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Biomedical subjects

P Harris

Publications and source records attributed to P Harris.

At least 19 recordsLinked to original sources

Rat renomedullary interstitial cells possess bradykinin B2 receptors in vivo and in vitro.

1. Renomedullary interstitial cells (RMIC), abundant throughout the medulla of the kidney, have been demonstrated to have binding sites for many vasoactive peptides, including atrial natriuretic peptide, endothelin, angiotensin II and bradykinin (BK). These observations would support the hypothesis that interactions between RMIC and vasoactive peptides are important in the regulation of renal function. 2. We aimed to localize the BK B2 receptor binding site to RMIC in vivo and to also demonstrate that these receptors are biologically active in vitro. 3. The present study demonstrates BK B2 binding sites on RMIC of the inner stripe of the outer medulla and the inner medulla of the rat kidney in vivo. 4. We further demonstrate that the BK B2 radioligand [125I]-HPP-Hoe140 specifically bound to rat RMIC in vitro. In addition, reverse transcription-polymerase chain reaction detected the mRNA for the BK B2 receptor subtype in cell extracts. 5. For RMIC in vitro, cAMP levels were increased at 1 min and cGMP levels were increased at 2 min after treatment with 10(-10) and 10(-7) mol/L BK, respectively. Inositol 1,4,5-trisphosphate was increased at 10 s treatment with both 10(-6) and 10(-7) mol/L BK. 6. For RMIC in vitro, BK induced an increase in cell proliferation ([3H]-thymidine incorporation) and an increase in extracellular matrix synthesis (ECM; trans-[35S] incorporation), both effects mediated by BK B2 receptors. 7. We conclude that BK B2 receptors are present on RMIC both in vivo and in vitro. These receptors are coupled to intracellular second messenger systems and, in vitro, their stimulation results in cellular proliferation and synthesis of ECM.

Animals

Longitudinal aneurysm shrinkage following endovascular aortic aneurysm repair: a source of intermediate and late complications.

PURPOSE: To report the incidence of delayed complications following endovascular abdominal aortic aneurysm (AAA) repair and the relationship of these sequelae to morphological changes in the sac and endograft. METHODS: Twenty-six AAA patients treated with Vanguard endografts had completed > or = 1-year follow-up. Postoperative angiograms and spiral computed tomographic (CT) scans with 3-dimensional reconstruction were compared to the 1-year images to determine morphological changes in the aneurysm sac and the endograft. These changes were then related to complications occurring between 1 and 12 months postoperatively in the study group. RESULTS: Comparison of angiograms uncovered endograft buckling in 18 (69%) patients and acutely angled or kinked endografts in 10 (38%). Measurements from the CT scans found that undistorted endografts had a mean change in sac length of +6.6 mm. Mean sac length change in buckled endografts was -3.1 mm, while kinked endografts displayed a mean change of -6.2 mm (p < 0.002, Student's t-test). Five (19%) patients, all with distorted endografts, demonstrated late (1 to 12 months) complications (4 endoleaks and 1 graft limb thrombosis) owing to component separation, distal stent migration, and acute angulation. No movement in the proximal stent was observed. Elongation of the endograft (flow line measurement) was observed in one tube graft only. CONCLUSIONS: In this study, longitudinal shrinkage of the sac following endovascular aortic aneurysm repair led to buckling or kinking of the endograft within 1 year in 69% of patients. This appears to be an important source of delayed complications.

Aged

Primary hypoadrenocorticism in a dog receiving glucocorticoid supplementation.

A 5-year-old, spayed, female husky-Labrador retriever cross was diagnosed with primary hypoadrenocorticism, an uncommon endocrine disorder caused by a deficiency of glucocorticoid and mineralocorticoid hormones. Subtle clinical signs and previous treatment with exogenous glucocorticoid drugs required an adrenocorticotropic hormone stimulation test to confirm the diagnosis.

Adrenal Insufficiency

Chronic orthostatic intolerance: a disorder with discordant cardiac and vascular sympathetic control.

BACKGROUND: Chronic orthostatic intolerance (COI) is a debilitating autonomic condition in young adults. Its neurohumoral and hemodynamic profiles suggest possible alterations of postural sympathetic function and of baroreflex control of heart rate (HR). METHODS AND RESULTS: In 16 COI patients and 16 healthy volunteers, intra-arterial blood pressure (BP), ECG, central venous pressure (CVP), and muscle sympathetic nerve activity (MSNA) were recorded at rest and during 75 degrees tilt. Spectral analysis of RR interval and systolic arterial pressure (SAP) variabilities provided indices of sympathovagal modulation of the sinoatrial node (ratio of low-frequency to high-frequency components, LF/HF) and of sympathetic vasomotor control (LFSAP). Baroreflex mechanisms were assessed (1) by the slope of the regression line obtained from changes of RR interval and MSNA evoked by pharmacologically induced alterations in BP and (2) by the index alpha, obtained from cross-spectral analysis of RR and SAP variabilities. At rest, HR, MSNA, LF/HF, and LFSAP were higher in COI patients, whereas BP and CVP were similar in the two groups. During tilt, BP did not change and CVP fell by the same extent in the 2 groups; the increase of HR and LF/HF was more pronounced in COI patients. Conversely, the increase of MSNA was lower in COI than in control subjects. Baroreflex sensitivity was similar in COI and control subjects at rest; tilt reduced alpha similarly in both groups. CONCLUSIONS: COI is characterized by an overall enhancement of noradrenergic tone at rest and by a blunted postganglionic sympathetic response to standing, with a compensatory cardiac sympathetic overactivity. Baroreflex mechanisms maintain their functional responsiveness. These data suggest that in COI, the functional distribution of central sympathetic tone to the heart and vasculature is abnormal.

Adult

Induction of MHC-class I restricted human suppressor T cells by peptide priming in vitro.

The induction of regulatory T cells may offer an effective means for specific immunosuppression of autoimmune disease and allograft rejection. The existence of suppressor T cells has been previously documented, yet their mechanism of action remains poorly characterized. Our studies demonstrate that T suppressor (Ts) cell lines can be generated by in vitro immunization of human PBMCs, with synthetic peptides or soluble proteins coupled to beads. Such Ts cells express the CD8+CD28- phenotype and show the following characteristics: (a) antigen specificity and restriction by self MHC Class I molecules; (b) limited TCR V beta gene usage; (c) ability to inhibit antigen-specific, MHC Class II restricted, Th proliferative responses; and (d) capacity to downregulate and/or inhibit the upregulation by Th of CD40, CD80, and CD86 molecules on APCs. The inhibitory activity of Ts on Th proliferation requires the tripartite interaction between Th, Ts, and APCs and results from inefficient costimulation of Th.

Amino Acid Sequence

Using multimedia for patient information--a program about nocturnal enuresis.

OBJECTIVES: To identify the information needs of children with nocturnal enuresis, and to design, produce and evaluate an interactive computer program to provide this information. SUBJECTS AND METHODS: The program was developed over an 18-month period using information provided by children, parents and professionals, and was evaluated in a hospital-based enuresis clinic in 65 children. Usability and knowledge gained were also evaluated in 43 healthy children aged 8-10 years attending a local inner-city primary school. RESULTS: An interactive program about nocturnal enuresis was developed, which runs on a personal computer and uses sound, voice, cartoon drawings and animation in a modular design. Knowledge scores increased in clinic attendees and in schoolchildren after using the program (Wilcoxon matched pairs test, P < 0.001). This improvement was maintained when the program was re-tested 6-10 months later. CONCLUSION: This interactive computer program holds children's attention and increases their understanding of enuresis. Interactive multimedia may be useful to complement the information provided by health professionals. This method of communication may be particularly useful for children with a low level of literacy.

CD-ROM

Localization and interactions of vasoactive peptide receptors in renomedullary interstitial cells of the kidney.

Vasoactive peptides regulate renal medullary microcirculation and tubular function, but the localization of their receptors and mechanisms of actions are currently unknown. Using electron microscopic autoradiography, we have mapped the receptors for angiotensin II (Ang II [AT1 and AT2]), endothelin (ET(A) and ET(B)), and bradykinin (B2) in the rat renal medulla. Although these peptide receptors show distinct vascular and tubular distributions, they overlap strikingly in renomedullary interstitial cells (RMICs) of the inner stripe and the papilla. Using reverse transcription-polymerase chain reaction (RT-PCR) and Southern analysis, mRNAs for AT1A, ET(A), and B2 receptors were detected in cultured adult RMICs. Ang II increases intracellular inositol 1,4,5-triphosphate (IP3) and [Ca2+]i and stimulates [3H]thymidine incorporation and extracellular matrix (ECM) synthesis via AT1A receptors. Endothelin and bradykinin also stimulate cell proliferation and ECM synthesis in RMICs through ET(A) and B2 receptors, respectively, but the actions of endothelin are modulated by concurrent nitric oxide production. By contrast, AT2 receptor mRNA was detected only in embryonic RMICs, in which Ang II inhibits cell proliferation through this receptor. These results suggest that multiple vasoactive peptides may interact with RMICs to exert endocrine and/or paracrine influences on renal medullary microcirculation and tubular function.

Animals

Mistakes around the clock: errors in memory for the orientation of numerals.

Recent research has demonstrated that when participants are required to draw from memory a standard clock with numbers represented by Roman numerals, they typically misrepresent the four as "IV" rather than as the correct "IIII." Participants do not make this mistake when they simply copy the clock while it remains in full view. A reanalysis of the data presented by Richards, French, and Harris (1996) is reported in which we investigated the representation of the orientation of the Roman numerals on the clockface and found that participants in the memory conditions (surprise and forewarned) were more likely than participants in the copy (control) condition to draw the numerals vertically rather than in their correct centripetal orientation. In addition, we found this error was even more likely to occur for participants when they had no warning that a memory task would take place.

Adult

Maximizing care outcomes of a patient with impaired bladder function: a PI project in a rehabilitation unit.

At Jamaica Hospital Medical Center Rehabilitation Unit, approximately 50 percent of patients have impaired bladder function due to disease and trauma. In 1996, the rehabilitation staff identified an opportunity to improve care outcomes of patients with impaired bladder function. Using five steps for performance improvement from the Joint Commission on Accreditation of Healthcare Organizations, a team consisting of a physician, nurse, therapist, and psychologist was formed to explore strategies for improving care of these patients. The goal was to investigate the advantages of using noninvasive devices in maximizing care outcomes.

Adult

[Evaluation of hemispatial dominance by the cancellation test].

Our objective was to study cultural (first language) and innate (handedness) influences on the performance (omissions, site of beginning) of the cancellation test. We studied 71 healthy subjects aged between 18 and 52 years. There were 41 right-handed and 14 left-handed with Spanish as first language in Buenos Aires study site, and 16 right-handed with Hebrew as first language in Israel study site, matched by age and education. We used the Mesulam verbal and non verbal cancellation test, and a modified verbal version in hebrew letters. Omissions in the right side were more frequent in right-handed Spanish-speaking subjects (p < 0.001). We did not find this asymmetry in the individuals from Israel. While all right-handed Spanish-speaking subjects began the test by the left upper corner, most of the left-handed did it by the right upper corner. We conclude that asymmetry in the performance of the cancellation test may have genetic and/or cultural influences.

Adult

[Differential cognitive profiles of fronto-temporal dementia and Alzheimer's disease].

INTRODUCTION AND OBJECTIVE: When the clinical picture consists of prominent cognitive impairments (e.g. amnesia) with relatively mild behavioral symptoms, it can be very difficult to distinguish frontal lobe dementia (FLD) from Alzheimer disease (AD). However, these conditions may have distinct cognitive profiles that could be detected by means of neuropsychological testing. The objective was to examine the early differential cognitive feature between FLD and AD. PATIENTS AND METHODS: Twelve patients with FLD, 20 patients with AD, and 20 normal subjects matched for age and educational level were evaluated with the Folstein Mini Mental State Examination, the Signoret Memory Battery, the Boston Naming Test, Verbal Fluency (FAS), the Wechsler Adult Intelligence Scale, and the Trail Making Test. The FLD patients met the Lund and Manchester criteria, and the AD patients met the National Institute of Neurological Disorders and Stroke-Alzheimer Disease and Related Disorders Association (NINDS-ADRDA) criteria for clinically probable AD. RESULTS: FLD and AD patients were matched for the severity of dementia using the Global Deterioration Scale (3.8 +/- 0.3 versus 3.9 +/- 0.5 respectively). Mean Z scores were calculated in order to facilitate the comparison between the neuropsychological profiles obtained. FLD patients scored significantly better than AD patients in memory test, calculation, visuospatial abilities, and the naming test. AD patients performed better on executive tasks. CONCLUSION: These findings suggest that neuropsychological examination may be useful in differential diagnosis between FLD and AD

Adult

[Biomechanical evaluation and clinical correlation of 3 methods of internal fixation of metacarpophalangeal arthrodesis of the thumb].

Three methods of internal fixation for MCP arthrodesis of fifteen cadaveric thumbs were used to analyze the biomechanical stability by applying a palmar force, lateral force, and torsion moment. The techniques used included two K-wires 0.045 in parallel (BK), 2 cerclage metallic wires #25 perpendicular to each other (CP), and a 6-holes plate and screws construct from Synthes (PV). The initial rigidity was measured using a Bionix MTS-858. The results after statistical analysis showed: 1) CP was just as rigid as PV for the palmar and lateral tests; 2) CP was, overall, superior to BK in palmar and lateral tests; 3) no difference existed in torsion between the three types of fixation. A comparison was done between the rigidity of the fixation techniques used and the rates of bony nonunion found in the literature. The mean rates of nonunion were reported to be 0-4.0% for the following techniques: CP, tension band wiring (TB), plate and screws, external fixation, compression screw. The rates of nonunion were higher, 7.5-12.5%, for BK, cerclages not perpendicular (CM), bone pegs. According to the results of this biomechanical study and the review of the literature, fixation with BK is the least rigid, and fixation with CP is just as rigid as with PV. The success clinically of CP is yet to be demonstrated. Other studies on the properties of CP for fatigue would be necessary to give a better analysis.

Analysis of Variance

[An anatomic study of the superficial radial nerve and its clinical implications].

In hand surgery, the k-wires are used frequently and effectively. Several texts mention complications following surgery of the wrist and hand. A safe zone has been described by Steinberg et al., where 40 K-wires were placed in the anatomic snuffbox of 10 cadaveric forearms. The placement of the k-wires were evaluated radiologically and by dissection to examine the underlying structures. A branch of the superficial radial nerve (NRS) was injured in 22% (2/9) of the specimens and the cephalic vein in 33% (3/9). The radial artery was never injured but had a K-wires at least 1 mm away in 22% of the specimens. The anatomy and pattern of distribution of the NRS was studied and compared with the data found in the literature. The NRS emerged between the tendons the muscles of brachioradialis and extensor carpi radialis longus in 9 of 10 specimens, and at a mean distance of 7.8 cm from the radial styloid. The first and second division were at a mean distance proximal to the radial styloid of 4.5 and 3.0 cm, respectively. The mean number of branches of the NRS at the radial styloid was 5.1. Despite a relatively consistent anatomy of the NRS, the anatomic snuffbox remains a complex and dangerous area due to the variability of the nerve's anatomy. An open surgical approach is thus preferred to avoid traumatizing the nerves and vascular structures.

Axillary Vein

Identification of a leader exon and a core promoter for the rat tuberous sclerosis 2 (Tsc2) gene and structural comparison with the human homolog.

Hereditary renal carcinoma in the Eker rat is an excellent example of predisposition to a specific cancer being transmitted as a dominant trait. Recently, we identified a germline mutation of the tuberous sclerosis 2 (Tsc2) gene in the Eker rat. In the present study, we analyzed the upstream region of the Tsc2 gene. A novel leader exon (exon 1a) in a CpG island was found, and core promoter activity was identified in a 242-bp region of this island. Exon 1a and the promoter region were conserved in the human TSC2 gene. In addition, a rat homolog of a gene found upstream of TSC2 in human has been identified, indicating that the genomic organization around Tsc2/TSC2 is conserved between the two species. Characterization of the 5' region of Tsc2 and TSC2 will facilitate studies of the regulation of the gene and its disregulation in tumorigenesis.

Animals

Primary structure of locust opsins: a speculative model which may account for ultraviolet wavelength light detection.

The sequences of two locust opsins have been determined by dideoxy nucleotide sequencing of PCR products from cDNA derived from eyecup tissue. The opsins (Lo1 and Lo2) are encoded by 381 and 380 amino acid residues, respectively, with hydropathy profiles and placement of key amino acid residues suggestive of a typical seven-transmembrane rhodopsin structure. The sequence alignment of Lo1 reveals significant homology to mantid opsin. These opsins contain retinal as their visual chromophore and have similarity to the Rh1 type sequences from Drosophila and Calliphora which use 3-hydroxy retinal. Lo2 is most closely related to the Rh3/4 type of visual pigments from Drosophila. The retinal-based opsins show reduced numbers of charged amino acids in the loop region connecting transmembrane segments V and VI compared to the 3-hydroxy retinal opsins. Sequence alignment of all the known insect visual pigments has shown that only those with maximal sensitivity in the blue/UV spectral range, Lo2 and the Rh3/4 opsins of Drosophila, have three charged amino acids in transmembrane segments II, IV and VII. The charged residue in transmembrane VII is two helical turns away from the positively charged Schiff base and could act directly as a counterion to it. From the secondary structure analysis of opsin, the two charged residues in transmembrane II and IV would be in close proximity to form a dipole. These polar motifs in Lo2 and Rh3/Rh4 could act in wavelength modulation of short wavelength sensitive pigments and substantiate the proposed external two-point charge model which accounts for the spectral sensitivity of visual pigments [Honig, B., Dinur, U., Nakanishi, K., Balogh-Nair, V., Gawinowicz, M.A. and Motto, M. (1979). Journal of the American Chemical Society, 101, 7084-7086].

Amino Acid Sequence

Comparative analysis of the polycystic kidney disease 1 (PKD1) gene reveals an integral membrane glycoprotein with multiple evolutionary conserved domains.

PKD1 is the major locus of the common genetic disorder autosomal dominant polycystic kidney disease (ADPKD). Analysis of the predicted protein sequence of the human PKD1 gene, polycystin, shows a large molecule with a unique arrangement of extracellular domains and multiple putative transmembrane regions. The precise function of polycystin remains unclear with a paucity of mutations to define key structural and functional domains. To refine the structure of this protein we have cloned the genomic region encoding the Fugu PKD1 gene. Fugu PKD1 spans 36 kb of genomic DNA and has greater complexity with 54 exons compared with 46 in man. Comparative analysis of the predicted protein sequences shows a lower level of homology than in similar studies with identity of 40 and 59% similarity. However key structural motifs including leucine rich repeats (LRR), a C-type lectin and LDL-A like domains and 16 PKD repeats are maintained. A region of homology with the sea urchin REJ protein was also confirmed in Fugu but found to extend over 1000 amino acids. Several highly conserved intra- and extra-cellular regions, with no known sequence homologies, that are likely to be of functional importance were detected. The likely structure of the membrane associated region has been refined with similarity to the PKD2 protein and voltage gated Ca2+ and Na+ channels highlighted over part of this area. The overall protein structure has therefore been clarified and this comparative analysis derived structure will form the basis for the functional study of polycystin and its individual domains.

Amino Acid Sequence