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Biomedical subjects

H Davies

Publications and source records attributed to H Davies.

At least 73 records · Page 4Linked to original sources

Localisation of androgen receptors in dermal fibroblasts, grown in vitro, from normal subjects and from patients with androgen insensitivity syndrome.

Human genital skin fibroblasts show the androgen receptor (AR) as bright red granules (0.5 micron in diameter) after treatment with one (of 3) primary polyclonal antibody and a secondary antibody linked to alkaline phosphatase. Almost all AR were cytoplasmic in 12 normal strains and in 8 strains from patients with partial (PAIS) and 6 with complete androgen insensitivity syndrome (CAIS). When 25.8 nM 5-alpha-dihydrotestosterone (DHT) or methyltrienolone was added to the medium, some AR were translocated into the nucleus in 13 experiments with 8 strains of normal fibroblasts; of 8 strains of patients with PAIS 3 failed to translocate to a detectable extent in the presence of androgen in the medium and none of the 6 strains from patients with CAIS translocated.

Androgens↗

A study of the nutritional status of elderly patients with Parkinson's disease.

Patients with Parkinson's disease tend to lose weight although the reasons are uncertain. Fifteen patients with stable Parkinson's disease who had lost at least 5 kg in weight, and 15 age- and sex-matched control subjects were studied. All subjects underwent physical examination, anthropometric measurements, biochemical and haematological screening, measurement of tumour necrosis factor and full dietary assessment. The Parkinson's disease patients who had lost a mean of 6.2 kg had significantly less body fat and a lower total peripheral lymphocyte count than the control subjects. Dietary analysis showed a higher daily intake of calories in the patients which was derived from an increased carbohydrate intake. Tumour necrosis factor was not detected in either the patients or control subjects. Parkinson's disease patients lose weight in spite of an increased calorie intake. This may reflect an increased metabolic rate.

Aged↗

Unproven treatment in childhood oncology--how far should paediatricians co-operate?

Parents of children with terminal illness may try many different types of alternative and unproven treatment, not all recognised by the medical establishment. When active participation is requested difficult ethical dilemmas may arise. We present one such case, a child of five years with an inoperable posterior fossa brain tumour.

Airway Obstruction↗

Defining the myofibroblast: normal tissues, with special reference to the stromal cells of Wharton's jelly in human umbilical cord.

Cells differing widely in tissue distribution, immunophenotype and ultrastructure have been described as myofibroblasts. The definition of the myofibroblast was analysed as applied to normal tissues, with original observations on Wharton's jelly stromal cells as an example. Stromal cells in Wharton's jelly were studied by conventional histology, immunohistochemistry, and electron microscopy. The normal architecture of the cord was confirmed by light microscopy. Stromal cells and the smooth-muscle cells of the umbilical vessels were positive for vimentin, desmin and alpha-smooth muscle actin, while only the stromal cells were positive for prolyl 4-hydroxylase. Electron microscopy revealed variable but sometimes only moderate amounts of rough endoplasmic reticulum, bundles of smooth-muscle type filaments with focal densities, a large Golgi apparatus with collagen secretion granules, lipid and glycogen. There was no convincing evidence for either lamina or fibronexus junctions. The nature of the stromal cell was discussed in the light of these findings. It was concluded that a myofibroblastic designation was inappropriate and that these cells had phenotypic similarities to vascular smooth muscle cells. The possibility is proposed that most examples of spindle cells cited in the literature as being myofibroblasts and seen in normal tissues not subjected to trauma or showing pathology may be pericytic or smooth-muscle in nature.

Desmin↗

Loss of glutamate immunoreactivity from mouse first somatosensory (SI) cortex following neonatal vibrissal lesion.

Whisker follicles were surgically ablated (lesioned) on two entire rows (B and C) of the left snout of two groups of Swiss mice, in the first 2 days after birth (neonatally lesioned) with the animals being allowed to survive for 4 weeks. In the second group at 8 weeks of age (adults), the whisker follicles of rows B and C were similarly lesioned and a survival period of 3 days allowed. Glutamate-immunoreactivity (Glu-IR) was examined in tangential sections of the first somatosensory (SI) 'barrel' cortex of these two groups (at which time it was also confirmed that the follicles had not regrown). In the neonatally lesioned mice, barrel rows B and C were more poorly defined in the right (experimental) hemisphere sections and a semi-quantitative study showed that there was a decrease in Glu-IR cell number (up to 41%) in rows B and C of the right hemisphere compared to the spared barrel rows (A and D). The loss appears to occur over almost the entire area of each deprived barrel rather than being confined to the sides or hollows. In contrast to neonatally lesioned animals, the barrels of the adult-lesioned mice appeared intact and visually similar in both the experimental (right) and control hemispheres (left). The only notable change in Glu-IR observed in the adult-lesioned animals was a decrease of 38% in the number of Glu-IR cells in the sides between the two deafferented rows of barrels (B and C), compared to the cell number between the unaffected barrels (D and E), a change also seen in the neonatally lesioned mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Methicillin resistant Staphylococcus aureus (MRSA) in New Zealand 1988-90.

AIMS: To survey methicillin-resistant Staphylococcus aureus (MRSA) in New Zealand during the three years 1988-90. METHODS: Isolates and accompanying epidemiological data referred and reported to the New Zealand Communicable Disease Centre were analysed. RESULTS: MRSA was isolated from 255 persons, 235 patients and 20 healthcare staff, over the three years. The majority (84%) of persons were, or were recent, hospital patients or staff. Among hospital patients, males and patients aged 0 to 14 years were more likely to have MRSA. While most (88%) of the 145 strains identified occurred sporadically, three caused large outbreaks each involving more than 20 people. A third of the strains originated overseas, most commonly Australia or one of the Pacific Islands. The rate of MRSA isolation was higher in the North Island than the South Island. Two-thirds of the MRSA had only a low level of methicillin resistance and were not multiresistant. CONCLUSIONS: MRSA continues to be isolated only infrequently in New Zealand and has not become endemic in our hospitals.

Adolescent↗

Autoimmune disease and molecular mimicry: an hypothesis.

Helper T lymphocytes are normally only stimulated to initiate an immune reaction through the recognition of peptides bound to class II major histocompatibility complex (MHC) molecules. Class II MHC molecules are constitutively expressed on antigen-presenting cells which play a critical role in the initiation of immune responses. In disease states, however, other cells often express class II MHC molecules inappropriately. This article suggests an hypothesis for the pathogenesis of autoimmune diseases based on molecular mimicry. The mimicry described is between microbial or viral peptides presented by antigen-presenting cells and self peptides presented inappropriately on a target tissue. This leads to helper T cells, stimulated by peptides derived from infectious organisms, initiating an autoimmune attack on the target tissue.

Amino Acid Sequence↗

Hope as a coping strategy for the spinal cord injured individual.

This case study described how one spinal cord injured individual used hope as a coping strategy. Using observations and unstructured interviews, the indicators of hope were explored, as well as how hope was sustained over time and during crises. Data were gathered while nursing the individual, and his family using the McGill Model of Nursing. Qualitative data analysis revealed four categories which reflected indicators of hope (focusing on progress, positive interpretation, selective attention, goal setting), and seven categories of how hope was sustained (family responsibility, meaning in life, significant others, uncertainty of physiological status, past experience, goal attainment). Analysis of data also revealed that hope was goal directed, and hope was based on the reality perceptions of the individual. Over time, all indicators of hope were gradually displayed more often, and there was a gradual increase in focus on the meaning in life, family responsibility and goal achievement to sustain hope. Implications for nursing and research are suggested.

Adaptation, Psychological↗

Induction of cytotoxic T lymphocytes with peptides in vitro: identification of candidate T-cell epitopes in human papilloma virus.

A set of overlapping peptides corresponding to the L1, E6, and E7 proteins of human papilloma virus 16 was tested for their ability to bind to major histocompatibility complex class I molecules and to stimulate cytotoxic T-lymphocyte (CTL) responses in vitro. A class I binding assay using intact RMA-S cells showed that 20 of the 99 human papilloma virus peptides bound to H-2Kb and/or Db molecules. Fifteen of the 20 class I-binding peptides stimulated primary CTL responses, whereas peptides that were negative in the binding assay failed to do so. Peptide-induced CTLs recognized the immunizing peptide very efficiently, requiring no more than 1-10 nM peptide for target cell lysis. However, two observations were made that have important implications for the design of peptide-based vaccines for inducing CTLs. (i) Not all major histocompatibility complex-binding peptides that contained known motifs characteristic of naturally processed peptides induced CTLs. (ii) The efficiency of CTL lysis was strongly decreased when the size of the target peptide differed by only one amino acid residue from that of the immunizing peptide. We conclude that peptides chosen for vaccination must correspond in length to naturally processed peptides.

Animals↗

Evaluation of the immunogenicity of attenuated feline calicivirus vaccines by ELISA.

An ELISA test was developed to measure the levels of IgG antibody in specific-pathogen-free (SPF) cats immunised with two doses of an attenuated feline calicivirus (FCV) vaccine. All eight vaccinates were protected from virus challenge, but four out of five non-vaccinates were not. There was a significant difference in respect of protection from virus challenge between SPF cats with and without three-fold or greater increase in antibody units (P = 0.01). Each serum absorbance was standardised against the reference positive which has an arbitrary value of 100 antibody units. In SPF cats, the 99% confidence level for seropositivity to FCV was determined as greater than or equal to 2.5 antibody units. The results suggest that the sensitive ELISA test can be used to monitor the antibody status of SPF cat colonies prior to FCV vaccine trials, and to measure the immunogenicity of attenuated FCV vaccines. Thus, the ELISA test may replace the need for virus challenge, with consequent reduction in animals used in future FCV vaccine trials.

Animals↗

The Achilles Functional Index.

The literature regarding the management of spontaneous rupture of the Achilles tendon is controversial and confusing. The relative infrequency of the condition in any one center prohibits the completion of well-designed clinical studies. Many of the disputes could be addressed and innovations tested if an appropriate animal model were available. We present a method for evaluating Achilles tendon function from measurements of the prints, preserved in bromphenol-blue-impregnated photocopying paper, of the hindfeet of walking rats. The stimulus for this study was derived from de Medinaceli's method for assessing the functional condition of rat sciatic nerves (de Medinaceli L, Freed WJ, Wyatt RJ: An index of the functional condition of rat sciatic nerve based on measurements made from walking tracks. Exp Neurol 77:634-643, 1982). Four variables were measured from these walking tracks, and comparisons between the damaged (experimental) and intact (normal) side were converted to proportional deficits. The relative contribution of each parameter to the overall deficit was determined by multiple linear regression analysis, and the variables were weighted accordingly to obtain an "Achilles Functional Index" (AFI). A sham operation produced no functional deficit, whereas animals subjected to a 0.5-cm midsubstance Achilles tendon defect demonstrated a markedly impaired AFI. Animals with repaired transected Achilles tendons also demonstrated a significant, but less severely impaired AFI. The functional deficit in this repair group returned to control values by postoperative day 15, whereas animals with a defect remained impaired at day 15. Furthermore, an excellent correlation was found between the functional recovery and biomechanical properties (ultimate failure load) of the healing tendon (r = 0.94; p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Achilles Tendon↗

The functional recovery of peripheral nerves following defined acute crush injuries.

This study evaluates the effect of crushing load on functional recovery of the sciatic nerve. Male Sprague-Dawley rats were divided into five groups: sham operation, resected sciatic nerve, and 100 g (13 mm Hg/mm2), 500 g (50 mm Hg/mm2), and 15,000 g (1,000 mm Hg/mm2) of sciatic crush load (groups 1-5). In groups 3-5, a 5-mm segment of sciatic nerve was crushed for 10 min using a specially designed crushing device. Motor functional recovery was assessed from hind-limb walking tracks by calculating a sciatic functional index. There was no detectable functional deficit in the group receiving sham operations, while the resected sciatic nerve group exhibited complete dysfunction for the full duration of the experiment. All groups subjected to crush exhibited an initial deficit that gradually recovered to normal by day 14 (100-g crush), day 39 (500-g crush), and day 53 (15,000-g crush). Histological changes were also related to the initial crushing load and the length of the recovery period. Results indicate that the crushing device described is able to administer an adjustable, defined crush injury to the rat sciatic nerve, and that the functional deficit resulting from such an injury can be easily monitored with a sciatic functional index. The rate of recovery of crushed nerves was directly related to the initial load. All crushed nerves recovered in this experiment, even after the application of a 15,000-g load for 10 min.

Animals↗

Effect of posture on regional ventilation in children.

Little information has been published concerning the pattern of regional ventilation in children, yet many differences in lung and chest wall mechanics in childhood, supported by clinical observation, have led to the hypothesis that the pattern of regional ventilation seen in children may not be the same as in adults. Forty-three children and 16 adult volunteers underwent Krypton (Kr) 81m radionuclide ventilation lung scans in the supine and right and left decubitus postures. In children aged 2-10 years mean fractional ventilation to the right lung (VfR) was 46.1%. This fell to 36% when dependent and rose to 56.1% in the uppermost position. Redistribution of ventilation away from the dependent towards the uppermost lung was seen in all children. In children aged 10-18 years VfR was 57.2% (supine), 48.0% (dependent), and 62.9% (uppermost). An identical pattern was seen in children with normal or abnormal pulmonary function tests (peak expiratory flow rate, and FEV1: FVC ratio). In subjects over 18 years of age a different pattern was seen: mean VfR was 52.4% (supine), rising to 53.4% (dependent), and falling to 48.9% (uppermost). Postural redistribution of ventilation, as assessed by Kr81m ventilation imaging, changes late in the second decade of life. This will have clinical consequences in the management of children with unilateral lung disease.

Adolescent↗

Definition of linear antigenic regions of the HPV16 L1 capsid protein using synthetic virion-like particles.

Mice of three haplotypes (H-2d, H-2b, and H-2d/b) were immunized with synthetic HPV16 virus-like particles (VLPs), produced using a vaccinia virus doubly recombinant for the L1 and L2 proteins of HPV16. The resultant anti-VLP antisera recognized HPV16 capsids by ELISA assay and baculovirus recombinant HPV16 L1 and L2 protein on immunoblot. Overlapping peptides corresponding to the HPV16 L1 amino acid sequence were used to define the immunoreactive regions of the L1 protein. The majority of the L1 peptides were reactive with IgG from the mice immunized with the synthetic HPV16 capsids. A computer algorithm predicted seven B epitopes in HPV16 L1, five of which lay within peptides strongly reactive with the murine antisera. The murine anti-VLP antisera failed to react with the two peptides recognized by anti-HPV16L1 monoclonal antibodies raised by others against recombinant L1 fusion protein. We conclude that the immunoreactive epitopes of HPV16 defined using virus-like particles differ significantly from those defined using recombinant HPV16 L1 fusion proteins, which implies that such fusion proteins may not be the antigens to look for HPV16L1 specific immune responses in HPV-infected patients.

Amino Acid Sequence↗