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Biomedical subjects

J Mayer

Publications and source records attributed to J Mayer.

At least 181 records · Page 10Linked to original sources

[Biological effects of allogenic leukocytes and leukocyte-depleted blood cell products].

The use of leukodepleted cellular blood components may reduce some adverse effect of transfusion in certain indications. This review presents the adverse effects of contaminating donor leukocytes in blood components: alloimmunisation, febrile nonhemolytic transfusion reactions, refractoriness to platelet transfusions, graft versus host disease, transmission of leukotropic infections and immunomodulation. The value of leukodepletion in preventing some of these complications, methods of leukodepletion and the current indications of use of leukodepleted components in clinical practice are discussed.

Humans↗

[Osteoporosis. 2].

Drug used to treatment osteoporosis can be grouped in two main categories: those that decrease bone resorption and those that increase bone formation. Long-term estrogen therapy as antiresorptive drugs are most effective when bone turnover is increased at time of menopause. Further antiresorptive drugs include oral calcium, calcitonin, bisphosphonates. Drugs that act by increasing bone formation produce an increase in bone mass, these agents are good candidates for the treatment of osteoporosis. Intermittent slow-release sodium fluoride administered for osteoporotic patients inhibits new vertebral fractures, increases the mean spinal bone mass and is safe to use. Calcium supplementation, and vitamin D supplementation have a beneficial effect in retardation of bone loss with very good tolerance. As to new preparations, the most promising ones seem to be drugs, which act on the level of cytokines and growth local factors in bone. In the conclusion authors present therapeutic possibility of postmenopausal women, the most risk group of osteoporotic patients.

Female↗

Biomarkers of environmental tobacco smoke in preschool children and their mothers.

BACKGROUND: Adverse health effects attributable to environmental tobacco smoke (ETS) include respiratory illness and lung cancer in nonsmokers. There is accumulating evidence that children may be at heightened risk of cancer later in life as a result of exposure to carcinogens during their early development. It is of concern that as many as 9 million American children under the age of 5 years may be exposed to ETS. PURPOSE: Our goal was to assess whether levels of cotinine and polycyclic aromatic hydrocarbon-albumin (PAH-albumin) are associated with ETS exposure in children and in women of reproductive age, after accounting for background exposures to PAHs in the diet, workplace, and the home environment. METHODS: The study cohort was composed of 87 Hispanic and African-American mothers and 87 of their preschool children (2-5 years of age). Plasma cotinine was analyzed by gas chromatography; PAH-albumin adducts in peripheral blood were analyzed by enzyme-linked immunosorbent assay. Exposure data were obtained by interview-administered questionnaires. RESULTS: Both cotinine and PAH-albumin were significantly higher in the children whose mothers smoked than in the children of nonsmoking mothers (P < .001 and P < .05, respectively). Among the children of nonsmoking mothers, cotinine levels were also significantly higher in those who had ETS exposure from others in the household compared with the unexposed children. By regression analysis, after adjustment for ethnicity, there was a significant dose-response relationship between cotinine and the number of cigarettes smoked per day by the mother, both in the children (partial r2 = .23; P = .01) and in the mothers (partial r2 = .22; P = .01). Among the nonsmoking mothers, regression of biomarkers against total passive smoking exposure also showed a significant association with cotinine (r2 = .25; P = .04). PAH-albumin did not show the same dose-related response with the smoking variables. Mothers' cotinine levels were significantly correlated with those of their children (r = .76; P < .001) as were PAH-albumin adducts (r = .27; P = .014). CONCLUSION: ETS exposure of young children via their mothers' smoking is associated with increases not only in the internal dose of ETS (cotinine), which has been previously reported, but also in the biologically effective dose of the carcinogenic (PAH) components of ETS (PAH-albumin adducts). This observation underscores the carcinogenic and public health hazard of ETS. IMPLICATIONS: Given the relatively low level of ETS exposure in this study, these results reinforce the need for effective programs aimed at smoking prevention and cessation among women, particularly women of reproductive age and minorities.

Adult↗

Effects of peptide length and composition on binding to an empty class I MHC heterodimer.

Class I major histocompatibility complex (MHC) proteins present peptide antigens to T cells during the immune response against viruses. Peptides are loaded into newly synthesized class I heterodimers in the endoplasmic reticulum such that most or all cell surface class I molecules contain peptides derived from endogenous or foreign proteins. We previously reported the assembly of empty heterodimers of the murine class I MHC molecule H-2Kd, from denatured heavy and light chains from which endogenous peptides had been removed [Fahnestock et al. (1992) Science 258, 1658-1662]. Here we measure thermal stability profiles of empty versus peptide-filled molecules and compare the effects of human versus murine light chains on the overall stability of the Kd heterodimer. The majority of empty heterodimers are stable at 37 degrees C regardless of the species of light chain, indicating that our previous report of the unexpectedly high thermal stability was an intrinsic property of the Kd molecule and not due to use of a murine/human chimeric protein. Binding constants are derived for a series of peptides interacting with empty Kd heterodimers. The dissociation constants of four known Kd-restricted peptides range from 2.3 x 10(-7) to 3.4 x 10(-8) M. Using a series of 24 analog peptides, the effects of length and peptide composition on binding affinity of one Kd-restricted peptide are explored, and the results are interpreted with reference to the known three-dimensional structures of class I MHC protein/peptide complexes.

Amino Acid Sequence↗

Positive and negative thymocyte selection induced by different concentrations of a single peptide.

T lymphocyte maturation is dependent on interactions between the T cell receptor (TCR) expressed on the developing thymocyte and intrathymic major histocompatibility complex (MHC)-peptide ligands. The relation between the peptide-MHC complex that results in negative or positive selection has not been identified. Here, the requirements for the maturation of thymocytes expressing a defined transgenic TCR specific for a viral peptide are studied in fetal thymic organ culture. Low concentrations of the viral peptide antigen recognized by this transgenic TCR can mediate positive selection, whereas high concentrations result in thymocyte tolerance. These findings support the affinity-avidity model of thymocyte selection.

Amino Acid Sequence↗

Exploration of requirements for peptide binding to HLA DRB1*0101 and DRB1*0401.

The individual amino acid contacts responsible for peptide binding to DRB1*0101 and/or DRB1*0401 were defined using a quantitative binding assay. The differential contribution of each amino acid in two well studied T cell determinants, HA307-319 and RMBP 90-102, was delineated by comparing the IC50 values of analogues of varying length. This analysis confirmed the importance of a hydrophobic amino acid located near the amino-terminus for binding to both alleles and revealed that the contribution of the carboxyl-terminal amino acids differed between DRB1*0101 and DRB1*0401. Taking advantage of previous experiments demonstrating that all of the residues could be replaced with alanine, with the exception of the key hydrophobic amino acid, simplified analogues composed of polyalanines were used to prove 1) optimal binding depended on the position of the hydrophobic side chain relative to the amino- and carboxyl-termini; 2) aromatic amino acids were superior to aliphatic side chains at this position; and 3) a significant amount of free energy of binding arises from hydrogen bonding between the class II binding site and the amide bonds of the ligand. The role of each carbonyl and amide nitrogen was measured by assaying analogues containing reduced peptide bonds or N-methyl amino acids. Serine, but not glycine, could be used as a framework amino acid for peptide ligands, indicating that the beneficial aspects of these simplified structures was the combination of retaining the correct orientation of the peptide bonds, the restriction of the conformational freedom by limiting the possible phi/psi angles of the peptide, and avoidance of deleterious side-chain contacts. Collectively, these data were consistent with the peptide binding in a nonrepeating conformation with the vast majority of the free energy of binding arising from hydrogen bonds with the peptide backbone and a single, key hydrophobic side chain interacting in a conserved pocket in both DRB1*0101 and DRB1*0401.

Amino Acid Sequence↗

[Increased bone density in patients with multiple myeloma treated with clodronate].

The indication of bisphosphonates in hypercalcemia is fully accepted, the long term therapy with bisphosphonates is still controversial. The aim of our study was to evaluate the influence of clodronate on the bone density of myeloma patients. Twenty patients were included in the study. Clodronate is administered in the total dose of 3,000 mg, which is delivered in 4-6 hour infusions, 600 mg/day, once in tree 3 months. The effect of clodronate on bone density is evaluated by CT-densitometry in a period of 6 months. At the beginning of May 1994, 15 patients had completed at least two estimations of bone density. The amount of hydroxyapatite in these six months increased in 9 patients, in one of them there was no change and in 4 of them decreasing bone density was detected. The mean bone density before the administration of clodronate was -2.6 SD (standard deviation of European standard of bone density for age and sex). After 6 months of therapy the bone density increased to -2.3 SD. The mean amount of hydroxyapatite in spongiosa was raised from the mean value 32.71 mg/ml before clodronate administration to 38.91 mg/ml after the 6 month treatment period. The mean increase in calciumhydroxyapatite in trabecular bone mass was 6.2 mg. Clodronate contributed to the amelioration of bone pain in the majority of patients, but this effect is difficult to evaluate because of other treatment modalities administered concomitantly. The tolerance of clodronate was good. No impairments of renal function or other adverse effects were observed. Only in 2 patients the decrease in calcium concentration caused slight tetania. Therefore close monitoring of the calcium level is recommended and in the case of its decrease below the physiological level peroral substitution of calcium was started.

Bone Density↗

[Is it possible to prevent mycotic infections in oncology patients?].

The authors give an account on prophylactic provisions focused on reduction of the risk of mycotic infections in oncological patients. After a brief introduction where they point out the importance of mycotic infections they pay their main attention to the prophylactic administration of drugs. They deal with procedures used and in the majority they quote original sources. Main emphasis is laid on the probably most perspective preparation-fluconazol. The authors present also their own views.

Antifungal Agents↗

[Cisplatin and carboplatin in the treatment of malignant lymphoma and multiple myeloma].

Experiences with cisplatin and carboplatin are summarized in this paper. The treatment response to monotherapy with cisplatin or carboplatin was proved in non-Hodgkin's lymphomas. This is necessary condition for the application of the drug in polychemotherapy. Cisplatin and carboplatin based combinations are not used as an initial therapy. The indications for these two drugs are primary resistant malignant lymphoma and multiple myeloma, or relapses of these diseases not responding to conventional therapy. Cisplatin based combination therapy can in these indications prolong the survival in 30-40% of patients. The role of carboplatin in malignant lymphoma is not clear yet and is under investigation. The effective antiemetic therapy (ondansetron, granisetron) miligated the fear of vomiting and therefore these combinations are used in resistant malignant lymphoproliferative diseases more then some years ago. In the tables are shown the chemotherapeutic combinations used in non-Hodgkin's lymphomas, Hodgkin disease and multiple myeloma.

Antineoplastic Combined Chemotherapy Protocols↗

Nocturnal hypertension and cardiovascular risk: consequences for diagnosis and treatment.

General use of ambulatory noninvasive 24-h blood pressure monitoring in many patients has shown that new criteria for arterial hypertension are useful. A classification of circadian blood pressure in "dippers" and "nondippers" (no physiologic drop of blood pressure) needs to be specified. An altered circadian blood pressure profile, like that in nondippers, was used as a diagnostic criterion for secondary hypertension. Recent epidemiologic studies in patients with essential hypertension have shown that nondippers are at higher risk for cardiovascular complications such as myocardial infarction and cerebrovascular insult. The studies also revealed that sleep-related breathing disorders (SRBD) are characterized by increased cardiovascular risk. Increases in blood pressure caused by SRBD could be documented, with the highest amount occurring during REM sleep. A study performed in a general practice showed a high incidence (40/112) of nondippers in a group of snoring middle-aged men with obesity and daytime fatigue. This indicates diagnostic and therapeutic consequences for the control of 24-h blood pressure, including nocturnal breathing pattern and daytime symptoms due to SRBD. The goal of antihypertensive drug therapy is to reduce blood pressure significantly during the day and during the night in different stages of wakefulness and sleep. A new protocol was designed to investigate blood pressure over 24 h under a standardized load, including nocturnal hypertension. The angiotensin-converting enzyme (ACE) inhibitor cilazapril was used in this test procedure and showed a significant and clinically relevant mean blood pressure reduction of 10.0 mm Hg (versus placebo 4.3 mm Hg) over 24 h.

Adult↗

[Sepsis. 1].

In the first part of the paper the author pays attention to new findings pertaining to the definition, clinical picture and pathophysiology of sepsis and septic shock. Facts with an immediate impact on clinical practice and therapy are specially emphasized.

Animals↗

[Pulmonary infection with Pneumocystis carinii in patients with malignant hematologic diseases].

The authors describe their experience with the diagnosis of pulmonary infection with Pneumocystis carinii in patients with malignant diseases. In the course of three years they recorded a total of 16 such cases. All cases were diagnosed by bronchoalveolar lavage. The authors analyze in detail the clinical symptoms and radiological picture. Attention is drawn to the fact that no finding is specific for the disease. The infection of Pneumocystis carinii was combined in 13 cases with another infection. Treatment was successful in 75% of the patients.

Adolescent↗

[Pulmonary infection with Pneumocystis carinii].

The author present extensive review on pulmonary infection with Pneumocystis carinii. He deals with the following aspects: history, pathophysiology, clinical picture and diagnosis. Diagnostic methods used at present are described in great detail. Therapy and prevention are not discussed.

Humans↗

[Sepsis. 2].

In part 2 author pays attention to new findings on treatment of sepsis and septic shock. He emphasizes facts which are of immediate importance for clinical practice and therapy. Possibilities of immunomodulating therapy (monoclonal antibodies, immunoglobulins) are described in detail.

Humans↗

[Use of bronchoalveolar lavage in the diagnosis of pulmonary complications in immunocompromised patients].

The authors examined, using bronchoalveolar lavage, 70 immunocompromised patients with pulmonary complications. The bronchoalveolar fluid was subjected to cytological and microbiological examination. The examination was not associated with any serious undesirable side effects, not even in patients who were in a serious general condition. Based on the examination the treatment was changed in 83% of the patients and the correctness of treatment was confirmed in 7% of the patients. In 76% of the patients the condition improved. It was possible for instance to diagnose pneumonia caused by Pneumocystic carinii, the Herpes simplex virus and fungi even in patients who did not expectorate sputum. The authors hold the view that this examination should be indicated early.

Adolescent↗