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Biomedical subjects

D Francis

Publications and source records attributed to D Francis.

At least 37 records · Page 2Linked to original sources

A very rare benign tumour in the parotid region: calcium pyrophosphate dihydrate crystal deposition disease.

Calcium pyrophosphate dihydrate crystal deposition disease, exhibits several clinical manifestations, from absence of symptoms to severely destructive arthropathy or conditions simulating neoplasm, which is frequently related to the temporomandibular joint. Fifteen of the 31 reported cases of tophaceous pseudogout were found in the head and neck region. A patient presented with a parotid swelling, which initially was suspected to be malignant because of the following findings: radiodensity, progression into the joint, osseous destruction of the major ala of the sphenoid and a fine needle aspirate with crystals, osteoblasts, megakaryocytes and irregular cells of varying size. At surgery there was found a tumour consisting of a white, firm gritty material. It progressed to the skull base where material had to be left, because of the presence of the nerves and vessels. A frozen specimen was reported to be benign. Histological examination showed inflammatory cells, macrophages, a chondroid material with embedded metaplastic chondroid cells and giant cells of foreign body type. Crystal examination of X-ray diffraction revealed calcium pyrophosphate dihydrate.

Chondrocalcinosis↗

What you ask is what you get: learning from interviewing in qualitative research.

This paper outlines some important issues discovered about undertaking qualitative interviews. A description of a study that involved interviewing the authors' students is followed by discussion of aspects of the interviewing process that became apparent during analysis of those interviews. Problems that were encountered with retrospective interviews, power differentials, question sequencing, some interview techniques, and a prior knowledge of the students are illuminated to assist other qualitative interviewers to be aware of these potential areas of difficulty.

Clinical Nursing Research↗

Ethylene induces cell death at particular phases of the cell cycle in the tobacco TBY-2 cell line.

It was examined whether ethylene induces programmed cell death in a cell cycle-specific manner. Following synchronization of the tobacco TBY-2 cell line with aphidicolin and its subsequent removal, ethylene was injected into the head space of 300 cm(3) culture flasks at 0 h or 3.5 h later and cells were sampled for 26 h. There were significant increases in cell mortality at G(2)/M in both the 0 h and 3.5 h ethylene treatments, and for the latter treatment, another peak in S-phase. The effect at G(2)/M was greater in the 3.5 h treatment, but was ameliorated by the simultaneous addition of silver nitrate (1.2 microM). In addition, the 3.5 h ethylene treatment resulted in a 1 h delay in the characteristic rise in the mitotic index following aphidicolin-induced synchrony. The addition of silver nitrate alone (1.2 microM), also delayed the entry of cells into mitosis but had no effect on cell cycle length compared with the controls (14 h throughout all treatments) but it induced a peak of mortality 2.5 h after its addition. Nuclear shrinkage was also a characteristic feature of dying cells at G(2)/M. Using Apoptag, an in situ apoptosis detection kit, nuclear DNA fragmentation was observed in the TBY-2 cells which were often isolated on the end of a filament of normal cells. In the 3.5 h ethylene treatment, a marked increase was noted in the percentage of such cells at the G(2)/M transition compared with the controls. Hence, the data show cell death occurring at a major phase transition of the cell cycle and the observations of nuclear shrinkage, isolation of dying cells and nuclear DNA fragmentation suggest a programmed mechanism of cell death exacerbated by ethylene treatment.

Aphidicolin↗

A phase II study of two HIV type 1 envelope vaccines, comparing their immunogenicity in populations at risk for acquiring HIV type 1 infection. AIDS Vaccine Evaluation Group.

Several immunogens induce HIV-specific neutralization and in vitro lymphoproliferation in adults at low HIV-1 risk, but responses in persons at high HIV-1 risk are not known. We performed a multicenter, double-blinded, adjuvant-controlled trial with two gp120 vaccines in 296 HIV-1-uninfected volunteers, including 176 reporting higher HIV-1 risk activities. The immunogens were remarkably well tolerated. After three immunizations, 210 of 241 vaccinees (87%) developed neutralizing antibodies, which persisted in 59% after 2 years. The injection drug users receiving SF-2/gp120 had decreased antibody responses relative to the lower risk groups. Envelope-specific lymphoproliferation peaked after two immunizations, and 54% of vaccinees mounted a DTH reaction to gp120 after 4 years. In summary, these immunogens have low adverse reactogenicity and induce durable antibody and T cell responses to the prototype strains. Unexpected differences in antibody responses among diverse HIV-1 risk strata lend support to the conduct of expanded phase II trials in populations other than low-risk volunteers.

AIDS Vaccines↗

Postnatal handling increases the expression of cAMP-inducible transcription factors in the rat hippocampus: the effects of thyroid hormones and serotonin.

Postnatal handling increases glucocorticoid receptor expression in the rat hippocampus, thus altering the regulation of hypothalamic synthesis of corticotropin-releasing hormone and the hypothalamic-pituitary-adrenal response to stress. The effect on glucocorticoid receptor gene expression represents one mechanism by which the early environment can exert a long-term effect on neural development. The handling effect on hippocampal glucocorticoid receptor expression is dependent on peripheral thyroid hormone release and the activation of ascending serotonergic pathways. In primary hippocampal cell cultures, serotonin (5-HT) increases glucocorticoid receptor expression, and this effect appears to be mediated by increased cAMP levels. In the current studies we examined the in vivo effects of handling on hippocampal cAMP-protein kinase A (PKA) activity. In 7-d-old rat pups, we found that (1) postnatal handling increased adenylyl cyclase activity and hippocampal cAMP levels, (2) the effect of handling on cAMP levels was completely blocked by treatment with either propylthiouracil (PTU), a thyroid hormone synthesis inhibitor, or the 5-HT receptor antagonist, ketanserin, and (3) handling also increased hippocampal PKA activity. We then examined the effects of handling on cAMP-inducible transcription factors. Handling rapidly increased levels of the mRNAs for nerve growth factor-inducible factor A (NGFI-A) (zif268, krox24) and activator protein-2 (AP-2) as well as for NGFI-A and AP-2 immunoreactivity throughout the hippocampus. Finally, we found that the effects of handling on NGFI-A and AP-2 expression were significantly reduced by concurrent treatment with either PTU or ketanserin, effects that paralleled those on cAMP formation. NGFI-A and AP-2 have been implicated in the regulation of glucocorticoid receptor expression during development. Thus, these findings suggest that postnatal handling might alter glucocorticoid receptor gene expression via cAMP-PKA pathways involving the activation of NGFI-A and AP-2.

Adenylyl Cyclases↗

AIDSVAX (MN) in Bangkok injecting drug users: a report on safety and immunogenicity, including macrophage-tropic virus neutralization.

A randomized, double-blind, placebo-controlled phase I/II study of AIDSVAX (MN) was conducted among injecting drug users in Bangkok, Thailand. Four doses of vaccine (300 microg of MN-rgp120 in alum) or placebo (alum) were given at study entry and at 1, 6, and 12 months. The objectives of the study were to evaluate (1) the feasibility of conducting vaccine trials in this population; (2) the safety of this candidate AIDS vaccine; and (3) the immunogenicity of this vaccine. Thirty-three volunteers (22 vaccine and 11 placebo recipients) were recruited. None were lost to follow-up during the 18-month study. Mild reactogenicity was noted, which was similar in both vaccine and placebo recipients. The vaccine induced anti-HIV-1 antibody in all vaccine recipients. Maximal titers of binding antibodies of MN-rgp120 and the V3 domain of MN-rgp120 were induced after the third (6 month) dose while maximal neutralizing antibodies followed the fourth (12 month) dose. The vaccine-induced antibodies from several volunteers were capable of neutralizing macrophage-tropic, subtype B viruses (301660 and JRCSF) detected in a PBMC-based assay. Binding and neutralizing antibodies declined about 10-fold in the 6 months after the last boost. Two vaccinees became infected during the trial, both with subtype E viruses. A phase III efficacy trial, using a bivalent gp120 vaccine containing antigens from a subtype B virus (MN) and a subtype E virus (A244), was initiated in March 1999 in injecting drug users in Bangkok.

AIDS Vaccines↗

Inactivation of DNA replication origins by the cell cycle regulator, trigonelline, in root meristems of Lactuca sativa.

The effects of trigonelline (TRG) on the cell cycle in root meristems of Lactuca sativa L. were examined in the knowledge that TRG is a cell cycle regulator that causes cell arrest in G2, and prevents ligation of replicons in S-phase. The hypothesis was tested that continuous exposure to TRG would perturb DNA replication which, in turn, would lengthen the cell cycle and impair root elongation. Using DNA fibre autoradiography, mean replicon size was 31 and 13 microm in the TRG (3 mM) and control treatments, respectively. Trigonelline also resulted in a lengthening of both S-phase and the cell cycle and a decrease in primary root elongation. Hence, replicon inactivation was responsible for the protracted S-phase. Trigonelline treatment also resulted in a 1.6-fold increase in fork rate (13.8 microm h(-1)) compared with the control (8.4 m h(-1)). The faster fork rate in the larger replicons is in accord with the highly significant positive relationship already established between fork rate and replicon size for various unrelated higher plants.

Alkaloids↗

Enhanced nucleus accumbens dopamine and plasma corticosterone stress responses in adult rats with neonatal excitotoxic lesions to the medial prefrontal cortex.

The medial prefrontal cortex modulates the nucleus accumbens dopamine response to stress and has been implicated in feedback regulation of hypothalamic-pituitary-adrenal axis activation by stress. Here we report on the effects of bilateral neonatal (postnatal day 7) ibotenate-induced lesions to the medial prefrontal cortex on nucleus accumbens dopamine and neuroendocrine function in adult rats. Voltammetry was used to monitor the dopamine response to each of five, once-daily exposures to tail-pinch stress whereas alterations in neuroendocrine function were determined from the plasma corticosterone response to a single 20-min episode of restraint stress. Potential lesion-induced deficits in sensory-motor gating were assessed by measuring prepulse inhibition of the acoustic startle response before and after repeated stress. Our data show that each daily stress episode elicited larger and longer-lasting dopamine increases in prefrontal cortex-lesioned animals than in sham-lesioned controls. Furthermore, greater stress-induced elevations in plasma corticosterone were seen in lesioned animals than in their sham-lesioned counterparts. However, while repeated stress potentiated startle responses in animals of both groups, there was no effect of lesion on the amplitude or on prepulse inhibition of the startle response.Together, these findings indicate that neonatal prefrontal cortex damage can lead to changes in mesolimbic dopamine and neuroendocrine function during adulthood. They also add to a growing body of experimental and clinical evidence implicating abnormal prefrontal cortex neuronal development in the pathophysiology of schizophrenia and other disorders linked to central dopamine dysfunction.

Animals↗

The effects of early rearing environment on the development of GABAA and central benzodiazepine receptor levels and novelty-induced fearfulness in the rat.

We compared the effects of handling or maternal separation from the day following birth until postnatal day 14 on behavioral responses to novelty and on GABAA and central benzodiazepine (CBZ) receptor levels in the rat. As adults, handled animals showed reduced startle responsivity, increased exploration in a novel open field, and decreased novelty-induced suppression of feeding relative to the handled (H) and/or maternal separation (MS) groups. As compared with handled animals, both nonhandled (NH) and MS animals displayed: (1) reduced GABAA receptor levels in the locus coeruleus (LC) and the n. tractus solitarius (NTS); (2) reduced CBZ receptor sites in the central and lateral n. of the amygdala, the frontal cortex, and in the LC and NTS; and (3) reduced levels of the mRNA for the gamma 2 subunit of the GABAA receptor complex, which confers high affinity BZ binding, in the amygdaloid nuclei as well as in the LC and NTS. Both the amygdala and the ascending noradrenergic systems have been considered as critical sites for the anxiolytic effects of benzodiazepines. These data suggest that early life events influence the development of the GABAA receptor system, thus altering the expression of fearfulness in adulthood.

Acoustic Stimulation↗

Immunohistochemical localization of inducible and endothelial constitutive nitric oxide synthase in neoplastic and autoimmune thyroid disorders.

AIM: To investigate the distribution of nitric oxide synthase in tissues derived from patients with autoimmune or neoplastic disorders of the thyroid gland in order to test whether the expression of inducible nitric oxide synthase or endothelial constitutive nitric oxide synthase (two subtypes of EC 1.14.13.39) may be related to the inflammatory activity or degree of neoplasia. EXPERIMENTAL DESIGN: The expression of nitric oxide synthases was examined by immunohistochemistry in tissues from patients with either Hashimoto's thyroiditis (n=6), hyperplastic glands (Graves' disease) (n=7), adenomas (n=8), multinodular goitres (n=7), papillary carcinomas (n=4) or follicular carcinomas (n=5). RESULTS: Expression of inducible nitric oxide synthase was found in 22 of the tissues and was not specific for any of the examined thyroid disorders. Expression of endothelial constitutive nitric oxide synthase was found in some of the epithelial cells in all the tissues. There was no correlation between the intensity and distribution of the immunostaining and the thyroid disorders. CONCLUSION: Demonstration of nitric oxide synthase cannot be used for diagnostic purposes. The expression of endothelial constitutive nitric oxide synthase in all tissues indicates that the enzyme may be of importance for the function or growth of the thyroid epithelial cells.

Adenocarcinoma, Follicular↗

Antibody repertoire development in fetal and newborn piglets, III. Colonization of the gastrointestinal tract selectively diversifies the preimmune repertoire in mucosal lymphoid tissues.

Changes in the VH-region repertoire of isolator piglets reared for 6 weeks under germ-free (GF) conditions and those colonized (COL) with a defined exclusion flora on the 1st day of life were compared. Although serum immunoglobulin levels were 20-100-fold higher in COL piglets than GF piglets, an analysis of peripheral blood B cells (PBBs) indicated that: GF and COL piglets used the same four VH genes and two DH segments during the 6-week period; proportional usage of VH genes and DH segments was the same as in fetal animals; and VH and DH usage did not differ between COL and GF animals. This pattern differed from the PBBs from 6-week-old conventional (CONV) piglets. When the sequences of 73 splenic CDR3 segments were analysed, DH usage and mutation frequency were the same in sequences from both 6-week-old GF and COL piglets; mutations were infrequent and occurred with the same frequency as in 110-day fetal spleen. However, the median CDR3 length in COL piglets was shifted upward due to 3' DH N-nucleotide additions. Neither COL nor GF animals made specific serum antibodies to phosphoryl choline given parenterally on a T-cell dependent carrier. In contrast to the near absence of a colonization effect in PBBs and splenic DNA, rearranged variable heavy-chain gene segments (VDJs) recovered from the DNA of mucosal lymphoid tissues of COL piglets showed pronounced differences from those recovered from GF animals in usage of DHA-, DHB-and VHB- and in the frequency of point mutation. The mucosal VDJ transcripts and those from the spleen were similarly affected by colonization. This effect on mucosal lymphoid tissue was consistent with the five-fold selective increase in serum immunoglobulin A (IgA) levels relative to IgM and IgG. Comparison of IgM and IgA transcripts from mucosal tissues suggested that IgA and IgM clones diversify in parallel. Our findings are the first to show that colonization of the gastrointestinal tract of offspring separated from their mothers, differs from 'conventionalized' GF animals in that colonization preferentially influences diversification and expansion of the preimmune IgM and IgA repertoire in mucosal lymphoid tissues but not in PBBs and seldom/modestly in VDJs from splenic DNA.

ATP-Binding Cassette Transporters↗

Identification of small FRAXA premutations.

BACKGROUND: Diagnosis of fragile X syndrome in mentally retarded individuals is satisfactorily achieved using a Southern blot test that detects the typical triplet repeat expansion (>200 repeats) within the FMR1 gene. All such individuals inherit the mutation from a carrier, who usually shows a lower triplet repeat number and may be asymptomatic. Having identified a fragile X proband, it is necessary to identify related carriers of this familial X-linked dominant mutation to provide family counseling and testing. METHODS AND RESULTS: For one family in which a fragile XA repeat expansion occurs, Southern blot hybridization did not give accurate sizing data because of the very small premutation associated with the unstable allele. PCR sizing methods and linkage analysis were adapted to identify family members with the premutation. CONCLUSION: Although most carriers can be detected using Southern blot and/or direct PCR sizing tests, very small expansions (55-70 repeats) are difficult to distinguish from larger, normal alleles. We have used linkage analysis in combination with direct allele analysis to identify carriers of very small expansions of a fragile X chromosome in a four-generation family.

Blotting, Southern↗

Lymphoproliferative responses to recombinant HIV-1 envelope antigens in neonates and infants receiving gp120 vaccines. AIDS Clinical Trial Group 230 Collaborators.

Children of mothers infected with human immunodeficiency virus type 1 (HIV-1) were immunized at birth and at 1, 3, and 5 months with 1 of 3 doses of recombinant gp120 vaccines prepared from SF-2 or MN strains of HIV-1. A total of 126 children were not infected; 21 received adjuvant only. Vaccine recipients developed lymphoproliferative responses on >/=2 occasions, responding more often to homologous HIV-1 antigens than did adjuvant recipients (56% vs. 14%; P<.001). Responses were appreciated after 2 immunizations and were maintained for >84 weeks after the last immunization. An accelerated immunization schedule (birth, 2 weeks, 2 months, and 5 months) with the lowest dose of the SF-2 vaccine produced responses in all 11 vaccinees by 4 weeks. Responses to heterologous envelope antigens were also detected. Immune responses to vaccination are achievable at an age when some infection (perinatal or breast milk exposure related) may be prevented.

AIDS Vaccines↗

The determination time of the carpel whorl is differentially sensitive to carbohydrate supply in Pharbitis nil.

A shoot apical meristem is florally determined if, following its removal from an induced plant, it flowers when cultured in non-inductive conditions. Determination times were measured in the short-day plant Pharbitis nil to examine whether floral whorls are determined simultaneously or sequentially. Shoot apices were excised at daily intervals following a 48-h dark-inductive treatment, cultured in non-inductive conditions for 4 weeks in continuous light, and the number of floral organs scored. The culture medium was White's supplemented with sucrose, glucose (Glc), fructose (Fru), or 1:1 Glc:Fru at 2% (w/v), 4% (w/v), or 6% (w/v) or sugar-mannitol combinations of osmotic potentials equivalent to 4% (w/v) or 6% (w/v). The minimum whorl determination time was 1 d for sepals, petals, and stamens regardless of carbon supply. However, for carpels it varied remarkably from 5 d on sucrose, to 2 to 3 d on Fru or Glc:Fru, to 1 d for 2% (w/v) and 6% (w/v) Glc. Therefore, depending on the carbon supply, the carpel whorl was determined at the same time or after the outer whorls. Generally, these effects could not be reproduced on the sugar-mannitol treatments.

Carbohydrate Metabolism↗

The inhibition of fatty acid elongation by pebulate can be effectively counteracted by the safener dichlormid.

The thiocarbamate herbicide pebulate inhibits fatty acid elongation, which is necessary for surface lipid biosynthesis. As both barley and wild oats are susceptible to pebulate, the safener dichlormid was used to study the reversal of its herbicidal effect. Fatty acid elongation was restored by a dichlormid pretreatment in barley, but not in pebulate-expressed oats.

Acetamides↗

Oscillatory breathing patterns during wakefulness in patients with chronic heart failure: clinical implications and role of augmented peripheral chemosensitivity.

BACKGROUND: Oscillatory breathing patterns characterized by rises and falls in ventilation with apnea (Cheyne-Stokes respiration [CSR]) or without apnea (periodic breathing [PB]) commonly occur during the daytime in chronic heart failure (CHF). We have prospectively characterized patients with cyclical breathing in terms of clinical characteristics, indices of autonomic control, prognosis, and the role of peripheral chemosensitivity. METHODS AND RESULTS: To determine cyclical breathing pattern, power spectral analysis was applied to 30-minute recordings of respiration in 74 stable CHF patients. Analyses of heart rate variability and baroreflex sensitivity were used to assess autonomic balance. Peripheral chemosensitivity was assessed with the transient hypoxia method. We also determined whether the suppression of peripheral chemoreceptor activity (hyperoxia or dihydrocodeine) would influence the respiratory pattern. Cyclical respiration was found in 49 (66%) patients (22 [30%] CSR, 27 [36%] PB) and was associated with more advanced CHF symptoms, impaired autonomic balance, and increased chemosensitivity (0.80 and 0.75 versus 0.34 L. min(-1). %SaO(2)(-1), P<0.001, for CSR and PB versus normal breathing, respectively). Transient hyperoxia abolished oscillatory breathing in 7 of 8 patients. Dihydrocodeine administration decreased chemosensitivity by 42% (P=0.05), which correlated with improvement in respiratory pattern. Cyclical breathing predicted poor 2-year survival (relative risk 9.41, P<0.01, by Cox proportional hazards analysis), independent of peak oxygen consumption (P=0.04). CONCLUSIONS: An oscillatory breathing pattern during the daytime is a marker of impaired autonomic regulation and poor outcome. Augmented activity of peripheral chemoreceptors may be involved in the genesis of this respiratory pattern. Modulation of peripheral chemosensitivity can reduce or abolish abnormal respiratory patterns and may be an option in the management of CHF patients with oscillatory breathing.

Aged↗