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Biomedical subjects

A Hough

Publications and source records attributed to A Hough.

At least 19 recordsLinked to original sources

A new, comprehensive normative database of lumbar spine ranges of motion.

AIMS AND OBJECTIVES: To generate gender-specific and broadly based age-related indices for normative lumbar ranges of motion for all planes of movement. DESIGN: This was a repeated measures prospective study of spinal range of motion in a sample of volunteer subjects utilizing a portable modified CA6000 Spine Motion Analyzer (Orthopedic Systems Inc., Union City, CA, USA). SETTING: Data collection was carried out in a variety of community locations including fire, police and ambulance stations, offices and community centres. SUBJECTS: A total of 405 asymptomatic subjects (196 female, 209 male) were recruited, aged 16-90 years, from sedentary, mixed and physically demanding occupations. METHODOLOGY: Indices of lumbar spine ranges of motion were measured in standing following a standardized protocol for sagittal flexion/extension, coronal lateral flexion and horizontal axial rotation movements. RESULTS: Male and female normative flexion ranges declined by approximately 40% (72-40 degrees) across the age spectrum. Extension declined the greatest, by approximately 76% (29-6 degrees) overall. In lateral flexion male and female ranges declined approximately 43% (29-15 degrees) in each direction (total 58-30 degrees). In axial rotation no age-related decline was observed and ranges of motion remained at approximately 7 degrees in each direction (total 14 degrees) across all the ages of the subject group. CONCLUSIONS: Data have been generated that provide comprehensive, gender-specific, broadly based and age-related indices for normative lumbar ranges of motion in all planes of movement. These are applicable to individuals throughout adult life, from adolescence through to old age.

Adolescent↗

The role of apoptosis in 2',2'-difluoro-2'-deoxycytidine (gemcitabine)-mediated radiosensitization.

The nucleoside analogue Gemcitabine [2',2'-difluoro-2'-deoxycytidine (dFdCyd)] is active against a wide variety of solid tumors and is a potent radiation sensitizer. Because apoptosis has been shown to be an important mechanism of cell death for many cancers, we wished to investigate the role of apoptosis in dFdCyd-mediated radiosensitization. We evaluated HT29 colon cancer cells, UMSCC-6 head and neck cancer cells, and A549 lung cancer cells, which differ substantially in the ability to undergo radiation-induced apoptosis. We hypothesized that if dFdCyd produced radiosensitization by potentiating preexisting death pathways, then only the apoptotic-prone HT29 cells would show a substantial increase in apoptosis when treated with the combination of dFdCyd and radiation and that UMSCC-6 cells and A549 cells would be radiosensitized through nonapoptotic mechanisms. We found that the radiosensitization of HT29 cells (enhancement ratio, 1.81 +/- 0.16) was accompanied by an increase in apoptosis and by caspase activation and that inhibition of this activation by the caspase inhibitor Z-Asp-Glu-Val-Asp-fluoromethylketone (DEVD) significantly decreased radiosensitization (to 1.36 +/- 0.24; P < 0.05). In contrast, UMSCC-6 cells and A549 cells were modestly radiosensitized (enhancement ratio, 1.47 +/- 0.24 and 1.31 +/- 0.04, respectively) via a nonapoptotic mechanism. These findings suggest that although apoptosis can contribute significantly to dFdCyd-mediated radiosensitization, the role of apoptosis in dFdCyd-mediated radiosensitization depends on the cell line rather than representing a general property of the drug.

Apoptosis↗

Incidence and impact of light chain associated (AL) amyloidosis on the prognosis of patients with multiple myeloma treated with autologous transplantation.

Little is known about the incidence of clinically occult AL amyloid in patients with multiple myeloma and its impact on prognosis of these patients. To address these issues, subcutaneous fat pad aspirates (SAFA) and bone marrow biopsies were evaluated for the presence of amyloid in a cohort of newly diagnosed patients with multiple myeloma prior to enrollment on a phase II study including tandem transplants. Organ directed biopsies were performed when clinically indicated. Presence of amyloid at > or = 1 site was noted in 32 patients (38%). SAFA was positive in 25 (31%), bone marrow in 8 patients (10%) and other organ sites in 7 patients. Patients with and without amyloid did not differ in disease characteristics, in particular no lambda predominance was observed in patients with amyloid. Event free survival (59+ vs 52 months; p = .9) and overall survival (59+ vs 66+ months; p = .9) were similar in both groups. Even the seven patients with symptomatic organ involvement with AL amyloid had a median overall survival of 38+ months. In conclusion, AL amyloidosis occurs more often than previously reported, but its presence does not influence the outcome of these patients after transplantation.

Amyloidosis↗

Nuclear magnetic resonance in pathology: I. Principles and general aspects.

Nuclear magnetic resonance (NMR) has become established as a powerful diagnostic imaging technique in medicine. The power of NMR as a tool for characterizing molecular structure and for quantitative analysis of complex mixtures in the clinical laboratory or even in vivo is beginning to be exploited. In the clinical laboratory, NMR can analyze the complex mixtures of bodily fluids, intact cells, tissues, and their extracts. Phosphorus-31 or 1H NMR spectroscopy in vivo can provide a noninvasive probe of high-energy compounds, amino acids, and compounds of phospholipid metabolism. The basic principles of NMR spectroscopy are presented here, with emphasis on the various NMR parameters and the information they provide. A companion article presents a survey of applications in pathology.

Magnetic Resonance Imaging↗

Effects of trimethyltin on the mouse hippocampus and adrenal cortex.

The effects of trimethyltin (TMT) on the mouse adrenal histology and its relationship with neuropathology occurrence was studied. Young, male CD-1 mice were divided into three groups: group I, injected on 3 consecutive days with 1.0 mg TMT/kg body weight (b.w.); group II, injected on 2 consecutive days with 1.5 mg TMT/kg b.w.; and group III, injected with a single acute dose of 3.0 mg TMT/kg b.w. Control animals were injected with saline solution. The brain and adrenal glands were sampled for light-microscopic examination. Although all animals received the same total amount of TMT, pathological changes in the granule cells of the fascia dentate appeared to be group III greater than group II greater than group I, suggesting that acute exposures produced a more severe damage to the fascia dentate neurons. Likewise, the adrenal weights of the animals were group III greater than group II greater than group I greater than or equal to control. Significant proliferation and enlargement of the eosinophilic or the "X zone" were observed in the TMT-treated, particularly groups II and III, animals. The expansion of the eosinophilic cell layer (X zone) was accomplished at the expense of the cortical fasciculata cells. Transformation of fasciculata cells into eosinophilic cells could also be demonstrated. As the eosinophilic cells are known to be active in corticosterone production as seen in stress situations, the proliferation of these cells may reflect a feedback response to the hippocampal hyperexcitation.

Adrenal Cortex↗

Characterization of a beta-adrenergic receptor in porcine trachealis muscle.

To establish a model of airway smooth muscle function we studied binding of [3H]dihydroalprenolol [( 3H]DHA), a beta-adrenergic antagonist, to membrane preparations of porcine trachealis muscle and investigated the response of adenylate cyclase to l-isoproterenol in tissue and plasma membranes. [3H]DHA binding was of high affinity (Kd = 1.0 +/- 0.1 nM), was saturable (Bmax = 87.6 +/- 13.2 fmol/mg protein), and was 90% beta 2 and 10% beta 1. Adenylate cyclase activity in the membrane preparation was (in pmol.10 min-1.mg protein-1 +/- SE): basal 420 +/- 74, guanosine 5'-triphosphate (GTP) (10 micron) 600 +/- 45, GTP (10 microM) + l-isoproterenol (100 microM) 660 +/- 63, NaF (10 mM) 1,500 +/- 134, and forskolin (100 microM) 3,000 +/- 410. Guanosine 5'-diphosphate (GDP) and GTP were active cofactors; l-isoproterenol appeared to function as an effector exchanging GTP for GDP on the guanine nucleotide regulatory protein. There was close agreement of the effective dose (ED50) of the l-isoproterenol-induced relaxation (0.95 +/- 0.45 microM) and the inhibitory constant of l-isoproterenol binding (0.39 +/- 0.10 microM). l-Isoproterenol (100 microM) induced a 100% increase in adenosine 3',5'-cyclic monophosphate (cAMP) levels in tissue strips over basal activity. Investigation of the difference in adenylate cyclase activity between tissue and plasma membranes revealed that l-isoproterenol responsive adenylate cyclase was diminished after initial homogenization. Electron microscopy demonstrated disruption of all cells at this early stage of preparation. The decrease in l-isoproterenol responsive adenylate cyclase following cell rupture is different from other tissues and suggests a difference in the actions of beta-agonist in smooth muscle compared with other tissues.

Adenylyl Cyclases↗

Somatomedin and analogues of cyclic AMP increase the number of cells synthesizing DNA in cartilage from hypophysectomized rats.

The effects of somatomedin and certain nucleotides on nuclear labelling of cartilage cells with [3H]thymidine were determined by autoradiography. Segments of costal cartilage from hypophysectomized rats were incubated for 24 h in a basal medium with or without additions and then pulsed for 2 h with [3H]thymidine in the basal medium. Both somatomedin (0.1 U/ml) and Bt2cAMP (10(-4)M) increased the number of labelled nuclei, and the combined effects were more than additive. A parallelism between the effects of these agents on nuclear labelling and their effects on total thymidine incorporation into DNA was demonstrated. The 8-bromated derivative of cAMP (10(-4)M) also enhanced chondrocyte nuclear labelling, but neither 8-Br-5'-AMP (10(-4)7) nor 8-Br-cGMP (10(-4)M) exhibited actions of the cAMP analogues. It is concluded that in cartilage obtained from hypophysectomized rats and incubated under the specified conditions (1) both somatomedin and cAMP analogues increase the number of cells synthesizing DNA as well as total thymidine incorporation into DNA, (2) the effects of the hormone and cyclic nucleotide in combination are synergistic, and (3) the increased incorporation of labelled thymidine into DNA reflects increased DNA synthesis and not merely an alteration of the specific activity of the intracellular thymidine nucleotide pool.

Animals↗

Pericardial disease in rheumatoid arthritis.

Six patients with rheumatoid constrictive pericarditis, five seen in a two and one half year period, are described. All patients were male, all had rheumatoid factor, and all had active arthritis. Diagnosis was suspected from careful physical examination and confirmed in five patients by cardiac catheterization. Pericardiectomy was successful in all five patients on whom it was performed. Rheumatoid constrictive pericarditis should be suspected in any patient with rheumatoid arthritis and unexplained signs of right heart failure.

Adult↗

Changes in bone and bone marrow of rabbits bearing the VX-2 carcinoma. A comparison of local and distant effects.

The VX-2 carcinoma in 32 New Zealand white rabbits was studied morphologically with respect to the osseous effects induced by the innoculation and subsequent growth of tumour in the soft tissues over periods ranging from 1 to 5 weeks. Although more severe changes were noted in bones of tumor-bearing than in non-tumor-bearing limbs, effects could be seen in both experimental situations. Severe bone marrow hyperplasia was noted consistently in tumor-bearing animals. A marked increase in numbers of osteoclasts over control rabbit bones was observed along the surface of bones near and distant from the tumor. Resorptive changes were also noted in the cortex of tumor-bearing rabbits. The increase in osteoclast numbers was related chronologically to the development of hypercalcemia and was proportional to the degree of hypercalcemia at the time the animals died. The number of osteoclasts was inversely proportional to the serum creatinine. A diminution of osteoclast numbers was noted in the latter stages of the disease. These changes may be the morphologic expression of humoral hypercalcemia accompanying the VX-2 carcinoma.

Animals↗