Showing papers by "Jewish Hospital published in 1991"

Effect of surgical menopause and estrogen replacement on cytokine release from human blood mononuclear cells.

Abstract: To determine whether mononuclear cell secretory products contribute to the changes in bone turnover that characterize the development of postmenopausal osteoporosis, we evaluated the effects of oophorectomy and subsequent estrogen replacement on the spontaneous secretion of interleukin 1 (IL-1) and tumor necrosis factor alpha (TNF-alpha) and on the phytohemagglutinin A-induced secretion of granulocyte-macrophage colony-stimulating factor (GM-CSF) from peripheral blood mononuclear cells. In 15 healthy premenopausal women who underwent oophorectomy, increases in GM-CSF activity were observed as early as 1 week after surgery, whereas elevations in IL-1 and TNF-alpha and in hydroxyproline/creatinine and calcium/creatinine ratios, two urinary indices of bone resorption, were detectable 2 weeks after the surgical procedure. Six of the oophorectomized women received no estrogen therapy after surgery and in these subjects hydroxyproline/creatinine and calcium/creatinine ratios plateaued 6 weeks postoperatively, and all three cytokines reached the highest levels 8 weeks after oophorectomy, when the study ended. In the remaining 9 women, who were started on estrogen replacement therapy 4 weeks after oophorectomy, decreases in the indices of bone resorption paralleled decreases in the secretion of the cytokines, with lower levels detected after 2 weeks of therapy. In the women who did not receive estrogen therapy, circulating osteocalcin, a marker of bone formation, increased beyond preoperative levels 8 weeks after oophorectomy, whereas in the estrogen-treated subjects osteocalcin remained unchanged in the entire study period. In 9 female controls who underwent simple hysterectomy, cytokine release and biochemical indices of bone turnover did not change after surgery. These data indicate that changes in estrogen status in vivo are associated with the secretion of mononuclear cell immune factors in vitro and suggest that alterations in the local production of bone-acting cytokines may underlie changes in bone turnover caused by surgically induced menopause and estrogen replacement.

Usefulness of systolic excursion of the mitral anulus as an index of left ventricular systolic function.

Abstract: Studies in both humans and nonhuman animals show that the mitral anulus changes its size, shape and position during the cardiac cycle. 1–3 Left ventricular (LV) contraction results in shortening along both the short and long axis of the left ventricle. With each systole, the mitral anulus moves toward the apex in a cephalocaudal direction. 1–3 It has also been observed that the displacement of the mitral anulus during the systole is reduced with dilated cardiomyopathy. 4 We examined the relation between the amount of systolic excursion of the mitral anulus and LV systolic function as measured by radionuclide ventriculography and a variety of echocardiographic techniques.

Relationships of Serum Plant Sterols (Phytosterols) and Cholesterol in 595 Hypercholesterolemic Subjects, and Familial Aggregation of Phytosterols, Cholesterol, and Premature Coronary Heart Disease in Hyperphytosterolemic Probands and Their First-Degree Relatives

Abstract: To assess relationships of serum phytosterols (plant sterols [P]) to serum cholesterol (C), P were measured by gas-liquid chromatography (GLC) in 595 hypercholesterolemics (top C quintile in screening of 3,472 self-referred subjects). A second specific aim was to determine whether high serum P would track over time and whether they would predict familial aggregation of high C, high low-density lipoprotein cholesterol (LDLC), high apolipoprotein (apo) B, and increased premature coronary heart disease (CHD) in hyperphytosterolemic probands and their first-degree relatives. Mean +/- (SD) C was 260 +/- 56 mg/dL, campesterol (CAMP) was 2.10 +/- 1.6 micrograms/mL, stigmasterol (STIG) 1.71 +/- 1.67, sitosterol (SIT) 2.98 +/- 1.61, and total P 6.79 +/- 3.66 micrograms/mL. Serum C correlated with CAMP (r = .15, P less than or equal to .001), STIG (r = .10, P less than or equal to .02), SIT (r = .34, P less than or equal to .0001), and total P (r = .29, P less than or equal to .0001). High serum CAMP and STIG were associated with a personal or family history of CHD in subjects less than or equal to age 55 years (premature CHD). In 21 hyperphytosterolemic probands who initially had at least one P at or above the 95th percentile and a second P at or above the 75th percentile, P were remeasured 2 years later. Initial and 2-year follow-up CAMP, STIG, and SIT did not differ (P greater than .7). Initial and follow-up CAMP were correlated (r = .47, P = .03).(ABSTRACT TRUNCATED AT 250 WORDS)

Stress-related activation of Epstein-Barr virus

Abstract: Herpesviruses characteristically persist in a latent state in the body over the lifetime of an individual. Under certain conditions, any one of the herpesviruses can be reactivated. The mechanisms underlying the establishment of latent virus infection or viral reactivation are not well understood; however, it is known that the cellular immune response plays a very important role in the maintenance of latency and in virus reactivation. One of the factors thought to be associated with the reactivation of latent herpes-viruses is psychological stress. Using an examination stress model with medical student subjects, we previously demonstrated the reactivation of latent Epstein-Barr virus (EBV), as measured by increases in antibody titers. In this follow-up study using the same group of medical students, we found evidence for incomplete reactivation of latent EBV, with only selective expression of the latent virus genome.

Cerebral Oxygen Metabolism after Aneurysmal Subarachnoid Hemorrhage

Abstract: Previous studies of cerebral oxygen metabolism and extraction in patients with subarachnoid hemorrhage (SAH) have yielded conflicting results. We used positron emission tomography (PET) to measure ...

Hypophosphatasia and the extracellular metabolism of inorganic pyrophosphate: clinical and laboratory aspects.

Abstract: Hypophosphatasia is a rare inherited disorder in which the activity of the bone/liver/kidney or tissue nonspecific form of alkaline phosphatase (ALP) is reduced. The clinical expression of the disease is highly variable, but in early life the severity tends to reflect the age of onset. Accordingly, the disease is often classified into perinatal, infantile, and childhood forms. Hypophosphatasia also occurs in adults. Some exhibit symptoms in adulthood for the first time, but others have a history of the disease in early life with an intervening symptom-free period. Defective mineralization of bones and teeth is the predominant clinical feature of all forms of the disease. Biochemically, the reduction in ALP activity is associated with alterations in the extracellular metabolism of various phosphorylated compounds, including inorganic pyrophosphate (PPi), phosphoethanolamine, and pyridoxal 5'-phosphate. Of these, PPi may have an especially important role in the development of the mineralization defect. Accordingly, the extracellular metabolism of PPi and its possible role in the regulation of mineralization will be discussed.

Interleukin 4 inhibits murine osteoclast formation in vitro.

Abstract: Interleukin 4 (IL-4) is a product of activated T cells and mast cells with effects on immunologic and hematopoietic processes We now report that IL-4 inhibits the formation of osteoclasts from murine bone marrow cells cocultured with stromal cells Numerous (3,000-4,000 cells/2 cm2) tartrate-resistant acid-phosphatase-positive multinucleated cells with the capacity to generate cAMP in response to salmon calcitonin (ED50 = 10(-10) M) developed within 10-12 days of culture IL-4 (ID50 = 10 U/ml) inhibited osteoclast generation in doses similar to those that induce proliferation of IL-4-responsive T cells Additionally, the rat antimurine IL-4 monoclonal antibody 11B11 antagonizes the IL-4-inhibitory effect on osteoclast formation These results suggest that IL-4 impedes agonist-induced in vitro bone resorption by inhibiting osteoclastogenesis

The risk factors of median sternotomy infection: a current review.

Abstract: Sternal sepsis following median sternotomy is an infrequent yet devastating complication of cardiac surgery, leading to prolonged hospitalization, increased hospital expense, and a high associated morbidity and mortality. The development of sternotomy infection is multi-factorial. Numerous prospective and retrospective studies have pointed to a multitude of clinical and perioperative variables as being causative, with as many other studies presenting evidence to the contrary. This has led to confusion about which clinical variables should be modified so as to minimize the individual patient's risk for developing this severe complication. Other less obvious factors also come into play. Malnutrition, whether overt or subclinical, is not uncommon in cardiac patients. Immune competency is affected by operative trauma, as well as a variety of perioperative factors including underlying nutritional status, transfusion, cardiopulmonary bypass, and anesthesia. This creates a complex milieu for the development of postoperative infection. In this review, the multiple risk factors of median sternotomy infection are studied and treatment options briefly discussed.

A new method for assessment of cultured cardiac myocyte contractility detects immune factor-mediated inhibition of beta-adrenergic responses.

Abstract: BACKGROUND Potentially reversible congestive heart failure accompanies disease states associated with an immune cell myocardial infiltrate such as cardiac allograft rejection and inflammatory myocarditis. We therefore examined the hypothesis that immune cells can produce noncytotoxic alterations in cardiac function. METHODS AND RESULTS A novel system to evaluate cultured cardiac myocyte contractility was developed using neonatal rat cardiocytes grown on human amniotic membrane segments. Spontaneous synchronous cell beating produced macroscopic distortion of these membranes. Movement of free-floating membranes anchored within a perfusion chamber was visualized under low-power microscopy and measured from recordings of the rhythmic displacement of membrane-adherent markers. Additions of graded concentrations of isoproterenol to the perfusate produced up to threefold increases in the initial contractile phase velocity (contractile index), with an EC50 of 10(-7) M. When the extracellular Ca2+ concentration was increased from 0.9 to 3.6 mM, 2.43-fold increases in this index occurred. Myocytes incubated for 72 hours in the presence of dilutions of medium conditioned by activated rat splenic macrophages and lymphocytes exhibited an isoproterenol contractile index inhibited by 62% compared with control cells. In contrast, responses of supernatant-exposed and control cells to increased extracellular Ca2+ concentrations were not significantly different. Parallel studies of increases in myocyte intracellular adenosine 3':5'-cyclic monophosphate concentrations in response to isoproterenol stimulation demonstrated correlative inhibition that was specific for exposure to medium conditioned by immune cells. CONCLUSION Thus, a new method of in vitro cardiac contractility assessment that has significant advantages over existing systems has been developed and characterized. This new method has enabled description of an inhibitor of cardiac contractile function produced by activated immune cells.

Absence of bacteremia during nasal septoplasty.

Abstract: • Episodes of staphylococcal bacteremia resulting in metastatic infection have occurred in association with nasal septoplasty, and this has suggested the possible need for antimicrobial prophylaxis. In a study designed to measure the actual frequency with which transient staphylococcal bacteremia occurs during nasal septoplasty, 50 healthy patients had blood cultures drawn immediately prior to and during the procedure. Although 46% of the 50 patients studied had their nasal mucosa colonized with Staphylococcus aureus , some of the blood cultures obtained from the 50 patients showed bacterial growth. The authors conclude that staphylococcal bacteremia during nasal septoplasty is a rare occurrence, and that antimicrobial prophylaxis is unnecessary. ( Arch Otolaryngol Head Neck Surg . 1991;117:54-55)

The neurology of aging: normal versus pathologic change.

Abstract: Mild changes in neurologic function occur with aging but generally do not substantially interfere with everyday activities unless disease intervenes. Not infrequently, older adults experience minor impairment in memory, speed of cognitive processing, sleep, vision and hearing, vibratory sense in the lower extremities, and gait and posture. In general, these changes correspond with age-associated neuroanatomic changes (eg, diminished brain weight), but there is wide variability in the extent to which these changes occur. Often, "normal" neurologic changes are difficult to distinguish from impairment associated with disease.

Molecular cloning and characterization of recombinant parasite antigens for immunodiagnosis of onchocerciasis.

Abstract: Immunological cross-reactivity among nematodes has hampered the development of specific serodiagnostic assays for onchocerciasis. In the present study, an Onchocerca volvulus adult worm complementary DNA expression library was differentially screened with human sera from patients infected with O. volvulus and with an omnibus anti-nematode serum pool comprised of sera from patients infected with Brugia malayi, Loa loa, Wuchereria bancrofti, Mansonella perstans, Strongyloides stercoralis, Ancylostoma duodenale, Ascaris lumbricoides, and Dracunculus medinensis. Seven Onchocerca-specific clones were identified and screened with individual onchocerciasis patient sera. Additional studies were performed to characterize the most immunoreactive clones, OC 3.6 and OC 9.3. OC 3.6 produced a 152-kD beta-galactosidase fusion protein that was recognized in dot-immunoblots by 54 of 55 sera from onchocerciasis patients (98%). The OC 3.6 DNA insert is 996 bp long with an open reading frame of 627 bp and a 369-bp untranslated 3' end. OC 3.6 is closely related to a previously reported clone (OV 33-3), but it differs from that clone at both the 5' and 3' ends. OC 9.3 contained a novel 565-bp insert and produced a 138-kD fusion protein that was recognized by 46 of 55 sera from onchocerciasis patients (83%). Additional studies are in progress to develop and evaluate immunodiagnostic tests for onchocerciasis based on measurement of antibodies to these promising recombinant antigens.

Cognitive screening tests

Abstract: at a lipid center, more highly motivated to lower their cholesterol levels and follow physician advice. Thus, while the formulary-policy may be a useful tool at the MVAMC, it may not be good strategy for all population groups. Although niacin may be an effective drug, 2 it is effective only as long as patients are will ing to take it properly. --ERIC M. BALL, MD, The Walla Walla Clinic, Walla Walla, WA 99362

CD8+ alpha/beta or gamma/delta T cell receptor-bearing T cells from athymic nude mice are cytolytically active in vivo.

Abstract: Phenotypic analysis of lymphocytes that mature extrathymically in congenitally athymic nude mice has revealed a large population of CD3+ CD8+ T cells that express gamma/delta-TCR. In euthymic mice, significant numbers of cells with this phenotype are found only in the intestinal epithelium. Intestinal intraepithelial lymphocytes have been shown to be cytolytically active in vivo, as measured by the redirected lysis assay. In this communication, freshly harvested T cell subsets obtained from pooled nude mouse spleen and lymph nodes and separated by flow cytometric cell sorting were assayed for their ability to lyse FcR+ P815 targets in the presence of mAb to the epsilon-chain of the CD3 complex. CD8+, but not CD4+ or CD4- CD8-, T cells in nude mice were cytolytically active. CD8+ alpha/beta- and gamma/delta-TCR-bearing T cells from the spleen and lymph nodes of nude mice demonstrated similar cytolytic activity. No cytolytic activity of purified cell subsets was apparent in the absence of anti-CD3 mAb, even when NK-susceptible target cells were used. These data indicate that, in contrast to euthymic mice, a large proportion of CD8+ cells from the spleen and lymph nodes of nude mice are cytolytically active in vivo. In addition, these results suggest that the intestinal epithelium is not the only anatomical location where constitutively cytolytic CD8+ alpha/beta- or gamma/delta TCR-bearing T cells may be found.

Activity of octreotide acetate in a total nutrient admixture

Abstract: The activity of octreotide acetate in a total nutrient admixture (TNA) and the effect of the drug on the stability of lipid emulsion in the TNA were studied. Octreotide acetate injection was added to a standard solution containing 3% lipids, amino acids, dextrose, electrolytes, vitamins, and trace elements to achieve a theoretical concentration of 45 micrograms/dL. Samples were stored at room temperature for 48 hours. Octreotide concentrations were determined in triplicate by radioimmunoassay; physical stability of the solutions was assessed by lipid particle-size determination, pH measurement, and visual observation of emulsion integrity at 0, 12, 24, and 48 hours. The activity of octreotide in two samples of each solution (with and without lipid) was analyzed immediately after preparation and after seven days under refrigeration. There was no evidence of emulsion breakdown or pH change in any solution over the study period. In addition, particle-size distributions at 48 hours and 7 days were comparable to those at time zero, suggesting physical stability. Octreotide acetate activity was not consistently greater than 90% (mean +/- S.D.) after storage for 48 hours. Octreotide acetate at a theoretical concentration of 45 micrograms/dL in a TNA solution containing 3% lipids appeared to be physically compatible for 48 hours at room temperature and for 7 days under refrigeration. However, the chemical activity of octreotide in TNA was not consistent after storage for 48 hours.

Improved in vitro antigen-specific antibody synthesis in two patients with common variable immunodeficiency taking an oral cyclooxygenase and lipoxygenase inhibitor (ketoprofen)

Abstract: In the process of performing a previously published study examining B cell function in 16 patients with common variable immunodeficiency (CVI)(J Allergy Clin Immunol 1991; 87:1138-49), we noted improved in vitro antibody (Ab) synthesis in a patient, H. B., while he was taking a cyclooxygenase and lipoxygenase inhibitor, ketoprofen. Addition of ketoprofen in vitro to B cells from patients with CVI resulted in improved proliferation and differentiation in four of five additional patients with CVI studied. One patient, besides H. B., M. K. B., whose B cells secreted increased amounts of antigen (Ag)-specific Ab in response to in vitro ketoprofen, underwent a trial of oral ketoprofen M. K. B., like H. B., demonstrated improved in vitro Ag-specific Ab production while she was taking oral ketoprofen. No increase in serum Ab levels was noted in either patient taking ketoprofen, but both patients remained infection free during the time of their ketoprofen trials (H. B., 9 months, and M. K. B., 36 months). No improvement in in vitro Ag-specific Ab synthesis was noted when H. B. and M. K. B. took oral cyclooxygenase inhibitors (naproxen or ibuprofen). Thus, additional study is warranted to examine the role of lipoxygenase products of arachidonic acid in the B cell dysfunction of CVI.

Amphotericin B selectively stimulates macrophages from high responder mouse strains.

Abstract: Lymphoid cells from most inbred mouse strains respond to amphotericin B (AmB)-induced immunostimulation. However, C57BL/6 mice and related strains display low or absent lymphoid cell stimulation by AmB and enhanced susceptibility to AmB toxicity. Experiments reported here show that in vitro incubation with AmB can stimulate AKR (AmB-high responder strain) macrophage proliferation. Intraperitoneal injection of AKR mice with AmB also elicits a population of macrophages primed for enhanced oxidative burst activity after triggering by zymosan particles. Under the same experimental conditions, AmB elicits a population of very weakly responsive macrophages from C57BL/6 mice. The low responsiveness of C57BL/6 macrophages correlates with previous observations that AmB is a potent immunoadjuvant and B cell mitogen in most inbred strains, but it selectively lacks immunoadjuvant effects in C57BL/6 mice and it also fails to induce polyclonal B cell stimulation in their spleen cell suspensions. Similarly, in measurements of protein synthesis in vitro, high concentrations of AmB produce a greater inhibition of protein synthesis in C57BL/6 peritoneal macrophages than in parallel cultures of AKR macrophages. These findings support the hypothesis that the macrophage is an important target cell in the mediation of AmB-induced immunomodulation.

Heparin-binding growth factor

Abstract: A novel heparin-binding growth factor of 18.9 kDa mol. wt. is disclosed which is purified from bovine uterus and human placenta and has a unique 25 N-terminal amino acid sequence as follows:

Stability of nizatidine in total nutrient admixtures.

Abstract: The stability of nizatidine in total nutrient admixtures (TNAs) and the effect of the drug on the stability of lipid emulsions in the TNAs were studied. Duplicate 1476-mL amino acid-dextrose base solutions were prepared; nizatidine 300 mg was added to one. TNAs were prepared by adding to 75-mL samples of the base solutions Intralipid (KabiVitrum) or Liposyn II (Abbott) and sterile water as needed to achieve final lipid concentrations of 3% and 5%. Triplicate 100-mL samples for each lipid product and concentration were prepared; fat-free samples containing nizatidine were also studied. The theoretical final nizatidine concentration was 150 micrograms/mL. Samples were stored at 22 degrees C for 48 hours. Initially and at 12, 24, and 48 hours, the samples were visually inspected, tested for pH and particle-size distribution, and assayed by high-performance liquid chromatography for nizatidine concentration. No color change, precipitation, creaming, or oiling out was noted. For the 12 TNAs containing nizatidine, mean solution pH during the study was 5.88; stability of the lipid products requires pH values greater than or equal to 5.5. Particle-size distribution did not differ appreciably between the nizatidine-containing and drug-free TNAs. Nizatidine concentrations remained greater than 90% of the initial concentration. Nizatidine at a theoretical concentration of 150 micrograms/mL was stable for 48 hours at 22 degrees C in TNA solutions containing 3% and 5% Intralipid or Liposyn II and did not appear to affect lipid emulsion stability.

Anticryptococcal activity of amphotericin B-stimulated macrophages.

Abstract: Amphotericin B (AmB) and its methyl ester derivative (AME) are immunoadjuvants with macrophage stimulating properties. Cultures containing AmB and murine peritoneal macrophages showed synergistic anticryptococcal activity. The antifungal activity was associated with AmB-stimulated macrophages and with their culture supernatants. Photoinactivation of the residual AmB in the macrophage culture supernatant did not result in the loss of antifungal activity. AmB-stimulated macrophage culture supernatants inhibited the growth of C. neoformans in a dose responsive manner and the activity was destroyed by incubation at 100 degrees C but not at 60 degrees C.