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Biomedical subjects

T Campbell

Publications and source records attributed to T Campbell.

At least 73 records · Page 4Linked to original sources
PubMed1992

Isolation of a lactoferrin cDNA clone and its expression in human breast cancer.

A cDNA library constructed from mRNA from a human breast carcinoma metastasis was screened with a polyclonal antibody to deglycosylated human milk fat globule membrane, resulting in the isolation of eight clones from a total of 10(5) plaques. One of these (J16) was identified as lactoferrin. It was highly expressed (as a 2.5 Kb mRNA) in lactating breast and in both normal resting tissue taken from adjacent to carcinoma or from reduction mammoplasties. Immunoreactive lactoferrin was localised to ductal cells and their secretions in both normal and mildly hyperplastic ducts. In a normal tissue screen J16 was highly expressed in stomach, poorly in skin and lymphocytes and absent from other organs examined. It was variably expressed in 33/59 invasive primary breast tumours; lactoferrin protein in these was heterogeneously distributed in epithelial tumour foci. Presence of J16 was inversely related to expression of oestrogen receptor protein (P = 0.0001). There was no significant relationship to other clinical parameters. We also found immunoreactivity in 20/41 (49%) cases of ductal carcinoma in situ. Expression was not observed in any breast or gastric cell line examined. Thus lactoferrin appears to be down regulated in some forms of cancer. The presence of lactoferrin could be a contraindication for effective endocrine therapy.

Biomarkers, Tumor↗
PubMed1991

Evidence of prenatal infection in the bottlenose dolphin (Tursiops truncatus) with the lungworm Halocercus lagenorhynchi (Nematoda: Pseudaliidae).

Adult lung nematodes identified as Halocercus lagenorhynchi were collected from the lungs of four Tursiops truncatus calves. The calves ranged in age from newborn to 3-wk-old and were found on both the Atlantic and Gulf coasts of Florida (USA). This finding suggests the possibility of a more cosmopolitan distribution of prenatal infection with lung nematodes in cetaceans than previously suspected.

Animals↗
PubMed1990

Esorubicin (4'-deoxydoxorubicin, NSC 267469) in advanced breast cancer. A phase II study of the CALGB.

Forty-six eligible women with advanced metastatic breast cancer were entered on a Phase II trial utilizing esorubicin (4'-deoxydoxorubicin) given in a dosage of 30 mg/m2 intravenously every 3 weeks. No patient had received anthracyclines or cytotoxic therapy for metastatic disease. Twenty-three (50% of patients) had prior adjuvant chemotherapy, 21 (46%) had prior hormonal therapy, and 32 (70%) were postmenopausal. Dominant site of disease was visceral in 26 (57%), bone in 14 (30%), and soft tissue in 6 (13%). There were 3 complete and 13 partial responders observed, for a 35% response rate; 95% confidence interval for response was 21-49%. Median response duration was 4.0 months (range 2-21 months), and one partial responder remains on study at 6.3 months. Thirty-nine of 46 patients have died; median survival was 10.1 months. Toxicity was primarily hematologic, with 2 drug-related septic deaths. In addition, 2 patients developed severe congestive heart failure secondary to esorubicin cardiotoxicity (at 687 and 770 mg/m2, respectively), which resulted in one patient death. Nausea and vomiting were severe in 16% of patients, but total alopecia was only noted in 4 (9%). Esorubicin is an active agent in metastatic breast cancer; its role in treatment remains undefined.

Adult↗
PubMed1990

Dopamine inhibits Na(+)-H+ exchanger activity in renal BBMV by stimulation of adenylate cyclase.

To determine a renal tubular mechanism for the natriuretic effect of dopamine (DA) and DA-1 agonists, we measured Na(+)-H+ exchange activity (amiloride sensitive) in rat renal cortical brush-border membrane vesicles (BBMV). Renal cortical tissues were preincubated with ligands before BBMV preparation to study Na(+)-H+ exchange activity in the absence of the added ligands that may compete for ion binding sites of the exchanger. DA and DA-1 agonist-inhibited Na(+)-H+ exchange activity was concentration and time dependent. The inhibitory effect was not due to increased permeability, collapse of the proton gradient, or change in vesicle size and did not extend to Na(+)-glucose symport. DA-2 agonists had no effect, whereas alpha-adrenergic agonists increased Na(+)-H+ exchange activity. Kinetic analysis revealed that the DA-1 agonist inhibited Na(+)-H+ exchange activity by a noncompetitive process. 2',5'-Dideoxyadenosine inhibited adenylate cyclase activity and reversed the inhibitory effect of DA-1 agonist on the exchanger. H4, an isoquinoline sulfonamide, which inhibits protein kinase A, also reversed the inhibitory effect of DA-1 agonist on the exchanger. Thus the DA-1 agonist-mediated inhibition of Na(+)-H+ exchange activity in BBMV is a receptor-mediated adenylate cyclase-linked process.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1989

Succinate-dependent energy generation in Ascaris suum mitochondria.

Phosphorylation in isolated Ascaris suum mitochondria was much greater in the presence of malate than succinate, but, in the absence of added adenine nucleotides, incubations in succinate resulted in substantial elevations in intramitochondrial ATP levels. Succinate-dependent phosphorylation was stimulated aerobically and this stimulation was due almost entirely to a site I, rotenone-sensitive, phosphorylation. Increased substrate level phosphorylation, coupled to propionate formation, or additional sites of electron-transport associated ATP synthesis were not significant. Under aerobic conditions, 14CO2 evolution from 1,4-[14C]succinate was stimulated and NADH/NAD+ ratios were elevated, but the formation of [14C]propionate was unchanged. It appears that succinate was metabolized to pyruvate and acetate, and NADH, generated from the decarboxylations of malate and pyruvate, was the primary source of reducing power fueling electron-transport. The terminal oxidase and final electron-acceptor are still not clearly defined. However, ferricyanide, H2O2, and 100% oxygen all stimulated succinate-dependent phosphorylation. A possible role for cytochrome c peroxidase in A. suum mitochondrial metabolism is discussed.

Adenine Nucleotides↗
PubMed1987

Anaerobic metabolism in Ascaris suum: acyl CoA intermediates in isolated mitochondria synthesizing 2-methyl branched-chain fatty acids.

Freshly isolated Ascaris suum mitochondria contained CoASH, acetyl CoA, propionyl CoA, 2-methylcrotonyl CoA, 2-methylbutyryl CoA, 2-methyl-2-pentenoyl CoA, and 2-methylvaleryl CoA, as determined by high-pressure liquid chromatography. Incubation of these mitochondria aerobically in the absence of substrate resulted in the conversion of the branched-chain enoyl CoA's to acetyl CoA and propionyl CoA. With the addition of malate to the incubation medium, succinyl CoA and methylmalonyl CoA accumulated and the levels of propionyl CoA decreased dramatically. However, the branched-chain fatty acids characteristic of A. suum's fermentative metabolism were not formed and it appears that the formation of propionyl CoA may be limiting in these mitochondria. Indeed, the addition of propionate to incubations with malate increased intramitochondrial levels of propionyl CoA and 2-methyl-2-pentenoyl CoA and stimulated significant 2-methylvalerate synthesis. The exclusion of air from these incubations further increased levels of 2-methyl-2-pentenoyl CoA and stimulated 2-methylvalerate synthesis. These studies suggest that in addition to elevated NADH/NAD ratios, elevated enoyl CoA/acyl CoA ratios also are important in the regulation of branched-chain fatty acid synthesis in A. suum mitochondria.

Acyl Coenzyme A↗
PubMed1987

Differing electrophysiological effects of class IA, IB and IC antiarrhythmic drugs on guinea-pig sinoatrial node.

Standard microelectrode techniques were used to study the effects of class IA (quinidine, disopyramide, procainamide), IB (lignocaine, mexiletine, tocainide) and IC (flecainide, encainide, lorcainide) antiarrhythmic drugs on action potentials in spontaneously beating sino-atrial node cells from guinea-pigs. The IA drugs all produced significant slowing of spontaneous rate in therapeutic concentrations. The IB agents did so only in concentrations well above therapeutic levels and the IC drugs were of intermediate potency. All nine drugs markedly slowed the repolarization rate and this was the major mechanism of sinus slowing for the IA and IC compounds. The IB drugs shared this effect but prolongation of phase 4 by reduction of the slope of diastolic depolarization was also a prominent feature of their action.

Action Potentials↗
PubMed1984

Effects of diethylstilbestrol on human natural killer cells in vitro.

Exposure of human peripheral blood lymphocytes to diethylstilbestrol (DES) in vitro resulted in inhibition of Natural Killer (NK) cell activity. DES inhibited NK activity in a dose and time-dependent manner with maximal effect after an 18 h exposure time. Significant reduction in cytotoxicity was obtained at concentrations of DES equal to or above 1 microM. The DES-induced inhibition of NK activity was reversible and totally abrogated within 18 h of culture in the absence of DES. Studies at the single cell level revealed that DES impaired the lytic activity of NK cells without interfering with recognition of target cells. The presence of indomethacin or aspirin during exposure to DES completely reversed the DES-induced inhibition of NK activity, indicating that a product of the cyclooxygenase system mediated the suppression.

Cell Line↗
PubMed1981

Treatment of primary breast cancer with chemotherapy and tamoxifen.

We studied the possibility that the addition of tamoxifen to L-phenylalanine mustard combined with 5-fluorouracil enhances the benefit from the latter two drugs that has been observed in women with primary breast cancer and positive axillary nodes. Recurrence of disease was reduced at two years in patients given the three-drug regimen whose tumor estrogen-receptor levels were greater than or equal to 10 fmol. Among patients greater than or equal to 50 years old treatment failure was significantly reduced (P less than 0.001): by 51 per cent in those with one to three positive nodes and by 64 per cent in those with four or more. Higher receptor levels were associated with a greater probability of disease-free survival. Patients less than or equal to 49 years old were less responsive: those with one to three positive nodes received no benefit from tamoxifen at any receptor level, whereas those with four or more appeared to have reduced treatment failure associated with higher receptor levels. This adjuvant chemotherapy is not indicated in patients less than or equal to 49 years old whose tumor receptor levels are below 10 fmol; there is a suggestion of benefit in patients greater than or equal to 50 years old whose levels are low.

Age Factors↗
PubMed1979

Personal identification using dental prostheses.

A personal identity mark may be added to a metal or an acrylic resin prosthesis. The importance of this technique, particularly in terms of forensic investigation and identification, should make it a compulsory dental procedure. Where metal is involved, engraving is the most desirable method of marking. The heat resistance of various labeling materials indicates that an acrylic resin prosthesis should contain a marked, heat resistant material together with a mark clearly visible from the denture surface.

Acrylic Resins↗
PubMed1978

Snake bite in cats.

In 6 years snake bite was diagnosed in 41 cats, with an average age of 20 months. The commonest presenting signs were dilated pupils, absence of the pupillary light reflex, depression and generalised muscle weakness. Other frequent findings were vomiting, dyspnoea, hindlimb ataxia and complete flaccid paralysis. Thirty-seven cases (90%) occurred in the 6 warmer months of the year. Tiger snakes were positively identified in 7 cases. A recovery rate of 89% was obtained in cases receiving 3000 units Tiger snake antivenene, fluid therapy and nursing. Cases presenting with a complete flaccid paralysis and sub-normal temperatures were poor prognostic risks.

Animals↗