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Biomedical subjects

M Kaplan

Publications and source records attributed to M Kaplan.

At least 163 records · Page 9Linked to original sources

Isolation of lysozyme-specific T cell clones that discriminate between native and denatured antigen.

Hen egg white lysozyme (HEL)-specific T cell lines and clones were generated from B6 and BDF1 mice. A variety of clonotypes were found among clones generated at an early stage (1 month) whereas fewer clonotypes were detected after several weeks of culture. Furthermore, a bulk line switched from its initial fine peptide specificity pattern (positive for fragment L2--aa. 13-105--and negative for fragment NC--aa. 1-17:Cys 6-Cys 127:120-129) to the opposite pattern (negative for L2 and positive for NC), indicating that in bulk lines, besides selection toward oligo- or monospecificity, clones previously silent can emerge after a period of time. Irrespective of early or late cloning, T cell clones could be isolated from three independent T cell lines from different mouse strains that were stimulated by either native or denatured HEL, but not both. Furthermore, 1 clone of 20 from a B6 line, 3 clones of 25 from a BDF1 line, and 1 T hybridoma clone of 10 of B10.A origin lost their capacity to respond to native HEL, yet continued to respond to reduced, carboxymethylated HEL or cyanogen bromide-cleaved, unreduced HEL. These results suggest that T cells may produce activation signals for efficient processing of native antigen.

Animals↗

Alterations in gene expression in the rat heart after chronic pathological and physiological loads.

Adaptive cardiac hypertrophy in the rat has been characterized as pathological or physiological reflecting the nature of the inciting stimulus. These two adaptations are distinguished by alterations in contractility and in the myosin ATPase composition of the affected muscle. We investigated the relative amounts of the mRNAs encoding cardiac sarcoplasmic reticular calcium ATPase (SERCA2), cardiac and skeletal troponin I (TnI), atrial natriuretic factor (ANF), and myosin light chain 1 (MLC1) in the hearts of rats that had been subjected to either conditioning by swimming (Sw), to renovascular hypertension (H) or to the combined stimulus (H-Sw) for 6 weeks. Compared to control animals, the mRNA levels for SERCA2 and cardiac TnI were slightly increased with Sw and moderately depressed with H. H-Sw animals showed a trend towards normalized mRNA levels for both genes. ANF mRNA levels were slightly elevated with Sw and markedly elevated with both H and H-Sw. MLC1 mRNA levels did not change with either or both stimuli. These data confirm that these two types of adaptive hypertrophy can be distinguished at the level of gene expression and suggest that the mechanical alterations seen in adaptive hypertrophy reflect a spectrum of pre-translational alterations which are not limited to changes in myosin heavy chain gene expression.

Animals↗

Low density lipoprotein isolated from patients with essential hypertension exhibits increased propensity for oxidation and enhanced uptake by macrophages: a possible role for angiotensin II.

In patients with essential hypertension, the increased risk for atherosclerosis is related not only to the blood pressure levels per se, but also to other, unknown, factors. Recent observations have indicated that oxidation of low density lipoprotein (LDL) and macrophage uptake of oxidized LDL are implicated in human atherosclerosis. We tested both the susceptibility of LDL, derived from hypertensive patients, to lipid peroxidation as well as its uptake by macrophages, in comparison with control LDL obtained from healthy subjects. The LDL that was derived from 25 patients with essential hypertension demonstrated increased propensity for lipid peroxidation with a 63%, 91% and 69% elevation in the content of the lipoprotein malondialdehyde, peroxides and conjugated dienes, respectively, in comparison with control LDL. Minimally modified LDL (MM-LDL) (prepared by 6 months' storage of the LDL at 4 degrees C) derived from the hypertensive patients also demonstrated increased lipid peroxidation with a 94%, 130% and 96% elevation in lipoprotein malondialdehyde, peroxides and conjugated dienes, respectively, compared with the control LDL. The susceptibility of the patients' LDL to lipid peroxidation decreased by 32% and 44% (measured as malondialdehyde) after 3 weeks of therapy with the angiotensin converting enzyme inhibitors captopril and enalapril, respectively, with no parallel reduction in the patients' blood pressure. The patients' LDL was shown to contain increased content of lipid peroxides and unsaturated fatty acids, which may explain its increased susceptibility to lipid peroxidation. In vitro experiments revealed that LDL can bind angiotensin II, and that angiotensin II has a stimulatory effect on copper-mediated oxidation of LDL, as well as on LDL degradation by macrophages. These results were secondary to cell-mediated oxidation of the LDL and to its cellular uptake via the scavenger receptor. We conclude that LDL derived from patients with essential hypertension is more susceptible to lipid peroxidation than control LDL, and this may be secondary to angiotensin II stimulation of LDL lipid peroxidation in these patients. Furthermore, this LDL demonstrates enhanced cellular uptake by macrophages in comparison with normal LDL which can also be related to angiotensin II-mediated LDL oxidation. Both these phenomena have been shown to be associated with accelerated atherosclerosis, and thus suggest a new mechanism for increased atherogenecity in hypertensive patients.

Adult↗

Enterobacter cloacae causing pneumatocele in a neonate.

Pneumatocele formation, a cyst-like rarefaction that develops within the lung parenchyma, is an unusual complication of pneumonia in the neonate. It has been reported to occur with Staphlococcus aureus, Escherichia coli, Klebsiella pneumoniae, Streptococcus pneumoniae, and Pseudomonas aeruginosa infections. We describe a case of a premature neonate with pneumonia and subsequent pneumatocele formation caused by Enterobacter cloacae.

Cysts↗

Neonatal screening for glucose-6-phosphate dehydrogenase deficiency: sex distribution.

Eight hundred and six newborn infants at high risk for glucose-6-phosphate dehydrogenase (G-6-PD) deficiency were screened; 30.2% of the boys and 10.4% of the girls had severe G-6-PD deficiency. Surprisingly, 14% of the enzyme deficient girls had a father from a low risk ethnic group. Girls of high risk mothers should be screened for G-6-PD deficiency regardless of paternal origin.

Fathers↗

Hypercalcemia of malignancy: a review of advances in pathophysiology.

PURPOSE/OBJECTIVES: To review normal calcium homeostasis, recent advances in understanding the pathologic mechanisms responsible for precipitating hypercalcemia of malignancy, the role of the kidneys in potentiating hypercalcemia, and the principles of antihypercalcemic treatment. DATA SOURCES: Journal articles, edited reference works, and selected texts. DATA SYNTHESIS: A complex set of changes in calcium processing in the intestine, kidney, and bone, mediated by humoral factors released from or induced by malignant cells, is responsible for development of humoral hypercalcemia of malignancy (HHM). CONCLUSIONS: A minor cause of cancer-induced hypercalcemia is bone destruction resulting from direct tumor invasion. Synergistic interactions between humoral factors stimulated by the presence of malignant cells enhance bone resorption of calcium and impair renal excretion of calcium ions resulting in HHM. Essential facets of antihypercalcemic treatment include controlling the precipitating malignancy, reversing dehydration, and inhibiting bone resorption. IMPLICATIONS FOR NURSING PRACTICE: The signs and symptoms of increasing serum calcium are difficult to distinguish from disease-related or cytotoxic treatment-related side effects. Oncology nurses must have an understanding of which malignancies pose increased risk and how pathophysiologic mechanisms precipitate or contribute to hypercalcemia of malignancy. Knowledge of the rationales for the various treatment modalities will assist nurses in implementing antihypercalcemic treatments, evaluating treatment effectiveness and side effects, instituting pain management programs, and providing comfort measures and emotional support.

Bone Resorption↗

Effectiveness of early therapy with corticosteroids in Stevens-Johnson syndrome: experience with 41 cases and a hypothesis regarding pathogenesis.

Evaluation of therapy for Stevens-Johnson syndrome was initiated as a retrospective analysis and then extended to a prospective series of patients treated with corticosteroids. This report extends the initial prospective study of patients with Stevens-Johnson syndrome treated with corticosteroids and evaluates the total series of 41 patients relative to outcome and the presumptive etiology. We propose that management of Stevens-Johnson syndrome requires corticosteroid therapy and that the survival of patients with Stevens-Johnson syndrome may depend on this therapy. No fatalities or adverse effects due to corticosteroids were noted. Stevens-Johnson syndrome due to a drug, a drug metabolite or viral infection may mimic a graft-versus-host reaction in which the patient rejects skin, mucous membrane, kidney or liver cells to which the drug, drug metabolite, or virus has bound. Corticosteroids suppress the inflammatory rejection until the activating agent has been eliminated.

Adolescent↗

Factor analysis of schizophrenic symptoms and comparison of different rating scales.

This study examines the factor structure of persistent schizophrenic symptoms and compares factors derived from different rating scales. Forty stable chronic schizophrenic patients were assessed for positive and negative symptoms. In factor analysis, 3 factors could be detected: a negative factor which correlated with low drug dose and increased involuntary movements, a thought disturbance/paranoid factor which correlated negatively with extrapyramidal side effects and a delusion/hallucination factor which correlated negatively with involuntary movements. These findings support the existence of a negative factor but only partly the trichotomous division of schizophrenic symptoms. Positive symptom organisation is heterogeneous but thought disorder marks one clear dimension and non-paranoid delusions and hallucinations may mark another. The type of scale used has very significant effects on the findings.

Adolescent↗

Survival in an infant with a prenatally diagnosed Meckel syndrome variant.

An infant with occipital encephalocele and unilateral multicystic kidney, diagnosed prenatally, was considered to have a variant of the Meckel syndrome (MS). This case is exceptional in that the infant was alive and healthy following surgical repair of the encephalocele, with normal function of the unaffected kidney, at age 5 months. Based on this experience, in fetuses or infants with MS, thorough evaluation of both kidneys is imperative prior to suggesting either termination of pregnancy, or withholding of life-sustaining medical treatment in infants already delivered.

Encephalocele↗

Perinatal infections with Streptococcus pneumoniae.

Perinatal infections with Streptococcus pneumoniae although rare, have caused morbidity and mortality in both neonatal and puerperal patients. To determine the incidence of proven pneumococcal sepsis in these patient groups, blood culture records from 1977 to 1989 were reviewed. Of 89 parturient patients with true positive blood cultures, two (2.2%) were positive for the pneumococcus, whereas of 240 infants with positive blood cultures, three (1.25%) grew pneumococcus. The incidence of maternal pneumococcal sepsis was 0.04/1000 live births, and that of the neonates, 0.06/1000, and the overall rate for sepsis in these two groups was 1.7 and 4.7/1000 live births, respectively. In three mother-infant pairs, the identical pneumococcal serotypes, 7, 18, and 23, were isolated from both mother and infant. Birthweights and gestational ages of the infants ranged from 2330 to 3730 gm and 34 to 40 weeks, respectively. Respiratory distress and poor peripheral perfusion were the predominant clinical signs in the infants with sepsis and became apparent from shortly after birth until 5 days of life. Pyrexia, poor general condition, and leukocytosis characterized the mothers with sepsis. All patients survived following antibiotic and supportive care. Our epidemiologic survey confirms the rareness of perinatal pneumococcal infection and the ability of these organisms to cause morbidity in both mothers and infants.

Adult↗

The influence of dietary salt and plasma renin activity on myosin heavy chain gene expression in rat hearts.

The renin-angiotensin system has been implicated as a possible mediator of the cardiac adaptations that develop in response to chronic pressure overload. In order to explore this, we studied rats that had elevated plasma renin activity (PRA) secondary to 6 weeks of either dietary salt restriction or renovascular hypertension (Htn)--conditions that exert distinctly different loads on the myocardium. Separate groups of sham and Htn animals were maintained on a high salt diet that resulted in a relative (Htn) or absolute (sham) reduction in PRA. Heart weight and heart/body weight ratios were increased only in animals with Htn. The ratio of alpha/beta myosin heavy chain (MHC) mRNA was significantly decreased with Htn. This ratio was markedly increased with low salt and was not influenced by high salt intake. Thus, the circulating renin-angiotensin system does not appear to play a primary role in defining cardiac myosin heavy chain adaptations to hemodynamic loads. However, sodium restriction, either via its hemodynamic or humoral effects, is sufficient to induce a physiologic change in myosin heavy chain gene expression in rats.

Animals↗

Genetic linkage studies map the multiple endocrine neoplasia type 2 loci to a small interval on chromosome 10q11.2.

We have carried out genetic linkage analyses using fifteen polymorphic loci in the pericentromeric region of chromosome 10 in families with the inherited cancer syndromes multiple endocrine neoplasia (MEN) type 2A or 2B. A highly polymorphic microsatellite from the locus D10S141 in q11.2 was found to be recombinant with respect to the disease locus in two individuals and defines a new proximal flanking marker for both MEN2A and 2B. An additional recombination provides evidence that the locus D10S94, also in q11.2, is the closet distal flanking marker for MEN2A. This localises the MEN2A gene to a small region of 10q11.2 flanked by the loci D10S141 and D10S94, which are separated by a sex-averaged genetic distance of 0.55 cM. The MEN2B gene maps to a larger region, flanked by D10S141 and RBP3.

Chromosome Mapping↗

Frailty and injuries in later life: the FICSIT trials.

Physical frailty and fall-related injuries present two of the biggest threats to older people's functioning and quality of life. The Frailty and Injuries: Cooperative Studies of Intervention Techniques (FICSIT) trials represent a set of eight different clinical trials concerning physical frailty and injuries in later life. This report documents the history and organization of the trials and provides an overview of the measures being collected at multiple sites and the analytic strategies to be used for multi-site investigations.

Accidental Falls↗

Enhanced degradation of high density lipoprotein by peritoneal macrophages from nude mice is attenuated by interleukin-1.

Athymic nude mice are characterized by deficient cellular immunity due to almost complete absence of functional mature T-lymphocytes. Plasma HDL (the major cholesterol carrier in mice) cholesterol levels in nude mice were found to be reduced by 1.7 fold in comparison to control Balb/c mice. Cellular degradation of HDL by peritoneal macrophages (MPM) that were obtained from nude mice, was 2.5 fold greater in comparison to MPM obtained from Balb/c mice. Since nude mice lack cytokines that can affect lipid metabolism, intravenous administration of 10 micrograms/100g body weight of interleukin-1 (IL-1), tumor necrosis factor (TNF), or transforming growth factor (TGF) on HDL degradation by their PM, were investigated. IL-1 (but not TNF) reduced HDL (50 micrograms of protein/ml) cellular degradation from 810 +/- 34 to 350 +/- 12 ng/mg cell protein (p < 0.01) in nude mice. In control Balb/c mice, however, IL-1 as well as TNF enhanced macrophage degradation of HDL by 56% and 280%, respectively. TGF injection into nude mice (but not control mice) decreased HDL degradation by their MPM by 50%. We, thus, suggest that in nude mice the reduced plasma and HDL cholesterol levels are probably due to increased HDL degradation, which may be secondary to IL-1 and TGF deficiency.

Animals↗

Indications for colonoscopy. An analysis based on indications and diagnostic yield.

Open access colonoscopy for patients with suspected colonic disease is often not practical and some form of patient selection may be necessary. One year's colonoscopic data from our unit were analysed to determine the major indications for the procedure and the diagnostic yield, and to evaluate the suitability of colonoscopy for each indication. The seven major indications were rectal bleeding, iron deficiency anaemia, cancer follow-up, polyp follow-up, abdominal pain, abnormal bowel habit and 'other'. Four hundred and forty-eight procedures were included in the analysis, with rectal bleeding, polyp follow-up and iron deficiency anaemia producing the highest diagnostic yields of 69.1%, 53.3% and 47.7% respectively. Lower yields were obtained for cancer follow-up (21%), abdominal pain (38.2%) and abnormal bowel habit (46.8%). The indication, 'other', produced a combined yield of 66.7%; the majority of patients in this group were known to have colitis. On the basis of these findings we propose that where facilities and expertise do not allow for routine colonoscopy, some form of patient selection should be employed and we believe this selection should take place according to the diagnostic yield for each indication.

Abdominal Pain↗