PubMed Health⌕ Search

Biomedical subjects

B J White

Publications and source records attributed to B J White.

At least 19 recordsLinked to original sources
PubMed2002

Synthesis and characterization of a novel double crosslinked hyaluronan hydrogel.

Hyaluronan has great potential in medicine as a biomaterial. However, in its native form, hyaluronan is rapidly metabolized in vivo by free radicals and enzymes such as hyaluronidase, and it is highly soluble. Various methods have been adopted therefore, to modify the physicochemical properties of hyaluronan, while maintaining biocompatibility, and thereby widen its spectrum of therapeutic applications. Hyaluronan has four reactive groups (acetamido, carboxyl, hydroxyl and the reducing end) available for crosslinking to itself or other polymers. Using a variety of crosslinking agents, researchers have developed a host of crosslinked hyaluronan derivatives with an increased in vivo residence time. This chemical modification has enabled the production of gels and films, which can be used in applications such as the prevention of post-surgical adhesions, wound healing and dermal augmentation. We have found that if hyaluronan is crosslinked to itself, or to other polymers (either synthetic or biopolymer), in two stages, then a high degree of crosslinking is achieved, conferring improved biostability. In each of the two stages, the same crosslinking agent is used, but different functional groups are bound by altering the reaction conditions. The novel process can be tailored to yield water insoluble gels and films with a broad range of physical and chemical characteristics, and greater resistance to degradation by hyaluronidase and free radicals. These derivatives are currently undergoing biocompatibility testing, and should ultimately lead to a series of innovative second-generation medical products.

Journal Article↗
PubMed2001

Formation of a new buried charge drives a large-amplitude protein quake in photoreceptor activation.

Photoactive yellow protein (PYP) is a eubacterial photoreceptor and a structural prototype of the PAS domain superfamily of receptor and regulatory proteins. We investigate the activation mechanism of PYP using time-resolved Fourier transform infrared (FTIR) spectroscopy. Our data provide structural, kinetic, and energetic evidence that the putative signaling state of PYP is formed during a large-amplitude protein quake that is driven by the formation of a new buried charge, COO(-) of the conserved Glu46, in a highly hydrophobic pocket at the active site. A protein quake is a process consisting of global conformational changes that are triggered and driven by a local structural "fault". We show that large, global structural changes take place after Glu46 ionization via intramolecular proton transfer to the anionic p-coumarate chromophore, and are suppressed by the absence of COO(-) formation in the E46Q mutant. Our results demonstrate the significance of buried charge formation in photoreceptor activation. This mechanism may serve as one of the general themes in activation of a range of receptor proteins. In addition, we report the results of time-resolved FTIR spectroscopy of PYP crystals. The direct comparison of time-resolved FTIR spectroscopic data of PYP in aqueous solution and in crystals reveals that the structure of the putative signaling state is not developed in P6(3) crystals. Therefore, when the structural developments during the functional process of a protein are experimentally determined to be very different in crystals and solutions, one must be cautious in drawing conclusions regarding the functional mechanism of proteins based on time-resolved X-ray crystallography.

Bacterial Proteins↗
PubMed1999

Rare interstitial deletion (2)(p11.2p13) in a child with pericentric inversion (2)(p11.2q13) of paternal origin.

An unbalanced 46,XY,der(2)del(2)(p11.2p13) inv(2)(p11.2q13) karyotype was found in a phenotypically abnormal child with a de novo interstitial deletion of band 2p12 associated with an inv(2)(p11.2q13) inherited from the father. The inv(2) is generally considered a benign familial variant without significant reproductive consequences. However, our findings led us to consider a previously proposed mechanism of unequal meiotic crossing over at the base of a parental inversion loop, which could lead to either a deletion or duplication of a segment adjacent to the inverted region in the offspring. This phenomenon has been reported in other inversions of chromosomes 1, 7, 13, 15, and 17 and may explain the origin of the deletion in our patient. Although repetitive sequences might be present around such inversions, which could predispose to de novo deletions independently of the inversion, current evidence including this case favors a proposed causal relationship between the parental inversion and the deletion in the child. Our review and results suggest there could be a small risk for a related imbalance to couples with an inv(2)(p11.2q13). For del(2)(p11.2p13), which is rare, a more distinct phenotype has been proposed herein. Our patient shared several findings with the three previously published cases, namely the broad nasal bridge, abnormal ears, high-arched palate, psychomotor retardation, and micrognathia. However, our patient also had sensorineural hearing loss and significant hypotonia, which have not been previously reported, thereby expanding our understanding of this rare deletion. Am. J. Med. Genet. 87:139-142, 1999. Published 1999 Wiley-Liss, Inc.

Abnormalities, Multiple↗
PubMed1999

A 6-year experience demonstrates the utility of screening for both cytogenetic and FMR-1 abnormalities in patients with mental retardation.

Cytogenetic abnormalities were found in 81 of 2,757 cases (2.93%) screened for both cytogenetic and FMR-1 mutations because of mental retardation from 1992 to 1997. Of these, 38 (46.9%) were unbalanced autosomal abnormalities, 23 (28.4%) sex chromosomal abnormalities, and 20 (24.7%) balanced autosomal rearrangements. Five subtle deletions were found, of which three involved the long arm of chromosome 7 (7q22-q31.1). Although a high-resolution banding method was used for screening, we concluded that a banding level of 450-550, generally achieved in routine analysis, was sufficient to detect all of these abnormalities. Fragile-X DNA studies revealed CGG expansion mutations in 72 other cases (2.61%). Of the abnormals, 36 (50%) were males and 8 (11.1%) females with full mutations, and 12 (16.7%) were males and 16 (22.2%) females with premutations. Together, our cytogenetic and DNA screening gave 5.5% abnormal results. In this report, these findings are compared with similar surveys of 3,940 subjects from five previous studies. From the combined data of 6,697 cases, this testing approach should reveal nearly equal numbers of cytogenetic and fragile X abnormalities in approximately 6-7% of subjects. It is productive, cost-effective, and consistent with American College of Medical Genetics (ACMG) guidelines for screening of mentally handicapped individuals.

Blotting, Southern↗
PubMed1999

Protecting the future of indigenous children and nations: an examination of the Indian Child Welfare Act.

The Indian Child Welfare Act is a landmark piece of legislation, passed in response to a long history of Native American children being alienated from their families and communities. The Act has far reaching implications for social workers and human service professionals who have any involvement with Native American children or families. Still, many professionals are either unaware of the Act all together or do not know how to effectively implement its provisions in their practice. This lack of awareness and other factors such as inadequate funding have meant that the Act has never realized its full potential to reduce the number of children in out-of-home care. In order to increase awareness about the Act and to make its implementation in day to day social services more practical, this article provides background information on the factors leading to the Act, information on the law itself, and recommendations for practitioners, administrators, and students in the human services.

Child↗
PubMed1999

Simultaneous occurrence of two supernumerary autosomal ring chromosomes r(1) and r(16) in twins.

Ring chromosomes are estimated to occur in 3/10000 newborns and the simultaneous occurrence of two autosomal rings must be a very rare event. Recently, the characterisation of these markers using fluorescence in situ hybridisation (FISH) has greatly enhanced cytogenetic-phenotypic correlations in patients with these marker chromosomes. This kind of analysis enabled us to clarify a unique karyotype containing a r(1) and a r(16) in identical twins born after a 26 week gestation with minimal somatic abnormalities. The origin of the rings was identified using a satellite and whole chromosome painting probes. FISH analysis showed the same abnormal female karyotype in both twins, 48,XX,+r(1)(p13q21),+r(16)(p11q11).ish r(1) (D1Z5+,wcpl+), r(16)(D16Z2+,wcp16+) in about two thirds of the cells. Each also had minor clones with a normal female karyotype or with one or the other supernumerary ring. Half of the r(1) contained CBG band negative material and the r(16) appeared to be totally CBG band positive. These twins represent the second report of the simultaneous occurrence of multiple autosomal rings. Their description may help to delineate a new chromosome disorder and shows the usefulness of FISH analysis.

Chromosomes, Human, Pair 1↗
PubMed1998

Familial eosinophilia: clinical and laboratory results on a U.S. kindred.

We describe a five-generation kindred with familial eosinophilia (FE; MIM131400), characterized by the occurrence of sustained eosinophilia of unidentifiable cause in multiple relatives. The inheritance pattern is consistent with an autosomal dominant pattern. Among 52 related subjects studied, 19 were affected and 33 were unaffected. Ten unaffected spouses were also evaluated. Four subjects with sustained eosinophilia were diagnosed with cardiac abnormalities and two of them also had neurologic symptoms. In comparison with the unaffected or spouses, evaluation of complete blood counts showed that the affected relatives had, as expected, significantly higher white cell (P < 0.005) and absolute eosinophil counts (P < 0.001) and lower red cell counts (P < 0.05). Evaluation of serum cytokine levels (IL-5, IL-3, and granulocyte-macrophage colony-stimulating factor (GMCSF) and serology for parasitic helminth infection demonstrated no differences between the affected and unaffected individuals; no individuals studied had serologic evidence for parasitic infection. There were also no differences in anti-nuclear antibody, serum cobalamin (vitamin B12) level, immunoglobulin level, leukocyte alkaline phosphatase, rheumatoid factor, HLA analysis, and stool findings for ova and parasites. Among eight affected persons who had peripheral blood or bone marrow karyotype analysis, two carried the same chromosome abnormality, a pericentric inversion of chromosome 10, inv (10) (p11.2q21.2). A gene mapping study is currently underway to study the underlying genetic mechanism(s) of this syndrome.

Adolescent↗
PubMed1997

A PET study of Turner's syndrome: effects of sex steroids and the X chromosome on brain.

Women with Turner's syndrome (TS) allow us to study the neurobiological associates of cognitive and behavioral abnormalities because they lack one/part of one X chromosome, and endogenous estrogen. We studied 13 healthy controls (mean age +/- SD, 28 +/- 6 years) and 16 TS subjects (mean age +/- SD, 26 +/- 6 years). We measured cognitive abilities using neuropsychological tests, and cerebral metabolic rates for glucose with positron emission tomography. Compared to controls, TS subjects had significant absolute hypermetabolism in most brain areas; however, normalized metabolism was significantly lower in TS subjects than controls in the insula and association neocortices bilaterally, and there were significant differences in functional metabolic associations of brain region pairs originating in occipital cortex bilaterally, and within the right hemisphere. There were significant correlations between right-left cognitive and metabolic asymmetries in the TS group. Also, within TS a preliminary analysis demonstrated "X chromosome dosage" effects in language ability and left temporal metabolism, asymmetry of right-left test scores, and parietal metabolism. We hypothesize that within TS: i) generalized brain hypermetabolism reflects global abnormalities in neuron packing; ii) neuronal abnormalities occur in association neocortex that differ in nature or extent from whole brain and are associated with significant differences in normalized metabolism; iii) cognitive deficits are related to brain metabolic abnormalities; and iv) social-behavioral problems may be related to abnormalities of brain metabolism. Moreover, in human brain the X chromosome involved in development of the association neocortices.

Adult↗
PubMed1997

A model of collaboration: the Academic Practice Council.

If the profession of nursing is to survive in the changing health care delivery system, new models of collaboration between nursing education and nursing practice must be developed. Nursing is both an academic discipline and a practice profession. The historic dissonance between education and practice has never served the profession of nursing; the pressing challenge is to blend one with the other now. In an effort to respond to the demands of the discipline and profession of nursing, an academic institution and a health care delivery system developed a model of interagency collaboration. This article addresses historical perspectives, and evolution, structure, activities, evaluation, and future plans to the Academic Practice Council.

Cooperative Behavior↗
PubMed1994

Molecular and cytogenetic studies of an X;autosome translocation in a patient with premature ovarian failure and review of the literature.

We have identified a patient with premature ovarian failure (POF) and a balanced X;autosome translocation: 46,X,t(X;6)(q13.3 or q21;p12) using high-resolution cytogenetic analysis and FISH. BrdU analysis showed that her normal X was late-replicating and translocated X earlier-replicating which is typical of balanced X;autosome rearrangements. Molecular studies were done to characterize the breakpoint on Xq and to determine the parental origin. PCR probes of tetranucleotide and dinucleotide repeat polymorphisms, and genomic probes were used to study DNA from the patient, her chromosomally normal parents and brother, and somatic cell hybrids containing each translocation chromosome. The translocation is paternally derived and is localized to Xq13.3-proximal Xq21.1, between PGK1 and DXS447 loci, a distance of 0.1 centimorgans. A "critical region" for normal ovarian function has been proposed for Xq13-q26 [Sarto et al., Am J Hum Genet 25:262-270, 1973; Phelan et al., Am J Obstet Gynecol 129:607-613, 1977; Summitt et al., BD:OAS XIV(6C):219-247, 1978] based on cytogenetic and clinical studies of patients with X;autosome translocations. Few cases have had molecular characterization of the breakpoints to further define the region. While translocations in the region may lead to ovarian dysfunction by disrupting normal meiosis or by a position effect, two recent reports of patients with premature ovarian failure and Xq deletions suggest that there is a gene (POF1) localized to Xq21.3-q27 [Krauss et al., N Engl J Med 317:125-131, 1987; Davies et al., Cytogenet Cell Genet 58:853-966, 1991] or within Xq26.1-q27 [Tharapel et al., Am J Hum Genet 52:463-471, 1993] responsible for POF.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

The effects of sex steroids, and the X chromosome, on female brain function: a study of the neuropsychology of adult Turner syndrome.

Sex steroids and the X chromosome can independently affect cognitive abilities. Because subjects with Turner syndrome (TS) have gonadal aplasia, and various alterations in X chromosome structure and number, they provide a model to study the effects of sex steroids and of the X chromosome on human brain function. We used neuropsychological tests to study the cognitive abilities of 18 TS adults and 19 age/sex matched healthy controls. Nine TS subjects were mosaic for the 45,X karyotype, and 9 were non-mosaic 45,X (full TS). The TS group as a whole, compared to controls, had (i) significantly lower scores in tests of language and visual-spatial function, attention and memory, and (ii) a significantly greater discrepancy between verbal and performance scores. Mosaic TS subjects were intermediate between full TS and controls in some tests of verbal ability, but did not differ significantly from controls in others. Visuospatial ability was significantly lower than controls in both mosaic and full TS. Within the mosaic TS group, there was a significant negative correlation between visuospatial ability and % lymphocytes having a 45,X karyotype. Memory test scores were reduced independently of "X chromosome dosage" in all TS subjects. We conclude that in humans, the X chromosome is involved in development of both cerebral hemispheres, but moreso of the association neocortices. Also, sex steroids may modulate this effect--particularly in hippocampus.

Adolescent↗
PubMed1994

Development of luteinized graafian follicles in patients with karyotypically normal spontaneous premature ovarian failure.

Despite having amenorrhea and markedly elevated serum gonadotropin levels, some women with karyotypically normal spontaneous premature ovarian failure, nevertheless, have ovarian follicles that function intermittently. Graafian follicles capable of responding to these high FSH levels are faced with high serum LH levels as well, which might induce inappropriate luteinization and prevent normal follicle function. We examined this possibility using weekly blood sampling and sonography in 65 patients. Nearly 50% of our patients demonstrated ovarian follicle function [serum estradiol, > 183 pmol/L (50 pg/mL)] during a median of 4 months of observation (range, 2-6 months). However, during this observation, only 16% achieved an ovulatory serum progesterone level [> 9.5 nmol/L (3.0 ng/mL)]. We imaged an antral follicle by sonography in over 40% of patients (27 of 65), and serum estradiol was significantly greater when an antral follicle was present. The follicles in these patients were not functioning normally, however. In contrast to normal women, patients with ovarian failure had poor correlation between follicle diameter and serum estradiol. We biopsied these antral follicles in 6 patients and found luteinized Graafian follicles in all cases. Therefore, luteinized Graafian follicles account for at least 60% of the antral structures imaged (95% confidence limit). Thus, inappropriate luteinization of Graafian follicles appears to be a major pathophysiological mechanism in patients with karyotypically normal spontaneous premature ovarian failure.

Adult↗
PubMed1993

X-chromosome effects on female brain: a magnetic resonance imaging study of Turner's syndrome.

Many neuropsychiatric disorders differ between the sexes in incidence, symptoms, and age at onset. To investigate the effects of X-chromosome aneuploidy and of sex steroid deficiency during childhood on brain structure and function, we used neuropsychological tests and quantitative magnetic resonance imaging (MRI) to study the brains of eighteen women with Turner's syndrome (TS) and nineteen healthy control women of similar age. Nine TS subjects had mosaic 45,X karyotypes, and 9 had non-mosaic 45,X. The TS group had significantly lower scores than the controls for all the Wechsler adult intelligence scale tests, except verbal comprehension and reading level. The greatest difference was in visuospatial construction (mean 90 [SD12] vs 118 [13], p < 0.0001). The TS subjects also had a greater discrepancy than controls between verbal and performance intelligence quotients (9 [8] vs -5 [9], p < 0.001). We found that TS subjects had significantly smaller values than controls in MRI-measured volumes of hippocampus, caudate, lenticular, and thalamic nuclei, and parieto-occipital brain matter, on both sides. Women with mosaic TS had values between the full TS and control groups for cerebral hemisphere and lenticular and thalamic nuclei volume and for verbal ability. Within the mosaic TS group, visuospatial ability was significantly correlated with the percentage of lymphocytes that had the 45,X karyotype. Hippocampal volume and memory test scores were significantly lower in mosaic and non-mosaic 45,X TS subjects than in controls. We postulate that in human beings the X chromosome plays an important part in the development and ageing of grey matter in striatum, diencephalon, and cerebral hemispheres.

Adult↗
PubMed1992

Gonadotropin suppression for the treatment of karyotypically normal spontaneous premature ovarian failure: a controlled trial.

OBJECTIVE: To determine if gonadotropin suppression improves ovarian follicle function or ovulation rates in patients with karyotypically normal spontaneous premature ovarian failure. DESIGN: Prospective, double-blind, placebo-controlled, crossover trial. SETTING: Tertiary care research institution. INTERVENTIONS: Two intervention phases lasting 4 months each: one placebo phase, and one treatment phase during which each patient received daily subcutaneous injections of 300 micrograms of the gonadotropin-releasing hormone agonist (GnRH-a) deslorelin. During both phases, patients took a standardized estrogen (E) replacement regimen. PATIENTS, PARTICIPANTS: Twenty-six patients with karyotypically normal spontaneous premature ovarian failure ranging in age from 18 to 39 years. MAIN OUTCOME MEASURES: We measured serum estradiol (E2) and progesterone (P) levels weekly during the 2 months after each intervention. We defined a serum E2 greater than 50 pg/mL (184 pmol/L) as evidence for ovarian follicle function and a serum P greater than 3.0 ng/mL (9.5 nmol/L) as evidence for ovulation. RESULTS: The GnRH-a therapy did not significantly enhance recovery of ovarian follicle function or the chance of ovulation. The power to detect a 40% and a 33% ovulation success rate with therapy was 0.95 and 0.83, respectively. We found evidence for ovarian follicle function in 11 of 23 women (48%), and 4 women (17%) ovulated. CONCLUSIONS: Patients with karyotypically normal spontaneous premature ovarian failure treated with E replacement did not benefit from the additional gonadotropin suppression achieved with GnRH-a. Because these patients have a significant possibility of spontaneous remission, attempts to induce ovulation should be limited to controlled trials designed to determine safety and effectiveness.

Adult↗
PubMed1992

Studies in a kindred with parathyroid carcinoma.

We report a family with primary hyperparathyroidism in four patients in two generations with apparent autosomal dominant transmission. A fifth member was probably affected. Two cases had definite parathyroid carcinoma (PC), and two had parathyroid adenoma with atypical features that could represent an early stage of cancer. In each of our patients, one parathyroid gland was abnormal. Five other parathyroid glands (in two patients) were normal in histology and size. There was no evidence of neoplasia in other tissues. Constitutional karyotypes were normal in all four patients. We identified three chromosomal abnormalities (a reciprocal translocation between chromosomes 3 and 4, trisomy 7, and a pericentric inversion in chromosome 9) in cultured PC tissue from one patient. These chromosomal changes are of unclear significance. Analyses on tumor DNA from one case of PC and one of atypical adenoma showed no evidence of ras gene mutations, PTH gene rearrangement, or allelic loss from chromosome 11q13 (locus of the gene for multiple endocrine neoplasia type 1). This family shows susceptibility to cancer without antecedent hyperplasia in all parathyroids. It could help identify a novel tumor susceptibility gene.

Adenoma↗