Search PubMed⌕ Search

Biomedical subjects

D G Lowe

Publications and source records attributed to D G Lowe.

At least 127 records · Page 7Linked to original sources
PubMed1989

Human atrial natriuretic peptide receptor defines a new paradigm for second messenger signal transduction.

We isolated cDNAs encoding a 115 kd human atrial natriuretic peptide (alpha ANP) receptor (ANP-A receptor) that possesses guanylate cyclase activity, by low-stringency hybridization with sea urchin Arbacia punctulata membrane guanylate cyclase probes. The human ANP-A receptor has a 32 residue signal sequence followed by a 441 residue extracellular domain homologous to the 60 kd ANP-C receptor. A 21 residue transmembrane domain precedes a 568 residue cytoplasmic domain with homology to the protein kinase family and to a subunit of the soluble guanylate cyclase. COS-7 cells transfected with an ANP-A receptor expression vector displayed specific [125I]alpha ANP binding, and exhibited alpha ANP stimulated cGMP production. These data demonstrate a new paradigm of cellular signal transduction where extracellular ligand binding allosterically regulates cyclic nucleotide second-messenger production by a receptor cytoplasmic catalytic domain.

Amino Acid Sequence↗
PubMed1989

Erythema induratum (Bazin's disease).

The clinical and histologic features of 26 cases of erythema induratum are reviewed. The characteristic cutaneous lesions on the legs of middle-aged women were violaceous, indurated nodules, 1 to 2 cm in diameter, which were painful, occasionally ulcerated, and could heal with scarring. The diagnosis was confirmed in all patients by a strongly positive Mantoux test result (1:10,000 dilution) and by clearing of lesions after antituberculosis therapy. The histologic features were varied but were predominantly those of a vasculitis with a paraseptal and lobular panniculitis. Although it was not possible to fulfill the required criteria for diagnosing tuberculosis in these lesions, we believe there is sufficient circumstantial evidence to support the hypothesis that erythema induratum is a true tuberculid.

Adult↗
PubMed1989

Genomic cloning and heterologous expression of human differentiation-stimulating factor.

Differentiation-stimulating factor (D-factor) purified from mouse Ehrlich ascites cells was sequenced partially and found to be almost identical to leukemia inhibitory factor (LIF) from mouse Krebs II ascites cells. In comparison to LIF, D-factor had an additional amino-terminal serine residue. Using synthetic oligonucleotide probes designed from the murine D-factor sequence, we cloned the human gene encoding D-factor. A partial D-factor cDNA was cloned from COS-1 cells transfected with the human D-factor gene under the control of a heterologous promoter. We used this cDNA to construct a vector for direct expression of the protein in Escherichia coli. A mammalian cell expression vector was constructed using the signal sequence of interferon-alpha A linked to the D-factor cDNA. Both forms of recombinant human D-factor were active on the murine myeloid leukemia cell line M1 in a dose- and time-dependent manner for the inhibition of [3H]thymidine incorporation, and also induced phagocytosis, Fc receptor expression, and prostaglandin E2 synthesis by M1 cells.

Amino Acid Sequence↗
PubMed1989

Bilateral testicular tumours in congenital adrenal hyperplasia: a continuing diagnostic and therapeutic dilemma.

Bilateral testicular tumours are a rare but well described complication of congenital adrenal hyperplasia (CAH). It can be extremely difficult to distinguish histologically between Leydig cell tumours and adrenocortical rest hyperplasia which may lead in some cases to unnecessary orchidectomy in young men. A 26-year-old male in whom CAH had been diagnosed neonatally, was referred for further investigation of a craggy mass in the left testis. Six months earlier, right orchidectomy had been performed after presentation with bilateral enlarged, hard testes and azoospermia. The tumour was interpreted to be a malignant interstitial cell tumour of the testis. Our investigations revealed that his CAH was inadequately controlled and that the hormonal secretion from the remaining left testicular mass was ACTH dependent. Percutaneous venous sampling revealed high concentrations of cortisol and other adrenocortical hormones coming from the gonadal vein. Dexamethasone suppressed these adrenal hormones and reduced the size and softened the consistency of the testicular mass. Total disappearance of the mass was achieved by using dexamethasone, given in a reverse circadian rhythm regimen. Spermatogenesis returned and the patient's wife became pregnant after 6 months; she gave birth to a normal male infant. To our knowledge, this is the first time in this clinical setting that fertility has been achieved. This case highlights the need for both a functional and histological assessment of such 'tumours' in CAH prior to orchidectomy.

Adrenal Hyperplasia, Congenital↗
PubMed1989

Human differentiation-stimulating factor (leukemia inhibitory factor, human interleukin DA) gene maps distal to the Ewing sarcoma breakpoint on 22q.

The human gene encoding differentiation-stimulating factor (D-factor) has previously been isolated and shown to be identical to leukemia inhibitory factor (LIF). We have determined a fine structure map of approximately 20-kb surrounding the D-factor/LIF gene. Southern blot analysis using a somatic cell hybrid panel shows that the gene maps to chromosome 22. D-factor/LIF was further sublocalized to 22q11.2----q13.1, distal to a Ewing sarcoma (ES) breakpoint, using a second somatic cell hybrid panel. Probes to the 5' and 3' regions of the locus and the cDNA were used to screen for restriction fragment length polymorphisms, but none were detected. Analysis by pulsed field gel electrophoresis suggests that D-factor/LIF is not near the ES breakpoint.

Animals↗
PubMed1989

A randomized trial to evaluate the effect of schedule on the activity of etoposide in small-cell lung cancer.

Etoposide is an increasingly used and well-tolerated drug in cancer medicine. Its cytotoxic action is phase-specific and it has demonstrated schedule dependency in both in vitro and animal studies, but clinical evidence of the importance of drug scheduling is uncertain. The two administration schedules of etoposide that have been compared in this randomized study of 39 patients with previously untreated extensive small-cell lung cancer treated with single-agent etoposide were 500 mg/m2 as a continuous intravenous (IV) infusion over 24 hours or five consecutive daily 2-hour infusions each of 100 mg/m2. Both regimens were repeated every 3 weeks, for a maximum of six cycles. Patients received combination chemotherapy with vincristine, doxorubicin, and cyclophosphamide (VAC) or radiotherapy on failure to respond or at relapse, depending on their Karnofsky performance status. The same therapy was used in both arms of the study. All patients are evaluable for response to etoposide. In the 24-hour arm, two patients achieved a partial remission, resulting in an overall response rate of 10%. In the 5-day schedule, 16 patients had a partial response and one had a complete remission, producing an overall response rate of 89%, which was significantly superior to that in the 24-hour arm (P less than .001). The median duration of remission to etoposide in the 5-day arm was 4.5 months. Bone marrow toxicity was similar in both schedules. Etoposide pharmacokinetics were measured in all patients, and total areas under the concentration versus time curves (AUCs) were equivalent in both regimens. This study has clearly demonstrated the importance of etoposide scheduling in humans, and the superiority of five daily infusions over a 24-hour continuous infusion. The response rate to single-agent etoposide using an efficacious schedule in extensive small-cell lung cancer has been determined to be in excess of 80%.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Membrane guanylate cyclase is a cell-surface receptor with homology to protein kinases.

Guanylate cyclase has been strongly implicated as a cell-surface receptor on spermatozoa for a chemotactic peptide, and on various other cells as a receptor for atrial natriuretic peptides. Resact (Cys-Val-Thr-Gly-Ala-Pro-Gly-Cys-Val-Gly-Gly-Gly-Arg-Leu-NH2), the chemotactic peptide released by sea urchin Arbacia punctulata eggs, is specifically crosslinked to A. punctulata spermatozoan guanylate cyclase. After the binding of the peptide the state of guanylate cyclase phosphorylation modulates enzyme activity. We report here that the deduced amino-acid sequence of the spermatozoan membrane form of guanylate cyclase predicts an intrinsic membrane protein of 986 amino acids with an amino-terminal signal sequence. A single transmembrane domain separates the protein into putative extracellular and cytoplasmic-catalytic domains. The cytoplasmic carboxyl-terminal 95 amino acids contain 20% serine, the likely regulatory sites for phosphorylation. Unexpectedly, the enzyme is homologous to the protein kinase family.

Amino Acid Sequence↗
PubMed1988

Chimeric proteins define variable and essential regions of Ha-ras-encoded protein.

The biological role of amino acid differences between the human 21-kDa Ha-ras protein (p21) and the human 23-kDa R-ras protein (p23) was investigated by engineering mutant Ha-ras p21 molecules containing divergent amino acid sequences from R-ras p23. Variant amino acids from R-ras p23 regions 1-30, 52-57, 67-78, 1-30 and 67-78 together, and 112-124 were substituted for the corresponding Ha-ras p21 amino acid regions 1-4, 26-31, 41-52, 1-4 and 41-52 together, and 86-98, respectively. Rat fibroblasts transfected with genes encoding these position-12 valine-substituted chimeric Ha-ras proteins displayed the same properties of morphological transformation and anchorage-independent growth as Ha-ras T24 oncogene-transformed fibroblasts. However, substitution of variant amino acids from the 80 C-terminal residues (amino acids 138-218) of R-ras p23 for the corresponding p21 amino acids (residues 112-189) inactivated the transforming activity of position-12 valine-substituted p21. The converse substitution of Ha-ras p21 C-terminal residues into R-ras p23 did not result in transformation by position-38 valine-substituted p23. These data are discussed in terms of the structure of ras proteins and the nature of interactions determining the specificity of effector function.

Amino Acid Sequence↗
PubMed1988

Immunoreactive human chorionic gonadotrophin from the cyst fluid and CSF of patients with craniopharyngioma.

A specific radioimmunoassay for the beta-chain of human chorionic gonadotrophin irHCG beta has demonstrated HCG-like material to be present in craniopharyngioma cyst fluid in nine consecutive patients with craniopharyngioma. There was no detectable LH/HCG bioactivity as assessed using testosterone production from isolated Leydig cells from rat testis in seven samples tested. One patient was also found to have measurable irHCG beta in the cerebrospinal fluid (CSF), which fell to undetectable levels following surgery; in this patient, there was clinical evidence that the cyst fluid had leaked into the CSF pre-operatively. Immunocytochemical staining for HCG beta and intact HCG was positive in five of the tumours. irHCG beta was not measurable in the serum of any of the patients.

Biological Assay↗
PubMed1988

Carcinoma of the cervix with massive eosinophilia.

Massive local eosinophilia of 100 or more eosinophils per high power field was found in 3.2% cases of invasive carcinoma of the cervix. The prevalence, length of history before presentation to surgery and histological features were similar in patients from Great Britain and Malawi, but in both populations the mean age at diagnosis was lower than in patients with cervical carcinomas without tissue eosinophilia. In some of the tumours, the malignant cells were very difficult to find because of the eosinophil infiltrate, and misinterpretation as an inflammatory lesion was possible. In the absence of circulating eosinophilia, cervical carcinomas with massive eosinophilia were found to have a better prognosis than tumours without. Five patients had circulating eosinophilia as well as local tumour eosinophil infiltration, and each of them had extensive tumour spread.

Adult↗
PubMed1988

Silver deposition in the cervix after application of silver nitrate as a cauterising agent.

Large amounts of metallic silver pigment were found in 10 cervical biopsy specimens taken for the histological grading of cervical intraepithelial neoplasia (CIN). The assessment of CIN was made much harder because the pigment obscured the morphological detail of the epithelial cells, and in some it was very difficult to determine whether koilocytosis or CIN I was present. The silver can easily be removed by a simple chemical method.

Adult↗
PubMed1988

Verrucous carcinoma of the female genital tract: a review.

The 102 cases of verrucous carcinoma of the female genital tract reported in the world literature have been reviewed. The difficulties in diagnosis of this tumor are discussed; correct diagnosis is heavily dependent on close collaboration between clinician and pathologist, and the provision to the latter of a sufficiently large biopsy specimen. Effective management requires surgical resection, which may at times need to be radical. Radiotherapy and chemotherapy are of doubtful value.

Carcinoma, Papillary↗
PubMed1987

Patterns of expression of a tumor associated antigen, defined by the monoclonal antibody HMFG2, in human epithelial ovarian carcinoma. Comparison with expression of the HMFG1, AUA1 and F36/22 antigens.

Binding to the antigen defined by the monoclonal antibody HMFG2 was demonstrated in more than 94% of human epithelial ovarian carcinomas by the indirect immunoperoxidase technique. The extent of the expression of this antigen related to tumor differentiation; well-differentiated tumors expressed more antigen than poorly differentiated tumors. Marked variation of tumor grade and antigen expression was demonstrated in individual tumors and this may be a limiting factor in the use of radioisotope linked HMFG2 for tumor therapy. A similar prevalence was found in the expression of the antigens defined by the monoclonal antibodies HMFG1 and F36/22; whereas the AUA1 antigen was demonstrated in 68% of cases. The patterns of expression of the HMFG1, HMFG2, and F36/22 antigens suggest that they may be related antigens.

Antibodies, Monoclonal↗
PubMed1987

Structure of the human and murine R-ras genes, novel genes closely related to ras proto-oncogenes.

The human R-ras gene was isolated by low-stringency hybridization with a v-H-ras probe. The predicted 218 amino acid R-ras protein has an amino-terminal extension of 26 residues compared with H-ras p21, and shows 55% amino acid identity; conserved domains include the p21 GTP-binding site and the carboxy-terminal membrane localization sequence. R-ras has at least six exons, with the position of the first intron conserved relative to the Drosophila ras64B and Dictyostelium ras genes; there is no similarity in the exon-intron structure of the R-ras gene and of the mammalian H-, K-, and N-ras proto-oncogenes. Cloned mouse R-ras cDNAs exhibit 88% nucleotide and 94.5% predicted amino acid identity to human R-ras. Human R-ras was localized to chromosome 19, a site different from ras p21 genes. Mouse R-ras is syntenic with c-H-ras on chromosome 7.

Animals↗
PubMed1987

Magnetic resonance imaging as a screening procedure for methotrexate induced liver damage.

Spin lattice relaxation time (TI) measured with a low field strength magnetic resonance imager in 51 patients with severe psoriasis did not correlate with the histological findings of liver biopsies taken during treatment with oral methotrexate. Liver TI measurement at low magnetic field is of no value as a screening procedure in monitoring methotrexate induced liver damage.

Adolescent↗
PubMed1987

Malignant lymphoma with eosinophilia of the gastrointestinal tract.

Lesions of the gastrointestinal tract with massive tissue eosinophilia may present a difficult diagnostic problem. In a series of 250 gastrointestinal lymphomas drawn from the files of St Bartholomew's and St Mark's Hospitals there were 28 cases of a lymphoma with distinctive histological features, characterized by a massive tissue eosinophilia. Two of these tumours were present in the stomach and 26 in the small intestine. Eight of the latter were associated with coeliac disease. On low power examination a zoning phenomenon was regularly seen and fissuring ulceration, with perforation and fistula formation, was a common finding. The tumour cells were large and pleomorphic with irregular nuclear morphology and prominent nucleoli. Eosinophils were the predominant inflammatory cell associated with the lymphoma but plasma cells, epithelioid histiocytes and small lymphocytes were also present. Vascular changes were prominent. Involved lymph nodes showed gross expansion of the paracortex by tumour. Immunohistochemical studies showed that this lymphoma was probably of T-cell origin.

Aged↗