 3.4 kb.(ABSTRACT TRUNCATED AT 250 WORDS)

DNA↗
PubMed1993

Patterns of smoking during pregnancy in Canterbury.

AIMS: To examine the prevalence and patterns of smoking in pregnancy with the object of improving smokefree programmes in the region. METHODS: A postal questionnaire on smoking in pregnancy was sent to all 1916 mothers giving singleton births in the Canterbury region over a five month period. There was a 71.7% response rate, however, smokers were significantly under represented. Data from nonresponders was obtained from obstetric records. RESULTS: Of the total sample, 30% smoked during their last pregnancy. There were significant differences between responders and nonresponders. The responders contained only 60% of all smokers. Nonresponders had twice the incidence of smoking, were more likely to identify as Maori, were younger and had lower birth weights. Nonresponders contained 40% of all smokers. Of the responders, 333 mothers smoked during at least some part of pregnancy: 113 (34%) quit, 168 (50%) cut down, and 48 (15%) made no change. Most (90%) of those who did quit did so during the first trimester. Lighter smokers (less than 10 per day) were more likely to quit or cut down. But smoking rates subsequently increased after the birth. CONCLUSIONS: In Canterbury, 30% of pregnant women smoke. Although 64% indicated a wish to quit and 30% to cut down, this contrasted with what they actually achieved: 34% quit and 50% cut down. Pregnancy influences smoking patterns and is an opportune time for smokefree promotion.

Adult↗
PubMed1993

Naltrexone treatment attenuates the inhibitory effect of nicotine treatment on serum LH in rats.

The hypothesis that endogenous opioids might have a role in mediating the suppressive effects of nicotine on serum LH concentrations in rats was investigated. Naltrexone treatment prevented the inhibitory effect of high doses of nicotine on serum LH concentrations. Nicotine treatment also prevented the stimulatory effect of naltrexone on serum LH concentrations. These results suggest that the inhibitory effects of nicotine on serum LH concentrations involve an opioidergic component.

Adrenalectomy↗
PubMed1991

Anti-cruciform DNA affinity purification of active mammalian origins of replication.

A novel approach that employs anti-cruciform DNA monoclonal antibodies was used to isolate segments of cruciform-containing DNA from genomic DNA, in an effort to obtain fragments containing active origins of replication. High molecular weight DNA (greater than 50 kb) was extracted from log phase CV-1 cells and 6 micrograms incubated with approximately 2.5 micrograms of a monoclonal antibody, 2D3, specific for cruciform-containing DNA. The 2D3-bound DNA was digested with EcoRI and antibody-bound fragments were recovered using rabbit anti-mouse immunobeads. The beads were washed free of nonspecifically bound DNA and the 2D3-bound DNA was eluted with 2% sodium dodecyl sulphate (SDS). The yield of DNA recovered by 2D3 was 2000-fold less than the initial amount and was 17-20-fold more than that recovered nonspecifically using the control mAb, P3. The 2D3-bound DNA ranged from 0.15- greater than 23 kb with a major peak at approximately 12 kb. Specific enrichment of origin-containing DNA by 2D3 over P3 was suggested by a 10-100-fold greater recovery of a 9 kb fragment hybridizable to a low-copy monkey autonomously replicating sequence, ors 8. 20 ng of affinity-purified DNA was cloned into lambda Zap II and excised into Bluescript phagemids in vivo. Of nine randomly-selected clones between 0.15 and 3.2 kb, four were able to replicate autonomously when transfected into HeLa cells. Two of the nine clones contained sequences hybridizable to both monkey alpha-satellite and human Alu DNA, and two others to Alu alone. The present work provides further evidence for the involvement of cruciforms at active mammalian origins of DNA replication.

Animals↗
PubMed1989

Intestinal bleeding in patients with Whipple's disease.

Five consecutive patients with Whipple's disease exhibited intestinal blood loss at the time of their initial presentation. Three had gross intestinal bleeding and the other 2 had occult bleeding with microcytic anemia. Although not generally emphasized, Whipple's disease needs to be considered in the differential diagnosis of acute and chronic gastrointestinal bleeding.

Aged↗
PubMed1989

The prevalence of Campylobacter pylori gastritis: a study of symptomatic nonulcer dyspepsia and bile gastritis.

We assessed the prevalence of Campylobacter pylori in various forms of endoscopic gastritis, including ulcer and nonulcer dyspepsia and bile gastritis and correlated it with histological evidence of inflammation. Multiple biopsy specimens were taken from 120 patients, including four normal controls, who underwent upper gastrointestinal endoscopy for evaluation of upper abdominal pain and discomfort, nausea, bilious vomiting, weight loss, and anemia. The patients included 58 men and 62 women, with a mean age of 53 years. Of these, 16 patients had gastric ulcers, 19 had duodenal ulcers, 26 had reflux gastritis (after either gastric surgery or cholecystectomy), one had a gastric polyp, one had Barrett's esophagus, and the remaining 53 had gastritis due to unspecified causes. Campylobacter-like organisms were demonstrated by light and electron microscopy in 50 of 69 patients of the nonbile gastritis group (72%) and in seven of 15 patients of the bile gastritis group (47%) (p0.05). The presence of bacteria in both groups correlated with histologically significant inflammation (particularly chronic active gastritis); similar histologic changes were noted in both major groups of nonbile gastritis and bile gastritis. Campylobacter pylori is common in all forms of gastritis in association with histologic inflammation.

Adult↗
PubMed1988

T-cell depletion with ricin A-chain T101 in allogeneic bone marrow transplantation to prevent severe graft-versus-host disease.

Bone marrow cells from 10 marrow transplant donors were treated with an immunotoxin, which couples A-chain of ricin with a monoclonal anti-T-cell antibody T101 to prevent graft-versus-host disease by the elimination of mature T-cells. Marrow cells treated with the anti human T-cell immunotoxin (IT101) were cultured for erythropoietic colonies, granulocytic colonies, and multilineage hematopoietic colonies (CFU-GEMMT) containing myeloid cells and T-cells, and optimal conditions were defined for the elimination of T-cells present in the harvested donor marrow prior to marrow transplantation. Marrow samples purged with IT101 were examined for residual T-cells by fluorescence activated cell sorting, using anti-T-cell antibodies, [3H]-thymidine incorporation after PHA stimulation, and an assay for clonogenic T-cells. The number of T-cell colonies observed in the treated marrows was less than 5% of the number in comparable unpurged donor marrows. Treatment with IT101 did not alter the plating efficiency of hematopoietic colonies compared to untreated donor marrow cells. These data suggest that multilineage progenitors responsible for the reconstitution of the recipient hematopoietic system are not affected by marrow IT101 purging. The clinical data on 10 patients indicate that the depletion of T-cells in the donor marrow with IT101 is effective in decreasing the severity of acute graft-versus-host disease in allogeneic marrow transplantation and warrants continued investigation.

Adult↗
PubMed1988

Gastrointestinal arterial fibromuscular dysplasia of childhood.

An unusual case of a progressive, noninflammatory stenosing vasculopathy, arterial fibromuscular dysplasia is presented. The distinctive features of this particular case include onset in early childhood with a predominant involvement of the gastrointestinal system, sparing of the renal arteries, lack of hypertension, and no cutaneous features of progressive systemic sclerosis. We discuss the clinical history over a decade and the pathologic features, including routine and electron microscopic findings of biopsy and autopsy tissues, and review the literature.

Adolescent↗
PubMed1987

Cytotoxic effects of tumour necrosis factor and gamma-interferon on acute myeloid leukaemia blasts.

We have studied the cytotoxic effects of recombinant tumour necrosis factor and recombinant gamma interferon on primary cultures of leukaemia cells. The agents were added alone or in a combination to cells from 17 patients. Eleven had acute myeloblastic leukaemia (6 at presentation, 5 at relapse), 4 had acute lymphoblastic leukaemia, one had hairy cell leukaemia, and 2 had chronic myeloid leukaemia--one of whom was in myeloid blast transformation. Cells from patients with lymphoid malignancies or from the patient with chronic phase CML were not affected by either agent in any dose combination. In contrast, reduction of viability of myeloid blasts was weakly accelerated by TNF and gamma-interferon individually. Combination of the agents invariably produced enhanced killing and additive or synergistic effects were seen when 20-500 IU ml-1 of each cytokine was present. This sensitivity was also shown by blast cells from 5 patients with relapsed AML. We therefore suggest that trials of such combination therapy may be indicated in drug resistant or relapsed AML.

Cell Survival↗
PubMed1986

Stop ourselves smoking: a smoking cessation programme.

The stop ourselves smoking (SOS) pilot programme, designed for those who want to stop smoking, is based on a self-help approach. It was developed in Christchurch to supplement existing smoking cessation programmes in the community. Of the 142 participants, 118 finished the course. Of these, 80 (68%) were not smoking at the end of the eighth week and 61 (52%) were still not smoking at the end of the 15-month followup period. The success of this programme exceeds that of any reviewed in the literature. The format of the programme is readily adaptable to other lifestyle programmes.

Humans↗
PubMed1985

Adenosquamous carcinoma of the colon.

Two cases of primary adenosquamous carcinomas of the sigmoid colon and rectum are presented. Clinical features and pathologic findings of both primary and metastatic lesions are reported (including immunohistochemistry and electron microscopy). We emphasize that the presence of a metastatic squamous tumor in a patient with an unknown primary does not exclude the possibility of colonic carcinoma. Comparison with other reports in the American medical literature indicates that these are very aggressive tumors that may have a worse prognosis than the more common form of colonic adenocarcinoma. Furthermore, the squamous component, in particular, may have a greater potential for metastasizing and can do so as an undifferentiated-appearing carcinoma. In view of this, the authors suggest that very poorly differentiated areas within colonic adenocarcinomas should be very carefully evaluated by means of immunoperoxidase stains and/or electron microscopy in an attempt to identify squamous features.

Adenocarcinoma↗