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Biomedical subjects

L Rubin

Publications and source records attributed to L Rubin.

At least 55 records · Page 3Linked to original sources
PubMed1992

Lymphadenopathy, oligoclonal T cell receptor rearrangement and systemic lupus erythematosus.

To investigate the cause of generalized lymphadenopathy in case of systemic lupus erythematosus (SLE), we performed a molecular genetic analysis of lymph node, peripheral blood mononuclear cell and bone marrow specimens with T cell receptor and immunoglobulin gene probes. Oligoclonal T cell receptor rearrangements were detected in the lymph node cells. The oligoclonal T cell expansion observed is the first such example reported in SLE, and may be indicative of an immune response to specific antigenic challenge. Alternatively, these changes may represent the earliest phases of a malignant process. Molecular genetic investigations in autoimmune disease such as SLE can provide opportunities to enhance our understanding of the underlying condition, or reveal unexpected abnormalities requiring further assessment.

Blotting, Southern↗
PubMed1992

Topoisomerase II-mediated DNA cleavage activity and irreversibility of cleavable complex formation induced by DNA intercalator with alkylating capability.

A group of chrysophanol and emodin derivatives with DNA-intercalating capability and with or without alkylating potential have been synthesized and shown to have antitumor activity in vitro. The topoisomerase II (Topo II)-mediated DNA cleavage activities induced by representative compounds 3-(2-chloroethylamino) methyl-1,8-dihydroxy-9,10-anthraquinone (SK-31690), 3-bis [(2-chloroethyl)amino]methyl-1,8-dihydroxy-9,10-anthraquinone (SK-31662), and 3-(2-hydroxyethylamino)methy-1,8-dihydroxy-9,10-anthraquinon e (SK-31694), and their cytotoxicities, have been investigated. All three compounds inhibited the kinetoplast DNA decatenation catalyzed by DNA Topo II. These compounds inhibited leukemia cell growth and stimulated, in a dose-dependent manner from 0.5 to 60 microM, the formation of Topo II-DNA cleavable complexes, when 3'-32P-labeled DNA was used. The mapping of Topo II-mediated DNA cleavage sites using HindIII-digested 3'-32P-labeled DNA showed that, at 10 microM, these compounds induced protein-linked DNA breaks that correlated with cytotoxicity, with respect to their maximal efficacy or the reciprocal concentration for the half-maximal effect. The reversibility study showed that the amounts of protein-linked DNA cleavage induced by 4'-(9-acridinylamino)methanesulfon-m-anisidide and VP-16 as well as SK-31694, which lacks alkylating potential, were markedly decreased during 30-sec exposure to 65 degrees or 0.5 M NaCl. In contrast, protein-linked DNA cleavages induced by SK-31662, which has two alkylating functionalities, and by SK-31690, which has one alkylating functionality in its structure, cannot be reversed during the 15-min exposure to 65 degrees or 0.5 M NaCl. These data suggest that Topo II is a major cellular target for cytotoxicity of these compounds. Furthermore, DNA intercalators with alkylating potential interact with Topo II-DNA cleavable complexes in an irreversible manner, with enhanced toxicity.

Alkylating Agents↗
PubMed1992

Foreign-body osteitis of the metacarpal bone.

Foreign-body granulomas in the hand can appear secondary to an unrecognized foreign material. In a six-year-old boy, an extensive sterile osteitis of the second metacarpal bone appeared adjacent to a wood splinter.

Child↗
PubMed1991

Comparison of titanium-mesh and porous disc electrodes for epicardial defibrillation.

The object of this study was to compare the effectiveness of chronically implanted porous electrodes with that of smooth mesh titanium electrodes of the same diameter but smaller effective surface area. The criteria used in evaluating the electrodes were (1) acute, subacute, and chronic resistance and (2) acute, subacute, and chronic defibrillation thresholds. Electrode pairs 2.5 cm in diameter were implanted in each of 17 dogs (ten mesh and seven porous). One electrode of each pair was sutured to the right ventricle and one to the left ventricle near the cardiac apex. Defibrillation threshold energy and total resistance were measured at the time of implantation and again 6 and 12 weeks after implantation. The mean initial resistance of the titanium electrodes was 131.7 omega; the mean defibrillation values for the porous electrode implant were 96.9 omega and 7.5 joules, respectively. Three to 6 weeks after implantation, the values for the titanium mesh electrode were 88.9 omega and 12.0 joules, while those for the porous electrode were 59.9 omega and 8.0 joules. In the chronic state, the figures for the titanium mesh electrode were 78.1 omega and 13.0 joules, while those for the porous electrode were 64.3 omega and 8.3 joules. We conclude that defibrillation can be achieved successfully with small epicardial electrodes. The findings suggest that a porous electrode, with its larger effective surface area, has lower electrode/tissue interface resistance in the acute and chronic phases, and, therefore, provides lower defibrillation threshold energy.

Animals↗
PubMed1990

Ingestion of Legionella micdadei inhibits human neutrophil function.

Legionella micdadei is a human pathogen which survives within leukocytes. To determine how this organism escapes intracellular destruction, we examined its effect on human neutrophil activity. Neutrophils were allowed to ingest L. micdadei prior to evaluation of functional activity. Compared with control cells which did not ingest organisms, cells ingesting L. micdadei showed significantly depressed production of superoxide anion (24.5 +/- 9.0 nmol/10(6) cells per 15 min versus 6.9 +/- 3.2 nmol/10(6) cells per 15 min, respectively; P = 0.002), chemotaxis (43.9 +/- 0.8 mm versus 0.9 +/- 1.3 mm of directed migration, respectively; P = 0.001) and bactericidal activity against Staphylococcus aureus (97.9% versus 37.6% of ingested organisms killed, respectively; P = 0.001). Similar degrees of inhibition could not be demonstrated when either Staphylococcus aureus or Escherichia coli was ingested by cells prior to evaluation. Inhibition of neutrophil function did not occur when phagocytosis of L. micdadei was prevented. However, inhibition occurred with heat-killed as well as with viable organisms. The inhibition of neutrophil function by ingested L. micdadei may help explain the bacterium's ability to survive intracellularly and may begin to explain the pathogenesis of this disease.

Chemotaxis, Leukocyte↗
PubMed1989

Cloning of a cDNA encoding the rat high molecular weight neurofilament peptide (NF-H): developmental and tissue expression in the rat, and mapping of its human homologue to chromosomes 1 and 22.

Neurofilaments (NFs) are the intermediate filaments specific to nervous tissue. They are probably essential to the tensile strength of the neuron, as well as to transport of molecules and organelles within the axon. Three peptides with apparent molecular masses of approximately 68 (NF-L), 145 (NF-M), and 200 (NF-H) kDa appear to be the major components of NF. The expression of these peptides is specific to nervous tissue and is developmentally regulated. Recently, complete cDNAs encoding NF-L and NF-M, and partial cDNAs encoding NF-H, have been described. To better understand the normal and pathophysiology of NFs we chose to clone the cDNA encoding the rat NF-H peptide. Using monoclonal antibodies that recognized NF-H, we screened a rat brain lambda gt11 library and identified a clone that contained a 2100-nucleotide cDNA insert representing the carboxyl-terminal portion of the NF-H protein. Anti-fusion protein antibodies recognized the NF-H peptide on immunoblots and stained fibrillar structures only in neurons. The cDNA recognized a 4500-nucleotide polyadenylated mRNA that was present only in nervous tissue and a 3500-nucleotide mRNA in adrenal. Brain NF-H mRNA levels were tightly developmentally regulated and paralleled the levels of NF-H peptide on immunoblots. Nuclear runoff studies showed that the 20-fold developmental increase in the NF-H message was due only in part to a 4-fold increase in its transcription rate. Levels of NF-H mRNA varied 20-fold among brain regions, with highest levels in pons/medulla, spinal cord, and cerebellum, and lowest levels in olfactory bulb and hypothalamus. Transcription studies revealed only a 2-fold difference in the transcription rates among these brain regions. Based on these results, we infer that half of the developmental increase and most of the interregional variation in the levels of the NF-H mRNA are mediated through message stabilization. Sequence information revealed that the carboxyl-terminal region of the NF-H peptide contained a unique serine-, proline-, alanine-, glutamic acid-, and lysine-rich repeat. The serine residues are likely sites of phosphorylation in the mature peptide. Genomic blots revealed a single copy of the gene in the rat genome and two copies in the human genome. In situ hybridizations performed on human chromosomes mapped the NF-H gene to chromosomes 1 and 22. Whether one copy is a pseudogene remains to be determined.

Aging↗
PubMed1987

Soluble serum interleukin 2 receptor levels in leprosy patients.

Soluble interleukin 2 receptors (IL-2R) in sera of leprosy patients from Chiang Mai, Thailand, were quantified with a solid phase enzyme immunoassay using two monoclonal antibodies to the IL-2R. The IL-2R levels of untreated lepromatous, borderline lepromatous or midborderline patients and treated lepromatous and borderline lepromatous or treated borderline tuberculoid and tuberculoid patients were comparable to those of the Thai household or nonhousehold contacts; and they were significantly higher than the levels of USA control subjects. In contrast, IL-2R of untreated tuberculoid or borderline tuberculoid patients were significantly reduced. Patients with ongoing reversal reaction had very high circulating IL-2R, the levels of which correlated with fever and extent of skin lesions. Although erythema nodosum leprosum patients also had elevated IL-2R levels, they were significantly below those of patients with reversal reaction. When treated with corticosteroid, precipitous reduction of IL-2R was noted in all patients with reversal reaction but not in patients with erythema nodosum leprosum.

Enzyme-Linked Immunosorbent Assay↗
PubMed1986

Fine structure of the photosensitive iris of the toad, Bufo marinus.

The iris of the toad Bufo marinus is directly photosensitive and will constrict in response to light striking only the iris. This is true even when the iris is isolated from the rest of the eye, and therefore from reflex neuronal influences initiated in the retina. This autonomous response is probably mediated by the sphincter pupillae muscle, since no specialized photoreceptors are present in the iris, nor does the sphincter exhibit any specializations likely to subserve a purely photoreceptive function. The photosensitive sphincter appears typical of smooth muscle and, like mammalian sphincters, possesses many intercellular junctions. The iris possesses a well-developed neuronal plexus with fibers projecting into the sphincter muscle layer. Nerve terminals contain small, agranular (30-70nm) and large, dense-cored (80-120nm) vesicles. No consistent postsynaptic specializations are seen on any cells of the iris, including the cells of the sphincter muscle. The anterior pigment epithelial cells of the iris appear specialized and resemble the myoepithelial dilator muscle described by Kelly and Arnold ('72) for the iris of rats.

Animals↗
PubMed1986

Atlantoaxial instability in adults with Down syndrome: a clinical and radiological survey.

A survey of 129 adults with Down syndrome was undertaken to determine the prevalence of atlantoaxial instability (AAI) and to establish a base line for long term prospective study. Clinical and radiological evaluations were performed to determine optimal screening methods for this condition. The findings indicate that radiological evidence of AAI was found in 40% with anterior atlanto-odontoid distance (AAOD) of 3 mm or more and in 10% with 5 mm or more. These findings are similar to those reported in the pediatric age group. A preponderance of females with symptomatic AAI is noted. Clinical evaluation suggested the presence of spinal cord compression, which was confirmed by CT scan of the atlantoaxial region. There were no false negative clinical results. Among the false positive clinical findings other explanations were present in some cases. A comparison with the literature is offered along with guidelines on screening and management.

Adult↗
PubMed1986

Characteristics of sheltered homeless families.

To describe the characteristics of homeless families, we interviewed 80 homeless mothers and 151 children living in 14 family shelters in Massachusetts (two-thirds of the shelters in the state). Ninety-four per cent of the families were headed by women, 91 per cent were on AFDC (aid to families with dependent children), with twice as many as the state average having been on AFDC for at least two years; most had long histories of residential instability. Although 60 per cent had completed high school, only a third had worked for longer than one month. One-third of the mothers reported having been abused during their childhood, and two-thirds had experienced a major family disruption. At the time of the interview, almost two-thirds either lacked or had minimal supportive relationships and one-fourth of these named their child as the major support. Eighteen mothers were involved with the Department of Social Services because of probable child abuse or neglect. Seventy-one per cent of the mothers had personality disorders. In contrast to many adult homeless individuals, however, deinstitutionalized persons or those suffering from psychoses were not overrepresented. About 50 percent of the homeless children were found to have developmental lags, anxiety, depression, and learning difficulties, and about half required further psychiatric evaluation. Two-thirds described housing and social welfare agencies as not helpful. Given the many serious problems of the mothers and the difficulties already manifested by their children, comprehensive psychosocial and economic interventions must be made to interrupt a cycle of extreme instability and family breakdown.

Adolescent↗
PubMed1985

Epicardial versus parietal pericardial defibrillation.

This study evaluated the energy requirements for porous electrodes implanted on the parietal pericardium versus those for porous electrodes implanted on the epicardial surface of the heart. Defibrillation with a 2.5-cm porous electrode implanted on the parietal pericardium was successful in 42% of all episodes of ventricular fibrillation. The minimal energy requirement ranged from 30-68 J, with an average of 46 J. Epicardial defibrillation was successful in approximately 80% of all episodes. The average maximal energy was 21.3 J. There was histological evidence of subepicardial damage in the parietal defibrillation group. This may be related to the higher energy required to defibrillate in this group. However, in this group frequent, large, external shocks were required to defibrillate the dogs' hearts. Theoretically, there may be some physiological and surgical advantages to an intact pericardium. However, the high energy requirement and the low success rate for defibrillation with a porous electrode on the parietal pericardium negate the feasibility of this route of defibrillation with a permanent implantable system.

Animals↗
PubMed1984

Homozygous protein C deficiency manifested by massive venous thrombosis in the newborn.

We studied a family in which two infants had died with massive venous thrombosis shortly after birth. Protein C antigen was undetectable by immunologic assays of plasma available from one infant. (Protein C is a potent naturally occurring anticoagulant that inactivates activated coagulation factors V and VIII). The parents, who were first cousins, both had partial protein C deficiency. Reduced protein C levels were also observed in 12 of 25 additional family members. None of the partially deficient family members (age range 4 to 70 years) had thrombotic episodes. Our data support the view that hereditary protein C deficiency is an autosomal disorder in which the homozygous state may be manifested by the virtual absence of plasma protein C and by fatal thrombosis in the neonatal period.

Adult↗
PubMed1984

Systemic lupus erythematosus with paraproteinemia.

Nine patients (2.2%) in a group of 415 who were followed in a longitudinal prospective study of systemic lupus erythematosus (SLE) were found to have various monoclonal (M) proteins in their blood (IgG [6 patients], IgA [2 patients], IgM [1 patient]). No other findings compatible with plasmacytic dyscrasia were found. Bence Jones proteinuria was absent. Bone marrow aspirates and skeletal radiographs did not reveal any associated features of malignancy. Four of the 9 patients were under the age of 50. From the point of view of the M components, 3 groups emerged: transient (2 patients), persistently stable (6 patients), and increasing serum concentrations (1 patient). Using current measures of disease status, no correlation was apparent between the presence, type, and concentration of the M protein and the clinical and laboratory variables of lupus activity. Thus, M proteins were found in 2% of our SLE patients, but their relationship to the polyclonal B cell activation seen in this disorder, or perhaps to therapeutic modalities used in its treatment, remains to be elucidated.

Adult↗