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Biomedical subjects

S Kennedy

Publications and source records attributed to S Kennedy.

At least 253 records · Page 14Linked to original sources

Psychological stress-induced modulation of interleukin 2 receptor gene expression and interleukin 2 production in peripheral blood leukocytes.

We explored the expression of the interleukin 2 receptor (IL-2R) and the synthesis of IL-2R messenger RNA by peripheral blood leukocytes obtained from medical students experiencing examination stress in three independent studies. The peripheral blood leukocytes obtained at low-stress baseline periods had significantly higher percentages of IL-2R-positive cells when compared with cells obtained from the same individuals during examinations. In addition, IL2-R messenger RNA in peripheral blood leukocytes decreased significantly during examination periods in a subset of 13 subjects. In one study, we found an increase in the accumulation of interleukin 2 in cultures of cells showing down regulation of IL-2R expression and IL-2R messenger RNA levels. While there are ample data demonstrating stress-associated decrements in the immune response in humans and animals, these data provide the first evidence that this interaction may be observed at the level of gene expression. The data suggest one mechanism whereby the central nervous system modulates the immune response during psychological stress.

Adult↗

A new high performance liquid chromatographic method for the simultaneous measurement of S-adenosylmethionine and S-adenosylhomocysteine. Concentrations in pig tissues after inactivation of methionine synthase by nitrous oxide.

A rapid gradient method has been established to measure simultaneously the tissue levels of S-adenosylmethionine (AdoMet) and S-adenosylhomocysteine (AdoHcy). The method involves application of a 15%-25% linear gradient of methanol over a period of 10 min to an initial mobile phase of 15% methanol with 25 mM sodium phosphate, 10 mM 1-heptanesulfonic acid solution at pH 3.2 and a flow rate of 1 mL/min. AdoHcy elutes at 9.5 min and AdoMet at 12.6 min. The assay has a detection limit of 10 pmol and is linear in the concentration range 30-800 pmol. The method was used to assess changes in AdoMet and AdoHcy concentrations of pig tissues after seven days exposure to the anaesthetic gas nitrous oxide which irreversibly inactivates methionine synthase and induces an inability to recycle homocysteine, particularly in neural tissues. The treatment caused significant alterations in cellular AdoMet:AdoHcy ratios which were principally due to a dramatic rise in AdoHcy concentrations.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗

Psychophysiological assessment of male sexual arousal following spinal cord injury.

Adult males with and without permanent damage to the spinal cord were contrasted in terms of their sexual responsiveness to erotic stimulation in film, spoken-text, and fantasy modes. Among the 16 spinal cord injured (SCI) men who were studied, several who had anticipated they would achieve erection failed to do so, whereas others demonstrated penile tumescence during erotic stimulation despite claiming they had lost the capacity for psychogenic erection. Self-report is thus not a valid index of sexual responsivity following spinal cord injury. Levels of tumescence varied across modalities of stimulation in the same manner for SCI and non-SCI men, and within each modality the two groups demonstrated similar rates of buildup of arousal over segments of stimulation. The SCI men without erections should not be considered asexual since their subjective arousal paralleled the subjective arousal of the non-SCI men and the SCI men with erections.

Adult↗

The effects of hormonal and chemotherapy on tumoral and nonneoplastic breast tissue.

One hundred four sequential pretherapy and posttherapy breast tissue specimens from 57 patients with locally advanced and metastatic breast cancer were evaluated in an attempt to define the effects of systemic chemotherapeutic agents on the tumors and residual nonneoplastic breast tissue. The patients were treated uniformly at the National Cancer Institute on an experimental protocol combining systemic chemotherapy with attempted hormonal synchronization. Tumors were sampled prior to and following several cycles of chemotherapy to a maximum objective clinical response (average number of cycles, 7). In 38 cases, the posttreatment biopsy was positive for tumor. The most striking histologic change was extreme vacuolization of tumor cells that often resembled histiocytes. Atrophy of the terminal duct lobular unit (TDLU) and atypia of epithelial cells in TDLU and large ducts were also seen. Severe degrees of epithelial atypia occasionally proved to be difficult to distinguish from residual intraductal carcinoma. Breast biopsies were stained with antibodies to cytokeratin, epithelial membrane antigen (EMA), B72.3, lactalbumin, and SP1 using immunoperoxidase techniques. The number of cases showing immunoreactivity with antibodies to cytokeratin, EMA, and B72.3 remained approximately the same before and after therapy, while SP1 expression decreased and lactalbumin expression increased after therapy. Recognition of chemotherapeutic changes in breast tissue is important since systemic chemotherapy plays an important role in the management of breast cancer.

Adenocarcinoma, Mucinous↗

Sensitivity and specificity of PC20 and peak expiratory flow rate in cedar asthma.

The diagnosis of red cedar asthma is usually confirmed by a specific challenge with plicatic acid, the compound responsible for the disease. We performed this study to determine the sensitivity and specificity of two other diagnostic tests, prolonged recording expiratory flow rate (PEFR) and measurement of bronchial responsiveness (provocative dose of methacholine causing a 20% fall in FEV1 [PC20 methacholine]). Twenty-three patients with suspected cedar asthma participated in the study. The patients recorded PEFR during 2 weeks away from work and 3 weeks at work. PC20 was measured both at the end of the nonworking and working period. An obvious decrease in PEFR in 2 of 3 working weeks, when PEFRs of weekends or holidays were compared (by visual inspection of the PEFR recording), and a decrease in PC20 by more than a twofold dilution, when the patient returned to work, were considered as positive tests for cedar asthma. Plicatic acid challenge test was performed at the end of the study; 14 patients reacted, whereas nine patients did not. With the results of the plicatic acid challenge test as the gold standard, the sensitivity and specificity of PEFR recordings were 86% and 89%; changes in PC20, 62% and 78%; and 93% and 45% for a positive clinical history. The combination of PEFR and clinical history revealed a 100% sensitivity with a 45% specificity. Combination of PEFR and PC20 did not improve the diagnostic accuracy.(ABSTRACT TRUNCATED AT 250 WORDS)

Allergens↗

Psychological stress and phorbol ester inhibition of radiation-induced apoptosis in human peripheral blood leukocytes.

Apoptosis is a process of genetically programmed alterations of cell structure that lead to failure of proliferation and differentiation, and eventual cell death. Apoptosis is induced by a variety of toxic insults including growth factor deprivation and ionizing radiation. This process may function to protect against the appearance of heritable phenotypic changes in cells and may be a critical factor in normal cellular immune function. Phorbol esters inhibit apoptosis, but little is known about factors that regulate this process physiologically. In this study, we demonstrate an association between an acute psychological stressor, taking examinations, and the induction of substantial and reversible changes in the response of peripheral blood leukocytes to gamma irradiation and to phorbol ester treatment. These data suggest that psychological stress may induce physiological changes that regulate the ability of immune cells to initiate apoptosis.

Adult↗

Methylmalonyl-CoA mutase (EC 5.4.99.2) and methionine synthetase (EC 2.1.1.13) in the tissues of cobalt-vitamin B12 deficient sheep.

The changes in the activities of the two vitamin B12-dependent enzymes methylmalonyl-CoA mutase (EC 5.4.99.2) and methionine synthetase (5-methyltetrahydrofolate-homocysteine methyltransferase, EC 2.1.1.13) are described in two groups of sheep maintained for 20 weeks on either a cobalt-deficient or a Co-sufficient whole-barley diet. At the end of that period, the plasma concentrations of vitamin B12 were depressed and those of methylmalonic acid were raised in the Co-deficient group. During the course of the experiment hepatic holo-mutase activity, measured on biopsy samples, declined in Co-deficient animals with a half-life of 73 d. There was a similar, but slower decline in lymphocyte holo-mutase activity which fell with a half-life of 125 d. At slaughter, there was no difference between Co-sufficient and Co-deficient animals in total mutase activity in liver, kidney, brain and spinal cord. In contrast, the total-synthetase activity of liver and kidney was reduced by 60 and 30% respectively in the Co-deficient animals. There was no change in either group of animals in total-synthetase activity, or in either holo-mutase or holo-synthetase activity, in brain and spinal cord. In the Co-deficient animals, holo-mutase and holo-synthetase activities in liver, the tissue with the greatest activity of both enzymes, fell to 25 and 39% respectively, of that of Co-sufficient animals. The corresponding reductions for kidney were 12 and 51% respectively. These results indicated that activity of both holoenzymes is greatly reduced in Co-deficient sheep.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗

Binding affinity for penicillin-binding protein 2a correlates with in vivo activity of beta-lactam antibiotics against methicillin-resistant Staphylococcus aureus.

The beta-lactam antibiotics ticarcillin, nafcillin, imipenem, and ampicillin, which differ in antibacterial activity against methicillin-resistant strains of Staphylococcus aureus, were examined for affinity to penicillin-binding protein (PBP) 2a, which mediates methicillin resistance. The relative efficacy of each antibiotic was compared to vancomycin in a rabbit model of aortic valve endocarditis caused by either a methicillin-susceptible or methicillin-resistant strain of beta-lactamase-producing S. aureus. beta-lactamase inhibitors clavulanate and sulbactam were used in combination with ticarcillin and ampicillin, respectively. All beta-lactam antibiotics were effective against the susceptible strain. beta-lactam antibiotic activity in vitro and in vivo against the resistant strain correlated with its affinity for binding to PBP 2a. Lack of efficacy of beta-lactam antibiotics for the resistant strain was due to an inability to eradicate the resistant subpopulation of cells. Vancomycin was the most effective agent.

Acyltransferases↗

Effects of dosage, peak and trough concentrations in serum, protein binding, and bactericidal rate on efficacy of teicoplanin in a rabbit model of endocarditis.

The effect of dosage and the relative importance of peak and trough concentrations in serum for efficacy of teicoplanin were examined in a rabbit model of aortic valve endocarditis. Concentrations of teicoplanin in serum exceeded the MIC by several hundredfold, yet teicoplanin was less rapidly bactericidal than penicillin both in vitro and for endocarditis caused by a strain of Streptococcus sanguis. Because teicoplanin was 90% protein bound in rabbit serum, low free-drug concentrations probably resulted in less activity in vivo than in vitro. Because teicoplanin has a relatively low bactericidal rate and a high degree of protein binding, a sustained concentration in serum several times greater than the MIC may be important for efficacy in vivo. An intravenous regimen with relatively high peak concentrations in serum was less effective than an intramuscular regimen for endocarditis caused by a strain of Staphylococcus aureus, indicating that high peaks are unlikely to be an important determinant of efficacy. The therapeutically more relevant concentration in serum may be the trough.

Animals↗

Outcome of patients with cedar asthma with continuous exposure.

After an average follow-up of 6.5 yr (range 1 to 13), 48 of 48 patients with cedar asthma, who were still working in the same industry, were re-examined. In all of them, the diagnosis of cedar asthma had been confirmed with a specific challenge inhalation test with plicatic acid. We graded the severity of asthma symptoms and the requirement for antiasthma medications at the time of diagnosis and at the time of follow-up visit. Spirometry and measurement of airway responsiveness to methacholine (PC20 methacholine) were also done on both visits. The increase or decrease in asthma symptoms, medications requirement, FEV1 and PC20 methacholine between the follow-up and the diagnostic visit were used to determine the outcome of the patients. Using these parameters, 10.4% of patients improved, 62.5% remained stable, 37.5% deteriorated, and none recovered. Among the characteristics of the patients observed at the time of diagnosis, the age of the patient, the atopic status, smoking habit, and the presence of specific IgE to plicatic acid were not useful in predicting the eventual outcome. Reduction of exposure by transfer to a less dusty job and the use of an airstream helmet did not prevent deterioration of asthma. Only the use of the twin-cartridge respirator was associated with a favorable outcome. We conclude that among cedar asthmatics who remained exposed to cedar dust for an average of 6.5 yr, over one-third showed marked deterioration of their asthma symptoms. There is also no way to predict who will deteriorate. A decrease in the amount of exposure to cedar dust does not prevent deterioration of asthma. This suggests that the ideal management of cedar asthma is removal from exposure.

Allergens↗

Humoral immune responses in seals infected by phocine distemper virus.

Recently the isolation and characterisation of a morbillivirus which caused high mortality in common seals (Phoca vitulina) in 1988 have been reported. Because of the clinical and pathological similarity of the disease in seals to that of distemper in dogs, the name phocine distemper virus (PDV) has been proposed. There are marked differences in the virus-induced proteins of PDV compared to other morbilliviruses and the humoral immune response of moribund and dead seals to PDV was restricted to some of the internal antigens of PDV, similar to the response described earlier for canine distemper virus infection in dogs.

Animals↗

Daptomycin (LY146032) for prevention and treatment of experimental aortic valve endocarditis in rabbits.

The efficacy of daptomycin (LY146032), a vancomycinlike lipopeptide antibiotic, was compared with that of antibiotics commonly in use for prevention and treatment of experimental aortic valve endocarditis in rabbits. Strains of Staphylococcus aureus. S. epidermidis, Streptococcus sanguis, and Enterococcus faecalis were used to establish endocarditis. A single 10-mg/kg dose of daptomycin and a single 25-mg/kg dose of vancomycin were both effective in prevention of endocarditis produced by strains of S. aureus and S. sanguis. Daptomycin was more effective than vancomycin for prevention of endocarditis caused by the strain of S. epidermidis. A single dose of daptomycin also was more effective in prevention of staphylococcal and enterococcal endocarditis than were single-dose regimens of cefazolin (100 mg/kg) and the combination of ampicillin (30 mg/kg) plus gentamicin (3 mg/kg), respectively. For treatment of endocarditis, daptomycin (10 mg/kg) as a single daily dose was as effective as regimens of either vancomycin or beta-lactam antibiotics for staphylococcal and enterococcal endocarditis. Daptomycin, however, was not as effective as a single daily dose of 600,000 U of procaine penicillin for endocarditis caused by the strain of S. sanguis.

Animals↗

Histopathologic and immunocytochemical studies of distemper in seals.

Thousands of harbor seals (Phoca vitulina) died in European seas during 1988. Respiratory distress and oculonasal discharge were common clinical signs. We necropsied 76 affected seals. The main necropsy finding was severe pneumonia. Microscopic lung changes were characterized by proliferation of type II pneumocytes, filling of alveolar lumina with serofibrinous exudate, leukocytes, and macrophages, and necrosis of bronchial and bronchiolar epithelium. Intracytoplasmic and intranuclear acidophilic inclusion bodies characteristic of morbillivirus infection were seen in bronchial and bronchiolar epithelial cells. Microscopic lesions of non-suppurative demyelinating encephalitis were seen in the brain. There was degeneration and necrosis of neurons, focal gliosis, perivascular cuffing, and patchy demyelination. Many neurons and astrocytes contained intracytoplasmic and intranuclear inclusions. Using an immunoperoxidase technique, we detected morbillivirus antigen in many tissues including lung, brain, spleen, and urinary bladder. The origin of the seal morbillivirus is unknown.

Animals↗