The family genogram: an underutilized clinical tool.
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Genetic Diseases, Inborn↗
Biomedical subjects
J Rogers
Publications and source records attributed to J Rogers.
Construction and partial characterization of a human liver cDNA library.
Total messenger RNA (mRNA) was isolated from adult human liver and copied to give complementary DNA (cDNA) with reverse transcriptase. Double stranded cDNA was cloned by GC tailing into the PstI site of the plasmid pAT153; approximately 2000 recombinant clones were isolated. The sensitivity of the bacterial cells to ampicillin was used as a marker to study the stability of the library during consecutive overnight growth in mixed liquid culture. A significant change in the composition of the library was observed after three overnight cultures. A heterologous rat albumin cDNA recombinant and two specific oligonucleotides were used to screen the library, and clones containing sequences of the human mitochondrial rRNA- and the alpha-1 antitrypsin-genes were isolated.
Albumins↗
Heavy and light chains of a mouse monoclonal autoantibody express the same idiotype.
We report on the detection of the same idiotype (Id62) on the heavy and light chains of a mouse monoclonal autoantibody to thyroglobulin. This result was obtained by a simple, sensitive, and reproducible technique, namely immunoblot on nitrocellulose paper of electrophoretically separated heavy and light chains by using a panel of 125I-labeled anti-idiotype probes. These included polyclonal heterologous and syngeneic affinity-purified antibodies and a syngeneic monoclonal antibody. The immunoblot findings were confirmed through the solid-phase radioimmunoassay binding of the anti-idiotype probes to isolated H and L polypeptide chains prepared by conventional chromatography methods. Because anti-idiotype probes define a putative regulatory idiotype of the BALB/c autoimmune response to thyroglobulin, it is suggested that the simultaneous presence of the same idiotype on H and L chains may confer to antibody regulatory properties within the idiotypic network. The significance of the existence of the same idiotype on H and L chains and the implication of this finding for the regulation of the immune response to self antigens are discussed.
Animals↗
Quantitative morphology and regional and laminar distributions of senile plaques in Alzheimer's disease.
Senile (neuritic) plaques are one of the two major neuropathologic hallmarks of Alzheimer's disease. Despite their obvious importance (e.g., they are significantly correlated with severity of dementia), there is little present information about their etiology, the specific neuronal elements that form them, or a quantitative definition of where in cortex they occur. We have sought clues to these issues by quantifying regional and laminar distributions of neocortical plaques and setting these data against the present wealth of information on neocortical cytoarchitecture and neurotransmitter-specific circuitry. Senile plaques are significantly more numerous in associative regions of neocortex than in sensory areas and are significantly more numerous in cortical laminae dominated by their role in corticocortical, associative relations. Plaques are also largest in those laminae characterized by large pyramidal cells subserving input/output functions. The quantitative distribution of senile plaques in Alzheimer's disease does not necessarily correspond to innervation patterns for any known subcortical afferent system. This, coupled with the finding that several different neurotransmitters can be immunocytochemically co-localized with plaques, casts doubts on a primary role of cholinergic deterioration in plaque etiology, and opens the possibility that neocortical senile plaques may derive from pathologic events initiated in the neocortex.
Alzheimer Disease↗
Action of phospholipase A2 on bilayers containing lysophosphatidylcholine analogs and the effect of inhibitors.
The effects of several lysophospholipid analogs on the phase properties of codispersions with diacylphosphatidylcholine with or without fatty acids were examined. These ternary codispersions were readily hydrolyzed by phospholipase A2, and they underwent a rapid change in turbidity. Nonideal mixing or phase separation in the ternary codispersions is postulated to be responsible for their enhanced susceptibility to pig pancreatic phospholipase A2, as well as for their tendency to undergo spontaneous change in turbidity, presumably due to spontaneous fusion of the vesicles. Both of these processes were inhibited by a variety of structurally unrelated solutes like n-hexanol and mepacrine. These and other observations are interpreted to suggest that structural defects in bilayers of ternary codispersions are a common locus for the binding of phospholipase A2 and are responsible for the process underlying the change in turbidity. The experiments described here suggest that many of the common inhibitors of phospholipase A2 owe their effects to their ability to modify the quality of the substrate interface, rather than to a direct interaction with the enzyme.
Fatty Alcohols↗
The mechanism of the calcium signal and correlation with histamine release in 2H3 cells.
Rat basophil leukemic (2H3) cells ( Siraganian , R.P., McGivney , A., Barsumian , E. L., Crews, F. T., Hirata , F., and Axelrod , J. (1982) Fed. Proc. 41, 30-34) loaded with fluorescent Ca2+ indicator quin 2 ( Tsien , R. Y. (1980) Biochemistry 19, 2396-2404) showed a rapid increase in free cytosol calcium concentration [( Ca]i) when histamine release was induced. Intracellular quin 2 concentrations up to 7 mM did not affect release of histamine in response to antigen (aggregated ovalbumin) or concanavalin A with cells primed with antigen-specific monoclonal IgE, or in response to Ca2+ ionophores. The [Ca]i increased from approximately 105 nM to a maximum of approximately 1200 nM within 2 to 3 min after antigenic stimulation and then declined slowly over 30 min toward the level in unstimulated cells. Histamine release was most rapid as [Ca]i reached the maximum value and then decreased continuously with [Ca]i over the subsequent 30 min. Neither the Ca signal nor histamine release was observed when the Ca2+ concentration in the medium [( Ca]o) was less than 50 microM, but both responses were restored on readdition of Ca2+ to 1 mM. The maximal Ca signal was obtained when [Ca]o was approximately greater than 1 mM and was half-maximal at [Ca]o congruent to 0.4 mM. In marked contrast [Ca]i in unstimulated cells varied very little with [Ca]o from 0.1 to 1 mM. Maintenance of the Ca signal required the continuous presence of stimulating ligand, external Ca2+, and the maintenance of cellular ATP; metabolic inhibitors blocked or reversed the Ca signal. La+ ions also caused a rapid and reversible block of the Ca signal and histamine release. The data are interpreted in a model in which the Ca signal is generated by a La3+-sensitive signal influx pathway that is functionally independent of the normal Ca2+ influx pathway in unstimulated cells, and that allows a 10-fold or greater increase in rate of Ca2+ entry. The Ca signal is maintained dynamically by the balance between the increased Ca2+ influx and active Ca2+ efflux across the plasma membrane.
Aminoquinolines↗
The isolation and characterization of cDNA clones for human apolipoprotein CII.
Recombinant clones containing cDNA sequences coding for human apolipoprotein CII have been isolated from a human adult liver cDNA library. The clones were detected by hybridization with a mixed probe consisting of 96 different oligonucleotides 17 bases long, complementary to the mRNA coding for amino acids 66 to 71 of apolipoprotein CII. The largest cDNA insert is 439 nucleotides long and contains the complete sequence for the mature protein, the 3' untranslated sequence, and sequence coding for 17 amino acids of a signal peptide. The cDNA clone was used to detect apolipoprotein CII mRNA approximately 500 bases long in human liver and intestine RNA.
Amino Acid Sequence↗
Autoreactive rat T-cell lines: establishment and cellular characteristics.
Stable self-reactive T-cell lines were established from the draining lymph nodes of Buffalo rats primed with rat thyroglobulin (Tg) in complete Freund's adjuvant. Following two rounds of in vitro selection with Tg or with purified protein derivative (PPD) of Mycobacterium tuberculosis, Tg- or PPD-specific lines were selected. Self-reactivity, manifested by a potent proliferative response of these lines to syngeneic stimulators in the absence of the selecting antigen (Tg or PPD), emerged by 3-4 weeks after the establishment of the lines. This proliferation could not be attributed to reactivity against heterologous serum components. Despite this syngeneic mixed-leukocyte reaction (SMLR) which was readily detectable, specific stimulation by Tg or PPD over the level of the SMLR could still be demonstrated. These lines also responded to concanavalin A but not to allogeneic stimulator cells. More than 95% of T cells of these lines displayed the rat T-helper-cell-specific (W3/25) marker and they secreted a defined lymphokine, T-cell growth factor (TCGF), upon stimulation with syngeneic stimulator cells, independent of the presence of soluble antigen. T-Cell lines such as the ones described here will be useful in elucidating the biological significance of the AMLR/SMLR and its relation to nominal antigen reactivity.
Animals↗
Senescent microstructural changes in rat cerebellum.
Senescent changes in Sprague-Dawley rat cerebellar microstructure have been quantified, focusing on the dominant element of cerebellar information processing, the Purkinje cell. In Golgi-Kopsch sections, many 26-month-old Purkinje cells appear defoliated, with small distal dendrites and spiny branchlets being most affected. The mean Purkinje cell area (soma plus dendrites) in computer-oriented sagittal sections is significantly decreased from 20,675 +/- 1,355 micron2/cell in 6-month-old rats to 17,088 +/- 1,107 micron2/cell in 26-month rats. These morphologic changes may be the hallmark of dying cells: in hematoxylin and eosin (H + E)-stained sections from the same rats we also observe a significant senescent decrease in Purkinje neuron density in every vermis lobule examined (lobules II-VII). Overall, the mean number of Purkinje cells/mm of Purkinje cell layer (measured in 10 micron thick sagittal sections) declines from 16.6 +/- 0.8 cells/mm in young rats to 12.5 +/- 0.2 cells/mm in old rats. As Purkinje cells are lost, so too are ethanolic phosphotungstic acid-stained (EPTA) synapses in the upper molecular layer of the cerebellar vermis (lobules VIII-X), and there is a highly significant within-subjects correlation between Purkinje cell density and synaptic density. Overall, synaptic density (in sagittal, 842 micron2 thin sections) decreases significantly from an average of 150,485 +/- 3,641 synapses/mm2 in 6-month rats to an average of 125,000 +/- 4,849 synapses/mm2 in 26-month rats. These changes are consistent with previous electrophysiologic and biochemical data showing age pathology of the cerebellum.
Aging↗
Urinary catabolites of ribonucleic acid as cancer markers: a preliminary report of their use in patients with lung cancer.
Rats with aflatoxin-B1-induced hepatomas and dimethylnitrosamine-induced nephroblastomas excreted greater than normal amounts of urinary modified nucleosides and bases, catabolites of ribonucleic acid (RNA). Although both neoplasms caused increased excretions of the same catabolites, their quantitative profiles differed, suggesting that it may be possible to distinguish between tumors. Rats with transplanted tumors (e.g., hepatomas and osteogenic sarcomas) did not excrete elevated levels of urinary RNA catabolites until approximately 20 days after transplantation despite rapid growth of the tumor for the first 15 days. These data suggest that the source of the elevated levels of these excretory products may be the host's tissue RNA. Preliminary studies in human beings with lung cancer showed marked elevation of one or more urinary RNA catabolites. Resection of the diseased tissue in 2 patients caused a drop in levels. The measurement of urinary RNA catabolites may be useful in the diagnosis, prognosis, and evaluation of therapy in patients with lung cancer.
Aflatoxin B1↗
Immunoglobulin RNA rearrangements in B lymphocyte differentiation.
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Amino Acid Sequence↗
Post tonsillectomy haemorrhage in children: The value of routine monitoring of the pulse.
Twenty-one children with reactionary haemorrhage after tonsillectomy were returned to theatre for the control of this haemorrhage. This group was matched for age and weight with 21 patients who underwent an uncomplicated tonsillectomy. The maximum pulse rate, the mean pulse rate and the maximum rise in pulse rate were recorded during the post-operative period and were noted for each group. No statistical difference existed between the groups. The monitoring of children in the period following tonsillectomy may be inadequate if the pulse alone is measured.
Adolescent↗
Stimulated release of histamine by a rat mast cell line is inhibited during mitosis.
Stimulated histamine release was depressed at least tenfold in mitotic 2H3 rat basophilic cells when compared with interphase cells even though both contained comparable amounts of histamine. Antigen stimulation of IgE-sensitized interphase cells initiated an influx of Ca2+ that preceded secretion of histamine and a similar Ca2+ influx occurred in stimulated mitotic cells. This strongly suggests that during mitosis there is a dramatic inhibition of one or more of the steps on the pathway leading from elevated intracellular Ca2+ to the fusion of secretory granules with the plasma membrane.
Animals↗
Life event stress: implications for the workplace.
In the light of recent research findings and clinical experience, the authors review the concept of "life event stress" and discuss the potential impact of major life events and crises on performance, work relationships and quality of life in the workplace. Because employees' responses to major life events and crises are affected by a number of factors, including personal resources and access to social support networks, it is in the interest of the employer to provide appropriate education, counselling and referral resources, reasonable accommodation regarding leave and responsibilities, and other forms of assistance and support in the wake of a major life event or crisis. Co-workers can also lend support.
Humans↗
Barriers faced by parents in obtaining dental treatment for young children: a questionnaire evaluation.
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Child↗
Induction of autoantibodies to thyroglobulin by anti-idiotypic antibodies.
We report on the induction of autoantibodies to thyroglobulin (Tg) and idiotype-positive molecules (Id') in naive BALB/c mice and Buffalo (BUF) rats after immunization with affinity-purified rabbit anti-Id antibodies directed against the Id of a mouse monoclonal antibody ( mAb62 ) specific for a hormone-containing epitope of Tg. Autoantibodies to Tg were produced in about one-half of anti-Id immunized mice, whereas Id' was detected in all but one mouse. Autoantibodies to Tg and Id' were not produced in control mice similarly immunized with non-anti-Id Ig. To clarify the relationship between molecules with Tg-binding activity and those referred to as Id', Tg-specific monoclonal antibodies were generated from an anti-Id-immunized mouse. By competitive inhibition experiments, we could determine that they were idiotypically very similar to the monoclonal antibody ( mAb62 ) at the origin of the immunologic cascade. Thus, autoantibodies induced by anti-idiotypic immunization alone are likely to be of the Ab1' type. Similarly, autoantibody to Tg and Id' molecules were induced in young normal rats of the autoimmune-prone BUF strain. Together, these results suggest that antibodies to Id directed against autoantigens are sufficient per se to activate self-reactivity.
Animals↗
Role of case studies in evaluating medical problem solving.
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Clinical Competence↗
Serum angiotensin-converting enzyme. Alterations in hyperthyroidism, hypothyroidism, and subacute thyroiditis.
Angiotensin-converting enzyme (ACE) activity was measured in the serum samples of 247 patients with varying thyroid states. In 60 hyperthyroid patients, the mean (+/- SD) ACE level of 29.5 +/- 9.7 units/mL was higher than in all other groups. The serum ACE level was 17.0 +/- 5.1 units/mL in 129 euthyroid subjects and differed from the level of 13.9 +/- 5.1 units/mL observed in 34 hypothyroid patients. Twenty-four patients receiving exogenous thyroid hormone had elevated serum thyroxine values. Their mean serum triiodothyronine level was in the normal range, and the mean ACE level did not differ from the euthyroid mean. The mean serum ACE level fell from 30.8 to 17.4 units/mL in 35 hyperthyroid patients studied before and after therapy. In 12 hypothyroid subjects, the mean serum ACE level rose from 11.6 to 15.8 units/mL after thyroid hormone replacement. In eight of ten patients with transient hyperthyroidism (subacute thyroiditis or painless thyrotoxic thyroiditis), their highest ACE levels were observed in the hyperthyroid or transition phase and fell progressively with the lowest values being recorded during the hypothyroid or early recovery phases. Thus, ACE activity may respond to thyroid hormone, and interpretation of serum ACE levels may require knowledge of the patient's thyroid status. Serum ACE may be useful as a probe for exploring peripheral thyroid hormone action.
Adolescent↗