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Biomedical subjects

S L Harris

Publications and source records attributed to S L Harris.

At least 37 records · Page 2Linked to original sources
PubMed1996

Tuberculosis outbreak in a Texas prison, 1994.

In 1994 a Texas prison containing a population of mentally retarded inmates experienced a large tuberculosis outbreak. Fifteen cases of tuberculosis were identified (8 confirmed by positive cultures for Mycobacterium tuberculosis) and more than 100 inmates became infected. The culture-confirmed patients were infected with an identical strain of tuberculosis as demonstrated by polymerase chain reaction (PCR) based DNA fingerprinting technique. The prison followed standard tuberculosis infection control policies, but these controls were inadequate to prevent tuberculosis transmission in this special population. Two hundred and thirty inmates (119 inmates showing evidence of new tuberculosis infection or active disease and 111 healthy controls) were enrolled in the investigation. Inmate cell assignments, job duties, and educational classes were identified and medical chart reviews were conducted on all inmates. Tuberculosis transmission was associated with residing on the D Wing of the prison (OR = 25.84, P < 0.01), attending school in Classroom A (OR = 8.34, P = 0.01) and working on the prison utility work crew (OR = 2.52, P < 0.01). The index case in the outbreak had been prescribed 6 months of isoniazid (INH) chemoprophylaxis in 1988.

Case-Control Studies↗
PubMed1996

Localization of a yeast early Golgi mannosyltransferase, Och1p, involves retrograde transport.

To analyze the mechanism of integral membrane protein localization in the early Golgi apparatus of Saccharomyces cerevisiae, we have used Och1p, a cis-Golgi mannosyltransferase. A series of influenza virus hemagglutinin (HA) epitope-tagged fusion proteins was constructed in which invertase is appended to the Golgi-luminal carboxy terminus of full-length Och1p. Several constructs included a Kex2p cleavage site between the Och1p and invertase moieties to monitor transit to the Kex2p-containing TGN. Cells expressing an Och1p-invertase fusion do not secrete invertase, but those expressing an Och1p-Kex2p site-invertase fusion protein secrete high levels of invertase in a Kex2p-dependent manner. The Och1p-Kex2p site-invertase fusion protein is cleaved with a half-time of 5 min, and the process proceeds to completion. Before cleavage the protein receives glycosyl modifications indicative of passage through the medial- and trans-Golgi, therefore cleavage occurs after ordered anterograde transport through the Golgi to the TGN. Transit to distal compartments is not induced by the invertase moiety, since noninvertase fusion constructs encounter the same glycosyltransferases and Kex2p as well. The Och1p-HA moiety, irrespective of whether it is generated by cleavage of the fusion protein in the TGN or synthesized de novo, is degraded with a half-time of about 60 min. Thus, the half-time of degradation is 12-fold longer than the time required to reach the TGN. At steady state, de novo-synthesized and TGN-generated HA epitope-tagged Och1p reside in a compartment with a buoyant density identical to that of wild-type Och1p and distinct from that of the vacuole or the TGN. Finally, och1 null cells that express an Ochlp fusion construct known to rapidly encounter the TGN glycosylate invertase to the same extent as wild-type cells, indicating that they have phenotypically wild-type Och1p activity. These results lead us to propose a model for Och1p-HA localization that involves movement to distal compartments, at least as far as the TGN, followed by retrieval to the cis compartment, presumably by vesicular transport.

Amino Acid Sequence↗
PubMed1995

Transferred nuclear Overhauser enhancement experiments show that the monoclonal antibody strep 9 selects a local minimum conformation of a Streptococcus group A trisaccharide-hapten.

Transferred nuclear Overhauser enhancement (TRNOE) experiments have been performed to investigate the bound conformation of the trisaccharide repeating unit of the Streptococcus Group A cell-wall polysaccharide. Thus, the conformations of propyl 3-O-(2-acetamido-2-deoxy-beta-D-glucopyranosyl)-2-O-(alpha-L-rhamnopyran osyl)- alpha-L-rhamnopyranoside [C(A')B] (1) as a free ligand and when complexed to the monoclonal antibody Strep 9 were examined. Improved insights about the conformational preferences of the glycosidic linkages of the trisaccharide ligand showed that the free ligand populates various conformations in aqueous solution, thus displaying relatively flexible behavior. The NOE HNAc-H2A', which was not detected in previous work, accounts for a conformation at the beta-(1-->3) linkage with a phi angle of approximately 180 degrees. Observed TRNOEs for the complex are weak, and their analysis was further complicated by spin diffusion. With the use of transferred rotating-frame Overhauser enhancement (TRROE) experiments, the amount of spin diffusion was assessed experimentally, proving that all of the observed long-range TRNOEs arose through spin diffusion. Four interglycosidic distances, derived from the remaining TRNOEs and TRROEs, together with repulsive constraints, derived from the absence of TRROE effects, were used as input parameters in simulated annealing and molecular mechanics calculations to determine the bound conformation of the trisaccharide. Complexation by the antibody results in the selection of one defined conformation of the carbohydrate hapten. This bound conformation, which is a local energy minimum on the energy maps calculated for the trisaccharide ligand, shows only a change from a +gauche to a -gauche orientation at the psi angle of the alpha-(1-->2) linkage when compared to the global minimum conformation. The results infer that the bound conformation of the Streptococcus Group A cell-wall polysaccharide is different from its previously proposed solution structure (Kreis et al., 1995).

Antibodies, Monoclonal↗
PubMed1995

Teaching children with autism to seek information: acquisition of novel information and generalization of responding.

A time delay procedure was used to teach 3 children with autism to ask the question "What's that?" when novel stimuli were presented during an instructional task. Once the ability to ask the question was acquired, the children's ability to learn novel information by asking the question was assessed. The children were then taught to ask the question within a less structured context. All three studies used a multiple baseline across participants. Generalization was assessed in a different room, to a new person, and to novel stimuli. All of the children learned to ask the question within the instructional context, while on a walk in the school building, and to request information about three-dimensional objects. The acquisition of novel information was consistent for receptive and expressive tests for 2 of the children, with varied results for the 3rd. These studies indicate that children with autism can be taught to ask questions that lead to the acquisition of new information.

Attention↗
PubMed1995

The effect of articular conformity and the size of the humeral head component on laxity and motion after glenohumeral arthroplasty. A study in cadavera.

We used a cadaveric model to examine the mechanical effects of changes in the conformity of the articular surfaces and the size of the humeral head component in glenohumeral arthroplasty. The experimental system permitted a manual clinical examination of the glenohumeral joint while sensors monitored the humeroscapular position and orientation as well as the forces and torques applied by the examiner. Four preparations were compared: an anatomical humeroscapular preparation and three glenohumeral arthroplasty preparations (one with anatomically sized components and a radius of curvature of the glenoid that was four millimeters larger than that of the humeral head, one with anatomically sized components and a radius of curvature of the glenoid that was equal to that of the humeral head, and one with a non-anatomical, large humeral head component and a radius of curvature of the glenoid that was equal to that of the humeral head). All motions, including flexion, external and internal rotation, and maximum elevation, were diminished with use of the non-anatomical, large humeral head component. Laxity of the joint on drawer and sulcus tests was not affected by the conformity of the articular surfaces but was decreased significantly by implantation of the large humeral head component. The kinematics of the glenohumeral joint were not markedly altered by reduction of the uniformity between the articular surfaces of the prosthetic components. In all preparations, obligate displacement of the humeral head associated with a passive range of motion occurred at smaller angles with the large humeral head component.

Aged↗
PubMed1994

Dominant lethal mutations in the plasma membrane H(+)-ATPase gene of Saccharomyces cerevisiae.

The plasma membrane H(+)-ATPase of Saccharomyces cerevisiae is an essential protein that is required to establish cellular membrane potential and maintain a normal internal pH. An Asp-378 to Asn substitution at the residue phosphorylated during catalysis is dominant lethal when the pma1-D378N mutation is expressed along with a wild-type plasma membrane H(+)-ATPase (PMA1) gene. Several mutations in the first two putative transmembrane domains are also dominant lethal. However, these dominant lethal mutants often appear to be innocuous, because they are frequently lost by gene conversion to the wild-type sequence during the process of introducing the mutant sequence and subsequently removing the wild-type gene. Loss of the mutation by gene conversion does not occur while introducing recessive lethal mutations. Cells carrying the wild-type PMA1 gene on the chromosome and a dominant lethal mutation under the control of a GAL1 promoter on a centromere-containing plasmid exhibit a galactose-dependent lethality. Indirect immunofluorescence staining using anti-Pma1 antibodies shows that induction of dominant lethal PMA1 mutations leads to the accumulation of a number of intensely staining cytoplasmic structures that are not coincident with the nucleus and its immediately surrounding endoplasmic reticulum. These structures also accumulate the endoplasmic reticulum protein Kar2. Expression of the dominant lethal protein also prevents transport of the wild-type ATPase to the plasma membrane.

Asparagine↗
PubMed1994

Arthroscopic labral repair to the glenoid rim.

The purpose of this study was to develop a new arthroscopic approach for traumatic instability that effectively reattaches avulsed capsulolabral tissue to the glenoid articular rim with sutures. This technique does not depend on fixation devices, trans-scapular drilling, or implantation of suture anchors. We attached a three-dimensional position sensor and force and torque transducer to the humerus and scapula of eight normal cadaveric shoulders to measure the normal, surgically unstable (arthroscopic Bankart lesion), and repaired preparations. We assessed eight motion ranges and six laxity tests. Capsulolabral release increased all passive ranges and allowed significant translational increases on posterior drawer and crank testing. After repair, motion was never decreased and there were no differences in laxity relative to normal. Neurovascular structures were never at risk. Our arthroscopic repair provides anatomic reattachment and effective deepening of the glenoid con-cavity similar to that achieved by open repair. This new method restores joint stability, preserves motion, and can withstand forceful loads. Ongoing clinical trials will substantiate whether the technique is as safe and reliable as shown cadaverically.

Adult↗
PubMed1994

Community-based behavioral training approaches for people with mental retardation and mental illness.

Challenges associated with behavioral training approaches for individuals with mental retardation and mental illness in the community are reviewed in this article. Family and nonfamily facilitated training are considered. Professional practice issues are reviewed, and justification for multifactor behavioral assessment is offered. Future research directions are discussed.

Behavior Therapy↗
PubMed1993

Convergent synthesis of an elusive hexasaccharide corresponding to the cell-wall polysaccharide of the beta-hemolytic Streptococcus group A.

A convergent synthesis of a hexasaccharide corresponding to the cell-wall polysaccharide of the beta-hemolytic Streptococcus Group A is described. The strategy relies on the preparation of a key linear trisaccharide unit beta-D-GlcpNAc-(1-->3)-alpha-L-Rhap-(1-->2)-alpha-L-Rhap which has previously resisted our efforts. The trisaccharide functions both as a glycosyl acceptor and donor to give an elusive hexasaccharide. This fully functionalized unit can serve, in turn, as a glycosyl acceptor or donor for the synthesis of higher-order structures. Deprotection gives a hitherto unknown hexasaccharide for use as a hapten in immunochemical studies. The characterization of all compounds by high-resolution 1H and 13C NMR spectroscopy is also described.

Carbohydrate Conformation↗
PubMed1993

Enhanced cytochrome-oxidase staining of the cuneate nucleus in the rat reveals a modifiable somatotopic map.

Existing cytochrome oxidase (CO)-staining techniques were modified to enhance sensitivity and contrast in order to examine patterns of CO-activity in the dorsal column nuclei (DCN) of adult Long-Evans rats. Within a rostrocaudally limited region in the middle of the cuneate nucleus (CN) distinctive blotches of intense CO-activity were observed. The CO-staining was maximally differentiated approximately 0.3-0.7 mm caudal to the obex. No CO-blotches were observed anywhere else in the DCN. Transganglionic labelling (WGA-HRP) demonstrated that some of the CO-blotches in the rat CN are related to the terminal projection fields of primary afferents from the skin of the forepaws. The corresponding location of primary afferent termination fields and CO-staining patterns supports a tripartite rostrocaudal division in the rat CN, similar to that described by other investigators in cats, monkeys and raccoons. Comparing the patterns of CO-staining to (1) the cytoarchitecture (Nissl-stained sections), or to (2) the dendritoarchitecture (distribution of microtubule-associated protein 2 (MAP2) or to (3) the organization of retrogradely labelled (WGA-HRP/HRP) cuneothalamic cells, revealed no topographical organization corresponding to the CO-blotches. Postnatal (at least up to 11 days postpartum) forepaw deafferentation or removal disrupted the CO-staining pattern in the CN.

Animals↗
PubMed1993

Inadvertent administration of rtPA to a patient with type 1 aortic dissection and subsequent cardiac tamponade.

Administration of thrombolytic agents to patients with misdiagnosis of acute myocardial infarction can result in serious side effects. A case of aortic dissection that was misdiagnosed as acute myocardial infarction and received rtPA is reported. Within 1 hour of rtPA infusion, the patient developed cardiac tamponade. Type 1 aortic dissection was diagnosed by aortic angiogram. The patient underwent emergency resection of the dissection and evacuation of the pericardial and anterior mediastinal hematoma. Although he required massive transfusion of blood products intraoperatively, he is doing well 22 months after his surgery.

Aged↗
PubMed1993

Rapid, synchronous, and stable induction of type 1 piliation in Escherichia coli by using a chromosomal lacUV5 promoter.

Type 1 pili are filamentous proteinaceous appendages produced by certain members of the family Enterobacteriaceae. In Escherichia coli, the adhesive properties of these pili are due to the binding of at least one minor pilus component to mannose, a sugar common to cell surface molecules of many eukaryotic cells. The study of pilus assembly may be benefited by a rapid way of inducing pilus synthesis de novo. We describe herein the construction and characterization of a strain in which piliation can be rapidly induced by the addition of lactose or its analog isopropyl-beta-D-thiogalactopyranoside. This was accomplished by placing the chromosomal fimA gene (encoding the major structural subunit of pili) under lacUV5 promoter control. Further experiments suggested that transcription of genes downstream of fimA, whose products are required for normal pilus assembly and function, may also be controlled by the lacUV5 promoter. The construction described herein may have a variety of applications apart from aiding the study of pilus assembly since its adhesive properties can be rapidly and easily turned on and off.

Bacterial Proteins↗
PubMed1992

Convergent synthesis of higher-order oligosaccharides corresponding to the cell-wall polysaccharide of the beta-hemolytic Streptococci group A. A branched hexasaccharide hapten.

A convergent synthesis of a hexasaccharide corresponding to the cell-wall polysaccharide of the beta-hemolytic Streptococci Group A is described. The strategy relies on the preparation of a key branched trisaccharide unit alpha-L-Rhap-(1----2)-[beta-D-GlcpNAc-(1----3)]-alpha-L-Rhap which functions both as a glycosyl acceptor and donor. The hexasaccharide is obtained after only three glycosylation reactions. This fully functionalized unit can serve, in turn, as a glycosyl acceptor or donor for the synthesis of higher-order structures. Deprotection gives a hexasaccharide for use as a hapten in immunochemical studies. The characterization of all compounds by high resolution 1H- and 13C-n.m.r. spectroscopy is also described.

Carbohydrate Sequence↗
PubMed1992

Genetic probing of the yeast plasma membrane H(+)-ATPase.

The H(+)-ATPase from Saccharomyces cerevisiae has been probed by a random genetic approach that has led to the isolation of primary and secondary site mutations. These H(+)-ATPase (PMA1) mutants help define specific functional, as well as interacting, regions of the H(+)-ATPase. Cellular resistance to hygromycin B has been an important selection tool for the isolation of pmal mutants. One prominent hygromycin B-resistant mutant, pmal-105, was found to have a S368F mutation near the site of phosphorylation (D378) in the catalytic core. This mutation prevents growth in low pH or NH(4+)-containing medium and induces an acid-sensitive Vmax for ATP hydrolysis, as well as a pronounced insensitivity to vanadate. The prominent cellular and biochemical phenotypes of this strain facilitated a detailed revertant analysis to identify protein structure domains that interact directly or indirectly with the localized region defined by the F368 mutation. Partial revertants were isolated which were resistant to low pH or NH4+ but retained hygromycin resistance. Second site mutations were found within the first and second cytoplasmic loop domains, as well as in transmembrane segments 1-3 & 7. All of the revertant enzymes have a stable Vmax but some show changes in the pH optimum for ATP hydrolysis; all display vanadate sensitivities ranging between the insensitive F368 mutant and the fully-sensitive wild type enzyme. Revertant analyses have also been performed on two other pma1 mutants which carry the mutations A135V and G158D in transmembrane segments 1 and 2, respectively. Compensating second site mutations to these mutations were identified in transmembrane segments 1, 2, 4 & 7, as well as within the central catalytic domain. These analyses have helped identify interacting protein structure domains that may participate in coupling ATP hydrolysis to proton transport. Furthermore, they facilitate the construction of structural models to account for these interactions.

Cell Membrane↗
PubMed1992

The role of the rotator interval capsule in passive motion and stability of the shoulder.

The purpose of this study was to characterize the role of the capsule in the interval between the supraspinatus and subscapularis tendons with respect to glenohumeral motion, translation, and stability. We used a six-degrees-of-freedom position-sensor and a six-degrees-of-freedom force and torque-transducer to determine the glenohumoral rotations and translations that resulted from applied loads in eight cadaver shoulders. The range of motion of each specimen was measured with the capsule in the rotator interval in a normal state, after the capsule had been sectioned, and after it had been imbricated. Operative alteration of this capsular interval was found to affect flexion, extension, external rotation, and adduction of the humerus with respect to the scapula. Modification of this portion of the capsule also affected obligate anterior translation of the humeral head on the glenoid during flexion. Limitation of motion and obligate translation were increased by operative imbrication and diminished by sectioning of the rotator interval capsule. Passive stability of the glenohumeral joint was evaluated with the use of anterior, posterior, and inferior stress tests. Instability and occasional frank dislocation of the glenohumeral joint occurred inferiorly and posteriorly after section of the rotator interval capsule. Imbrication of this part of the capsule increased the resistance to inferior and posterior translation.

Aged↗
PubMed1991

Evidence for coupling between membrane and cytoplasmic domains of the yeast plasma membrane H(+)-ATPase. An analysis of intragenic revertants of pma1-105.

A genetic approach was used to identify interacting portions of the plasma membrane H(+)-ATPase from Saccharomyces cerevisiae. The cellular sensitivity of the pma1-105 strain (S368F) to low external pH and to NH4+ was used to select intragenic revertants of two classes: phenotypically wild-type full revertants and partial revertants that were low pH-resistant but retained resistance to hygromycin B. All 10 full revertants had S368 restored. Among five partial revertants mapping to the original site within the phosphorylation domain, S368L and S368V were each found twice. One revertant contained an E367V substitution adjacent to the original S368F alteration. Four of 13 independently isolated second-site revertants mapped to one site, V289F, in the proposed phosphatase domain. Mutations within the proposed phosphatase and phosphorylation domains resulted in enzymes with increased vanadate sensitivity relative to the vanadate-insensitive S368F enzyme. These results suggest that sites S368, E367, and V289 contribute to a vanadate (Pi) binding domain or are able to interact with such a site within the catalytic domain. The remaining nine partial second-site revertants mapped to six sites within the putative transmembrane regions. Mutations within the transmembrane region had less of an effect on vanadate sensitivity. Most revertant enzymes showed small but significant increases in the rate of ATP hydrolysis relative to the S368F enzyme. Several enzymes no longer displayed the acid-sensitive pH-dependence seen in the S368F enzyme. These data provide novel evidence for an interaction between putative transmembrane helices 1-3 and 7 and the ATP hydrolytic portion of the enzyme.

Adenosine Triphosphate↗
PubMed1991

Percutaneous transluminal coronary angioplasty utilizing prolonged balloon inflations: initial results and six-month follow-up.

Coronary angioplasty (PTCA) using prolonged balloon inflation has obviated emergency coronary bypass surgery in some patients with acute occlusions at the time of PTCA. However, the use of prolonged balloon inflations has not been shown to improve long-term restenosis rates. As an alternative to the passive autoperfusion catheter, we evaluated a hemoperfusion system in which blood was obtained from the side arm of an arterial sheath and infused through the central lumen of standard balloon catheters via a modified Medrad IV pump during balloon inflation. PTCA was performed in 71 male patients (median age 57 yr). The median balloon inflation time was 4.8 minutes and the median rate of blood perfusion was 30 ml/min. PTCA was successful (lumen increase by 20 percentage points) in 83% of patients (59/71) with diameter stenosis decreasing from a median 82% to 30%. Emergency coronary bypass was required in four patients (5%). Angiographic data for six-month followup was available on 37 patients. The restenosis rate (loss of 50% of gain) was 46% (17/37). The conclusion is that prolonged balloon inflation angioplasty has a role in complicated PTCA but offers no advantage in improving long-term restenosis rates in elective PTCA.

Adult↗