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Biomedical subjects

T A Miller

Publications and source records attributed to T A Miller.

At least 127 records · Page 7Linked to original sources

A new test for measuring diapause in the pink bollworm Pectinophora gossypiella Sunders.

An ELISA test was developed to assay for the presence of a protein, pectinophorin, that is expressed only in diapausing last instar larvae of the pink bollworm, Pectinophora gossypiella Saunders. Use of the test provides a good estimation of the percent of diapause larvae in populations of pink bollworm in cotton fields in California and Arizona. All plow down dates are chosen before the majority of larvae enter diapause so as to eliminate as many overwintering survivors as possible. These dates may now be determined more precisely for any given field by use of the new ELISA procedure.

Animals↗

Bacterial flora of the gastrointestinal tract of opossums.

The bacterial flora of the stomach, small intestine, cecum and bile from 20 healthy opossums (Didelphis virginiana) captured from the wild was studied. Results showed that their gastrointestinal flora was similar to that found in other small mammals but, in addition, opossums are heavily colonized by Salmonella spp., which might adversely affect their adequacy as laboratory animals for some experimental protocols.

Animals↗

A biomechanical perspective on exercise countermeasures for long term spaceflight.

Many systems of the body undergo adaptation on exposure to hypogravity, with the lower extremity skeleton experiencing considerable mineral loss during relatively short periods of hypogravic exposure. To date, a variety of countermeasures have had limited success in preventing demineralization, though it is now accepted that mechanical deformation is critical for bone homeostasis on Earth. In the present study, three exercises under active consideration for use in the Space Station were compared in 1 G in terms of the peak loads and rates of change of load elicited under the feet. Peak loading rates were in the ratio of 34.7:1.9:1 for running, rowing, and cycling, respectively. With regard to peak foot loads, the corresponding values were in the ratio of 5.3:1:1.2. These results suggest that exercise during spaceflight must be considered from both biomechanical and physiological perspectives if optimal response is to be obtained.

Adult↗

Latrodectism: bite of the black widow spider.

Latrodectism, the clinical syndrome that follows envenomation by the black widow spider, may easily be confused with more common conditions. Acute manifestations are characterized by agonizing pain and muscle spasm. Prolonged symptoms, primarily related to neurologic dysfunction, may occur. Familiarity with the manifestations of latrodectism is the key to diagnosis. Family physicians should consider latrodectism in patients presenting with severe pain and muscle cramps, particularly if the setting and history are consistent with a possible spider bite. Optimal therapy remains controversial. Early use of specific antivenin in severely envenomated patients may prevent the development of lingering symptoms, usually related to neurologic dysfunction.

Adult↗

Disseminated gonococcal infection.

The most frequent systemic complication of acute, untreated gonorrhea is disseminated infection, which develops in 0.5 to 3 percent of the more than 700,000 Americans infected with Neisseria gonorrhoeae each year. The classic triad of features consists of dermatitis, tenosynovitis and migratory polyarthritis. Disseminated gonococcal infection is most common in young women but may develop in sexually active persons of any age. The diagnosis often is not suspected because the initial mucosal infection is frequently asymptomatic, providing no clue to an infectious etiology. Prompt identification and treatment are essential to prevent complications such as endocarditis, meningitis, perihepatitis and permanent joint damage.

Age Factors↗

A functional c-myb gene is required for normal murine fetal hepatic hematopoiesis.

The c-myb proto-oncogene encodes a sequence-specific DNA-binding protein. To better understand its normal biological function, we have altered the c-myb gene by homologous recombination in mouse embryonic stem cells. Resulting homozygous c-myb mutant mice displayed an interesting phenotype. At day 13 of gestation these mice appeared normal, suggesting that c-myb is not essential for early development. By day 15, however, the mutant mice were severely anemic. Analysis indicated that embryonic erythropoiesis, which occurs in the yolk sac, was not impaired by the c-myb alteration. Adult-type erythropoiesis, which first takes place in the fetal liver, was greatly diminished in c-myb mutants, however. Additional hematopoietic lineages were similarly affected. These results are compatible with a role for c-myb in maintaining the proliferative state of hematopoietic progenitor cells.

Animals↗

Colloidal gold localization of type IV collagen in the extracellular matrix of rat gastric mucosa: influence of alcohol and prostaglandin.

The effect of acute alcohol exposure on the gastric mucosal basal lamina, and its major structural protein type IV collagen, was assessed by transmission electron microscopy (TEM) and immunogold (IG) labeling of this collagenous material. Fasted rats orally received either 50% or 100% ethanol. Five or 60 minutes later animals were sacrificed and mucosal samples were obtained from the glandular epithelium for TEM or IG localization of type IV collagen. For IG studies, the number of gold particles/area lamina densa was quantified in interfoveolar, pit, and gland regions as an index of the molecular integrity of type IV collagen. Both ethanol concentrations induced epithelial exfoliation with pleating of the denuded lamina densa. Absolute ethanol, and to a lesser extent 50% ethanol, caused frequent rupture of a thickened, precipitated lamina densa. Immunolabeling of type IV collagen varied with the experimental protocol. In control tissues exposed to oral saline, binding was greatest in the interfoveolar zone. Low binding occurred with 100% ethanol in all regions when compared with controls, but 50% ethanol evoked significantly higher binding in interfoveolar regions, in a similar fashion to controls. In additional studies in which 16,16 dimethyl prostaglandin E2 (PGE2) (10 micrograms/kg) was injected subcutaneously prior to oral ethanol exposure, PGE2 pretreatment prevented the large decrease in IG binding induced by absolute ethanol, but the level still remained significantly less than with corresponding controls. In contrast, pretreatment with PGE2 prior to 50% ethanol exposure restored type IV collagen immunolabeling to control levels. These results indicate that ethanol induces a concentration-dependent lowering of IG binding to type IV collagen which also effects its reversibility by PGE2.

Animals↗

Stress erosive gastritis.

Bleeding from stress erosive gastritis continues to be a potential problem in critically ill and injured patients, but fortunately its incidence has decreased dramatically over the last decade. The explanation for this circumstance is probably multifactorial, but clearly relates to our increased knowledge of its pathophysiology. This understanding has led to the routine use of measures to reduce intragastric acidity (luminal acid being a prerequisite for stress ulcer to occur), coupled with improved techniques for the treatment of shock and the accompanying gastric mucosal hypoperfusion (another prerequisite for the formation of stress ulcers). A number of measures have been used to lower intragastric acidity with H2 receptor blockers emerging as the agents of choice to accomplish this goal. In the unlikely event that bleeding occurs despite these prophylactic measures, aggressive medical management will result in cessation of hemorrhage in over 80% of patients. In those few individuals requiring surgery to control bleeding, no operation has emerged as the recognized procedure of choice. Thus, we believe that a conservative operative approach is indicated in this setting and recommend vagotomy and pyloroplasty with oversewing of the bleeding erosions as appropriate therapy for most patients requiring surgical intervention.

Gastritis↗

The role of the gut in the development of sepsis in acute pancreatitis.

The pathogenesis of sepsis in acute pancreatitis is unknown. Since the intestinal tract has recently been identified as a possible source for sepsis in other conditions, we explored whether the gut may serve as a reservoir for bacteria causing systemic and pancreatic infection in acute pancreatitis. Bacterial translocation, alterations of intestinal microflora, and intestinal motility, as reflected by gut propulsion, were studied in a rat pancreatitis model. Acute pancreatitis was induced by biliopancreatic obstruction (AP); sham manipulated animals served as controls (sham). Bacteriologic cultures were obtained from various segments of the intestinal tract and from blood, liver, spleen, pancreas, and mesenteric lymph nodes 48 and 96 hr after induction of AP or sham. Bacteria were recovered from mesenteric lymph nodes of all 12 animals with AP, but only from 3/14 sham animals (P less than 0.05). Spread to distant organ sites occurred in 4 of 12 animals with AP compared to none of the sham animals (P less than 0.05). A disruption of the intestinal microflora was found in the cecum, where the gram-negative bacterial count (log/g) was significantly higher during AP when compared with sham controls: 10.62 +/- 1.04 vs 8.05 +/- 1.45 at 48 hr and 7.92 +/- 0.62 vs 6.79 +/- 0.87 at 96 hr, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Adaptive cytoprotection against alcohol injury in the rat stomach is not due to increased prostanoid synthesis.

This study evaluated the effects of 25% ethanol, a mild irritant, on endogenous prostanoid synthesis in the rat stomach before and after exposure to oral 100% ethanol. Rats received water or 25% ethanol orally. After 15 min, a portion of each group was sacrificed and the remaining animals treated with 100% ethanol prior to sacrifice one minute later. Microsomal membrane fractions were prepared from the glandular gastric mucosa in all groups and incubated with 14C arachidonic acid in the presence of cofactors. Endogenous mucosal prostanoid synthesis was analyzed by radiochromatography and results correlated with the presence or absence of gastric injury macroscopically. Prostanoids measured included PGI2, PGF2 alpha, PGE2, PGD2, PGA2, and thromboxane A2. Additional experiments were performed in like manner to those just described with the exception that indomethacin (5 mg/kg intraperitoneally) pretreatment was rendered. Stomachs exposed to water or 25% ethanol alone demonstrated a modest and equivalent level of synthesis of all prostanoids measured. Exposure to 100% ethanol (with and without mild irritant pretreatment) significantly increased prostanoid synthesis (especially PGI2, PGF2 alpha, and PGE2) compared with stomachs exposed to water or 25% ethanol alone; only mild irritant treated mucosa was protected from injury by 100% ethanol. Indomethacin pretreatment reversed the increased prostanoid synthesis in mucosa exposed to 100% ethanol, with or without mild irritant pretreatment, and partially reversed the protective effect of 25% ethanol. Other experiments using tissue slices in which perturbations in mucosal levels of prostanoids were measured by radioimmunoassay under identical experimental conditions exhibited similar results. These data dispute the notion that adaptive cytoprotection is mediated by increased endogenous prostanoid synthesis. The partial reversal of this process by indomethacin was most likely secondary to some other action of this agent, such as a reduction in gastric blood flow, rather than direct effects on prostanoid synthesis.

Animals↗

The induction of bone by an osteogenic protein and the conduction of bone by porous hydroxyapatite: a laboratory study in the rabbit.

The influence of the addition of an osteoinductive protein, capable of inducing extraskeletal ossification, on bone ingrowth into coralline porous hydroxyapatite was evaluated in the rabbit using a calvarium onlay model. Twenty-three rabbits received hydroxyapatite implants (10 x 10 x 2 mm) prepared with and without osteoinductive protein. These were implanted on the frontal bone and secured by wire fixation after 0.25 mm of the cortical surface was abraded. The implants were harvested at 3 and 4 months and analyzed for percentage of bone ingrowth by histologic examination of decalcified H&E sections and by scanning electron microscope backscatter image analysis. The osteoinductive protein-treated implants demonstrated significantly greater amounts of bone ingrowth at both 3 (52.0 versus 10.3 percent; p less than 0.001) and 4 months (66.1 versus 39.2 percent; p less than 0.005) than the untreated implants. The type of bone found in all osteoinductive protein-treated implants was predominantly lamellar. Untreated implants contained mostly woven bone at 3 months, with increasing amounts of lamellar bone appearing at 4 months. These results suggest that the combination of a bone-inducing protein and a suitable osteoconductive matrix may provide an alternative to bone grafting.

Animals↗

Protection against ethanol injury in the canine stomach: role of mucosal glutathione.

The present study determined the role that mucosal glutathione (GSH) levels play in mediating the protective effects of a prostaglandin and a mild irritant against alcohol-induced gastric injury. An in vivo canine chambered stomach preparation was used in which the exteriorized mucosa was partitioned into two equal halves, one serving as control. Animals (5-8/group) received a subcutaneous injection of either normal saline (NS) or the GSH depletor N-ethylmaleimide (NEM; 50 mg/kg) and then were assigned to one of a variety of groups based on the perfusate used to bathe the experimental side of the chamber; NS bathed the control mucosa. At completion of the studies, mucosa from each side of the chamber was assayed for total GSH (mumol/g wet wt) and evaluated for microscopic damage. Both 16,16-dimethyl prostaglandin E2 (PGE2) (1 microgram/ml) and the mild irritant 8% ethanol, when topically applied to the gastric epithelium, increased mucosal GSH levels by approximately 20% compared with control values, and elicited no deleterious effects to the mucosa. Treatment of animals with NEM prevented these GSH effects by PGE2 and 8% ethanol without damaging the mucosa. Application of 40% ethanol to the mucosa markedly reduced levels of GSH and caused significant injury to the mucosal surface, much of it extending to the level of the gastric glands. When mucosa was pretreated with PGE2 or 8% ethanol before 40% ethanol exposure, deep gastric gland injury was virtually abolished. In animals receiving NEM, the protective effects of these agents against injury by 40% ethanol were prevented. Perturbations in tissue levels of GSH under these various experimental conditions failed to correlate histologically with the status of gastric mucosal integrity.

Animals↗

N-acetyl-cysteine: protective agent or promoter of gastric damage?

N-acetyl-cysteine (NAC), when given orally, has been shown to prevent gastric damage induced by ethanol, but when administered intraperitoneally, it appears to potentiate such damage. In an effort to resolve these seemingly discordant findings, fasted rats (six per group) received 1 ml of saline or 20% NAC orally or intraperitoneally (ip). Two hours or 15 min later, they received 1 ml of 100% ethanol orally. At sacrifice 5 min later, rats receiving oral pretreatment with 20% NAC at both 15 and 120 min prior to ethanol exposure demonstrated a significant reduction in the magnitude of gastric injury when compared with saline controls. In contrast, actual promotion of ethanol damage was noted when NAC was given intraperitoneally, but was more pronounced when NAC was administered 15 min prior to exposing the mucosa to 100% ethanol. In all animals receiving intraperitoneal NAC, large amounts of peritoneal fluid (4-6 ml/rat) were recovered at the time of sacrifice, most of which occurred within 15 min of NAC administration; these more pronounced peritoneal effects at 15 min after NAC correlated with the more severe injury from ethanol at this time period compared to 120 min after intraperitoneal NAC. Saline controls had no peritoneal fluid. Mucosal glutathione (GSH) levels generally paralleled these results in that a significant decrease in tissue GSH occurred at 15 min following intraperitoneal NAC when compared with controls; at 120 min after intraperitoneal NAC, GSH levels were similar to control values. Additional experiments demonstrated that within 15 min following NAC administration, systemic blood pressure dropped by approximately 20% and basically remained unchanged over the next 2 hr; intraperitoneal saline had no sustained adverse effects on blood pressure. It was concluded that the inability of NAC to prevent ethanol injury when given intraperitoneally in contrast to orally is related to the drop in blood pressure secondary to NAC's peritoneal irritant effects, which presumably altered gastric mucosal blood flow, thus obivating its ability to prevent ethanol damage under these conditions. Furthermore, the decreased levels in mucosal GSH following the hypotension induced by intraperitoneal NAC suggest that perturbations in GSH metabolism may also have contributed to the decreased resistance to ethanol injury.

Acetylcysteine↗