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Biomedical subjects

T A Miller

Publications and source records attributed to T A Miller.

At least 19 recordsLinked to original sources

A diapause associated protein of the pink bollworm Pectinophora gossypiella Saunders.

A diapause associated protein was electrophoretically isolated from the hemolymph of diapausing last instar larvae of the pink bollworm Pectinophora gossypiella. This protein (M(r) approximately 490,000, glycolipoprotein) was given the name Pectinophora diapause protein (PDP). It is composed of one subunit (M(r) 103,000). The concentration of PDP increased dramatically in the hemolymph of diapausing larvae from 17.4% in prediapause (PD) phase to 29.2% in early diapause (ED) phase reaching a level of 38.6% in larval hemolymph of middiapause (MD) phase. The concentrations of total proteins in the hemolymph of active feeding (A), PD, ED, and MD larvae were 69.8, 106,6, 113.3, and 118 mg/ml, respectively, while those in the fat body of the same larvae were 7.1, 7.4, 8.8, and 4.5 mg/g, respectively. In Pectinophora a drop in the concentration of fat body proteins coincided with a corresponding increase in hemolymph proteins, which suggests an active release of protein from the fat body into the hemolymph during the development of diapause. A partial amino acid sequence of pectinophorin showed the first 15 amino acids starting from the amino terminus of the peptide chain: N-ALA-LYS-THR-ILEU-VAL-GLU-ASN-MET-PRO-PRO-THR-PRO-LEU-ASN-ALA-C.

Amino Acid Sequence

Abnormalities in ureter and kidney development in mice given acetazolamide-amiloride or dimethadione (DMO) during embryogenesis.

These experiments more accurately define the effects of the combination acetazolamide-amiloride or a single dose of dimethadione (DMO), the active metabolite of trimethadione, on the development of the ureter. When acetazolamide-amiloride was administered in C57BL/6NCrlBR mice on day 9, 9.5, or 10 of gestation (plug = day 0) a second ureter was formed, anterior to the original ureter, inducing a second kidney. The second ureter then fails to make a connection with the developing bladder and remains attached to the mesonephric duct. The mesonephric duct becomes the vas deferens in the male and deteriorates completely in the female leading to either a restricted ureter or a blocked ureter depending on the sex of the fetus. Administration of a single dose of DMO between gestational day 9 and 10.3 produced both renal agenesis and ureters of varying lengths. Some ureters were of normal length with a tuft of one or two nephrons at their tip, while others were one half or one quarter of their normal length. In some instances the ureter was completely absent. The reason for this strong effect on the ureter is unknown.

Abnormalities, Drug-Induced

Protective effect of dimethylthiourea against mucosal injury in rat stomach. Implications for hydroxyl radical mechanism.

The present study was undertaken to determine whether dimethylthiourea (DMTU), a hydroxyl radical scavenger, could prevent gastric injury in the rat stomach induced by various noxious agents. Fasted rats (N = 6-8/group) were given a 1-ml oral bolus of saline or DMTU over the dose range 10-500 mg/kg. After 30 min, animals received 1 ml of 100% ethanol orally and were sacrificed 5 min later. At sacrifice, stomachs were harvested and the degree of macroscopic damage was assessed by planimetry. In selected animals, specimens of gastric mucosa were also processed for histology. Saline pretreatment prior to ethanol exposure resulted in 22.5% injury to the glandular epithelium when assessed macroscopically. DMTU pretreatment prevented such injury in a dose-related fashion with only 2% of the mucosa showing injury with a 500 mg/kg dose (P less than 0.01 vs control). Although the superficial injury involving surface mucous cells induced by ethanol was not altered by DMTU, the deep damage to gastric glands was almost completely prevented. Other experiments in which DMTU was given intraperitoneally demonstrated similar protective effects against ethanol injury. Additional studies showed that indomethacin did not prevent the protective effects of oral or intraperitoneal DMTU, excluding a role for endogenous prostaglandins, and that DMTU was equally protective when administered within minutes or as long as 2 hr prior to ethanol exposure. Furthermore, DMTU was also shown to be protective against gastric injury induced by concentrated acid or base. In in vitro studies in which hydroxyl radicals were actually generated, DMTU was noted to scavenge the hydroxyl radical in a dose-related fashion. The ability of DMTU to prevent gastric injury by three different damaging agents suggests that the hydroxyl radical may play a major role in the pathogenesis of such injury and that DMTU mediated its protective action by scavenging this radical species.

Animals

Influence of shock on development of infection during acute pancreatitis in the rat.

This study tested the hypothesis that hypovolemic shock elicits or promotes the development of infection during acute pancreatitis. Pancreatitis was induced in rats by ligation of the common biliopancreatic duct; nonlaparotomized animals served as controls. After 24 hr, the animals were subjected to either sham-shock (instrumented only) or to shock by withdrawal of blood through a femoral artery line by maintaining the mean arterial blood pressure at 30 mm Hg for 1 or 2 hr. After completion of the shock period, the shed blood was returned to the animal. All animals were sacrificed 24 hr later and specimens obtained from portal and systemic blood, liver, spleen, pancreas, and mesenteric lymph nodes for bacteriologic culture using standard techniques. The pancreas was also analyzed by morphometric techniques. The histologic changes of pancreatitis induced by biliopancreatic obstruction were characterized by marked edema with accompanying mild inflammation, hemorrhage, and necrosis. Concomitant with these morphologic findings was an associated translocation of enteric organisms to the mesenteric lymph nodes without spread to distant organs. Shock by itself induced only a mild edema in the pancreas and did not cause bacterial translocation. Furthermore, shock failed to aggravate the morphologic alterations of acute pancreatitis and did not promote bacterial spread to mesenteric nodes over that observed with pancreatitis alone. Thus, we conclude that periods of severe shock lasting up to 2 hr do not play a major role in the pathogenesis of infection in our model of pancreatitis.

Acute Disease

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