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Biomedical subjects

J R Hill

Publications and source records attributed to J R Hill.

At least 19 recordsLinked to original sources

Cell-specific translation of S-adenosylmethionine decarboxylase mRNA. Regulation by the 5' transcript leader.

The mRNA encoding S-adenosylmethionine decarboxylase (AdoMetDC) has an unusual distribution in polysomes from cells of T lymphocyte origin. It associates predominantly with monosomes and small polysomes with none located in the preribosomal or ribonucleoprotein pool. In sharp contrast, it associates broadly with larger polysomes in several nonlymphoid cell lines, including fibroblasts and the adrenal carcinoma line, Y1. The AdoMetDC 5'-transcript leader (5'-TL) is highly conserved between human and bovine mRNAs. It has a length of about 330 nucleotides and contains a 21-nucleotide upstream open reading frame (uORF) approximately 14 nucleotides downstream of the cap site. The AdoMetDC 5'-TL, when used to replace the 5'-TL of the human growth hormone gene in a chimeric expression construct, causes a suppressed polysomal distribution of the chimeric mRNA identical to that of the endogenous AdoMetDC mRNA in the T cell line, Jurkat. In contrast, mRNA encoded by the same chimeric construct, when expressed in Y1 cells, mimics the broad polysomal distribution of the endogenous AdoMetDC mRNA. Mutations that remove the uORF, or prevent its initiation, abolish the translational suppression in T cells, establishing that the uORF is a negative element that modulates the cell-specific polysomal distribution of AdoMetDC mRNA.

Adenosylmethionine Decarboxylase

Maxillofacial injuries following steering wheel contact by drivers using seat belts.

Maxillofacial injuries are common sequelae in road traffic accidents. For the restrained driver, impact against the steering wheel is the most prevalent cause of injury. A sample of drivers restrained by seat belts with facial injury caused by the steering wheel was taken from data at the Accident Research Unit, University of Birmingham, UK. Two hundred and forty facial injuries occurred in 135 drivers, and these are described. Superficial contusion, laceration and nasal fractures predominated. There were 504 injuries at other body regions, and these were often caused by other vehicle components. These were, for 57% of drivers, no more serious than the facial injury caused by steering wheel contact. The role of steering wheel design in maxillofacial trauma is discussed and new solutions briefly reviewed.

Abbreviated Injury Scale

An empirical assessment of saddlepoint approximations for testing a logistic regression parameter.

Saddlepoint methods provide quick and easy approximations to significance levels for conditional tests of logistic regression parameters. We evaluate the accuracies of saddlepoint approximations for three well-known conditional tests: Bartlett's test for no three-factor interaction in a 2 x 2 x 2 table, the test for trend in a series of probabilities, and the exact test of no association in stratified 2 x 2 tables with a common odds ratio. General recommendations are suggested regarding the use of saddlepoint approximations for exact conditional significance levels.

Mathematics

Cutaneous effects of transdermal levonorgestrel.

The irritation of transdermal devices delivering levonorgestrel and the permeation enhancer ethyl acetate with or without ethanol was evaluated in rabbits. Erythema and oedema were assessed 24, 48 and 72 hr and 7 days after application of the 24-hr delivery system. The devices were found to be mild to moderately irritating, with erythema the primary manifestation. No differences were observed between devices using pure ethyl acetate or ethyl acetate-ethanol (7:3, v/v) as enhancers. Devices using pure ethanol as an enhancer gave levels of irritation similar to those using ethyl acetate-ethanol (7:3) or pure ethyl acetate. Control devices containing only water (no drug) were also found to be mildly irritating to rabbits following a 24-hr exposure period. A histological evaluation of the application sites of two of the formulations confirmed the visual observations of mild subacute irritation. The changes produced by transdermal levonorgestrel were reversible. The problems of skin irritation of transdermal devices is discussed with particular reference to the use of ethyl acetate and ethanol as skin penetration enhancers.

Acetates

Ultrasound tissue characterization of breast biopsy specimens.

Results of measurements of ultrasound speed and absorption coefficients in the range 3 to 8 MHz in breast tissues at 37 C are reported and analyzed in attempts to identify a set of ultrasound parameters capable of discriminating normal, benign, and malignant tissues. We analyzed 118 tissue regions, comprising 47 normal, 55 benign, and 16 malignant by straight-line fitting of frequency dependence of attenuation. Data for ten additional regions, for a total of 128, became available and were added to the cohort when we subsequently fitted quadratic curves. Sound speed consistently emerged as the variable with greatest discriminating power, particularly for separating normal from benign and malignant tissue. Great difficulty was encountered in discriminating benign from malignant, even when the jackknife technique was used. More success was found with classification and regression trees (CART), although results were sensitive to assigned misclassification costs. Best results from straight-line fits were obtained when discriminating malignant from combined normal/benign data after randomly assigning 75 percent of the data to the learning set and 25 percent to the test set. Then, 23 out of 25 normal/benign and 4 out of 4 malignant cases in the test set were correctly classified. With quadratic fitting, best results were obtained in the three-class case--the false positive rate for malignancy was reduced to zero in the learning (0/31) and test (0/10) sets. Nevertheless, the false negative rate increased to 13 out of 31 (42 percent) in the learning set, while attaining zero (0/4) in the test set.

Adenofibroma

The durability of hydrogel extended-wear contact lenses worn for daily wear by USAF aircrew members.

Hydrogel extended-wear contact lenses, worn on a daily-wear regimen, were tested for 1 year by USAF aircrew members. A total of 62 eyes were fitted with Hydrocurve II (55% water content) spherical lenses, 29 with Hydrocurve II (55% water content) toric lenses, and 61 with CSI-T (38.5% water content) spherical lenses. The mean lens replacement rate for torn lenses per aircrew member was determined to be 1.45 lenses a year. The replacement rate of Hydrocurve II spherical lenses compared to CSI-T lenses was not statistically significant. However, the replacement rate for Hydrocurve II toric lenses was significantly lower than both Hydrocurve II spherical lenses and CSI-T lenses (p less than 0.01). The extended-wear lenses tested in this study appeared to be durable enough for the rigors of daily wear.

Adult

The 1987 Comprehensive Blood Bank Survey of the College of American Pathologists.

The 1987 Comprehensive Blood Bank Survey consisted of four shipments of samples. Each presented graded challenges in ABO and D typing, crossmatching, and antibody detection and identification and ungraded challenges for antigen typing and ungraded serum samples for educational purposes. Practice patterns were elicited through supplemental questions, generally about issues raised by the survey samples. Two of the surveys showed significant problems. Set J-C included serum with anti-Lea, which was not detected by some participants. Anti-Dia was one of two antibodies in the J-D graded sample, and this additional antibody was not detected by a significant number of participants. Although minor problems were encountered in other challenges, in general performance was good.

ABO Blood-Group System

Canine epidermotropic cutaneous lymphoma.

The histologic features of an epidermotropic cutaneous lymphoma in a dog are presented. The neoplasm, which was intensely epidermotropic, thoroughly invaded the follicular and apocrine gland epithelium. The intense epidermotropism was retained in the tumor stage. By comparison to human mycosis fungoides, the cell nucleus was less convoluted and the infiltrate was less polymorphic. The lymphoid cell appeared to undergo neoplastic transformation into a cell with a large pale nucleus, often with a prominent nucleolus and variable cytoplasm. In situ marker studies are needed to clarify the cell type in this neoplasm. These studies could have relevance for the pathogenesis of human epidermotropic lymphoma.

Animals

Oral toxicology studies with xylene isomers and mixed xylenes.

Xylene isomers and mixed xylenes were administered to male and female Sprague-Dawley rats to evaluate their effects on standard toxicological parameters which included body and organ weights, hematology, serum chemistries, urinalysis and histopathological examination. In the initial study, m, o- or p-xylene were administered in corn oil by gavage for 10 consecutive days at dose levels of 250, 1000 and 2000 mg/kg/day. The most noteworthy changes were increased liver weight in both sexes for all three isomers while decreases in spleen and thymus weights were seen less frequently. Rats were subsequently exposed to mixed xylenes by gavage in corn oil for 90 consecutive days at dose levels of 150, 750 and 1500 mg/kg/day. The most significant findings of the subchronic study were enlarged livers and kidneys. Histopathological evaluation of liver and kidney tissues revealed an increased incidence of minimal chronic renal disease in only female rats, while treatment related hepatic histopathological changes were not detected in either sex.

Administration, Oral

Morphologic and immunocytochemical study of young dogs with diabetes mellitus associated with pancreatic islet hypoplasia.

In 11 dogs (7 males, 4 females; 10 purebred, 1 mixed breed), diagnosed as having diabetes mellitus before the age of 6 months, the pancreas was evaluated histologically; in 6, the pancreas also was examined by use of electron microscopy and/or immunocytochemical methods. Each dog was placed in 1 of 3 groups (A through C) on the basis of pancreatic histopathologic findings: Group A (n = 3)--no recognizable islets, but the pancreas in 2 dogs contained scattered endocrine cells detectable by use of immunoperoxidase staining or electron microscopy; Group B (n = 4)--no recognizable islets, but the pancreas had severe vacuolation of ducts and acini, as well as acinar atrophy; Group C (n = 4)--scant shrunken islets; 1 pancreas had reduced numbers of recognizable islets, hydropic beta-cell vacuolation attributable to glycogen deposition, and islet and nonislet endocrine cells in expected proportions. Insulitis was not observed in any pancreas, although scattered lymphocytes were seen in the pancreatic interstitial fibrous tissue of 3 dogs. Histologic pancreatic lesions in these young dogs were distinct from those of type-I (insulin-dependent) diabetes mellitus in human beings, as well as from those of diabetes mellitus in aged dogs, but were similar to those described in other young diabetic dogs. This uncommon syndrome is distinct from commonly recognized canine diabetes mellitus, on the basis of age of onset, predisposition for purebred dogs, lack of predisposing endocrinopathies or obesity, and pancreatic histologic features. The cause(s) is unknown, but is related to pancreatic endocrine hypoplasia and not to insulitis or to exocrine pancreatic inflammation. The term pancreatic islet hypoplasia is chosen as best describing this disorder.

Age Factors

The pharmacokinetics of bupivacaine when injected intra-articularly after knee arthroscopy.

Bupivacaine pharmacokinetics were determined in 11 patients receiving the drug intra-articularly after knee arthroscopy performed under general anesthesia. Forty ml 0.25% bupivacaine was given at the end of surgery and the thigh tourniquet was released 2 to 3 minutes after injection. Blood samples were obtained up to 5 hours after tourniquet release and plasma bupivacaine concentrations were determined. Pharmacokinetic parameters determined were (mean +/- SD): volume of distribution (Vd beta) 206 +/- 88 L, clearance (Cl) 0.816 +/- 0.378 L/min, terminal half-life (T1/2) beta 189 +/- 84 minutes, absorption rate constant (ka) 9.92 +/- 6.79/min, estimated peak plasma concentrations (Cpmax) 0.48 +/- 0.20 micrograms/mL, and time to peak concentration (tmax) 43.4 +/- 23.1 minutes. Results indicate that injections of 100 mg bupivacaine intra-articularly after knee arthroscopy produce peak blood concentrations within the first hour after surgery, and that these will be well below concentrations associated with toxic reactions. Peak concentrations can be minimized with shorter tourniquet inflation times and with longer intervals between injection and tourniquet release.

Adolescent

Elongation of arachidonic and eicosapentaenoic acids limits their availability for thrombin-stimulated release from the glycerolipids of vascular endothelial cells.

This study has examined the thrombin-stimulated release of polyunsaturated fatty acids from endothelial glycerolipids. Human umbilical vein endothelial cells were incubated with 1.25 microM [14C]arachidonate or [14C]eicosapentaenoate and then exposed to thrombin in buffered saline plus albumin. After an incorporation period of 0.5 h, the thrombin-stimulated release of the two radiolabeled fatty acids was quite similar. By contrast, after 24 h of fatty acid incorporation, the thrombin-stimulated release of radiolabeled fatty acid from cells incubated with [14C]eicosapentaenoate was only 25-30% of that from cells with [14C]arachidonate. Analysis of cellular glycerolipids indicated that 23 and 72%, respectively, of the incorporated [14C]arachidonate and [14C]eicosapentaenoate had been elongated to 22-carbon fatty acids in 24 h. Both 20- and 22-carbon 14C-labeled fatty acids were released to albumin in the medium in control incubations. Addition of thrombin stimulated the release of [14C]arachidonate and [14C]eicosapentaenoate, but not of their respective elongation products. Furthermore, endothelial cells incorporated exogenous [14C]docosatetraenoate into cellular glycerolipids but did not release it in response to thrombin. Thus, the thrombin-stimulated release of polyunsaturated fatty acids from vascular endothelial cells is highly selective for arachidonate and eicosapentaenoate. These results suggest that the extensive elongation of eicosapentaenoate by these cells serves to remove n - 3 polyunsaturated fatty acids from the pool of cellular acyl groups which are released in response to thrombin and are thus made available for metabolism by cyclooxygenase and lipoxygenase enzymes.

Arachidonic Acid

Diabetes mellitus in the juvenile dog: a report of four cases.

In four cases of diabetes mellitus in juvenile dogs, clinical and clinicopathologic findings were similar to those of juvenile onset diabetes mellitus in man. However, histopathologic findings varied from the usual findings in the human disease, and lack of plasma insulin was not proved in the canine cases.

Animals