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Biomedical subjects

P Holland

Publications and source records attributed to P Holland.

At least 19 recordsLinked to original sources
PubMed1992

Homeobox genes in vertebrate evolution.

A wide range of anatomical features are shared by all vertebrates, but absent in our closest invertebrate relatives. The origin of vertebrate embryogenesis must have involved the evolution of new regulatory pathways to control the development of new features, but how did this occur? Mutations affecting regulatory genes, including those containing homeobox sequences, may have been important: for example, perhaps gene duplications allowed recruitment of genes to new roles. Here I ask whether comparative data on the genomic organization and expression patterns of homeobox genes support this hypothesis. I propose a model in which duplications of particular homeobox genes, followed by the acquisition of gene-specific secondary expression domains, allowed the evolution of the neural crest, extensive organogenesis and craniofacial morphogenesis. Specific details of the model are amenable to testing by extension of this comparative approach to molecular embryology.

Animals↗
PubMed1992

Loss and renewal of thick myofilaments in glucocorticoid-treated rat soleus after denervation and reinnervation.

Denervation of rat soleus muscle and simultaneous administration of high doses of corticosteroids for 7 days caused marked muscle fiber atrophy and selective loss of thick myofilaments from many muscle fibers by light and electron microscopy. Myosin heavy chain/actin ratios were greatly reduced on polyacrylamide gel electrophoresis. Nerve crush instead of cut permitted reinnervation after 2 weeks and demonstrated the reversibility of the muscle changes within a week after reinnervation. There was formation of new thick filaments and their reintegration into myofibrils without further breakdown, although large areas of Z-disc streaming appeared. The mechanism of A-band breakdown remains obscure, but it presumably starts with limited proteolysis and continues with disaggregation of myosin molecules. This is consistent with our observation that the muscle fibers retain a relatively good reactivity to antibodies against myosin heavy chain 1 week after denervation and corticosteroid administration. A syndrome recalling these experiments is seen in severely asthmatic patients receiving corticosteroids and pharmacologically paralyzed for mechanical respiration.

Actin Cytoskeleton↗
PubMed1992

A chronic myopathy with coated vesicles and tubular masses.

Two muscle biopsies from a 38-yr-old man with a lifelong mild chronic nonprogressive myopathy, showed accumulations of randomly oriented tubules of T-tubular origin, some of which had become greatly dilated and had accumulated osmiophilic material. The tubular masses lacked oxidative enzyme activity but during their evolution acquired esterase and acid phosphatase activity. Tubular areas appeared to break down and lead to intrusions of extracellular space into the center of fibers. Coated vesicles were numerous and often appeared to arise from the tubules. No abnormality could be detected on SDS PAGE electrophoresis of fractions from sucrose gradients.

Adult↗
PubMed1992

Uptake of hepatitis B vaccination amongst West Midlands radiologists.

A postal survey of 150 radiologists within the West Midlands Regional Health Authority was undertaken to obtain information about hepatitis B vaccination uptake and its relationship, if any, to their involvement in interventional radiology. Overall, 64% were vaccinated, the rate being higher amongst trainees (81%). No significant relationship existed between vaccination and regular involvement in interventional radiology. Few side effects were reported by radiologists (11%). Failure to seroconvert occurred in 3.5%. A telephone survey throughout the region suggests that many Occupational Health Departments still believe radiologists are not at risk from hepatitis B and therefore do not warrant, and are not invited for, vaccination.

Adult↗
PubMed1992

Sustained expression of the pim-1 kinase is specifically induced in myeloid cells by cytokines whose receptors are structurally related.

We have examined the effects of myeloid growth factors on expression of the pim-1 kinase protein in human and murine myeloid cells. pim-1 protein was identified in K562 cells by immunoblotting as a 33 kDa protein. In the human factor-dependent myeloid leukemia cell line M07E, pim-1 protein was induced by interleukin 3 (IL-3) or granulocyte-macrophage colony-stimulating factor (GM-CSF), with maximum expression by 4 h. Expression continued for the duration of growth factor exposure, but declined rapidly when cytokines were removed. GM-CSF induced pim-1 protein in a dose-dependent manner, with expression being proportional to the proliferative effect of the cytokine. To examine the specificity of pim-1 protein induction, we compared pim-1 protein levels in myeloid cells which demonstrated different GM-CSF response phenotypes. We also examined the effects on pim-1 protein expression of different growth factors which induced similar response phenotypes. GM-CSF induced pim-1 protein in several myeloid cell lines, most of which demonstrated a proliferative response, but did not induce pim-1 protein expression in neutrophils or monocytic cells. In contrast, the murine cell line Mac-11 expressed pim-1 message in response to IL-3 and GM-CSF, but not in response to bryostatin or M-CSF, which were equivalent mitogens. In human U937 myeloid cells sustained expression of pim-1 protein was induced by GM-CSF, G-CSF and IL-6, but not by bryostatin. Expression of the pim-1 kinase protein in response to myeloid cytokines depends on both the nature of the growth factor and the response phenotype. The pim-1 kinase may be an important intermediate in transmembrane signaling or response phenotype induced by IL-3, GM-CSF and other cytokines whose receptors are structurally similar. Its constitutive expression in some myeloid leukemia cell lines suggests activation of signal cascades utilized by myeloid growth factors.

Cell Division↗
PubMed1991

Pharmacogenetics and drug metabolism: an Irish perspective.

Genetic factors, particularly in relation to control of liver drug metabolism, are a major cause of variability in the response to drugs. In 145 Irish subjects 48% were fast acetylators of sulphadimidine in contrast to 80% in Chinese subjects. Eleven (7.6%) of our Irish population showed an improved ability to oxidise delrisoquine. The therapeutic implications of these findings are discussed.

Acetylation↗
PubMed1991

Prevalence of antibody to hepatitis C virus in a blood donor population.

Blood samples from 2000 accepted blood donors and 343 deferred donors with antibody to hepatitis B core antigen (anti-HBc) and/or an alanine aminotransferase (ALT) elevation were evaluated for antibody to hepatitis C virus (anti-HCV). Sixteen (0.8%) of the 2000 sera initially reacted on enzyme-linked immunosorbent assay (ELISA); 12 (0.6%) were repeatably reactive. One repeatably reactive sample had an elevated ALT; two reacted on anti-HBc testing and had ALT elevations. When the repeatably reactive ELISA samples were tested by an immunoblot assay, four reacted, three were indeterminate, and five did not react. Among the 343 deferred donors, HCV antibodies were detected in 8 (3.8%) of 210 anti-HBc-reactive samples, 12 (11.8%) of 104 elevated-ALT samples, and 15 (52%) of 29 combined elevated-ALT and anti-HBc-reactive samples; 25 of 28 reacted on immunoblot. The anti-HBc-reactive sera were subdivided into groups according to strength of anti-HBc reactivity (weak or strong) and antibody to hepatitis B surface antigen status and then were compared for anti-HCV reactivity rates. The group of samples showing the greatest frequency of anti-HCV had strong anti-HBc reactivity. For blood donors, the anti-HCV test correlates with the surrogate tests for non-A, non-B hepatitis (anti-HBc and ALT); however, most anti-HCV-reactive units remain undetected by surrogate tests, so that implementation of anti-HCV screening should further reduce the transmission of HCV via transfusion.

Alanine Transaminase↗
PubMed1991

Extracellular organelles (prostasomes) are immunosuppressive components of human semen.

Numerous reports have ascribed immunosuppressive activity to human seminal plasma and there is growing agreement that much of this activity can be accounted for by the very high levels of E series prostaglandins present (up to 300 microM 19-hydroxy prostaglandin E). However not all suppressive activity is due to prostaglandin since several reports have appeared of high molecular weight active substances and we have found that stripped seminal plasma is still effective in inhibiting the mitogen-induced proliferation of lymphocytes. In this study such immunosuppressive activity has been separated by molecular size fractionation and the activity has been found to be particulate and corresponded to the previously reported prostasomes. These are trilaminar to multilaminar vesicles (150 nm diameter) which are secreted by the prostate. Pure preparations of prostasomes inhibited mitogen-induced lymphoproliferation in a dose-dependent manner with a concentration of prostasomes equivalent to 40% of that seen in seminal fluid giving 69% suppression of thymidine incorporation. The suppressive activity survived boiling and therefore was unlikely to be due to enzymatic action associated with these organelles. Interaction with the accessory cells, involved in full development of the lymphoproliferation induced by mitogen, was indicated and this possibility was supported by the demonstration of a direct effect of prostasomes on macrophage function using a mouse macrophage cell line. The prostasomes in semen may play a complementary role to the prostaglandins in neutralizing the immune defences of the female reproductive tract. This combination would allow the alloantigenic spermatozoa the best chance of achieving fertilization, but at the same time leave the recipient open to any infection present in the semen.

Analysis of Variance↗
PubMed1991

Real-time digital contrast enhancement and magnification in the assessment of acute elbow injuries.

The elbow is a common site of injury and missed fractures may lead to disability and litigation. An assessment was made of a commercially available desk-top digital contrast enhancement and magnification unit (DETECT system) in a series of 320 patients with an acute elbow injury. Five radiologists of varying experience independently viewed elbow radiographs on a conventional light-box, and subsequently using the digitizer, indicating the presence or absence of a fracture. The overall results demonstrated no difference in performance when using the unit, though small improvements in the confidence with which a definite diagnosis was made were observed. Assessment of soft tissues with the digitizer was less reliable.

Acute Disease↗
PubMed1991

Cholangiography in liver transplantation: a comparison of two types of biliary reconstruction.

Orthotopic liver transplantation has been performed in Birmingham since 1982. Two types of biliary reconstruction have been used, the choledocho-choledochostomy and the choledocho-cholecysto-choledochostomy (gallbladder (GB) conduit). A retrospective study was undertaken to compare the biliary tract complications encountered at cholangiography in these two groups to assess which reconstruction is safest. In the gallbladder (GB) conduit reconstruction, the incidence of biliary leakage (20.4%) and stricture formation (14.4%), the two most serious complications, was higher than in end-to-end duct anastomosis (11% and 10%, respectively), though these differences did not reach statistical significance. This supports evidence from other centres that the choledocho-choledochostomy is the procedure of choice to minimize biliary complications. Biliary debris (14.2%) presented additional problems and was strongly associated with biliary strictures. T-tube related problems were least troublesome. The close relationship between hepatic artery occlusion and biliary complications, particularly leakage, noted in other studies is also emphasized.

Anastomosis, Surgical↗
PubMed1991

Inhibition of myosatellite cell proliferation by gamma irradiation does not prevent the age-related increase of the number of dystrophin-positive fibers in soleus muscles of mdx female heterozygote mice.

In skeletal muscles of young mdx female heterozygote mice, there is a mosaic of dystrophin-positive and dystrophin-negative fiber segments. In older animals, there is a marked decline in the number of dystrophin-negative fiber segments. This phenomenon might be due to a fusion of dystrophin-competent satellite cells into the originally dystrophin-negative fiber segments during growth. To study this possibility, soleus muscles of 10-day-old mdx female heterozygotes were gamma irradiated (2000 rads) to inhibit subsequent myosatellite cell proliferation and fusion. In the irradiated soleus muscles of animals at 60 days, the relative amount of dystrophin measured by quantitative immunoblots was not significantly different from that of the contralateral nonirradiated muscles. The prevalence of dystrophin-negative fibers in the 60-day-old irradiated solei was not higher than in the nonirradiated contralateral muscles, implying that dystrophin-competent satellite cell fusion was not a significant factor in the observed conversion. A longitudinal expansion of the cytoplasmic domain of the original dystrophin-competent myonuclei during growth could explain the observed conversion phenomenon.

Aging↗