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Biomedical subjects

J Nicholson

Publications and source records attributed to J Nicholson.

At least 73 records · Page 4Linked to original sources

Studies on plaque fluoride after use of F-containing dentifrices.

Increased fluoride levels in plaque and saliva have been associated with improved protection against dental caries for dentifrices which contained sodium monofluorophosphate (Duckworth et al., 1992). The main aim of the present work was to test whether oral fluoride retention depended on F source after use of dentifrices containing either NaF or Na2FPO3. In study 1, plaque samples were collected from 474 subjects who had been using one of six test dentifrices for two years, and analyzed by F extraction with water. The dentifrices contained 1000 or 1500 micrograms F/g as either NaF or Na2FPO3. Significantly more fluoride was found in plaque from subjects who were using the NaF dentifrices than in plaque from subjects who were using Na2FPO3 dentifrices of the same F content. Subsets of plaque samples were large enough to divide into two parts for extraction by both acid and water. No significant difference was found between mean fluoride contents, indicating that the majority of fluoride retained in plaque from these conventional dentifrices appears to be relatively labile. The results of two small-scale human enamel studies showed that NaF dentifrices gave elevated F concentrations in plaque and saliva, respectively, compared with Na2FPO3 dentifrices of equivalent F content, consistent with the main plaque study 1. These findings demonstrate that oral F retention from dentifrices is dependent on the source of ionic fluoride and support the view that NaF dentifrices may be more clinically effective than dentifrices which contain the same amount of F as Na2FPO3.

Adolescent↗

Real time measurement of gene expression in living endocrine cells.

The mechanisms underlying hormonal gene expression are complex, and key regulatory events are often temporally separated. Our understanding of these dynamic processes has been hindered in part by the lack of a method suitable for making dynamic measurements of gene expression. In an attempt to develop such a system, we modified conventional luciferase reporter technology to enable real time measurement of gene expression in living endocrine cells.

Animals↗

Almost two centuries with amalgam: where are we today?

Amalgam has provided valuable and comparatively inexpensive service to patients for a longer time than any other restorative material. Despite the excitement surrounding the use of each new restorative material, each has a shortcoming that amalgam hasn't.

Composite Resins↗

DNA binding alters the protease susceptibility of the p50 subunit of NF-kappa B.

The subdomain structure of the p50 subunit of NF-kappa B (amino acids 35-381) was investigated by partial proteolysis of the native protein. Trypsin cleaves p50 at a limited number of sites with an initial cleavage at low trypsin concentration occurring after R362 and a second cleavage taking place at higher trypsin concentration after K77. The cleavage after R362 does not alter the DNA binding characteristics of p50 but removes the nuclear localisation signal indicating that this region occupies a highly exposed position on the surface of the protein. The second cleavage after K77 generates a protein that although dimeric is incapable of binding DNA, thus emphasising the importance of residues 35-77 in DNA recognition. However p50 dimers containing one molecule cleaved after K77 and one molecule with this region intact are capable of binding DNA. When very high concentrations of trypsin are employed p50 is completely degraded. However if p50 is bound tightly to DNA containing its specific recognition site prior to trypsin addition the cleavage after K77 is almost completely blocked and the protein becomes highly resistant to proteolysis. These data suggest that bound DNA may mask critical trypsin cleavage sites or that DNA binding is accompanied by a conformational change in protein structure that renders the protein resistant to proteolysis.

Cross-Linking Reagents↗

Determination of platinum in urine, ultrafiltrate, and whole plasma by isotope dilution gas chromatography-mass spectrometry compared to electrothermal atomic absorption spectrometry.

Isotope dilution gas chromatography-mass spectrometry (GC-MS) and electrothermal atomic absorption spectrometry (EAAS) are compared for platinum (Pt) determination in urine, plasma ultrafiltrate, and plasma samples from a patient undergoing cisplatin therapy. The isotope dilution GC-MS method is based on the use of lithium bis(trifluoroethyl)dithiocarbamate as a chelating agent and enriched 192Pt as an internal standard. Pt isotope ratios were measured using a Finnigan MAT 8230 organic mass spectrometer, and Pt concentrations were calculated from different sets of isotope ratios in the molecular ion of the Pt-chelate. In the EAAS method, Pt concentrations were determined using three different approaches. These were: (i) calibration curve based on aqueous standards containing Pt in 10% HCl, (ii) standard addition, and (iii) matrix digestion followed by standard addition. Good agreement was obtained for Pt concentrations determined by GC-MS and EAAS in urine samples while there were significant differences in Pt concentrations of ultrafiltrate and whole plasma samples by the two methods. Discussion of possible reasons for these differences emphasizes the need for future critical evaluation of these methods.

Carcinoma, Squamous Cell↗

State policies and programs that address the needs of mentally ill mothers in the public sector.

OBJECTIVE: The authors sought to determine whether state departments of mental health have specific policies and programs addressing the needs of mentally ill women served in the public sector who have preschool-age children. METHODS: A questionnaire was sent to the commissioner of mental health for each state and the District of Columbia. Questions addressed whether information was routinely collected on the parenting status of women who receive public-sector psychiatric services, whether services targeting mentally ill women with young children were available, and whether the state had policies concerning hospitalized women who are pregnant or who have young children. RESULTS: Sixteen states routinely collect data on whether women who receive public-sector services have young children. Four states have residential programs for mentally ill women and their children. About half of the states have programs for assessing parenting skills and outpatient services focused on improving those skills. No state has a policy about visitation between a hospitalized mentally ill mother and her children. Twenty states have policies for the care of hospitalized pregnant patients, primarily for their medical management. CONCLUSIONS: Further efforts are needed to identify mentally ill women in the public sector who have young children, to enhance the parenting skills of mentally ill patients, and to promote positive outcomes for their children.

Child↗

Large granular lymphocyte proliferation with the natural killer-cell phenotype.

Lymphoproliferated disorders involving large granular lymphocytes (LGL) can be divided into a common T-cell subset (CD3+, CD8+) and a rarer natural killer (NK)-cell subset (CD2+, CD3-). The immunophenotype, clinical pathologic features, and cytogenetic and molecular genetic analyses are reported for seven patients with NK-cell-LGL proliferation. The typical immunophenotype was CD2+, CD3-, CD4-, CD11b+, and CD16+ or CD56+. A low but variable percentage of cells were CD8+ or CD57+. Unusual phenotypes with CD2- (1 of 7), CD11b- (1 of 7), or CD16-/CD56- (1 of 7) cells were seen. Strong NK-cell activity was observed in all cases, indicating that none of the NK-cell markers (CD11b, CD16, CD56, CD57) is essential for NK-cell activity. One patient died shortly after diagnosis from coexistent refractory multiple myeloma and another patient died within 1 month from the LGL proliferation. The other patients had been followed for 12 to 70 months, with a median follow-up period of 38 months. There was no progression of their LGL proliferation. Lymphocyte counts varied from 3.3 x 10(3)/microL to 58.4 x 10(3)/microL at the time of diagnosis. Unexplained anemia and neutropenia were observed in one patient. Cytogenetic abnormalities were detected in two of four patients studied with t(6;12) in one and der(5), der(6), and der(11) in the other. The approximately T gamma and T beta genes were in the germline configuration and Epstein-Barr virus DNA was undetectable in five of five patients studied. Natural killer-cell LGL proliferations were morphologically indistinguishable from T-cell LGL proliferations. However, the two were immunophenotypically and genotypically distinct and NK-cell activity was consistently observed in the former. Most of the NK-cell proliferations also were chronic indolent disorders and the incidence of associated cytopenias seemed to be lower than T-cell LGL proliferations.

Adult↗

Type 1 neurofibromatosis gene: identification of a large transcript disrupted in three NF1 patients.

Von Recklinghausen neurofibromatosis (NF1) is a common autosomal dominant disorder characterized by abnormalities in multiple tissues derived from the neural crest. No reliable cellular phenotypic marker has been identified, which has hampered direct efforts to identify the gene. The chromosome location of the NF1 gene has been previously mapped genetically to 17q11.2, and data from two NF1 patients with balanced translocations in this region have further narrowed the candidate interval. The use of chromosome jumping and yeast artificial chromosome technology has now led to the identification of a large (approximately 13 kilobases) ubiquitously expressed transcript (denoted NF1LT) from this region that is definitely interrupted by one and most likely by both translocations. Previously identified candidate genes, which failed to show abnormalities in NF1 patients, are apparently located within introns of NF1LT, on the antisense strand. A new mutation patient with NF1 has been identified with a de novo 0.5-kilobase insertion in the NF1LT gene. These observations, together with the high spontaneous mutation rate of NF1 (which is consistent with a large locus), suggest that NF1LT represents the elusive NF1 gene.

Adult↗

Cardiac effects induced by chemically activated neurons in canine intrathoracic ganglia.

Regional or global cardiac responses were elicited when various chemicals were injected into discrete loci within acutely decentralized stellate and middle cervical ganglia. Nicotine (100 micrograms), acetylcholine (100 micrograms), or isoproterenol (1, 2, or 5 micrograms) in 1 microliters of normal saline was administered individually into 30 discrete loci within each stellate ganglion and 25 within each middle cervical ganglion. Cardiac augmentation was elicited when approximately 1 site per ganglion was injected with nicotine or acetylcholine. Similar injections into sites approximately 1-2 mm away from an active site usually failed to elicit cardiac responses. Isoproterenol elicited cardiac augmentations when injected into, on average, 3 different loci per ganglion. The responses elicited by isoproterenol injections were eliminated when the efferent sympathetic nerves arising from an injected ganglion were divided or when timolol maleate (0.1 mg/microliters normal saline) was previously injected into the same locus. These data indicate that the effects elicited by injecting isoproterenol into an intrathoracic ganglion locus were not due to leakage of this agent into the blood in sufficient quantities to directly activate cardiac myocytes. When L-glutamic acid (100 microliters of 1 M solution in normal saline) or L-aspartic acid (100 microliters of 1 M solution in normal saline) was injected into a stellate ganglion or middle cervical ganglion, positive chronotropic and/or inotropic responses were elicited. When DL-homocysteic acid (100 microliters of 1 M solution in normal saline) was administered no augmentation occurred. It is concluded that intrathoracic ganglion cardiac neurons can be activated by nicotinic or beta-adrenergic agonists, as well as by specific amino acids. These neurons are located throughout the stellate and middle cervical ganglia, cardiac neurons in one ganglionic locus being capable of activation by more than one of these chemicals.

Acetylcholine↗

Delayed visual maturation: ophthalmic and neurodevelopmental aspects.

Delayed visual maturation (DVM) can present as an isolated anomaly (type 1A), but can be compounded by perinatal problems (type 1B), severe neurodevelopmental delay (type 2), or ocular anomalies/nystagmus (type 3), in which group the common feature appears to be nystagmus. The neurodevelopmental and ophthalmic aspects of 26 infants with DVM were studied. Onset of visual improvement, rate of acquisition of normal vision and eventual outcome were studied quantitatively, using an adaptation of the acuity card procedure. Neurodevelopmental assessment was performed after visual improvement. The results support the long-held clinical impression that if blindness is the presenting feature, neurodevelopmental outlook is excellent. DVM could represent a defect in the extrageniculostriate visual system, and the onset of vision in all types--and the development of nystagmus in type 3--could herald the emergence of geniculostriate function.

Blindness↗

Enhancer binding protein (EBP1) makes base and backbone contacts over one complete turn of the DNA double helix.

The simian virus 40 (SV40) enhancer consists of multiple DNA sequence motifs that represent the binding sites for a large number of trans-acting factors. We have purified one such factor, EBP1, which binds to a region encompassing the "core" of the SV40 enhancer, and appears to be involved in transcriptional activation. The interaction of EBP1 with its recognition site has been analysed by nuclease protection and by a variety of chemical probes. Enhancer sequences protected from cleavage with DNase I in the presence of EBP1 extend from position 232 to 250 on one strand and from 233 to 251 on the other strand. Methylation protection and alkylation interference studies have identified purine bases and backbone phosphate groups that participate in the formation of a specific EBP1-DNA complex. Within a ten base-pair region, every purine base interferes with binding when methylated and six phosphate groups on each strand interfere with binding when the attached oxygen groups are ethylated. "Footprinting" with hydroxyl radicals, generated by the 1,10-orthophenanthroline-copper ion, revealed sugar residues in the binding site that were protected from cleavage in the presence of EBP1. Computer graphics analyses of the contact point data indicate that EBP1 makes base and backbone contacts with the DNA over one complete turn of the DNA double helix, and suggest a model in which EBP1 makes sequence-specific contacts in the major groove, although binding may be influenced by interactions in the minor groove. Comparison of the EBP1 contact points with that of other known DNA-binding proteins indicates that EBP1 employs a unique mechanism to recognize a specific DNA sequence.

Base Sequence↗

Large granular lymphocyte proliferation: an analysis of T-cell receptor gene arrangement and expression and the effect of in vitro culture with inducing agents.

The status of the T cell receptor beta and gamma genes in natural killer (NK) cells was investigated in two patients with a marked expansion of CD2+, CD3- NK cells. Both genes were found to be in the germline state. The T alpha and complete T beta gene transcripts were not detected, but a 1.0-kilobase T beta gene transcript could be demonstrated at low levels in freshly isolated cells and at a much higher level in interleukin-2 (IL-2)-cultured cells. The transcript coding for the delta chain of the CD3 complex was also absent. These cells were cultured in IL-2 with or without the addition of the differentiation-inducing agents: retinoic acid, N,N-hexamethylene bisacetamide, and sodium butyrate. The cultured cells retained their NK activity except in culture with sodium butyrate at greater than or equal to 1 mmol/L. Expression of CD3 or other T cell surface markers by the NK cells was not observed in these cultures. Either CD2+, CD3- NK cells are derived from a non-T lineage, or they have diverged from the T cell lineage earlier than the stage of T gamma gene rearrangement and CD3 delta chain expression; they are refractory to many induction signals in undergoing further T cell differentiation.

Acetamides↗

Unemployment and child abuse.

The employment state of men living in the homes of children at the time that child abuse was diagnosed was determined. The series included a wide range of abuse, including non-accidental injury, failure to thrive, neglect, and emotional deprivation. Two cohorts of children seen during 1974-9 and 1980-5 were compared; these periods were chosen because a large increase in unemployment began in Sheffield in 1980. Although the proportion of the men without work was significantly increased during the second period, this increase could not be ascribed to the rise in either long term or short term unemployment among those who had previously been in regular employment. It was accounted for by a rise in the proportions of single parent families and families in which the resident man had never had regular employment. This may reflect an increase in pregnancies among young mothers. There was no evidence to support the belief that the loss of a job in otherwise stable families leads to an increase in child abuse.

Child↗

Regulatory effects of S-100 protein and parvalbumin on protein kinases and phosphoprotein phosphatases from brain and skeletal muscle.

In the eluted fractions of histone-treated crude extracts separated by Sephadex G-200 filtration, multiple protein kinase (PK) activities, including three from brain and two from skeletal muscle, were augmented by both S-100 protein and parvalbumin on the phosphorylation of endogenous substrates. One additional PK activity suppressed by both S-100 and parvalbumin was also found in muscle. In comparison, phosphoprotein phosphatases (PPase), which were also prepared by the same procedure of initial step of histone-treatment followed by the steps of Bio-Gel P-6DG for brain and DNA-cellulose for muscle, were all activated by S-100 while inhibited by parvalbumin and phosphatidylserine.

Animals↗

Probable occurrence of brain basic protein factor I, an activator of phosphoprotein phosphatases.

Basic protein factor I (BPFI was purified to homogeneity from bovine brain by boiling and trichloroacetic acid-precipitation of tissue homogenate, followed by DEAE-cellulose, Sephadex G-150, Affi-Gel-phenothiazine, and Bio-Gel P-6DG chromatographic procedures. The preparation appeared as a single protein band in the SDS-polyacrylamide gel electrophoresis with a minimal Mr of 13,200. The factor was a basic protein as indicated by an estimated isoelectric point of pH 8.3 and a high content of amino acids including arginine, histidine, lysine and others. In the absence of Mn2+, the factor stimulated the phosphoprotein phosphatases (PPase) from rabbit brains. Unlike histones or protamine, the factor was a poor substrate for megamodulin-dependent protein kinase. In addition, the factor did not interact significantly with E. coli megamodulin.

Amino Acids↗