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Biomedical subjects

D Hewitt

Publications and source records attributed to D Hewitt.

At least 19 recordsLinked to original sources
PubMed2006

Eukaryotic organisms in Proterozoic oceans.

The geological record of protists begins well before the Ediacaran and Cambrian diversification of animals, but the antiquity of that history, its reliability as a chronicle of evolution and the causal inferences that can be drawn from it remain subjects of debate. Well-preserved protists are known from a relatively small number of Proterozoic formations, but taphonomic considerations suggest that they capture at least broad aspects of early eukaryotic evolution. A modest diversity of problematic, possibly stem group protists occurs in ca 1800-1300 Myr old rocks. 1300-720 Myr fossils document the divergence of major eukaryotic clades, but only with the Ediacaran-Cambrian radiation of animals did diversity increase within most clades with fossilizable members. While taxonomic placement of many Proterozoic eukaryotes may be arguable, the presence of characters used for that placement is not. Focus on character evolution permits inferences about the innovations in cell biology and development that underpin the taxonomic and morphological diversification of eukaryotic organisms.

Biological Evolution↗
PubMed2004

Predicting biomarkers for ovarian cancer using gene-expression microarrays.

Ovarian cancer has the highest mortality rate of gynaecological cancers. This is partly due to the lack of effective screening markers. Here, we used oligonucleotide microarrays complementary to approximately 12 000 genes to establish a gene-expression microarray (GEM) profile for normal ovarian tissue, as compared to stage III ovarian serous adenocarcinoma and omental metastases from the same individuals. We found that the GEM profiles of the primary and secondary tumours from the same individuals were essentially alike, reflecting the fact that these tumours had already metastasised and acquired the metastatic phenotype. We have identified a novel biomarker, mammaglobin-2 (MGB2), which is highly expressed specific to ovarian cancer. MGB2, in combination with other putative markers identified here, could have the potential for screening.

Biomarkers, Tumor↗
PubMed2003

Gene expression array profile of human osteosarcoma.

The aims of this pilot study were to determine whether needle and open biopsies from osteosarcoma (OS) provide sufficient quality of mRNA for cDNA array analyses to gain insights into the expression profile of OS. A total of 22 samples collected from OS were used for array analyses. A primary cell culture was also established from one of the OS biopsies. Total RNA was extracted and probes were generated for cDNA arrays. cDNA probes were made for all the 22 samples. Two of these samples were needle core bone biopsies. Statistical analysis confirmed the reliability of array data obtained in 16 of the 22 samples. Known genes involved in bone metabolism and osteosarcoma were identified as highly expressed, and the putative new marker Ezrin was also identified. Confirmatory immunohistochemical staining using the Ezrin antibody was performed in a selection of samples.

Adolescent↗
PubMed2002

The implications of the Human Rights Act 1998 for the removal and detention of persons in need of care and attention.

The Human Rights Act 1998 ('HRA 1998') requires public authorities to act compatibly with the European Convention on Human Rights ('ECHR'). The ECHR contains rights, inter alia, to liberty and to respect for private life. Those rights--and, therefore, the HRA 1998--may be breached by provisions in the National Assistance Act 1948 and the National Assistance (Amendment) Act 1951 that enable persons in need of care and attention to be removed compulsorily to hospital. However, legal proceedings brought against a public authority that invoked its statuatory powers of removal may themselves be defensible under the HRA.

England↗
PubMed1999

Primary cell cultures isolated from Penaeus monodon prawns.

We have devised a cell culture system for Penaeus monodon prawn cells that uses a defined synthetic medium. Organs were removed from adult prawns ranging in size from 13--19cm rostrum-to-telson length. Cultures consisted of either a blend of hematopoietic and lymphoid cells or ovarian cells. The cells divide rapidly in culture, doubling on average once per week for 5 to 6 weeks. These cultures continue to survive for at least 5 months but the rates of cell division are low after the first 5--6 weeks. In the literature, unicellular eukaryotic marine organisms such as chytrids may contaminate marine cell cultures. In some cases these eukaryotic contaminants may be difficult to distinguish from prawn cells unless detailed ultrastructure or characteristic developmental stages such as zoospores can be observed. Alternatively, we prepared molecular probes from repeated DNA sequences 100--400 bp in length in the P. monodon genome. These species-specific probes were hybridised to genomic DNA from cell culture to confirm proliferation of P. monodon cells in our cultures.

Animals↗
PubMed1999

Harm reduction: concepts and practice. A policy discussion paper.

This paper provides an overview of the context, definition, and key features of the harm reduction approach, and provides several examples of current programs in various countries. Both licit and illicit drugs are included in these illustrations. Some of the critical issues, and the strategies needed to advance harm reduction, are discussed. [Translations are provided in the International Abstracts Section of this issue.]

Canada↗
PubMed1997

Localisation of a 10q breakpoint within the PAX2 gene in a patient with a de novo t(10;13) translocation and optic nerve coloboma-renal disease.

We describe a 5 year old boy with a de novo t(10;13) translocation and optic nerve coloboma-renal disease (ONCR). On the basis of GTG banding analysis of prometaphase chromosomes, the patient's karyotype was interpreted as either 46,XY,t(10;13)(q24.3;q12.3) or t(10;13) (q25.2;q14.1). Fluorescence in situ hybridisation (FISH) studies using a YAC clone containing the PAX2 gene and YAC clones adjoining FRA10B at 10q25.2 showed that the 10q breakpoint had occurred just within the PAX2 gene and was proximal to FRA10B. These FISH results suggest that the translocation causes a disruption of the PAX2 gene and leads to ONCR, in agreement with the recent reports of PAX2 mutations in two unrelated families with ONCR. Furthermore, we refined the regional mapping of the human PAX2 gene to the junction of bands 10q24.3 and 10q25.1.

Child, Preschool↗
PubMed1996

Pain in ambulatory AIDS patients. I: Pain characteristics and medical correlates.

The characteristics and impact of pain were evaluated in a prospective cross-sectional survey of 438 ambulatory AIDS patients recruited from health care facilities in New York City. More than 60% of the patients reported 'frequent or persistent pain' during the 2 wks preceding the study. Patients with pain reported an average of 2.5 different pains. On the 0-10 numerical scale of the Brief Pain Inventory (BPI), mean pain intensity 'on average' was 5.4 (SD = 2.2; range = 0-10), and mean pain 'at its worst' was 7.4 (SD = 2.0; range = 1-10). The pain-related functional interference index (sum of the seven item BPI subscale) was 42.6 (SD = 17.2; range = 0.70). Demographic variables were not associated with the presence of pain, but the number of current HIV-related symptoms, treatment for HIV-related infections, and the absence of antiretroviral medications were significantly associated with the presence of pain. Female gender, non-Caucasian race, and number of HIV-related physical symptoms were significantly associated with pain intensity. Presence of pain and increasing pain intensity were significantly associated with greater impairment in functional ability (Karnofsky Performance Status, BPI functional interference index) and physical symptom distress (Memorial Symptom Assessment Scale). Results demonstrate high levels of pain and pain-related functional impairment among patients with AIDS. The presence and intensity of pain are associated with more advanced HIV disease and pain intensity is also associated with demographic factors (gender, race).

Acquired Immunodeficiency Syndrome↗
PubMed1996

A comparison of proliferation markers (BrdUrd, Ki-67, PCNA) determined at each cell position in the crypts of normal human colonic mucosa.

Samples of microscopically normal human sigmoid colon fixed in 70% ethanol from 15 patients who had received bromodeoxyuridine (BrdUrd) prior to surgery have been reanalyzed using a combination of proliferation markers. The specimens have been immunostained for proliferating cell nuclear antigen (PCNA) and after microwave treatment, they have been stained for BrdUrd and Ki-67. The 15 patients selected comprised 5 patients whose mucosa previously gave high BrdUrd labelling indices in the crypt, 5 that gave median values for BrdUrd labelling and 5 that gave low values for bromodeoxyuridine labelling on a previous analysis using tissue fixed in 70% ethanol and formal saline and using a different antibody (Potten et al., 1992). The relative levels of labelling at each cell position in the crypts has been compared using the 3 proliferation markers with the data being compared with the BrdUrd labelling as a standard labelling for S phase cells. One objective was to see whether all three proliferation markers discriminated equally well between the three groups of patient samples. The data show that the distinction between high, medium and low values seen with BrdUrd labelling was retained when Ki-67 immunostaining was analysed. PCNA immunostaining resulted in high levels of labelling and the different levels of labelling seen with BrdUrd and Ki-67 were largely lost.

Aged↗
PubMed1995

Stimulation and inhibition of proliferation in the small intestinal crypts of the mouse after in vivo administration of growth factors.

The effects of epidermal growth factor (EGF), transforming growth factor alpha (TGF alpha), insulin-like growth factor (IGF) I and II, acidic fibroblast growth factor (FGF), tumour necrosis factor alpha (TNF alpha), macrophage inhibitory protein 1 alpha (MIP-1 alpha) (LD78), and TGF beta-1 on cell proliferation in the crypts of the small intestine of mice were investigated. Various doses and dosing regimens were tested. Three in vivo assays were developed, in each case involving detailed cell positional analysis of methyl tritiated thymidine labelling and mitotic activity. These allowed deductions to be made about the regions of the crypt and hence regions of the proliferative hierarchy (stem cells versus dividing transit cells) that are affected by treatment with growth factors. The assays involved: (1) normal untreated mice (an assay most likely to be effective for detecting inhibitors); (2) mice shortly after whole body irradiation when compensatory proliferation has been endogenously triggered (another assay for inhibitory factors, possibly ones associated specifically with the regenerative process); and (3) mice at late times (96 hours) after irradiation in the regression phase after a proliferative overshoot (an assay designed to detect stimulators). Little effect was seen after treatment with acidic FGF, TNF alpha, or MIP-1 alpha but EGF, IGF-I and II, and TGF alpha can all be seen to exert some stimulatory effects on labelling or mitosis. EGF and IGF-I stimulate both unirradiated mice and 96 hour recipients, while TGF alpha had a greater effect on the 96 hour animals. In all cases, multiple doses were used. TGF beta-1 was an effective inhibitor of proliferation in unirradiated and early regenerating (18 hour) animals. EGF was the most effective of the stimulators, raising the levels of proliferation at all positions in the crypt, but particularly in the upper crypt. IGF-I also exerted its effect predominantly in the upper crypt, while TGF alpha raised proliferation at all cell positions. TGF beta-1 tended to have its strongest inhibitory effects in the lower (stem cell) regions of the crypt.

Animals↗
PubMed1990

Noradrenergic reinnervation of the rat spleen following chemical sympathectomy with 6-hydroxydopamine: pattern and time course of reinnervation.

The time course and pattern of reinnervation of noradrenergic (NA) sympathetic nerve fibers into the spleen following acute chemical sympathectomy with the catecholamine neurotoxin 6-hydroxydopamine (6-OHDA) was examined in young adult male Fischer 344 rats using glyoxylic acid fluorescence histochemistry and neurochemical measurement of NE. Reinnervation proceeds initially along the splenic artery as it enters the hilus (1-5 days), extends into the hilar region (5-10 days), and later proceeds into the regions distal to the hilus (21-56 days), suggestive of orderly growth from the hilar region to distal regions. In all 6-OHDA-treated spleens, the compartmentation of NA innervation was similar to that observed in saline-injected controls, but the density of NA nerve fibers in these compartments differed according to the distance from the hilus. By 56 days postlesion, regions distal to the hilar blood vessels contained fewer NA profiles than their age-matched controls, suggesting that the anatomical process of reinnervation does not restore the density of fibers in a fashion identical to that of nondenervated controls. In contrast, splenic NE concentration at 56 days postdenervation did not differ from the concentration seen in nondenervated control spleens. We suggest that functional restoration of splenic innervation may involve metabolic and receptor compensation for the lack of complete fiber regrowth into regions of white pulp distal from the hilus.

Adrenergic Fibers↗
PubMed1990

Effects of lactulose and lactitol on protein digestion and metabolism in conventional and germ free animal models: relevance of the results to their use in the treatment of portosystemic encephalopathy.

Protein digestion and metabolism have been studied in laboratory rats and miniature pigs to investigate the mechanisms of action of lactulose and lactitol when used in the treatment of patients with portosystemic encephalopathy. Lactulose (beta-D-galactopyranosyl-(1----4)-beta-D-fructofuranose) and lactitol (beta-D-galactopyranosyl-(1----4)-D-glucitol) increased the excretion of nitrogenous material in the faeces and decreased nitrogen excretion in the urine in a similar degree to that reported for human patients. In studies with germ free rats given lactulose no such effect was observed, suggesting that, for lactulose at least, these effects are mediated by the gut flora. Measurement of the alpha-, epsilon-diaminopimelic acid content of the faeces confirmed that the enhancement of faecal nitrogen was due to an increased contribution from bacteria. The similarity in the results for lactulose and lactitol suggests that, from the perspective of protein metabolism, lactitol acts in a similar way to lactulose in the treatment of portosystemic encephalopathy.

Animals↗
PubMed1989

Vessel invasion by tumour cells. An ultrastructural study.

The present electron microscopic investigation explored the mechanism through which the cells of an experimental fibrosarcoma implanted in the liver of syngeneic mice broke through the continuous (unperforated) endothelium of peri-tumour veins to enter the blood stream, as well as the immediate reaction of blood cells to the tumour breakthrough. It was found that at their point of contact with the endothelial tube of the peri-tumour vein, the tumour cells caused the endothelial basement membrane to disappear and they entered the vein lumen either by inducing an opening of interendothelial junctions, or by causing intensive vacuolation and disintegration of individual endothelial cells--and thus producing gaps for their passage into the lumen. Both mechanisms of entry were sometimes observed in the same tumour. At their point of breakthrough into the vein lumen, many neoplastic cells were immediately covered by a dense platelet aggregate or they were surrounded by numerous polymorph leucocytes (neutrophils more often than eosinophils) that stuck to their surfaces and sometimes caused a focal disappearance of the tumour cell plasma membrane at the site of polymorph-tumour cell contact. Occasionally polymorph lysosomal granules migrated to such contact areas, and the plasma membrane of the contacting polymorph disappeared as well. Finally, some polymorphs apparently plunged into the cytoplasm of vessel-invading tumour cells, while others were seemingly phagocytised by the latter.

Animals↗
PubMed1989

Sensory tics in Tourette's syndrome.

Sensory tics are localized uncomfortable sensations for which patients attempt to obtain relief by producing movements or vocalizations. We report 3 patients with Tourette's syndrome (TS) and sensory tics to illustrate this poorly recognized symptom. A survey of 34 randomly selected TS patients indicates that sensory tics are common and should be considered part of a clinical spectrum of tics and associated sensory phenomena.

Adult↗
PubMed1988

Toward a classification of sex and sexual behavior.

This paper presents a classification of sexual behaviors bases on Foa and Foa's resource exchange theory. They postulated six classes of resources: information, services, possessions, money, love, and status. We expanded and applied this theory to sexual behavior through three modalities: 1) Doing (information and services), which relates to sex as performance; 2) Having (possessions and money), which relates to sex as product; and 3) Being (love and status), which relates to sex as presence. Implications of this framework for sexual deviations, empirical verification, diagnostic evaluation, and therapeutic interventions are discussed.

Humans↗