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Biomedical subjects

M Jones

Publications and source records attributed to M Jones.

At least 631 records · Page 35Linked to original sources

Acute and chronic stress in duodenal ulcer disease.

Acute and chronic life event stressors were objectively assessed in a sample of duodenal ulcer patients and community controls. Stress was assessed on two dimensions, "personal threat" and "goal frustration." Chronic stressors (those of 6 months' duration or more) involving high goal frustration were significantly and independently associated with the onset and relapse of duodenal ulcers, as were acute events of high immediate but transient personal threat.

Acute Disease↗

Balloon expandable stent implantation in stenotic right heart valved conduits.

Although valved conduits have been used successfully in severe forms of right ventricular-pulmonary artery discontinuity, progressive valved conduit stenosis is an important clinical problem. To determine the feasibility of reducing right heart valved conduit stenosis with a balloon expandable stent, a baboon model was used, in which the pulmonary artery was ligated and a right ventricular to pulmonary artery 14 mm bioprosthetic Dacron valved conduit implanted. In five baboons, at an average of 40 months after valved conduit implantation, fibrointimal stenosis at the valve site resulted in narrowing and a mean transconduit pressure gradient of 49 mm Hg (range 33 to 65). A tubular slotted steel stent (1.2 cm long) was deployed within the valved conduit after inflation of an 8 to 15 mm diameter balloon catheter that was introduced through the femoral vein. A stent was delivered to all valved conduits; however, in two baboons, balloon undersizing resulted in stent dislodgment. In the remaining three baboons, the transconduit gradient was reduced by 59% (49 to 20 mm Hg) and right ventricular systolic pressure decreased acutely by 35% (77 to 50 mm Hg). It is concluded that stent deployment is feasible in right ventricular to pulmonary artery stenotic valved conduits and may result in significant hemodynamic improvement. However, successful stent delivery is critically dependent on the proper selection of stent length and balloon diameter.

Animals↗

Total synthesis of the four stereoisomers of dihexadecanoyl phosphatidylinositol and the substrate stereospecificity of human erythrocyte membrane phosphatidylinositol 4-kinase.

A new and convenient method for the preparation of the four stereoisomers of dihexadecanoyl phosphatidylinositol has been developed. An enantiomeric pair of acid-labile, pentaprotected myo-inositol building blocks was synthesized in high yield and coupled with chiral phenyl dihexadecanoylglyceryl phosphates to give the fully protected phosphatidylinositols. These were subsequently deprotected by hydrogenolysis and self-hydrolysis in aqueous ethanol to give the desired pure products. Comparison of these compounds as potential substrates for a partially purified phosphatidylinositol 4-kinase (EC 2.7.1.67) derived from human erythrocyte membranes revealed that the chirality of the inositol ring is crucial for efficient phosphorylation, whereas the chirality of the glycerol moiety is relatively unimportant. Moreover, the similarity in phosphorylation rates of the naturally occurring mammalian phospholipid, I, and its synthetic stereochemical counterpart, compound 10a, suggests that the enzyme is relatively tolerant to changes in fatty acid composition.

1-Phosphatidylinositol 4-Kinase↗

Purine derivatives as competitive inhibitors of human erythrocyte membrane phosphatidylinositol 4-kinase.

The possibility of deriving a potent, cell-penetrating inhibitor of human erythrocyte PI 4-kinase, competitive with respect to ATP, has been investigated in a series of purine derivatives and analogues. The purine nucleus is not essential for binding to the ATP site but offers the advantage of synthetic accessibility to its derivatives. The optimum substitution pattern in purine was found to be an electron-releasing substituent in the 6-position (e.g. amino, as in adenine, 1) and a compact, lipophilic group in either the 8-position or, preferably, the 9-position, suggesting the importance of the N-1 lone pair and hydrophobic contributions of the 8- and 9-substituents to binding. The most potent inhibitor synthesized was 9-cyclohexyladenine (54), which has an apparent Ki value of 3.7 microM.

1-Phosphatidylinositol 4-Kinase↗

Is group psychotherapy feasible for oncology outpatients attenders selected on the basis of psychological morbidity?

Of 120 consecutive attenders at an oncology outpatients department, 108 were screened for psychological symptoms using the Hospital Anxiety and Depression Scale (Zigmond & Snaith, 1983). Thirty-nine patients had significant scores indicating moderate anxiety and/or depression. We felt that this warranted an offer of group psychotherapy in the belief that sharing issues and exploring personal concerns may alleviate some of the experienced psychological distress. Only 10 patients consented to and were able to attend this group, with which five patients persisted. Thus in this group of patients with advanced cancer group psychotherapy was applicable only to a limited number of selected patients. The nature of this study and the size of the population markedly limited our ability to comment on the usefulness of group psychotherapy. Many patients, particularly the most severely psychologically distressed, continued to require other forms of support, particularly domiciliary individual therapy.

Aged↗

The establishment, characterization and calibration of human ovarian carcinoma xenografts for the evaluation of novel platinum anticancer drugs.

Twenty-three serially transplantable ovarian carcinoma xenografts have been established in female nude mice from forty-two donor samples provided by both previously treated and untreated patients. The lines are all of human karyotype and mirror the histopathology of the original explant. Sixteen examples have been calibrated against four reference platinum drugs: cisplatin, carboplatin, iproplatin, tetraplatin. Three distinct patterns of response were observed: (i) tumours which were comparably sensitive to all four drugs (2 lines); (ii) tumours which were comparably refractory to treatment with all four drugs (5 lines); (iii) tumours which exhibited "individual" patterns of response to the group of calibrating drugs (9 lines). The "response rate" overall of the tumour panel to each of the clinically used drugs was 44% (7/16), though the pattern of response was not identical for each drug. Only 2/16 tumours (13%) were sensitive to tetraplatin, these also being the same tumours which were particularly sensitive to the other three drugs. It was also possible to confirm in 8/9 lines that the therapeutic response of the xenograft reflected that of the corresponding patient's tumour to platinum-based chemotherapy. This tumour panel has now been adopted for evaluating novel platinum-based drugs designed specifically for the treatment of ovarian cancer.

Animals↗

The cycling of combination antirheumatic drug therapy in rheumatoid arthritis.

In this open pilot study a combination of hydroxychloroquine, prednisolone and alternating months of treatment with sulphasalazine or oral weekly pulse methotrexate has been investigated in 16 patients with rheumatoid arthritis (RA) refractory to a total of 67 disease suppressive medications. Results at 3 months indicated significant improvements in visual analogue score for pain, joint count, Ritchie index, scale of disability related to activities of daily living, ESR, rheumatoid factor and C-reactive protein. This degree of improvement, however, was not maintained 6 and 12 months after commencement of treatment. Pain score, Ritchie index and ESR were the only parameters demonstrating significant improvement at 12 months. Therapy was terminated in eight patients, half due to lack of efficacy and half because of side effects.

Activities of Daily Living↗

Analysis of complications in 168 pectoralis major myocutaneous flaps used for head and neck reconstruction.

One hundred sixty-eight pectoralis major muscular and myocutaneous flaps performed at the University of Texas M. D. Anderson Cancer Center during the past five years were reviewed retrospectively to determine complication rates following operation and to evaluate the effect of risk factors such as smoking, obesity, sex, previous radiotherapy, and tumor stage on the incidence of such complications. The overall rate of complications was 63%; however, most of these complications were self-limited, and the rate of total flap loss was only 2.4%. The risk of a complication developing was increased slightly in patients who smoked cigarettes and in patients with larger tumors. Obesity and previous radiotherapy had no effect on complication rates. Women who underwent pectoralis major myocutaneous flaps had a higher rate of flap necrosis than did men, presumably because of the interposition of breast tissue between the muscle and the skin paddle. In patients who had muscle flaps (without skin paddles), sex had no influence on complication rates. In all groups of patients, flaps consisting of muscle alone had fewer complications than did flaps with a cutaneous component.

Female↗

What rate of infusion of intravenous nutrition solution is required to stimulate uptake of amino acids by peripheral tissues in depleted patients?

We examined the effect of varying the quantities (0, 0.1, 0.2, 0.3, and 0.4 gN.kg-1.[day]-1) of nitrogen input on N balance, 3-methylhistidine (3MH) excretion, plasma amino acid concentration and the net flux of amino acids across the leg in depleted patients requiring parenteral nutrition. The calorie-to-nitrogen ratio was 140 to 1 (kcal:1 gN) and consequently the patients received varying amounts of calories (8, 14, 28, 42, and 56 kcal.kg-1.[day]-10. There was negative nitrogen balance and net loss of amino acids from the limb during fasting. An infusion of 0.2 gN.kg-1.[day]-1 of IVN reversed the net catabolic process and resulted in equilibrium of peripheral total amino acid flux and of tyrosine flux without a decrease in 3MH excretion. Net uptake of total amino acids and tyrosine in peripheral tissues was achieved with 0.4 gN.kg-1.[day]-1 and 56 kcal.kg-1.[day]-1. This was associated with a fivefold increase in 3MH excretion (p less than 0.01), indicating that net anabolism occurred with increased protein turnover. Fifty per cent of the amino acids taken up by peripheral tissues during infusions of 0.4 gN.kg-1.[day]-1 was due to the uptake of glutamate (Glu) and 20% was due to the uptake of branched chain amino acids (BCAA). Plasma Glu concentration, [Glu], did not increase with increasing IVN infusion, but BCAA concentrations did. Although the mean plasma [Glu] did not change with IVN infusion, there was an independent effect of plasma [Glu] (p less than 0.0001) and of N input (p less than 0.0001) on Glu flux, indicating that even at high infusion rates the maximal capacity of peripheral tissues to take up Glu had not been reached.

Amino Acids↗

Megakaryocytes in myelodysplasia: an immunohistochemical study on bone marrow trephines.

Megakaryocytes in 63 bone marrow trephine biopsies were examined for their staining characteristics, location and size distribution using the monoclonal antibody Y2/51 directed against platelet glycoprotein IIIa (CD61). Megakaryocytes in normal bone marrow were evenly distributed and demonstrated homogeneous staining with Y2/51. In addition, there was little variation in their size or shape. In contrast, myelodysplastic and myeloproliferative bone marrow trephines showed considerable dysmegakaryopoiesis demonstrated by heterogeneity of staining, an altered architectural distribution with a predominantly paratrabecular location and considerable variation in size and shape. Furthermore, in myelodysplasia 25% of the CD61 positive cells were micromegakaryocytes as opposed to less than 10% in normal or reactive marrows. Such dysmegakaryopoiesis is believed to be a clinically important feature of myelodysplasia, although until now it has only been possible to assess it subjectively. The availability of the monoclonal antibody Y2/51 provides a rapid and reproducible means of studying megakaryocyte size, shape and distribution in routine trephine specimens and may help to overcome some of the diagnostic problems currently associated with myelodysplasia and other intrinsic bone marrow neoplasias.

Antibodies, Monoclonal↗

Autoantibody and idiotype profile of lung involvement in autoimmune rheumatic disease.

Several reports have linked the presence of certain serum autoantibodies with particular clinical manifestations of autoimmune disease. For example, the Jo-1 antibody is now established as a marker for fibrosing alveolitis in polymyositis. To investigate the possible association of further autoantibodies or idiotypes with fibrosing alveolitis in autoimmune rheumatic disease a panel of autoantibodies was measured in serum samples from 28 patients with systemic lupus erythematosus (SLE) (10 with and 18 without lung involvement), 21 patients with scleroderma (12 with fibrosing alveolitis and nine without), and 41 patients with 'lone' fibrosing alveolitis. Antibodies measured were IgM and IgG anti-dsDNA and anti-ssDNA antibody; IgG and IgM anticardiolipin antibody; anti-poly (ADP-ribose) antibody; antibodies to two common idiotypes of anti-DNA antibodies, designated 134 and 16/6; and IgM, IgG, and IgA isotypes of rheumatoid factor. None of these antibodies was specifically associated with lung involvement in SLE or scleroderma, but a trend was found towards an increase in all autoantibodies in association with lung disease in SLE, while the reverse trend was seen in scleroderma.

Antibodies, Antinuclear↗

A prospective study of principal care among Colorado neurologists.

We initially surveyed the practice patterns of 24 private sector neurologists in Colorado between June and September, 1985, having chosen representative practices from each of 4 practice types (solo [6], nonsolo single discipline [11], nonsolo multispecialty [4], and nonsolo HMO [3]) and from both urban (14) and rural (10) practice locations. Among 2,373 consecutive new patient visits initially surveyed, we reexamined 2,359 (99%) charts 1 year later to investigate patterns of principal care. We defined principal care as 2 or more follow-up visits in the year following the initial office visit. One-fifth of initial visits received principal care, and the mean number of follow-up visits per year among those receiving principal care was 4 (range, 2 to 32 visits). The best indicators of principal care were Medicare coverage, a classic neurologic diagnosis (seizure, stroke), rural practice location, and solo neurology practice. The best indicators of consultative care were self-pay coverage, a diagnosis of musculoskeletal, psychiatric, or pain disorder, urban practice location, and HMO neurology practice. Age, sex, race, and type of referring physician were unimportant in determining subsequent principal care. Projections of future manpower needs must reflect both consultative as well as principal care services provided by neurologists, as well as the cost-effectiveness of such care.

Adult↗

Immunization of ovariectomized ewes against progesterone, oestrogen or cortisol to detect effects of adrenal steroids on reproduction.

Ovariectomized ewes were immunized against cortisol, oestrogen or progesterone to determine whether steroids of non-ovarian origin occur in sufficient amounts to influence the reproductive system. Ewes immunized against oestrogen (oestrone + oestradiol) had smaller uteri (P less than 0.05) and a lower concentration of oestradiol in uterine tissue (P less than 0.05), while the adrenal gland was heavier (P less than 0.05). In the peripheral plasma of immunized ewes, the concentration of FSH, but not LH, was increased (P less than 0.05). Ewes immunized against cortisol also had smaller uteri (P less than 0.05) and heavier adrenal glands (P less than 0.05), but gonadotrophins and the concentration of oestradiol in the uterus were unaffected. Immunization against progesterone, or injection with synthetic glucocorticoids, did not affect any of the characteristics measured. We conclude that the adrenal gland of the ewes produced sufficient oestrogen or aromatizable androgen to have significant effects on the reproductive system. In contrast, adrenal production of progesterone did not produce detectable biological effects. Immunization against cortisol did affect the reproductive system, but the mechanism of this action could not be determined.

Adrenal Glands↗

Activation of human monocytes occurs on cross-linking monocytic antigens to an Fc receptor.

Murine mAb to CD13, CD14, and class II MHC, are able to mobilize calcium in normal human monocytes and enhance superoxide production in primed cells. Antibodies to CD35 (CR1) also cause a minor calcium response in some individuals. Antibodies to CD11a, CD11b, CD11c, CD15, CD17, CD18, and CD45 do not activate monocytes. The ability of mAb to cause monocyte activation is not only dependent on the Ag with which they react but also on the isotype of the antibodies and the individual from whom the monocytes were obtained. It is shown that this is because the mAb that activate monocytes do so by formation of Ag-antibody-FcR complexes. F(ab')2 fragments of mAb to CD13 and CD14 do not therefore activate monocytes even when cross-linked with F(ab')2 anti-mouse Ig but do so when cross-linked with intact anti-mouse Ig. These data indicate that activation via the FcR requires perturbation of this receptor but does not necessarily require cross-linking of one FcR to another. Antibody-coated particles or cells able to bind to cell surface receptors on monocytes other than the FcR would thus augment FcR-mediated activation.

Antibodies, Monoclonal↗