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Biomedical subjects

J H Smith

Publications and source records attributed to J H Smith.

At least 109 records · Page 6Linked to original sources

Does delay in fixation affect the number of mitotic figures in processed tissue?

The effect of delay in fixation on the number of mitotic figures in tissues has received little attention, and previous studies have reached differing conclusions. The numbers of mitotic figures in the normal mucosa of six colectomy specimens were counted with delays in fixation of 30 minutes, one hour, two hours, three hours and six hours for samples from each specimen. The numbers of mitotic figures were counted in 50 whole crypts in each specimen by two observers. All phases of mitosis were counted. The number of observable mitotic figures declined by about 30% with a delay in fixation of two hours and by 50% with a delay of six hours. This observation has important implications for the handling of surgical specimens.

Colon↗

Pathology of experimental Sarcocystis falcatula infections of canaries (Serinus canarius) and pigeons (Columba livia).

Sarcocystis falcatula is an apicomplexan parasite with a broad range of avian intermediate hosts. The pathology and pathogenesis of infection with this parasite has been studied experimentally in the budgerigar (Melopsittacus undulatus). The present study quantitatively examines the pathology of this parasite in canaries (Serinus canarius) and pigeons (Columba livia) and compares it with that found in budgerigars. The general progression of merogony and cyst formation is similar qualitatively to that seen in budgerigars, but it differs quantitatively. The principal site of precystic merogony is in pulmonary endothelial cells. The magnitude of pulmonary meront burdens (at similar inoculated dosages) varies in different intermediate host species. Merogony is less persistent than in budgerigars. Among the various species of birds, the magnitude of precystic merogony correlates differently with the magnitude of skeletal muscle cyst burdens. The distribution of cyst burdens among various muscles also differs. The composition of inflammatory cells differs among various avian species' response to S. falcatula. Pathologic changes quantitatively parallel tissue meront burdens (except possibly in the liver of canaries), resulting in an interstitial pneumonitis, hepatitis, and mild inflammatory lesions of other organs.

Animals↗

Naturally occurring apicomplexan acute interstitial pneumonitis in thick-billed parrots (Rhynchopsitta pachyrhyncha).

This report describes acute interstitial pneumonitis due to an apicomplexan parasite with schizogony in endothelial cells of pulmonary vessels accompanied by early and metrocyte stages of sarcocysts in the heart of a thick-billed parrot (Rhynchopsitta pachyrhyncha). The pattern of this disease is similar to that of the acute phase (approximately 10-15 days postinoculation) of experimental infections of budgerigars, Melopsittacus undulatus, with high doses of sporocysts of Sarcocystis falcatula.

Acute Disease↗

Osteopontin, a transformation-associated cell adhesion phosphoprotein, is induced by 12-O-tetradecanoylphorbol 13-acetate in mouse epidermis.

A murine mRNA (provisionally called 2ar) is described whose abundance is greatly increased by the tumor promoter 12-O-tetradecanoylphorbol 13-acetate both in JB6 epidermal cells in vitro and in epidermis in vivo. We have previously shown induction of 2ar in epidermal or fibroblast cell lines by tumor promoters, growth factors, and transformation with H-ras. The 2ar mRNA appears to be derived from a single copy gene. It encodes the mouse homolog of rat osteopontin, a 41.5-kDa glycosylated bone phosphoprotein that binds to fibroblasts and osteosarcoma cells and to hydroxylapatite (bone matrix). The rat and mouse sequences are 84% identical at the amino acid level and 87% identical at the nucleotide level. Many of the primary structural features are conserved, including a run of 9-10 aspartic residues and a Gly-Arg-Gly-Asp-Ser cell adhesion sequence. Antiserum raised against portions of the predicted polypeptide immunoprecipitated proteins of apparent Mr 55,000-70,000 both from reticulocyte lysates containing the translation products of hybrid-selected mRNA and from cell culture medium containing metabolically labeled proteins secreted by JB6 cells. The results presented here demonstrate that osteopontin is identical to a transformation-associated phosphoprotein whose level of expression by cultured cells and abundance in human sera has been correlated with tumorigenicity. These results suggest a role for osteopontin in carcinogenesis. The murine version of osteopontin has been given the formal name "secreted phosphoprotein 1" and the designation spp.

Amino Acid Sequence↗

Evidence for two pathways of protein kinase C induction of 2ar expression: correlation with mitogenesis.

2ar is a cDNA clone of an mRNA that is inducible by 12-0-tetradecanoylphorbol-13-acetate (TPA) in mouse JB6 epidermal cells. This mRNA is stably induced in confluent cells but only transiently induced in subconfluent cells; the elevated level of 2ar mRNA in TPA-treated cells appears to be the result of enhanced transcription (Smith and Denhardt: Journal of Cellular Biochemistry 34:13-22, 1987). Phorbol dibutyrate, teleocidin, and aplysiatoxin, which activate protein kinase C and are also tumor promoters, are shown here to induce 2ar to the same extent as TPA at both cell densities. The increased expression by TPA was prevented by cycloheximide and by H7, a specific inhibitor of protein kinase C. Epidermal growth factor, platelet-derived growth factor, and the nonphorbol promoter diethylhexylphthalate were more effective inducers in confluent than in subconfluent cultures. All-trans retinoic acid, dexamethasone and fluocinolone acetonide, inhibitors of tumor promotion, diminished 2ar induction in both acetonide, inhibitors of tumor promotion, diminished 2ar induction in both confluent and subconfluent cells. In TPA-treated subconfluent cultures indomethacin produced a slight inhibition, whereas difluoromethyl ornithine potentiated the induction. In TPA-treated confluent cultures, in contrast, indomethacin enhanced 2ar mRNA levels and difluoromethyl ornithine was inhibitory. We conclude that the protein kinase C-mediated induction of 2ar expression is controlled by different pathways in subconfluent cultures and confluent cultures, indicative of apparent changes in the regulation of gene expression as proliferating cells become quiescent.

Animals↗

Evaluation of bond strength of six porcelain repair systems.

The shear bond strength of six porcelain repair systems was evaluated in vitro at 48 hours and 3 months. Water storage and thermocycling significantly lowered the mean shear bond strength for all kits tested. However, at the end of 3 months Scotchprime resin had the highest mean bond strength. With current products, porcelain repair remains an interim clinical procedure.

Dental Bonding↗

Is there any justification for the routine examination of bowel resection margins in colorectal adenocarcinoma?

The proximal and distal bowel resection margins of 339 specimens of colorectal adenocarcinoma were examined for the presence of tumour. In only five cases was tumour found in a resection margin. In four of these cases macroscopic examination showed that the tumour extended to the resection margin. In the fifth case the tumour was present in the pericolic fat. These results and reported data on the intramural spread of colorectal cancer suggest that examination of bowel resection margins is unnecessary unless the tumour extends to within 2 cm of the resection margin. Examination of the deep radial margins of the tumour and slides to show other prognostic indicators would be a more effective use of histopathological resources.

Adenocarcinoma↗

Inhibitors of sterol synthesis. Morphological studies in rats after dietary administration of 5 alpha-cholest-8(14)-en-3 beta-ol-15-one, a potent hypocholesterolemic compound.

The morphological effects of short-term (9 days) dietary administration (0.1% in a laboratory chow diet) of 5 alpha-cholest-8(14)-en-3 beta-ol-15-one, a novel regulator of cholesterol metabolism with significant hypocholesterolemic activity, has been studied in young male rats. Control animals included rats fed the basal diet ad libitum and a series of rats pair-fed to the individual experimental animals. At the time of necropsy, the morphological changes in rats which have been observed in rats following treatment with other absorbable hypolipidemic agents (myeloid bodies with triparanol, increased peroxisomes with clofibrate, and proliferation of smooth endoplasmic reticulum with compactin and mevinolin) were not apparent on ultrastructural examination of livers of rats treated with the 15-ketosterol. Two changes were observed in the rats fed the 15-ketosterol: a decrease in adipose tissue and enlargement of the small intestine. Diminished fat was also noted in the pair-fed controls and was presumably due to decreased food consumption. The intestines of rats fed the 15-ketosterol were morphometrically most enlarged in the jejunal region. Morphologically, this increase was distinguished by increased depth of crypts of Lieberkuhn and pseudostratification of epithelium at the base of the villi. These changes were qualitatively and quantitatively similar to the adaptive changes reported in the rat after resection of small bowel or following intestinal bypass (segment of bowel remaining in continuity). The morphological changes induced in the rat by administration of the 15-ketosterol were not observed in 4 baboons which received the compound orally at doses of 50, 75, or 100 mg per kilogram of body weight for up to 3 months.

Animals↗

Remission and relapse in heroin users and implications for management: treatment control or risk reduction.

A general practice based study of 117 heroin users receiving minimal intervention for their drug use examines the patterns and frequency of use from onset to last medical contact. Patterns of abstinence and relapse, and episodes of dependent and nondependent use are defined and quantified, demonstrating variations between and within individuals over time. This evidence of both controlled heroin use and remission and relapse not related to intervention is discussed and contrasted with the continued fixed belief of the public and professionals that heroin use is continuous, incurable, and permanent. Implications for therapy, especially in a "post-AIDS" era, are discussed.

Adult↗

Relationships among mineral balance in the diet, early growth manipulation, and incidence of tibial dyschondroplasia in different strains of meat type chickens.

In two experiments, a high dietary level of available phosphorus (.65%) in the presence of high chloride concentrations (.36%) was associated with a significant increase in the incidence of tibial dyschondroplasia (TD) in male broiler chickens. The level of dietary calcium and the interaction between Ca and available P had no effect on TD. Heterozygous normal (DW/DW) male broilers had a significantly lower incidence of TD than homozygous normal (Dw/Dw) chicks (Experiments 1 and 2). In Experiments 3 and 4, there were no significant differences between BW at 14 days for roaster-broiler cross and broiler chicks. At 21 and 28 days, however, the roaster-broiler cross chicks weighed significantly less than the broilers and had a significantly lower incidence of TD. Decreasing growth rates in broiler chicks after 14 days of age resulted in a significant decrease in the incidence of TD (Experiments 4 and 5), but did not decrease the severity of TD lesions at 28 days (Experiment 5). Depressed growth from 0 to 14 days decreased, but did not eliminate, TD lesions (45%) at 28 days, but it did significantly decrease the severity of the lesions compared with that in the 14 to 28-day manipulation treatments (Experiment 5). In Experiment 5, chicks were growth restricted from 0 to 14 or 14 to 21 days and then ad libitum fed the control diet until 28 days of age. The serum growth hormone concentrations at 28 days were inversely related to the rate of BW gain from 21 to 28 days of age, independent of BW at 21 or 28 days or feed consumption from 21 to 28 days. There were no differences in serum concentration of thyroxine or triiodothyronine at 28 days.

Analysis of Variance↗

Pathogenesis of Sarcocystis falcatula (Apicomplexa: Sarcocystidae) in the budgerigar (Melopsittacus undulatus). III. Pathologic and quantitative parasitologic analysis of extrapulmonary disease.

Forty-four budgerigars (Melopsittacus undulatus) were administered sporocysts of Sarcocystis falcatula orally and were examined at necropsy intervals from less than 12 hr to 168 days. Tissue were examined by touch preparations (of organ cut surfaces), light microscopy, and electron microscopy. Meront and cyst burdens were determined in various organs and correlated with duration of infection, inoculum, and the meront or cyst burdens of other organs. Host inflammatory tissue reactions were quantitated and correlated with meront and cyst burdens. Quantitation of meronts was more accurate in tissue sections than in touch preparations, but quantitation of merozoites was better in touch preparations. More than 97% of meronts were found in capillary, venular, and venous endothelial cells. Cysts were found only in cardiac and skeletal myocytes. Merogony began in the lamina propria of the small intestine less than 12 hr postinoculation (PI). Meronts were in liver and lung by the second day PI and in other organs by 3-7 days PI. Mean meront burdens were highest in lung (33 meronts/mm2), lower in liver and kidney (1-3 meronts/mm2), and infrequent in other organs (less than 0.9 meronts/mm2). Cysts were first seen in cardiac myocytes 7 days PI. They developed through the metrocyte stage and then degenerated, rarely reaching maturity. Cysts were first noted in skeletal muscle at 8 days PI. In leg, upper esophagus, and tongue, cysts matured between 44 and 77 days PI. In pectoral muscles, the majority of cysts degenerated during the late metrocyte and early intermediate stages (28-42 days PI). In addition to a previously reported and often fatal acute interstitial pneumonitis, S. falcatula-infected budgerigars also sustained a chronic active hepatitis, interstitial myocarditis, myositis, nephritis, splenitis, and encephalitis. These lesions weakly correlated with meront burdens in most sites during early infection (up to 50 days PI).

Animals↗

Comparative toxicity and renal distribution of the platinum analogs tetraplatin, CHIP, and cisplatin at equimolar doses in the Fischer 344 rat.

Tetraplatin [tetrachloro(dl-trans)1,2-diaminocyclohexane platinum(IV), NSC-363812] is a new anticancer platinum drug analog targeted for clinical development because of its effectiveness against cisplatin-resistant tumor cell lines and its improved formulation. The toxicity of tetraplatin was compared at equimolar doses to that of cisplatin [cis-diamminedichlorophatinum(II)] and CHIP [cis-dichloro,trans-dihydroxybis-isopropylamine platinum(IV), NSC-256927]. Adult male Fischer 344 rats received an iv bolus injection of 6.7, 13.3, 26.7, or 53.3 mumol/kg of one of these drugs in saline and were killed on Day 1, 3, 5, 8, or 15 postinjection for assessment of toxicity with emphasis on evaluation of nephrotoxicity. Rats to be killed on Day 15 were housed in metabolism cages for daily urine collection. Tetraplatin was less nephrotoxic than cisplatin at equimolar doses; CHIP was not nephrotoxic at these doses. Renal platinum contents were similar after all three drugs and did not appear to be related directly to the nephrotoxicity. Nephrotoxicity was detected 4-5 days after 6.7 mumol/kg cisplatin, was localized to the corticomedullary junction, and progressed with time and dose. Tetraplatin-induced alterations of renal function were first observed after 13.4 mumol/kg on Day 4 as an elevation of urine volume (up to 10-fold) and a smaller elevation of urinary glucose excretion. Tetraplatin lesions were localized in the mid- and outer cortex and, even at the highest dose, were less severe than those observed with cisplatin. There were other prominent toxic effects of tetraplatin, such as gastrointestinal toxicity and myelosuppression, which indicate that factors other than comparative nephrotoxicity may impact the clinical potential of this new agent.

Animals↗

In vivo biochemical indices of nephrotoxicity of platinum analogs tetraplatin, CHIP, and cisplatin in the Fischer 344 rat.

In vivo biochemical indices of nephrotoxicity were investigated in Fischer 344 rats treated with a new platinum analog, tetraplatin [tetrachloro(dl-trans)1,2-diaminocyclohexane platinum(IV), NSC-363812], in comparison with rats receiving equimolar dosages of cisplatin and CHIP [cis-dichloro,trans-dihydroxybis-isopropylamine platinum(IV), NSC-256927]. The goals of this study were to assess the comparative nephrotoxicities and to determine which battery of tests might be useful for the assessment of platinum analog-induced nephrotoxicity in future clinical investigations of these drugs. An iv bolus injection of 6.7, 13.3, 26.7, and 53.3 mumol/kg of each drug in saline was administered and assessment of biochemical parameters was conducted for 15 days postinjection. A combination of urinary enzyme and protein excretion rates along with blood urea nitrogen (BUN) determinations was used to assess the nephrotoxicity of these compounds. At equimolar dosages, tetraplatin appeared to be less nephrotoxic than cisplatin, and CHIP was not nephrotoxic. At all dosages tested, cisplatin increased the rate of urinary excretion of protein, lactate dehydrogenase (LDH), and N-acetylglucosaminidase (NAG) between Days 1 and 5. Tetraplatin did not affect these parameters until the 13.3 mumol/kg dosage. Cisplatin had little effect on the excretion rates of the brush border enzymes alkaline phosphatase and maltase, whereas tetraplatin caused an initial elevation with delayed onset of peak excretion rates at 8 days postinjection. Changes in BUN were not evident until after the 13.3 mumol/kg dosage of cisplatin and the 26.7 mumol/kg dosage of tetraplatin. BUN was useful for ranking the relative toxicities of the three compounds tested, but was not as sensitive in detecting the onset of injury that correlated with early histopathological changes. Tetraplatin appeared to be less nephrotoxic than cisplatin on an equimolar basis and the specific manifestations of its toxicity were different from those observed with cisplatin. Urinary excretion rates for LDH, NAG, and protein proved to be sensitive indicators of platinum analog-induced nephrotoxicity. These indices, combined with BUN determinations and functional assessments, facilitated comparisons of the nephrotoxicity induced by cisplatin and tetraplatin in rats.

Animals↗