Search PubMed⌕ Search

Biomedical subjects

C Neumann

Publications and source records attributed to C Neumann.

At least 199 records · Page 11Linked to original sources

Interferon production by Corynebacterium parvum and BCG-activated murine spleen macrophages.

Macrophages were identified to be a major source of interferon produced in murine spleen cell cultures after intravenous injection of Corynebacterium parvum (C. parvum), strain CN 6134 or Bacille Calmette Guérin (BCG). Another strain of C. parvum, CN 5888, which lacks RES stimulating activity and adjuvant activity in vivo, was not effective when injected intravenously. Protein synthesis was required for interferon activity to be produced and protein synthesis was also required for the antiviral state to be expressed. The antiviral activity was relatively stable to pH 2 and neutralized by an antiserum against virus-induced fibroblast interferon, thus exhibiting some properties of type I interferon. In vitro only CN 6134, the biologically active strain, could induce small amounts of interferon in spleen macrophage cultures. Macrophages from CN 6134 or BCG-infected athymic nu/nu mice produced similar interferon titers as their controls. It is concluded that infection with certain immunomodulators can activate splenic macrophages via a predominantly T-cell independent mechanism. Interferon in turn may operate locally as a mediator of immunoregulation.

Animals↗

Detection of plasminogen activator in macrophage culture supernatants by a photometric assay.

Plasminogen activator is usually detected indirectly through the lysis of radioiodinated fibrin. Here, it was investigated whether the fibrinolysis test may be substituted by a photometric assay using a synthetic chromogenic substrate (H-D-Val-Leu-Lys-p-nitroanilide; S-2251). Supernatants from cultured murine macrophages served as source of plasminogen activator. It is shown that under standard conditions the photometric assay is about twice as fast and 2--4-fold more sensitive than the fibrinolysis assay. Furthermore, reproducibility of the photometric test was found within 1.5--3.5% standard deviation compared to the fibrinolysis test which was found between 10--20% standard deviation.

Animals↗

Immune interferon. II. Different cellular site for the production of murine macrophage migration inhibitory factor and interferon.

The production of macrophage migration inhibitory factor (MIF) and immune interferon (IF) by concanavalin A (Con A)-stimulated cultures of thymus, lymph node and spleen cells was investigated. It was found that all cultures produced MIF activity, whereas only spleen cells produced marked IF activity. The capacity to produce IF was found to be correlated with the macrophage content of a cell preparation as evidenced by staining for esterase-positive cells. Furthermore, column-purified spleen T cells produced MIF but no IF. Migration inhibition caused by residual mitogen could be ruled out. On the other hand, when macrophages grown from bone marrow cells were pre-exposed to supernatants of mitogen-stimulated lymphocytes, IF activity was released into freshly added medium while no significant MIF activity was found. IF was also found in supernatants of macrophage cultures after exposure to conventional inducers in vitro (polyinosinic-polycytidylic acid, Corynebacterium parvum) or in vivo (C. parvum), whereas no MIF was detected. An anti-Type I IF serum neutralized IF in supernatants from Con A-stimulated spleen cells but did not affect MIF in the same supernatants. This indicates that IF and MIF activity are associated with different molecules. It is, therefore, concluded that under the described conditions, IF and MIF are produced by different cells. T cells are the prime producers of MIF while IF is released by macrophages following induction by lymphokines.

Animals↗

Mutations that alter the covalent modification of glutamine synthetase in Salmonella typhimurium.

glnD and glnE mutant strains of Salmonella typhimurium lack three of the four activities required for reversible covalent modification of glutamine synthetase (GS; EC 6.3.1.2). The glnD strains, which are unable to deadenylylate GS and therefore accumulate the adenylylated or less active form of the enzyme, were isolated as glutamine bradytrophs. They lack the activity of PIIA uridylyl-transferase, one of the proteins required for deadenylylation of GS; in addition, they lack PIID uridylyl-removing activity. Mutations in glnD are suppressed by second-site mutations in glnE that eliminate the activity of GS adenylyltransferase (EC 2.7.7.42) and thus prevent adenylylation of GS. The glnD and glnE strains have one-third to one-half as much total GS as the wild-type strain when they are grown in a medium containing a high concentration of NH4+. The wild-type strain derepresses synthesis of GS fourfold in response to nitrogen limitation; glnD and glnE strains derepress synthesis of the enzyme fourfold and sevenfold, respectively. Thus, mutations that alter covalent modification of GS in Salmonella do not significantly affect derepression of its synthesis. The glnD gene lies at 7 min on the Salmonella chromosome and is 50% linked to pyrH by P22-mediated transduction.

Chromosome Mapping↗

Mutant strains (nit) of Salmonella typhimurium with a pleiotropic defect in nitrogen metabolism.

We have isolated mutant strains (nit) of Salmonella typhimurium that are defective in nitrogen metabolism. They have a reduced ability to use a variety of compounds including glutamate, proline, arginine, N-acetyl-glucosamine, alanine, and adenosine as sole nitrogen source. In addition, although they grow normally on high concentrations of ammonium chloride (greater than 1 mM) as nitrogen source, they grow substantially more slowly than wild type at low concentrations (less than 1 mM). We postulated that the inability of these strains to utilize low concentrations of ammonium chloride accounts for their poor growth on other nitrogen sources. The specific biochemical lesion in strains with a nit mutation is not known; however, mutant strains have no detectable alteration in the activities of glutamine synthetase, glutamate synthetase, or glutamate dehydrogenase, the enzymes known to be involved in assimilation of ammonia. A nit mutation is suppressed by second-site mutations in the structural gene for glutamine synthetase (glnA) that decrease glutamine synthetase activity.

Acetylglucosamine↗

Mucocutaneous autoimmune syndrome following fludarabine therapy for low-grade non-Hodgkin's lymphoma of B-cell type (B-NHL).

A 40-year-old patient with low-grade B-NHL developed a generalized macular-papular rash following the first cycle of fludarabine treatment which progressed to a complete epidermal necrolysis following the second cycle. Clinical symptoms and the results of the direct and indirect immunofluorescence were consistent with a mucocutaneous autoimmune syndrome (pemphigus). Immunohistochemical analysis demonstrated a dense epidermal infiltration of CD8+ lymphocytes associated with the histological features of single-cell necrosis of keratinocytes. Early and aggressive immunosuppressive treatment with steroids, cyclophosphamide, and high-dose immunoglobulins resulted in regression of symptoms and complete reconstitution of epidermal integrity. The malignant lymphoma has completely regressed. The findings suggest a fludarabine-induced defect in immunosurveillance--resulting in the uncontrolled activation of autoaggressive T-cell clones--as a pathogenetic mechanism of this life-threatening dermatological complication.

Adult↗

MR findings in asymptomatic shoulders: a blind analysis using symptomatic shoulders as controls.

We performed a blind prospective analysis of the shoulders of 20 asymptomatic volunteers, aged 25 to 55 years, to determine the frequency of magnetic resonance (MR) findings considered abnormal in symptomatic patients. Twenty symptomatic patients were used as controls. With regard to the asymptomatic shoulders, all 20 had intact rotator cuff tendons, although six (30%) of the tendons had abnormal internal signal, and one (5%) had abnormal morphology. Subdeltoid and subacromial fat planes were intact in 20 (100%) and 19 (95%) shoulders respectively. Subdeltoid or subacromial fluid was not present in any shoulder. Acromioclavicular osteophytes and supraspinatus depression were seen in seven (35%) and six (30%) respectively. The glenoid labrum was intact in all volunteers, although it had abnormal internal signal in 10 (50%). MR findings of abnormal signal in the glenoid labrum, and of abnormal signal and morphology of the rotator cuff tendons, supraspinatus depression, and acromioclavicular osteophytes have been reported as signs of instability, tendinitis, and impingement. Similar findings were seen in asymptomatic volunteers, indicating that these findings may not be a sign of clinically significant pathology.

Adult↗

PROTECT interim results: a large multicenter study of patients with type II diabetes. Precose Resolution of Optimal Titration to Enhance Current Therapies.

The Precose Resolution of Optimal Titration to Enhance Current Therapies (PROTECT) study is an ongoing Phase IV clinical trial designed to assess the effectiveness, tolerability, and safety of acarbose tablets in patients with type II diabetes when the dosage is slowly titrated upward. This multicenter, open-label, 28-week trial will enroll approximately 7,000 type II diabetic patients. The present report describes the interim results for 2,139 patients who completed the trial as of November 1, 1996. Patients with type II diabetes enrolled in the study were inadequately controlled either with diet alone or with a sulfonylurea. The dosage of acarbose was titrated from 25 mg three times a day (TID) to 100 mg TID based on tolerability and efficacy. Efficacy of glycemic control was assessed by changes in glycated hemoglobin A1c (Hb A1c) and 1-hour postprandial plasma glucose (PPG) levels. Tolerability and safety were determined by patient reports of treatment-emergent adverse events and by review of laboratory tests. The PROTECT study confirms the previously demonstrated efficacy and safety of acarbose in improving glycemic control in patients with type II diabetes regardless of a patient's age, body weight, ethnic background, time since diagnosis, or severity of disease. mean 1-hour PPG levels declined throughout the entire treatment period, with a mean decrease from baseline of -47 mg/dL at the end of treatment. Hb A1c, the most reliable indicator of long-term glycemic control, decreased over the course of treatment, resulting in a mean decrease of -0.7% (P < 0.001). Although all patient types enrolled in the study responded positively to therapy, certain subgroups responded particularly well, such as those patients diagnosed with the disease less than 1 year ago, those treated with acarbose as monotherapy, and those with higher baseline Hb A1c levels. Adverse events were experienced by 36% of all patients and consisted primarily of gastrointestinal disturbances (flatulence, diarrhea, abdominal pain). Moderate renal insufficiency (serum creatinine levels between 1.5 and 2 mg/dL) was present in 259 patients, and no patients developed serum hepatic transaminase levels more than twice the normal range.

Acarbose↗

A prospective comparison of computerized arthrotomography and magnetic resonance imaging of the glenohumeral joint.

Twenty-five patients with shoulder instability or shoulder pain of undetermined etiology were prospectively evaluated with magnetic resonance imaging and computerized arthrotomography. Actual lesions were determined by arthroscopy or at the time of open surgical repair. The images obtained were interpreted independently by three radiologists blinded to both surgical results and the results of previous diagnostic tests. Sensitivity, specificity, and accuracy were determined for each imaging technique for a variety of pathologic entities, including anterior and posterior labral abnormalities, capsular redundancy, biceps-labral complex abnormalities, humeral head (Hill-Sachs) impression lesions, and glenohumeral loose bodies. Analysis of imaging techniques also included construction of receiver operator curves for labral abnormalities. Magnetic resonance imaging showed better diagnostic results in the evaluation of glenoid labral and humeral head impression lesions (P < 0.05). Both imaging techniques were equally successful in identifying biceps-labral lesions and intraarticular loose bodies within the glenohumeral joint. Neither imaging technique was consistent in the evaluation of capsular redundancy. Receiver operator curve analysis confirmed that magnetic resonance imaging was the more accurate imaging study in evaluating anterior and posterior glenoid labral abnormalities.

Adolescent↗

A risk/falls program.

Patient falls are a commonplace and costly occurrence in health care settings. Approximately two years ago, the professional nursing staff on an acute care, 28-bed division in Hanna Pavilion began developing a program to address the issue of patients at risk for falling. The need for such a program evolved as the elderly patient population increased in number. The acute psychiatric service showed an increase in patients over 65 years old, from 13 percent in 1983 to 19.8 percent in 1984. An increased number of falls was documented on the division as the numbers of elderly became larger. During 1984, patient falls constituted 42.8 percent of al reported incidents on this division. The critical concerns related to patient falls were, and still are, the potential for injury leading to chronic disability, prolonged hospital stay, need for extended care, and ultimately the catastrophic effects on the quality of life for the population.

Accident Prevention↗