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Biomedical subjects

B Oliver

Publications and source records attributed to B Oliver.

At least 37 records · Page 2Linked to original sources

Calcified microspheres as biological entities and their isolation from bone.

Calcified microspheres, about 1 microm in diameter, appear at sites of bone formation where they invest the collagenous matrix, become confluent and disappear. Evidence that the particle boundaries are not lost with compaction but merely deformed is supported in section by the granular histochemical staining of the inorganic phase for bone salt, lipid, fibronectin and acid phosphatase in osteomalacic, acid-etched and normal human bone. Their persistence as discrete objects is confirmed by the application of methods for their isolation from the collagenous matrix of immature mouse calvarium and mature bovine femur. Five methods have been used to extract them and include (i) biochemical, (ii) chemical, (iii) mechanical, (iv) pyrogenous and (v) biological separation. Under the optical microscope, all isolates consisted of similar discrete objects and bridged assemblies, whose birefringence varied with treatment. After decalcification, their organic 'ghosts' remained. Each isolated microsphere had a complex substructure of clusters of non-collagenous calcified filaments surrounding a less dense centre. The filaments were 5 nm in diameter with a 5 nm periodicity and regular fine interfilamentous connections. It is concluded that the microspheres are independent, complex, pervasive and central to the containment (i.e. packaging) of calcium phosphate in bone. Their extraction will enable further analysis.

Adult↗

Genetic and environmental origins of verbal and performance components of cognitive delay in 2-year-olds.

The authors investigated the etiology of several measures of cognitive delay. Verbal (V) and performance (P) abilities were assessed in over 3,000 pairs of 2-year-old twins. Group-differences heritability for general delay (the lowest 5% of the V and P composite) was 35%. However, V and P delays considered independently showed large differences in group heritability (77% for V vs. 40% for P). Specific delays with comorbid cases eliminated showed an even greater difference in group heritability (78% vs. 22%, respectively). The small sample comorbid for both V and P delay also yielded high group heritability for both V (77%) and P (93%) scores. Shared environmental factors also differed in magnitude for V (20%) and P (41%) delays. Because the genetic and environmental origins of V and P delays in infancy differ, they are better considered separately rather than combined into a composite measure of general cognitive delay.

Child, Preschool↗

Recovery of hypopituitarism after neurosurgical treatment of pituitary adenomas.

Surgery is the treatment of choice for many pituitary tumors; pituitary function may suffer after operation, but relief of pressure on the normal pituitary may also favor postoperative recovery of hypopituitarism. The aim of this study was to investigate the frequency of new appearance and recovery of hypopituitarism after neurosurgery and try to identify features associated with it. Pre- and postoperative anterior pituitary functions were investigated in 234 patients with pituitary adenomas (56 nonfunctioning, 71 PRL-secreting, 66 GH-secreting, 39 ACTH-secreting, 1 LH/FSH-secreting, and 1 TSH-secreting tumors). Eighty-eight new postoperative pituitary hypofunctions appeared in 52 patients (12 NF, 14 PRL-secreting, 15 GH-secreting, 10 ACTH-secreting, and 1 LH/FSH-secreting adenomas). They corresponded to 27% ACTH deficiencies (in 29 of the 107 patients with normal preoperative ACTH in whom postoperative evaluation was complete), 14.5% (15 of 103) new GH deficiencies, 10.5% (15 of 143; P < 0.0005, significantly less than ACTH deficiency) new TSH deficiencies, 16.5% (20 of 121) new gonadotropin deficiencies, and 13% (9 of 71) new PRL deficiencies. Preoperatively, 93 were deficient in at least 1 pituitary hormone; after surgery, 45 (48%) recovered between 1 and 3 hormones. The 2 patients with LH/FSH- and TSH-secreting macroadenomas did not recover pituitary function. Factors associated with a higher probability of postoperative pituitary function recovery were: no tumor rests on postoperative pituitary imaging (P = 0.001) and no neurosurgical (P = 0.001) or pathological evidence (P = 0.049) of an invasive nature. Tumor size did not differ significantly between those who did and those who did not recover pituitary function after surgery. Even if clear hypofunction is observed at initial work-up, patients should be reassessed after surgery without substitution therapy, because practically half the preoperative pituitary hormone deficiencies recover postoperatively, eliminating the need for life-long substitution therapy.

Adenoma↗

Suppression of distinct ovo phenotypes in the Drosophila female germline by maleless- and Sex-lethal.

Mutations in ovo result in several different phenotypes, which we show are due to the regulation of distinct developmental pathways. Two X (female) germ cells require ovo+ activity for viability, but 1X (male) germ cells do not. In our study, we observed suppression of the ovo germline-lethality phenotype in loss-of-function maleless (mle) females indicating that ovo+ and mle+ have opposing effects in female germ cells; or that they are hierarchically related. Gain-of-function Sex-lethal (Sxl) alleles and male specific lethal-2 alleles did not suppress the ovo germline death phenotype. Many of the surviving germ cells in females mutant for both ovo and mle showed ovarian tumors. In contrast to the germline viability phenotype, we did observe suppression of the tumor phenotype in females heterozygous for gain-of-function alleles of Sxl. Further, females mutant for some hypomorphic ovo alleles were rendered fertile by Sxl gain-of-function alleles. Thus, ovo+ is required for at least two distinct functions, one involving mle+, and one mediated by Sxl+ gene products. The existence of ovo+ functions independent of mle+ and Sxl+ is likely.

Animals↗

New AUG initiation codons in a long 5' UTR create four dominant negative alleles of the Drosophila C2H2 zinc-finger gene ovo.

Promoters active in the germline produce OVO-A and OVO-B mRNAs encoding isoforms of a putative transcription factor. The isoforms have a common C2H2 zinc-finger domain but different N-termini that include potential effector domains. Single point mutations in three dominant-negative ovoD mutations result in new in-frame initiation codons in OVO-B mRNAs and amino acid substitutions within charged regions of OVO-A proteins. Three lines of evidence suggest that the dominant activity is due to the new initiation codons in OVO-B mRNAs and not the amino acid substitutions in OVO-A. First, we made a fourth ovoD allele by inserting a new in-frame AUG. This ovoD4 allele encodes a nearly full-length OVO-A isoform from OVO-B mRNAs. Second, engineered stop codons in ovoD1 downstream of the new AUG abolished dominant negative activity. Third, a substantial deletion of an OVO-A region encoding a highly charged amino acid domain fully rescued loss-of-function ovo alleles. These data suggest that ovoD mutations result in inappropriate expression of OVO-A in the female germline.

Alleles↗

Drosophila OVO zinc-finger protein regulates ovo and ovarian tumor target promoters.

The ovo+ and ovarian tumor+ genes function in the germline sex determination pathway in Drosophila, but the hierarchical relationship between them is unknown. We found that increased ovo+ copy number resulted in increased ovarian tumor expression in the female germline and increased ovo expression in the male germline. The ovo locus encodes C2H2 zinc-finger proteins. Bacterially expressed OVO zinc-finger domain bound to multiple sites at or near the ovo and ovarian tumor promoters strongly suggesting that OVO is directly autoregulatory and that ovarian tumor is a direct downstream target of ovo in the germline sex determination hierarchy. Both positive and negative regulation by OVO proteins appears likely, depending on promoter context and on the sex of the fly. Our observation that two strong OVO-binding sites are at the initiator of the TATA-less ovo-B and ovarian tumor promoters raises the possibility that OVO proteins influence the nucleation of transcriptional pre-initiation complexes.

Amino Acid Sequence↗

Genetic influence on language delay in two-year-old children.

Previous work suggests that most clinically significant language difficulties in children do not result from acquired brain lesions or adverse environmental experiences but from genetic factors that presumably influence early brain development. We conducted the first twin study of language delay to evaluate whether genetic and environmental factors at the lower extreme of delayed language are different from those operating in the normal range. Vocabulary at age two was assessed for more than 3000 pairs of twins. Group differences heritability for the lowest 5% of subjects was estimated as 73% in model-fitting analyses, significantly greater than the individual differences heritability for the entire sample (25%). This supports the view of early language delay as a distinct disorder. Shared environment was only a quarter as important for the language-delayed sample (18%) as for the entire sample (69%).

Child, Preschool↗

Multiple developmental requirements of noisette, the Drosophila homolog of the U2 snRNP-associated polypeptide SP3a60.

We report the cloning of the noisette gene (noi), which encodes the Drosophila melanogaster ortholog of a U2 snRNP-associated splicing factor, SF3a60 (SAP61) in humans and PRP9p in Saccharomyces cerevisiae. Antibodies raised against human SF3a60 recognized NOI in flies, showing a nuclear localization in all the stages examined, including the embryo, the dividing cells of imaginal discs, and the larval polyploid nuclei. NOI is expressed in somatic and germinal cells of both male and female gonads. By mobilization of P transposons, we have generated a large number of noi mutations. Complete loss of function resulted in lethality at the end of embryogenesis, without obvious morphological defects. Hypomorphic alleles revealed multiple roles of noi for the survival and differentiation of male germ cells, the differentiation of female germ cells, and the development of several adult structures.

Alleles↗

Impaired estimation of word occurrence frequency in frontal lobe patients.

Neuroanatomical correlates of the estimation of occurrence frequency have received little attention. This study investigates the possible role of the frontal lobe in estimating word occurrence frequency. A sample of 27 patients with frontal lesions were matched with normal controls by sex, age and years of education. Significant differences between patients and controls were found for frequency estimation, but not for item recognition. Studying accuracy of estimation as a function of actual frequency, the frontal group performed worse, especially at high frequencies of occurrence. As far as lesion lateralization is concerned, the right frontal subgroup performed worse than the control group in the estimation of frequency. Our results suggest that the prefrontal cortex plays a role in estimating word occurrence and that there is a dissociation between frequency memory and recognition memory, pointing to the involvement of two different cerebral systems.

Adult↗

A retrospective six-months clinical trial of adhesive precoated brackets and bonding system.

This study investigated bond failures in two groups of 75 patients. Either adhesive precoated (APC) or control brackets were bonded from bicuspid to bicuspid in the mandibular and maxillary arch by a single experienced operator. Observations on failure were recorded at initial arch wire insertion and for the first six months of treatment. The APC bracket failed significantly more often than the control at initial arch wire insertion in both maxillary and mandibular teeth. Further examination disclosed that the APC bracket, when bonded to mandibular teeth, also failed significantly more often than the control during the subsequent six months of treatment. At the six-month point of the study, a total of 53 bond failures had occurred at 671 bond sites in the APC group (7.89 per cent failure rate), compared to 27 bond failures at 977 bond sites in the control group (2.76 per cent failure rate). Fourteen patients in the APC group and two patients in the control group experienced bond failure at initial arch wire insertion. Twenty-eight patients in the APC group and 13 in the control group experienced bond failures within the first six months following initial arch wire insertion.

Adhesiveness↗

Flow cytometry analysis of pituitary adenomas.

UNLABELLED: Using flow cytometry, DNA content and index, and/or proliferative capacity (measuring proliferating cell nuclear antigen PCNA) in operated pituitary tumors, control pituitaries obtained at necropsy, and experimental pituitary hyperplasia induced in rats were analyzed. Simultaneous measurement of cell ploidy and proliferation differentiated normal pituitary (diploid DNA index and negative PCNA) from pituitary hyperplasia (diploid DNA index with intensely positive PCNA, between 30 and 72% of cells). In the tumors 83% (19/ 23) were positive for PCNA (between 3 and 84%) and 73% (17/23) aneuploid; only 1 tumor was diploid and negative for PCNA. CONCLUSIONS: Differentiation between normal and abnormal (neoplastic or hyperplastic) pituitary is possible by flow cytometry, but in the adenomas no correlation with postoperative clinical outcome was observed.

Adenoma↗

Sharp increase in rat lung water channel expression in the perinatal period.

Three members of the water channel (aquaporin) family are expressed in adult rat lung: CHIP28 (AQP-1), MIWC (AQP-4), and AQP-5. Because water channels may be important in the clearance of fluid from the newborn lung, the expression of water channels just before and after birth was investigated using the ribonuclease (RNAse) protection assay. RNA was isolated from lungs, brain, and heart of prenatal rats (fetal days F19, F20, and F21) and postnatal rats (days +1, +2, +5, +7, +21, and adult). Transcript expression was measured relative to a beta-actin control by quantitative densitometry. Whereas beta-actin mRNA expression was nearly constant over time, distinct expression patterns were observed for the three water channels. CHIP28 mRNA expression rose slowly from days F19 to +1, then strongly at day +2, and remained elevated over the first week. MIWC mRNA was weakly expressed prenatally, but strongly increased just after birth. AQP-5 mRNA increased slowly and monotonically between days F20 and +7. These patterns contrasted sharply with the developmental expression of CHIP28 in heart, which decreased over time, and MIWC in brain. Immunocytochemistry showed CHIP28 protein expression in capillary endothelia and MIWC in airway epithelia by day +1; quantitative immunoblot analysis showed increased CHIP28 protein expression over time. These findings are consistent with a role of lung water channels in perinatal fluid clearance; however, proof of physiologic significance will require functional measurements of air space-capillary water permeability.

Animals↗

Suboccipital dermatomyotomic stimulation and digital blood flow.

The effect of gentle, soft tissue manipulation in the suboccipital region on digital blood flow, as a measure of sympathetic nervous system activity, was studied. Digital strain gauge plethysmography was used to measure the changes in pulse contour during (1) a normative test period with the subject in the supine position, (2) after a control interval (placebo) during which the investigator placed his hands under the suboccipital region, and (3) after an interval during which the investigator's fingers applied slow, steady, circular kneading in the suboccipital triangle region. Twenty-five studies were performed in a crossover design with the patient as his or her own control. Total pulse amplitude (Y) and the height from the dicrotic notch to the peak (X) were measured. Examination of the total data of all subjects revealed the occurrence of a significant change in X and Y with simply touching the suboccipital region with the hands. An even more favorable response ensued when suboccipital manipulation was applied. Those subjects reporting comfort or neutral responses had larger significant changes with manipulation when compared with the group reporting the experience as uncomfortable. The response within each group suggests that favorable autonomic changes (sympathetic dampening) occur with specific suboccipital manipulation as well as, indeed, the simple touching of the suboccipital triangle.

Adolescent↗

Identification of regions interacting with ovoD mutations: potential new genes involved in germline sex determination or differentiation in Drosophila melanogaster.

Only a few Drosophila melanogaster germline sex determination genes are known, and there have been no systematic screens to identify new genes involved in this important biological process. The ovarian phenotypes produced by females mutant for dominant alleles of the ovo gene are modified in flies with altered doses of other loci involved in germline sex determination in Drosophila (Sex-lethal+, sans fille+ and ovarian tumor+). This observation constitutes the basis for a screen to identify additional genes required for proper establishment of germline sexual identity. We tested 300 deletions, which together cover approximately 58% of the euchromatic portion of the genome, for genetic interactions with ovoD. Hemizygosity for more than a dozen small regions show interactions that either partially suppress or enhance the ovarian phenotypes of females mutant for one or more of the three dominant ovo mutations. These regions probably contain genes whose products act in developmental hierarchies that include ovo+ protein.

Alleles↗

A phenomenological study of sensory defensiveness in adults.

This article describes the experiences of five adults who are defensive toward sensations of touch, movement, vision, smell, sound, and taste that most people consider harmless. It also describes the strategies that they use when they perceive environmental stimuli to be aversive. These coping strategies are avoidance, predictability, mental preparation, talking through, counteraction, and confrontation. A conceptual framework is presented to enhance understanding and guide further study of sensory defensiveness in adults.

Adaptation, Psychological↗

Evidence for sex transformation of germline cells in ovarian tumor mutants of Drosophila.

Mutations at a few genetic loci in Drosophila cause ovarian tumors with hundreds of poorly differentiated germ cells. We examined several of these mutants to test the hypothesis that such ovarian tumors contain sex-transformed cells. By testing for expression of male germline traits, we determined that partial germline sex transformation occurs in otu, snf, Sxlfs, and bam ovarian tumors. Thus these genes are likely to be required for proper establishment of germline sexual identity.

Animals↗

Parvalbumin and calbindin-D28k immunocytochemistry in human neocortical epileptic foci.

Serial sections of cortical resection of 30 patients suffering from drug-resistant epilepsy were processed for parvalbumin and calbindin-D28k immunocytochemistry to determine local circuit neuron populations. Our findings indicate that there is not a simple mechanism to explain neocortical epileptic foci. On the basis of the present results it can be suggested that: (1) reduced percentage of local circuit neurons in the vicinity of neoplasms may account for a decreased intracortical inhibition. (2) Abnormal morphology and distribution of local circuit neurons may result in abnormal cortical inhibition in patients with focal cortical dysplasia, and, probably, in other focal migrational disorders, including neuronal nests in the white matter. (3) Increased percentages of immunoreactive local circuit neurons and fibers in focal neocortical necrosis (cavernous angiomas), diffuse hypoxic encephalopathy, and hippocampus in patients with temporal lobe epilepsy due to mesial sclerosis, may play a role in epilepsy. These neurons can be activated by reduced excitatory inputs, or they may establish abnormal synaptic contacts with other inhibitory neurons. (4) Lack of consistent morphologic abnormalities in the neocortex of patients with temporal lobe epilepsy, and in patients with cryptogenetic frontal lobe epilepsy, suggests that electrically abnormal neocortical foci in these cases are probably epiphenomena.

Adolescent↗

What is needed for resective epilepsy surgery from a neurosurgical point of view?

Invasive versus non-invasive epileptogenic zone definition was analyzed in a series of 89 patients operated on for drug-resistant epilepsy. In the group of 69 cortical resections, 26% needed invasive recordings, 13.5% when foreign-tissue lesions had been detected by MRI and 32% when were absent. In this last group temporal resections had invasive EEG recordings in 23.5% versus 54.5% when the epileptogenic zone was extratemporal. In a group of 43 temporal resections with more than one year follow-up MRI has detected some abnormality in 84%. Excluding focal lesions, MRI detected hippocampal/temporal lobe atrophy in 66% of the cases in agreement with other noninvasive tests and in 4% contralateral to the epileptogenic zone located by subdural strips. The outcome analysis showed that 85% of the patients with MRI-EEG agreement were seizure free in contrast to only 43% when MRI was non-lateralizing. Future studies has to be oriented to better understand the epileptic process of patients without MRI abnormalities.

Brain↗