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Biomedical subjects

R S Hill

Publications and source records attributed to R S Hill.

At least 19 recordsLinked to original sources
PubMed2005

Filamin A mutations cause periventricular heterotopia with Ehlers-Danlos syndrome.

OBJECTIVE: To define the clinical, radiologic, and genetic features of periventricular heterotopia (PH) with Ehlers-Danlos syndrome (EDS). METHODS: Exonic sequencing and single stranded conformational polymorphism (SSCP) analysis was performed on affected individuals. Linkage analysis using microsatellite markers on the X-chromosome was performed on a single pedigree. Western blotting evaluated for loss of filamin A (FLNA) protein and Southern blotting assessed for any potential chromosome rearrangement in this region. RESULTS: The authors report two familial cases and nine additional sporadic cases of the EDS-variant form of PH, which is characterized by nodular brain heterotopia, joint hypermobility, and development of aortic dilatation in early adulthood. MRI typically demonstrated bilateral nodular PH, indistinguishable from PH due to FLNA mutations. Exonic sequencing or SSCP analyses of FLNA revealed a 2762 delG single base pair deletion in one affected female. Another affected female harbored a C116 single point mutation, resulting in an A39G change. A third affected female had a 4147 delG single base pair deletion. One pedigree with no detectable exonic mutation demonstrated positive linkage to the FLNA locus Xq28, an affected individual in this family also had no detectable FLNA protein, but no chromosomal rearrangement was detected. CONCLUSION: These results suggest that the Ehlers-Danlos variant of periventricular heterotopia (PH), in part, represents an overlapping syndrome with X-linked dominant PH due to filamin A mutations.

Adolescent↗
PubMed2003

Autosomal recessive form of periventricular heterotopia.

BACKGROUND: Familial periventricular heterotopia (PH) represents a disorder of neuronal migration resulting in multiple gray matter nodules along the lateral ventricular walls. Prior studies have shown that mutations in the filamin A (FLNA) gene can cause PH through an X-linked dominant inheritance pattern. OBJECTIVE: To classify cortical malformation syndromes associated with PH. METHODS: Analyses using microsatellite markers directed toward genomic regions of FLNA and to a highly homologous autosomal gene, FLNB, were performed on two pedigrees to evaluate for linkage with either filamin gene. RESULTS: Two consanguineous pedigrees with PH that suggest an autosomal recessive inheritance pattern are reported. MRI of the brain revealed periventricular nodules of cerebral gray matter intensity, typical for PH. Seizures or developmental delay appeared to be a common presenting feature. Microsatellite analysis suggested no linkage to FLNA or FLNB. CONCLUSIONS: Autosomal recessive PH is another syndromic migrational disorder, distinct from X-linked dominant PH. Further classification of these different syndromes will provide an approach for genetic evaluation.

Adult↗
PubMed2000

Increases in water potential gradient reduce xylem conductivity in whole plants. Evidence from a low-pressure conductivity method.

A new method using hydrostatic suctions (less than 0.02 MPa) was used to measure whole-root conductivity (K(r)) in saplings of two angiosperm pioneer trees (Eucalyptus regnans and Toona australis) and two rainforest conifers (Dacrycarpus dacrydioides and Nageia fleurii). The resultant K(r) was combined with measurements of stem and leaf hydraulic conductivity to calculate whole-plant conductivity and to predict leaf water potential (Psi(l)) during transpiration. At normal soil temperatures there was good agreement between measured and predicted Psi(l) during transpiration in all species. Changes in the soil-to-leaf water potential gradient were produced by root chilling, and in three of the four species, changes in Psi(l) corresponded to those expected by the effect of increased water viscosity on K(r). In one species, however, root chilling produced severe plant wilting and a decline in Psi(l) significantly below the predicted value. In this species Psi(l) decreased to a value close to, or below, the Psi(l) at 50% xylem cavitation. It is concluded that decreased whole-plant conductivity in T. australis resulted from a decrease in xylem conductivity due to stress-induced cavitation.

Algorithms↗
PubMed2000

Proton magnetic resonance spectroscopic imaging in children with recurrent primary brain tumors.

PURPOSE: Proton magnetic resonance spectroscopic imaging ((1)H-MRSI) is a noninvasive technique for spatial characterization of biochemical markers in tissues. We measured the relative tumor concentrations of these biochemical markers in children with recurrent brain tumors and evaluated their potential prognostic significance. PATIENTS AND METHODS: (1)H-MRSI was performed on 27 children with recurrent primary brain tumors referred to our institution for investigational drug trials. Diagnoses included high-grade glioma (n = 10), brainstem glioma (n = 7), medulloblastoma/peripheral neuroectodermal tumor (n = 6), ependymoma (n = 3), and pineal germinoma (n = 1). (1)H-MRSI was performed on 1. 5-T magnetic resonance imagers before treatment. The concentrations of choline (Cho) and N-acetyl-aspartate (NAA) in the tumor and normal brain were quantified using a multislice multivoxel method, and the maximum Cho:NAA ratio was determined for each patient's tumor. RESULTS: The maximum Cho:NAA ratio ranged from 1.1 to 13.2 (median, 4.5); the Cho:NAA ratio in areas of normal-appearing brain tissue was less than 1.0. The maximum Cho:NAA ratio for each histologic subtype varied considerably; approximately equal numbers of patients within each tumor type had maximum Cho:NAA ratios above and below the median. Patients with a maximum Cho:NAA ratio greater than 4.5 had a median survival of 22 weeks, and all 13 patients died by 63 weeks. Patients with a Cho:NAA ratio less than or equal to 4.5 had a projected survival of more than 50% at 63 weeks. The difference was statistically significant (P =.0067, log-rank test). CONCLUSION: The maximum tumor Cho:NAA ratio seems to be predictive of outcome in children with recurrent primary brain tumors and should be evaluated as a prognostic indicator in newly diagnosed childhood brain tumors.

Adolescent↗
PubMed1997

Immunoisolation of adult porcine islets for the treatment of diabetes mellitus. The use of photopolymerizable polyethylene glycol in the conformal coating of mass-isolated porcine islets.

Functional porcine islets, free of known pathogens, can serve as a source of insulin producing cells for the treatment of experimentally induced insulin dependent Diabetes Mellitus. Porcine islets can be conformally coated (microencapsulated) with a covalently linked, stable permselective membrane while maintaining islet viability and function. The PEG conformal coating is immunoprotective in a discordant xenograft animal model (porcine islets to rat).

Animals↗
PubMed1996

Upper gastrointestinal tract and abdomen: water as an orally administered contrast agent for helical CT.

PURPOSE: To evaluate the use of orally administered water as a negative contrast agent and intravenously administered glucagon in helical computed tomography (CT) of the upper abdomen. MATERIALS AND METHODS: Ninety-eight adult patients underwent 102 helical CT examinations. Patients received 700 mL of water orally 30 minutes before and another 350 mL of water orally with 1 mg of glucagon intravenously just before CT. The amount of water actually ingested was recorded. Luminal distention at five sites was graded on a three-point scale; depiction of six normal anatomic structures was evaluated. RESULTS: Luminal distention improved with the amount of water ingested in four of the five sites (P < .03 in three sites). Depiction of all six normal anatomic structures improved with increasing luminal distention (P < .001). The normal duodenal papilla was seen in 42% (83 of 198) of the examinations. Of 87 patients who had previously undergone CT with positive oral contrast agents, 89% (n = 77) preferred the water, 11% (n = 10) had no preference, and none preferred the positive agent (P < .001). Upper gastrointestinal tract abnormalities were easily recognized and depicted. CONCLUSION: Water is an efficacious negative contrast agent for evaluation of the upper gastrointestinal tract during helical CT.

Administration, Oral↗
PubMed1995

Ankle equinus. Prevalence and linkage to common foot pathology.

One hundred seventy-six of 209 consecutive new patients were examined over a 6-week period for the presence or absence of equinus deformity in the course of their workup for their primary complaint. Of the patients examined, 96.5% exhibited restricted ankle dorsiflexion requiring compensation during gait. Foot complaints were categorized into medial, lateral, and rearfoot problems. The high incidence of equinus reflects "acquired deformity" related to factors of lifestyle that leave the posterior muscles at a physiologic disadvantage toward maintaining flexibility. There is a significant relation between compensation for ankle equinus and podiatric pathology. More attention should be directed at the evaluation of ankle range of motion during examination of common foot problems. Gastrosoleal stretching is an important treatment modality that can lead to a higher success rate of conservative treatment. It can decrease the need for foot surgery, and significantly reduce the number of failed or serial surgical procedures.

Adolescent↗
PubMed1991

Engraftment after infusion of CD34+ marrow cells in patients with breast cancer or neuroblastoma.

The CD34 antigen is expressed by 1% to 4% of human and baboon marrow cells, including virtually all hematopoietic progenitors detectable by in vitro assays. Previous work from our laboratory has shown that CD34+ marrow cells can engraft lethally irradiated baboons. Because the CD34 antigen has not been detected on most solid tumors, positive selection of CD34+ cells may be used to provide marrow cells capable of engraftment, but depleted of tumor cells. In seven patients with stage IV breast cancer and two patients with stage IV neuroblastoma, 2.5 to 17.5 x 10(9) marrow cells were separated by immunoadsorption with the anti-CD34 antibody 12-8 and 50 to 260 x 10(6) positively selected cells were recovered that were 64 +/- 16% (range 35% to 92%) CD34+. The patients received 1.0 to 5.2 x 10(6) CD34-enriched cells/kg after marrow ablative therapy. Six patients engrafted, achieving granulocyte counts of greater than 500/mm3 at 34 +/- 10 (range 21 to 47) days and platelets counts of greater than 20,000/mm3 at 46 +/- 14 (range 28 to 66) days posttransplant. Five of these patients showed durable engraftment until the time of death 82 to 386 days posttransplant. One patient failed to sustain engraftment associated with metastatic marrow disease. Three patients died at days 14, 14, and 17 posttransplant, two of whom had evidence of early engraftment. These studies suggest that CD34+ marrow cells are capable of reconstituting hematopoiesis in humans.

Antigens, CD↗
PubMed1991

Induction of islet cytodifferentiation by fetal mesenchyme in adult pancreatic ductal epithelium.

Recombinant tissue consisting of adult ductal epithelium isolated from pancreas and fetal mesenchyme was transplanted subcutaneously in the inguinal region of nude mice or epididymal fat pads of rats with a tissue chamber device for short-term (8-day) or long-term (6- to 12-wk) duration. We found that recombinant tissue underwent morphogenesis and cytodifferentiation, thereby forming islets that contained cells immunocytochemically positive for insulin and glucagon. Islet cytodifferentiation occurred in approximately 20% of the recombinants. In recombinants that developed into islets, the tissue was always in close association with an extracellular matrix, nerves, and blood vessels. Controls consisting of mesenchyme alone or duct epithelium alone showed no evidence of morphogenesis of cytodifferentiation. Pancreatic rudiments were also implanted to serve as positive controls. This is the first demonstration of islet cytodifferentiation from adult duct epithelium.

Animals↗
PubMed1991

Current perception threshold in evaluating foot pain. Two case presentations.

Two cases are reported in which patients presented with complaints of foot pain, and a clinical suspicion of radiculopathy was supported by current perception threshold testing. Chiropractic manipulation of the lumbar spine resulted in alleviation of the lower extremity symptoms. Current perception threshold testing is a valuable neurologic testing modality that is noninvasive, nonaversive, and highly reliable for evaluation of sensory nerves where neuropathy is suspected. This technology has been described for evaluation of diabetic neuropathy, uremic screening, and alcohol and chemical toxicity. Additionally, current perception threshold is useful for evaluation of other neuropathies, such as carpal tunnel syndrome and other entrapment neuropathies. The authors encourage further investigation of this modality in the diagnosis and evaluation of peripheral neuropathy and unexplained foot pain secondary to spinal nerve impingement.

Adult↗
PubMed1990

Modification of the Kalish osteotomy to correct the proximal articular set angle.

A preliminary report of a new bunion procedure is described. This new procedure provides a relative reduction of the intermetatarsal angle and corrects the proximal articular set angle, yet incorporates the principles of compressive rigid internal fixation. The procedure is best summarized as a combination of the Kalish modification of the Austin bunionectomy and the Green-Laird modification of the Reverdin bunionectomy.

Adolescent↗
PubMed1990

Positive selection of hematopoietic progenitors from marrow and peripheral blood for transplantation.

The ability to obtain large numbers of purified hematopoietic progenitors (HPC) will facilitate the understanding of elements that influence the growth and differentiation of bone marrow. Furthermore, HPC isolation will have direct application to autologous marrow transplantation (AMT) for malignancies as well as facilitate the transfer of genes in marrow cells for the correction of genetic disorders. The transplantation of HPC will help delineate the cells or factors responsible for graft rejection and graft-versus-host-disease. Or several techniques that have been utilized for the separation of HPC, only the avidin-biotin immunoadsorption (ABIA) method has been shown capable of separating the number of cells required for large animals and man. The application of this technique to AMT in man requires the identification of an antigen found predominantly on HPC in peripheral blood or marrow but not on malignant cells that could potentially contaminate bone marrow. Studies have demonstrated that the CD34 antigen is expressed by the majority of human marrow HPC measured in long-term marrow culture and is expressed on cells capable of autologous engraftment in lethally irradiated baboons. Although the CD34 antigen is not detectable by FACS analysis on peripheral blood cells, ABIA can enrich for such cells. The CD34 antigen is not detected on cells from patients with breast cancer or neuroblastoma thus allowing clinical studies to proceed. Preliminary results suggest that CD34(+)-enriched cells are depleted of tumor cells and are capable of autologous reconstitution in man.

Antigens, CD↗
PubMed1989

Effect of rise in cAMP levels on Ca2+ influx through voltage-dependent Ca2+ channels in HIT cells. Second-messenger synarchy in beta-cells.

With a glucose-responsive beta-cell line (HIT cells), we tested the hypothesis that the cytosolic free-Ca2+ level ([Ca2+]i) is an intracellular signal through which a rise in cyclic AMP (cAMP) levels is transmitted to potentiate glucose-stimulated insulin secretion. In these cells, glucose stimulates the acute release of insulin without increasing [Ca2+]i or altering cAMP content. Either forskolin or 3-isobutylmethylxanthine (IBMX) potentiated glucose-stimulated insulin secretion and increased cAMP levels. At either a submaximal glucose concentration or maximally stimulatory glucose concentration, both IBMX and forskolin triggered a rapid rise in [Ca2+]i (1.9- and 1.5-fold increase over basal levels, respectively). Similarly, glucagon stimulated a 1.3-fold increase in [Ca2+]i over basal levels. The effect on [Ca2+]i required glucose and was secondary to Ca2+ influx through voltage-dependent Ca2+ channels because it was blocked by either chelation of extracellular Ca2+ with EGTA or by the Ca2+-channel blockers verapamil and nimodipine. Verapamil also inhibited IBMX potentiation of glucose-stimulated insulin secretion and the IBMX-induced rise in [Ca2+]i in a dose-dependent manner with IC50s of 2 x 10(-5) and 4 x 10(-6) M, respectively. We conclude that in the beta-cell, a rise in cAMP levels increases Ca2+ influx through voltage-dependent Ca2+ channels and that this represents a mechanism by which cAMP potentiates glucose-stimulated insulin secretion in beta-cells.

1-Methyl-3-isobutylxanthine↗
PubMed1989

Engraftment in 86 with patients lymphoid malignancy after autologous marrow transplantation.

The kinetics of marrow engraftment was retrospectively analysed in 55 patients with malignant lymphoma (ML) and 31 patients with acute lymphoblastic leukemia (ALL) after marrow-ablative therapy followed by autologous bone marrow transplantation. Thirty-eight percent of patients with ML, most of whom were transplanted in relapse and 13% of patients with ALL, mostly transplanted in remission, showed failed or delayed engraftment. Analysis of the total patient group showed that failure to recover platelet counts was significantly correlated with detection of disease in the marrow early after transplantation (p less than 0.001). Platelet recovery was also correlated with survival (p = 0.0001), disease-free survival (p = 0.0001), and the probability of relapse (p = 0.02). In those patients achieving engraftment, multivariate regression analysis failed to reveal any single in vitro test of marrow nucleated cell or progenitor cell numbers that significantly influenced time to achieve recovery of either granulocyte or platelet counts.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

The effect of heat shock on the morphology of amphibian lampbrush chromosomes.

Isolated oocytes of Triturus cristatus carnifex cultured in Barthe's medium respond to a sudden increase in temperature of 35 or 37 degrees C by the rapid condensation of their lampbrush chromosomes. The degree of condensation depends on the severity of the heat shock and is accompanied by the retraction of the transcriptionally active lampbrush loops. The oocytes were kept at 20 degrees C for 12 h after the period of heat shock, before the chromosomes were isolated. The minimum period required to effect loop retraction in immature oocytes of 0.7 mm in diameter was 10 min at 35 degrees C; although more extensive and complete retraction occurred if the oocytes were incubated for periods of up to 40 min. Chromosomes from more mature oocytes (1.4 mm in diameter) require longer periods of heat shock before undergoing condensation. The oocytes themselves do not show any obvious morphological changes after heat shock, although the germinal vesicles are initially too fragile to isolate manually for several hours. When the oocytes are returned to ambient temperatures, they can be cultured in Barthe's medium for several days, enabling the chromosomes to be isolated and studied. Generally, the chromosomes and loops from immature oocytes remain in a condensed state for about 48 h but then the chromosomal axis begins to relax and the loops begin to re-form. Depending on the severity of the initial heat shock, complete recovery of the normal lampbrush morphology is attained after a few days. The re-formed loops are morphologically indistinguishable from untreated loops in control preparations and are of the same length on average. This response of lampbrushes to heat shock is a reliable and repeatable process and should therefore become a valuable model system for the study of chromatin and chromosome structure during changes in transcriptional activity. The time taken for the lampbrushes to recover their normal morphology, is discussed in terms of the return to normal cellular transcription.

Animals↗
PubMed1988

Soft X-ray contact imaging of nucleolar chromatin using synchrotron radiation: a comparative scanning and transmission electron microscope study.

Contact images (CI) of dehydrated, nucleolar chromatin from amphibian oocytes have been produced by soft X-rays from a synchrotron radiation source. These CI have been compared with the morphology of the original chromatin as seen in scanning and transmission electron microscopes. The quality and informational content of the CI depend very much on certain preparative procedures. The following factors have a marked effect on image quality and need to be carefully controlled: the total X-ray dose, the time and nature of development and the distance of the specimen from the photoresist. The preparation of the chromatin itself, providing that it is critically point dried, is less important. By following a regime of high X-ray dose, sufficient for penetration of the rather thick chromatin rings, and gentle development so that fine detail is not dissolved from the resist surface, it has been possible to obtain images which closely resemble the original chromatin, although the detailed resolution of the CI is not as clear. The smallest biological structures clearly resolved in the CI are ribonucleoprotein granules, which vary in size from 200 to 800 nm. However, by further refinement of preparative conditions it should be possible to improve on the informational content of these images.

Animals↗