Biomedical subjects
Publications and source records attributed to J Rogers.
Many issues surround self-directed care, and individuals who need habilitation services have brought those issues to the fore in recent years. The Visiting Nurse Association of Texas participates in a program with the state of Texas that allows individuals with disabilities to direct their own care while it also ensures that safety measures are addressed. The program is a success on many fronts.
Numerous markers of inflammation have been reported in the Alzheimer's disease brain. Although other pathogenic mechanisms certainly apply, there is now compelling evidence that inflammation is not simply a response to already existing Alzheimer's pathology, but ultimately becomes a significant source of pathology. The pathogenic potential of inflammation in Alzheimer's disease follows from the inherent destructiveness of inflammatory mechanisms, the postmitotic status of neurons, and the unique interactions of inflammatory markers and cells with pathologic hallmarks of Alzheimer's such as amyloid beta-peptide. These conclusions from basic science are borne out by recent clinical efforts, though the latter are still limited and require further confirmation.
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OBJECTIVE: To test the evolutionary hypothesis for joint failure by comparing the prevalence of osteoarthritis (OA) in 2 primate hands with different thumb usage. METHODS: We studied the hand skeletons of 32 humans and 32 macaques for OA. We defined OA as the presence of joint eburnation. RESULTS: The prevalence of OA in the distal interphalangeal joints was 26.7 and 50% for humans and monkeys, respectively. For the thumb base it was 37.5% in humans compared with 3.3% in macaques. The relative risk of thumb base OA in macaques may be due to the rudimentary design of the thumb. This finding supports the evolutionary hypothesis for joint failure and it may be applicable to many other joint sites.
Lysinomicin, a naturally-occurring pseudodisaccharide, inhibits translation in prokaryotes. We report that lysinomicin (and three related compounds) are able to inhibit the self-splicing of group I introns, thus identifying pseudodisaccharides as a novel class of group I intron splicing inhibitors. Lysinomicin inhibited the self-splicing of the sunY intron of phage T4 with a Ki of 8.5 microM (+/- 5 microM) and was active against other group I introns. Inhibition was found to be competitive with the substrate guanosine, unlike aminoglycoside antibiotics, which act non-competitively to inhibit the splicing of group I introns. Competitive inhibitors of group I intron splicing known to date all contain a guanidino group that was thought to be required for inhibition; lysinomicin lacks a guanidino group.
Several lines of evidence now suggest that aggregation of soluble amyloid beta peptide (A beta) into a cross beta sheet configuration may be an important factor in mediating potential neurotoxicity of A beta. Synthetic A beta has been shown to self aggregate in vitro. Here, we demonstrate that coincubation of freshly solubilized A beta with C1q, a complement component known to bind A beta in vitro and to colocalize with A beta in vivo, results in as much as a 7-fold enhancement of A beta aggregation, as well as a 2-4-fold enhancement of beta structure within aggregates. The addition of C1q to preformed A beta aggregates also results in significantly increased resistance to aggregate resolubilization.
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Activation-induced cell surface molecules are involved in mediating bidirectional T-B lymphocyte signaling that is important in the induction of T or B lymphocyte effector functions. In this regard, T-BAM/CD40-L is an activation-induced CD4+ T cell surface molecule known to be important in inducing B cell effector functions. This report demonstrates that T-BAM/CD40-L molecules on a Jurkat T cell leukemia subclone (D1.1) or nonlymphoid 293 kidney cell transfectants induce B cells or B-CLL cells to express CD80 (B7/BB-1) in a manner that is specifically inhibited by anti-T-BAM/CD40-L mAb 5C8. Because activation-induced B cell surface molecules, such as CD80, deliver costimulatory signals to T cells that augment T cell proliferation, the functional costimulatory capacity of T-BAM/CD40-L-primed B cells and B-CLL cells was studied. T-BAM/CD40-L-primed B cells or B-CLL cells augment the proliferative responses of allogenic T cells. Furthermore, T-BAM/CD40-L priming is specifically inhibited by mAb 5C8. Together, these studies demonstrate that T-BAM/CD40-L induces CD80 expression on resting B cells or B-CLL cells. Moreover, T-BAM/CD40-L signaling enhances B cell costimulatory capacity. These studies suggest that T-BAM/CD40-L molecules not only induce B cell differentiative processes that result in Ab secretion, but also enable B cells to prime Ag-specific T cells for subsequent clonal expansion.
Amyloid beta-peptide (A beta) has been shown to activate the classical complement pathway in vitro. Here, we demonstrate that this interaction is fully capable of killing cells and damaging cellular processes in mixed hippocampal cultures from embryonic day 18 rat fetuses. Lactic acid dehydrogenase (LDH) release and morphologic changes were used to evaluate toxicity.
Cardiac rH1 Na+ channel alpha subunits were expressed in cells of the Chinese hamster lung 1610 cell line by transfection, and a stable cell line expressing cardiac Na+ channels (SNa-rH1) was isolated. Mean Na+ currents of 2.2 +/- 1.0 nA were recorded, which corresponds to a cell surface density of approximately 1-2 channels active at the peak of the Na+ current per micron2. The expressed cardiac Na+ current was tetrodotoxin resistant (Kd = 1.8 microM) and had voltage-dependent properties similar to those of the Na+ current in neonatal ventricular myocytes. Activation of protein kinase C by 1-oleoyl-2-acetyl-sn-glycerol (OAG) (10 microM) decreased this current approximately 33% at a holding potential of -114 mV and 56% at -94 mV. This reduction in peak current was caused in part by an 8- to 14-mV shift of steady-state inactivation in the hyperpolarized direction. Na+ channel activation was unchanged. Effects of OAG in SNa-rH1 cells and in neonatal rat cardiac myocytes were similar, except that the time course of inactivation was slowed either transiently or persistently when protein kinase C was activated in myocytes bathed in low-Ca2+ (1 microM) or Ca(2+)-free solution but was unaffected in SNa-rH1 cells. The effects of OAG on cardiac Na+ current were blocked in cells that had been previously microinjected with a peptide inhibitor of protein kinase C but not with a peptide inhibitor of cAMP-dependent protein kinase, indicating that protein kinase C is responsible for the effect of OAG. Single-channel recordings from SNa-rH1 cells showed that the probability of channel opening was reduced by OAG, but the conductance was unaffected. OAG did not induce the late Na+ channel openings observed with PKC modulation of neuronal and skeletal muscle Na+ channels. Thus, the substantial reduction in Na+ current at normal diastolic depolarizations with 10 microM OAG is due to failure of channel opening in response to depolarization. Such Na+ current reductions may have profound effects on cardiac cell excitability.
The tuberactinomycins are a group of cyclic peptide antibiotics, which are potent inhibitors of prokaryotic protein synthesis. We report the inhibitory effect of viomycin, di-beta-lysyl-capreomycin IIA and tuberactinomycin A on group I intron self-splicing. They compete with the guanosine cofactor for the G-binding site located in the conserved core of the intron. They are 100-fold more active than all other competitive inhibitors described so far (dGTP, arginine or streptomycin), inhibiting splicing at concentrations between 10 and 50 microM. Mutation of the G-binding site leads to partial resistance, and the inhibitory effect of these drugs is dependent on Mg2+ concentration. This suggests that the tuberactinomycins have more than one contact site with the intron RNA: via the G-binding site and via additional contacts with the RNA backbone. Positioning the tuberactinomycins in the three-dimensional model of the td intron core suggests that the charged lysyl side-chain (R1) is in contact with the backbone of the P1 helix. Structure/function analyses with various tuberactinomycin analogues with different activities confirm the involvement of this sidechain in inhibition of group I self-splicing. The demonstration of a new class of splicing inhibitors, the peptide antibiotics, illustrates how antibiotics may interact with catalytic RNA.
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Molecular data are widely used to reconstruct phylogenetic relationships among species, and these phylogenies are often used as the basis for inferences about the history of evolutionary change in other nonmolecular characters. This approach is an appropriate and powerful one in many circumstances. But when several lineages diverge over a relatively short period of time, the assumption that a molecular (gene) tree will always be a valid basis for such inferences may not hold. Empirical evidence from humans, nonhuman primates, and other mammals indicates that the relationships among molecular divergence, morphological differentiation, and the origin of reproductive isolation between diverging lineages are complex. The simple dichotomously branching trees that result from molecular systematic studies of Homo, Gorilla, and Pan may be a misleading basis for reconstructions of evolutionary change in nonmolecular characters.
Thoracoscopic mobilization was performed in nine patients with oesophageal cancer. Five principles emerged as essential for successful dissection: (1) the selection of patients with mobile oesophageal tumours without evidence of local invasion; (2) double-lumen anaesthesia and complete collapse of the right lung during surgery; (3) simultaneous use of a flexible gastroscope; (4) high-quality illumination; and (5) minimal blood loss during dissection. The surgeon should have adequate training in thoracic operations. Further experience should permit mediastinal lymph node dissection. Postoperative pulmonary complications were common, requiring prolonged intensive care management. Widespread adoption of the technique cannot be recommended.
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Under standardized conditions, the manometric motility of the distal colon following rectosigmoid anastomosis (N = 11, median age 70 years, range 47-80), was compared to that following laparotomies not involving colonic anastomosis (N = 9, 56 years, 32-65). Microtransducer probes were inserted peroperatively and colonic activity recorded continuously (median 96 hr, range 48-109 anastomotic and 75 hr, range 46-107 control group) employing an ambulatory system. Quantitative indices of motility were calculated with an automated analysis program. Total postoperative analgesic doses and duration of surgery were similar in both groups. The first return in the anastomotic group of isolated waveforms [median 1.8 hr, interquartile range (IQR) 1-3] and propagated waves (92 hr, 79-100), was comparable to the control group (4 hr, 1.8-7, and 73 hr, 72-101, respectively). Motor complexes, characterized by bursts of regular contractile activity at 3-5 cpm, returned faster in the control group (3 hr, 2-24 vs 24 hr, 19-30, P < 0.05). Motility index was significantly depressed during the first 72 hr following surgery in the anastomotic group compared to controls (P < 0.001). Flatus was passed at a median of 72 hr (IQR 45-79) in the control and 94 hr (81-105) in the anastomotic group (P = 0.05). The presence of a left-sided colonic anastomosis has a major inhibitory effect on distal colonic motility, compared to nonanastomotic surgery of similar severity, in the early postoperative period.