Stability of the glycoproteins from a primary human pancreatic carcinoma during cell culture and in vivo passage in nude mice.
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Biomedical subjects
Publications and source records attributed to M J Smith.
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The nucleotide sequence of the proviral genome of Abelson murine leukemia virus (A-MuLV), an acute transforming virus of murine origin, has been determined. Like other transforming viruses, A-MuLV contains sequences derived from its helper virus, Moloney murine leukemia virus (M-MuLV), and a cell-derived protooncogene (abl) insertion sequence. By comparison of the A-MuLV sequence with that of M-MuLV, it was possible to precisely localize and define sequences contributed by the host cellular DNA. From the nucleotide sequence, we have predicted the amino acid sequence of p120gag-abl, the product of the A-MuLV gag-abl hybrid gene. The amino acid sequence of the putative abl gene, when compared with the sequences of other tyrosine-specific protein kinases (src, fes, fps, and yes), revealed significant homologies, indicating that all these functionally related transforming genes are derived from divergent members of the same protooncogene family. In addition to the gag-abl sequence, the proviral genome was found to contain an additional open reading frame that could code for an 18,000-dalton protein, whose role is at present undetermined.
Cyclophosphamide is a well established cytotoxic drug used in the treatment of lymphoproliferative disorders, certain solid tumors, and nonneoplastic disorders such as the nephrotic syndrome, systemic lupus erythematosus, and rheumatoid arthritis. Hemorrhagic cystitis can be a complication of this drug in from 2% to 40% of patients so treated. At times, the hemorrhage may be severe, protracted, and life-threatening. Cyclophosphamide therapy has also been implicated as the causative agent in 32 cases of carcinoma of the bladder and three cases of carcinoma of the renal pelvis.
The effect of pre-eclampsia on selected maternal and neonatal coagulation factors was studied by comparing plasma concentrations in 5 severely pre-eclamptic and 5 normal pregnancies. Pre-eclampsia was associated with appreciably lower maternal values of antithrombin III, plasminogen, and platelet count in late pregnancy but umbilical cord blood values showed no notable differences from normal pregnancy.
Leukotriene B4 (LTB4), generated from arachidonic acid following lipoxygenase activity by a variety of inflammatory leucocytes, has been shown to be present in synovial fluid from patients with active rheumatoid arthritis. It does not persist as such, being converted to less active metabolites. The role of LTB4 as one of the natural mediators of inflammation is discussed.
Mycobacterium xenopi comprised 56% of all non-tuberculous mycobacteria isolated in the Brompton Hospital laboratory during six years. M xenopi alone was cultured from the sputum of 23 patients, whose clinical and bacteriological features are reviewed. Pulmonary disease was considered to be due to the organism present in 15 of these patients on the basis of strict criteria for a causal relationship. Radiographs of all these patients were consistent with mycobacterial disease, showing pulmonary cavitation in 11, apical shadowing in three, and upper lobe fibrosis in one. In nine patients the disease was chronic, progressing very slowly with longstanding respiratory symptoms and extensive radiographic abnormalities developing over many years (mean 19 years). In six patients the disease was subacute, being of recent onset with radiographic shadowing of limited extent. M xenopi was isolated as a saprophyte from four patients who had lung disease of known cause and single isolates were obtained from four patients who had no lung disease attributable to this organism. In vitro drug sensitivity tests showed the sputum cultures of 17 of 22 patients to be sensitive to two or more of the drugs rifampicin, isoniazid, and ethambutol. Response to chemotherapy was unpredictable and did not always correlate with the results of sensitivity tests. Of 11 patients treated with at least two drugs to which their organisms were sensitive, two remained sputum positive, one relapsed after 18 months of chemotherapy, and eight have remained sputum negative during a minimum of three years' follow-up.
Studies of adrenal function were performed on 54 asthmatic patients who were taking long term high doses of inhaled beclomethasone dipropionate ranging from 500 to 2000 micrograms/day for between six and 60 months. Of the 43 patients taking up to 1500 micrograms/day, 39 (91%) had normal basal plasma cortisol concentrations and normal short tetracosactrin responses and 24 hour urinary free cortisol excretion was within the normal range in eight of nine patients tested. Some evidence of adrenal suppression was found in patients taking 2000 micrograms/day, with basal plasma cortisol below the normal range in four out of 11 patients and 24 hour urinary free cortisol excretion below the normal range in five out of six patients tested. Only one of the 11 patients taking 2000 micrograms/day had a short tetracosactrin response below the normal range: the mean rise in plasma cortisol was, however, significantly lower in this group than in those taking 1000 micrograms/day (328 (SE 30) and 506 (34) nmol/l respectively) (p less than 0.01). Patients taking more than 1500 micrograms/day of inhaled beclomethasone may require systemic corticosteroids during prolonged stress.
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Hydroxyurea in a morning dose of 500 mg along with Macrodantin, 100 mg, has been used for more than five years as an adjunct to the management of retained struvite stones. Mild reversible toxicity occurs in 10 per cent. Urine sterility can be achieved in ninety per cent and no growth of the retained stone occurs.
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Leukotriene B4 (LTB4), a metabolite of arachidonic acid and a potent cytotaxin, is generated by human peripheral polymorphonuclear leucocytes (PMNs) exposed to monosodium urate crystals (MSU). The leukotriene is present in gouty effusions in concentrations significantly greater than those found in synovial fluid from patients with active rheumatoid arthritis or osteoarthritis. Further metabolism and biological deactivation of LTB4 by PMNs are partly inhibited by MSU. It is concluded that LTB4 is an important chemical mediator in an acute gouty attack.
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The sequence homology in the single copy DNA of sea stars has been measured. Labeled single copy DNA from Pisaster ochraceus was reannealed with excess genomic DNA from P. brevispinus, Evasterias troschelii, Pycnopodia helianthoides, Solaster stimpsoni, and Dermasterias imbricata. Reassociation reactions were performed under two criteria of salt and temperature. The extent of reassociation and thermal denaturation characteristics of hybrid single copy DNA molecules follow classical taxonomic lines. P. brevispinus DNA contains essentially all of the sequences present in P. ochraceus single copy tracer while Evasterias and Pycnopodia DNAs contain 52% and 46% of such sequences respectively. Reciprocal reassociation reactions with labeled Evasterias single copy DNA confirm the amount and fidelity of the sequence homology. There is a small definite reaction of uncertain homology between P. ochraceus single copy DNA and Solaster or Dermasterias DNA. Similarly Solaster DNA contains sequences homologous to approximately 18% of Dermasterias unique DNA. The thermal denaturation temperatures of heteroduplexes indicate that the genera Pisaster and Evasterias diverged shortly after the divergence of the subfamilies Pycnopodiinae and Asteriinae. The two Pisaster species diverged more recently, probably in the most recent quarter of the interval since the separation of the genera Pisaster and Evasterias.
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Principal component analysis is a powerful method of feature extraction which can be applied to continuous-wave Doppler waveforms. A microprocessor system for the on-line calculation of the coefficients of principal components has been devised and tested in an experimental model. Doppler waveforms were obtained from positions distal to stenoses of known severity implanted in the iliac arteries of three dogs and classified into one of four groups. By reference to data from a previous series of experiments the microprocessor correctly classified 75% of stenoses. The remaining 25% were all classified as being one group more severe than they actually were.