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Biomedical subjects

S Gandhi

Publications and source records attributed to S Gandhi.

At least 19 recordsLinked to original sources

Feasibility of continuous transthoracic cardiac imaging using a novel ultrasound transducer.

BACKGROUND: The feasibility of hands-free transthoracic continuous ultrasonic cardiac imaging has not been demonstrated previously. We developed a 2.5-MHZ spherical transducer mounted in an external housing to permit steering in 360 degrees (CONTISON). The external housing was attached to the chest wall using an adhesive patch. METHODS AND RESULTS: The transducer was placed in the third or fourth interspace at the left sternal border to permit imaging of the left ventricle (LV) in its short axis and attached to the chest wall. The transducer then was attached to an ultrasound machine. Ten normal subjects and 20 patients with previous myocardial infarction were studied. The following maneuvers were performed at the beginning of the study: (1) The patient was rotated from the supine position (0 degrees ) in 20 degrees increments to the left lateral decubitus position (90 degrees ). The echocardiogram was displayed continuously and was recorded on videotape (parasternal short-axis view) at 0 degrees, 20 degrees, 40 degrees, 60 degrees, 80 degrees, and 90 degrees. (2) The patient was returned to the supine position and an echocardiogram was obtained. The patient was then seated up 20 degrees, 40 degrees, 60 degrees, 80 degrees, and 90 degrees by using the controls on the bed. (3) The patient then was returned to the supine position and the echocardiogram was displayed continuously on the monitor. The echocardiogram was recorded every 15 minutes for a period of 4 hours. All segments of the LV were visualized in the supine position and during lateral rotation (0 degrees -90 degrees ). Thus, body position did not affect the image. All segments of the LV were visualized during sitting up (0 degrees -90 degrees ), and all segments were visualized during the 4 hours of imaging. The patients were able to move around without distortion of the image. CONCLUSION: The CONTISON transducer permitted continuous imaging of LV wall motion. Body position did not affect interpretation of wall motion. This device has potential applicability in monitoring LV function in the intensive care setting.

Adult↗

Location of the polysensory zone in the precentral gyrus of anesthetized monkeys.

Neurons in the premotor cortex of macaques respond to tactile, visual and auditory stimuli. The distribution of these responses was studied in five anesthetized monkeys. In each monkey, multiunit activity was studied at a grid of locations across the precentral gyrus. A cluster of sites with polysensory responses was found posterior to the genu of the arcuate sulcus. Tactile and visual responses were represented in all five monkeys, while auditory responses were rarer and found in only two monkeys. This polysensory zone (PZ) was located in the caudal part of premotor cortex. It varied in extent among the monkeys. It was mainly ventral to the genu of the arcuate, in the dorsal and caudal part of the ventral premotor cortex (PMv). In some monkeys it extended more dorsally, into the caudal part of dorsal premotor cortex (PMd). Sensory responses were almost never found in the rostral part of PMd. We suggest that the polysensory zone may contribute to the guidance of movement on the basis of tactile, visual and auditory signals.

Acoustic Stimulation↗

Glycosylphosphatidylinositol-anchored proteins play an important role in the biogenesis of the Alzheimer's amyloid beta-protein.

The Alzheimer's amyloid protein (Abeta) is released from the larger amyloid beta-protein precursor (APP) by unidentified enzymes referred to as beta- and gamma-secretase. beta-Secretase cleaves APP on the amino side of Abeta producing a large secreted derivative (sAPPbeta) and an Abeta-bearing C-terminal derivative that is subsequently cleaved by gamma-secretase to release Abeta. Alternative cleavage of the APP by alpha-secretase at Abeta16/17 releases the secreted derivative sAPPalpha. In yeast, alpha-secretase activity has been attributed to glycosylphosphatidylinositol (GPI)-anchored aspartyl proteases. To examine the role of GPI-anchored proteins, we specifically removed these proteins from the surface of mammalian cells using phosphatidylinositol-specific phospholipase C (PI-PLC). PI-PLC treatment of fetal guinea pig brain cultures substantially reduced the amount of Abeta40 and Abeta42 in the medium but had no effect on sAPPalpha. A mutant CHO cell line (gpi85), which lacks GPI-anchored proteins, secreted lower levels of Abeta40, Abeta42, and sAPPbeta than its parental line (GPI+). When this parental line was treated with PI-PLC, Abeta40, Abeta42, and sAPPbeta decreased to levels similar to those observed in the mutant line, and the mutant line was resistant to these effects of PI-PLC. These findings provide strong evidence that one or more GPI-anchored proteins play an important role in beta-secretase activity and Abeta secretion in mammalian cells. The cell-surface GPI-anchored protein(s) involved in Abeta biogenesis may be excellent therapeutic target(s) in Alzheimer's disease.

Alzheimer Disease↗

A multidisciplinary surgical approach to superior sulcus tumors with vertebral invasion.

BACKGROUND: Vertebral body invasion by superior sulcus tumor has traditionally been considered a contraindication to surgical resection. Attempts at definitive radiation or chemoradiation have not been successful. Recent advances in spinal instrumentation have allowed more complete resection of vertebral body tumors. We, therefore, reviewed our recent experience with vertebral resection of superior sulcus tumors. METHODS: All patients (n = 17) undergoing resection of superior sulcus tumors with T4 involvement of the vertebrae from October 18, 1990 to September 21, 1998 at the University of Texas M.D. Anderson Cancer Center (MDACC) were evaluated. Their clinical and pathologic data were reviewed and analyzed for short- and long-term outcomes. RESULTS: Total vertebrectomy was performed in 7 patients (42%), partial vertebrectomy in 7 (42%), and 3 (18%) underwent neural foramina or transverse process resection. The median hospital stay was 11 days. Postoperative complications occurred in 7 patients (42%) and included pneumonia (6, 36%), arrhythmia (2, 12%), cerebrospinal fluid leak (2, 12%), wound breakdown (1, 6%), and reoperation for bleeding (1, 6%). Sixteen out of 17 patients received preoperative or postoperative radiation therapy. No perioperative mortality occurred. All patients remained ambulatory after spinal reconstruction. Overall actuarial survival at 2 years was 54%, with 11 patients still alive 2 to 50 months after resection. Locoregional tumor recurrence was noted in all 6 patients who had positive surgical margins, as opposed to 1 out of 11 patients (9%) with negative margins (p < 0.006). Additionally, the 2-year actuarial survival of patients with negative microscopic margins was 80% versus 0% for positive margins (p < 0.0006). CONCLUSIONS: An aggressive multidisciplinary approach to superior sulcus tumors with vertebral invasion can lead to long-term survival with acceptable morbidity if negative margins can be obtained. Vertebral body invasion should no longer be considered a contraindication for resection of superior sulcus tumors.

Adult↗

Color signals in human motion-selective cortex.

The neural basis for the effects of color and contrast on perceived speed was examined using functional magnetic resonance imaging (fMRI). Responses to S cone (blue-yellow) and L + M cone (luminance) patterns were measured in area V1 and in the motion area MT+. The MT+ responses were quantitatively similar to perceptual speed judgments of color patterns but not to color detection measures. We also measured cortical motion responses in individuals lacking L and M cone function (S cone monochromats). The S cone monochromats have clear motion-responsive regions in the conventional MT+ position, and their contrast-response functions there have twice the responsivity of S cone contrast-response functions in normal controls. But, their responsivity is far lower than the normals' responsivity to luminance contrast. Thus, the powerful magnocellular input to MT+ is either weak or silent during photopic vision in S cone monochromats.

Adaptation, Ocular↗

Haemangiopericytoma of the adult male breast.

Haemangiopericytoma is an uncommon, usually benign, soft tissue tumour which has been rarely reported to occur in the female breast. Haemangiopericytoma of the adult male breast has been reported only once before. We report another such case.

Breast Neoplasms, Male↗

An analysis of the incidence and risk factors of developing severe keratopathy in eyes after megavoltage external beam irradiation.

OBJECTIVE: To investigate the incidence and risk factors of developing severe keratopathy in eyes exposed to megavoltage external beam irradiation. DESIGN: Retrospective noncomparative case series. PARTICIPANTS: The authors evaluated 88 eyes of 88 consecutive patients who had received irradiation of an entire orbit during radiation therapy for nasopharyngeal carcinoma. Mean follow-up was 40 months (range, 24-106 months). INTERVENTION: Slit-lamp biomicroscopic findings of the cornea after irradiation were categorized into four grades in accordance with a standard protocol. Grade 3 or above changes were defined as severe radiation keratopathy. MAIN OUTCOME MEASURES: The incidence of severe radiation keratopathy was evaluated along with patient's age, radiation dose, lacrimal shielding, and tumor involvement of the trigeminal nerve. RESULTS: Severe radiation keratopathy developed in 32 patients. Mean latency was 15 months (range, 4-36 months). Its incidence increased from 0% after doses less than 59 Gy to 100% after doses greater than 70 Gy. Between 59 Gy and 69 Gy, the adverse factor was omission of lacrimal shield during radiation therapy (P < 0.01). CONCLUSION: Radiation dose to the cornea is the most important factor in determining the outcome of radiation keratopathy. When the threshold dose is reached, visual prognosis is grave despite protection of the lacrimal gland. Clinical trials on newer strategies to treat ocular surfaces exposed to heavy irradiation are necessary.

Adult↗

Novel binding sites for regulatory factors in the human papillomavirus type 18 enhancer and promoter identified by in vivo footprinting.

The E6 and E7 genes of human papillomaviruses (HPVs) associated with anogenital cancers are largely responsible for the oncogenic activity of these viruses, and regulation of these genes has been intensively studied. Transcription of the E6 and E7 genes is controlled by the viral upstream regulatory region (URR). We have used in vivo footprinting to examine the occupancy by regulatory factors of the HPV type 18 (HPV18) URR enhancer and promoter in the cervical carcinoma cell lines HeLa and C4-II. While corroborating occupancy in vivo of all of the elements previously implicated in the transcriptional control of the HPV18 E6 and E7 genes by in vitro DNase I footprinting, gel retardation assays, and transfection studies, we also detect occupancy in vivo of several enhancer and promoter sequences which have not been previously identified as HPV18 URR regulatory elements. Our data suggest that the HPV18 enhancer and promoter are more densely occupied by DNA-binding proteins than previously thought and raise the possibility that additional, possibly novel factors contribute to transcription of the HPV18 early genes.

Base Sequence↗

Nucleated red blood cells in cord blood of singleton term neonates.

OBJECTIVE: This study aims to establish normal values for nucleated red blood cells in term singletons and factors associated with their elevation. STUDY DESIGN: Cord blood was prospectively collected from term singleton gestations from Feb. 1 to July 31, 1995. Umbilical vein white blood cells and nucleated red blood cells were counted and umbilical arterial pH was determined. Medical records provided maternal and neonatal information. RESULTS: Cord blood from 1112 cases was obtained and evaluated for nucleated red blood cells per 100 white blood cells. Nine outliers were censored (nucleated red blood cells per 100 white blood cells = 126 to 830); five cases were excluded because of missing data. The mean value of nucleated red blood cells per 100 white blood cells was 8.55, the SD was 10.27, and the range was 0 to 89. The value did not very by maternal tobacco or drug use, anemia, fetal presentation, or mode of delivery. Both maternal diabetes and meconium were associated with elevated values, p < 0.01. Apgar scores and cord pHs showed trends toward inverse proportionality to the number of nucleated red blood cells per 100 white blood cells. CONCLUSION: The mean number of nucleated red blood cells per 100 white blood cells was 8.55, with a wide range and SD. Elevated values may be associated with markers of intrauterine hypoxia such as meconium, lower Apgar scores, and lower pH values.

Adolescent↗

Neovascular glaucoma developing after uncomplicated cataract surgery for heavily irradiated eyes.

PURPOSE: The purpose of the study was to evaluate the effect of cataract surgery and postoperative panretinal photocoagulation (PRP) on the development of neovascular glaucoma (NVG) in heavily irradiated eyes. PATIENTS AND METHODS: The authors performed a retrospective study on the incidence of NVG in 90 eyes that had received megavoltage external beam irradiation at a retinal dose of 56 to 80 Gy and that had at least 48 months of follow-up. These eyes were categorized into different groups depending on whether cataract surgery or PRP was performed. Rates and proportions of NVG occurring in these groups were compared and analyzed with one-tailed Fisher's exact test. RESULTS: The incidence of NVG was significantly higher in patients who underwent cataract surgery without postoperative PRP (P < 0.01). Neovascular glaucoma did not develop in any patient who underwent cataract surgery and PRP. CONCLUSIONS: Cataract surgery may accelerate the development of NVG in heavily irradiated eyes. Photoablation of ischemic retina is recommended before cataract surgery or soon thereafter if cataract density precludes laser treatment.

Adult↗

Expression of a mutant myosin light chain that cannot be phosphorylated increases paracellular permeability.

A murine leukemia retroviral vector was engineered to contain the DNA encoding either the wild-type, rat aorta 20-kDa myosin light chain (MLC20) or a mutant form of MLC20 in which Thr18 and Ser19 were mutated into alanines. These mutations result in a MLC20 that cannot be phosphorylated by myosin light chain kinase. An 11-amino acid epitope from c-myc was added to both MLC20 sequences to facilitate identification of these proteins. Madin-Darby canine kidney cells were stably transduced, and MLC20 expression was demonstrated by Western blot analysis using a myc-specific antibody. MLC20 exchange was demonstrated by purifying myosin from the transduced cells and repeating the Western blot analysis. Actin-activated adenosinetriphosphatase assays on the purified myosins demonstrated approximately 50% decrease in the rate of ATP hydrolysis by the myosin containing the mutant MLC20. Transepithelial electrical resistance was decreased and mannitol flux was increased across monolayers of cells expressing mutant MLC20. These data demonstrate that MLC20 phosphorylation is involved in regulating paracellular permeability and epithelial barrier function.

Adenosine Triphosphatases↗

Restriction isotyping of the premature termination variant of lipoprotein lipase in Alberta Hutterites.

OBJECTIVE: Lipoprotein lipase (LPL) plays a pivotal role in lipoprotein metabolism. A relatively common LPL variant results from a C --> G transversion in exon 9, which creates a premature termination codon (S447X) and results in a truncated LPL molecule lacking the C-terminal dipeptide Ser-Gly. We wished to determine the functional relevance of this variant. DESIGN AND METHODS: We used Mn/l restriction digestion of amplified genomic DNA to genotype Alberta Hutterites for the S447X variant. We tested for association with biochemical phenotypes. RESULTS: Complete linkage disequilibrium between alleles of an LPL genomic variant in intron 6 and LPL S447X was detected. However, as a single independent variable, LPL S447X genotype was not significantly associated with variation in any dependent biochemical variable in the Hutterites. CONCLUSIONS: Restriction isotyping for S447X permits large-scale screening of individuals to identify linkage relationships between this marker and other DNA variations of LPL and to study associations with clinical phenotypes.

Alberta↗

Resistant hypertension. Suggestions for dealing with the problem.

With appropriate evaluation of both patient- and physician-related factors, many cases of resistant hypertension can be resolved. Patients often do not understand the implications of their disease and need specific information regarding the importance of compliance with medication schedules and dietary restrictions. Physicians should also consider the possibility of drug resistance or the presence of an identifiable secondary cause, such as renal artery stenosis, chronic renal parenchymal disease, or pheochromocytoma.

Antihypertensive Agents↗

Conservation of the Down syndrome critical region in humans and great apes.

A quarter century ago, a chimpanzee with trisomy 22 was reported to have the clinical manifestation of Down syndrome. The features of Down syndrome in human have been associated with chromosome 21 band q22.3. The recent availability of chromosome and loci specific probes has prompted us to utilize the human cosmid probe (D21S65) for the trisomy 21 region in the chromosomes of the chimpanzee (Pan troglodytes), gorilla (Gorilla gorilla) and orangutan (Pongo pygmeus). Interestingly, the hybridization site for the Down syndrome region was found on the equivalent ape chromosome 22 in all three primates (the human equivalent of chromosome 21). Apparently, these results support the notion that the Down syndrome critical region of human chromosome 21 band q22.3 is conserved in great apes, which has displayed mongolism in a chimpanzee when present in triplicate conditions. Furthermore, other probes can be used as phylogenetic signals to enhance the understanding of human descent.

Animals↗