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Biomedical subjects

J A Miller

Publications and source records attributed to J A Miller.

At least 55 records · Page 3Linked to original sources
PubMed1999

Fetal alcohol exposure and temporal vulnerability: regional differences in cell loss as a function of the timing of binge-like alcohol exposure during brain development.

This study was conducted to determine the temporal and regional vulnerability of the brain as a function of exposure to alcohol during brain development. Our goal was to manipulate the timing of alcohol exposure and assess the relative risk of cell loss in two different brain regions. Groups of timed pregnant Sprague-Dawley rats received binge-like alcohol exposure during either the first 10 days (first-trimester equivalent) or second 10 days of gestation (second-trimester equivalent), or the combination of first- and second-trimester equivalents for prenatal treatments. Offspring from some of the animals exposed to alcohol during the combined first- and second-trimester equivalent were reared artificially from postnatal days (P) 4 through 9 (part of the third-trimester equivalent) and also received binge-like alcohol during this period, producing animals that were exposed to alcohol during all three trimesters equivalent. Offspring from untreated dams were also reared artificially and received alcohol from only P4-9, thus creating animals that were exposed to alcohol only during part of the third-trimester equivalent. All pups were perfused on P10. Appropriate controls (nutritional and normally reared) were matched to every alcohol treatment combination. Peak blood alcohol concentrations were not different among the treatment groups for a given sampling time. Total cell numbers in the cerebellum (Purkinje and granule cells) and the olfactory bulb (mitral and granule cells) were estimated by the unbiased stereological technique, the optical disector. In terms of temporal vulnerability, alcohol exposure during the equivalent of all three trimesters resulted in a greater reduction in cerebellar Purkinje cell numbers compared with exposure to alcohol during the third-trimester equivalent, whereas both groups had a significant reduction in cell number compared with all other timing groups. Cerebellar granule cell number was reduced after alcohol exposure during all three trimesters equivalent, compared with all other timing groups. Alcohol exposure during the third-trimester equivalent resulted in a decrement in the number of olfactory bulb mitral cell numbers compared with all other groups, but there were no differences among the timing groups in numbers of olfactory bulb granule cells. When the cell loss in the two regions was compared within each alcohol treatment group to determine the relative regional vulnerability, the primary salient finding was that cerebellar Purkinje cells were more vulnerable to alcohol-induced loss subsequent to exposure during all three trimesters equivalent. No other regional differences were detected. These results extend earlier findings by showing that alcohol exposure during different periods of brain development results in regional differences in cell loss as a function of the timing of alcohol exposure during brain development and illustrate the variability of alcohol-induced neuronal loss.

Alcohol Drinking↗
PubMed1999

Effect of adrenocorticotrophic hormone on sodium appetite in mice.

A main vector of the effects of stress is secretion of corticotrophin releasing factor (CRF), adrenocorticotrophin (ACTH), and adrenal steroids. Systemic administration of ACTH (2.8 microgram/day sc) for 7 days in BALB/c mice caused a very large increase of voluntary intake of 0.3 M NaCl equivalent to turnover of total body sodium content each day. Intracerebroventricular infusion of ACTH (20 ng/day) had no effect. Intracerebroventricular infusion of ovine CRF (10 ng/h for 7 days) caused an increase of sodium intake. The large sodium appetite-stimulating effect of systemic ACTH was not influenced by concurrent systemic infusion of captopril (2 mg/day). Induction of stress by immobilization of mice on a running wheel caused an increase in Na appetite associated with a 50% decrease of thymus weight, indicative of corticosteroid effects. The present data suggest that stress and the hormone cascade initiated by stress evoke a large sodium appetite in mice, which may be an important survival mechanism in environmental conditions causing stress.

Adrenocorticotropic Hormone↗
PubMed1999

Impact of hyperglycemia on the renin angiotensin system in early human type 1 diabetes mellitus.

It has been demonstrated previously that moderate hyperglycemia without glucosuria can increase plasma renin activity and mean arterial pressure in young healthy males with early uncomplicated type 1 diabetes mellitus. This study was conducted to extend these observations by testing the hypothesis that mild to moderate hyperglycemia can affect renal function by increasing renin angiotensin system (RAS) activity in diabetic humans. The study included 10 men and women with early, uncomplicated type 1 diabetes (duration <5 yr), all ingesting a controlled sodium and protein diet. They were studied on four separate occasions, during a subdepressor dose of the angiotensin II (AngII) receptor blocker losartan, and during graded AngII infusion, 1.5 and 2.5 ng/kg per min, while euglycemic (blood glucose 4 to 6 mmol/L) and again while hyperglycemic without glucosuria (blood glucose 9 to 11 mmol/L), according to a randomized crossover design. Outcome measures included mean arterial pressure (MAP), GFR, effective renal plasma flow (ERPF), renal vascular resistance (RVR), filtration fraction (FF), and urine sodium excretion (UNaV) at baseline and in response to the above maneuvers. During hyperglycemic conditions, MAP was significantly higher compared with euglycemia, as were RVR and FF. After the administration of losartan, a significant renal and peripheral depressor effect was noted, with decreases in MAP, RVR, and FF, whereas during euglycemia the responses to losartan were minimal. AngII infusion resulted in elevations in MAP, RVR, and FF and a decline in UNaV during both glycemic phases, but the responses during hyperglycemia, most significantly at the 1.5 ng/kg per min infusion rate, were blunted. These data support the hypothesis that hyperglycemia affects renal function by activating the RAS. The mechanism remains obscure, but these contrasting responses may provide a link between the observations that maintenance of euglycemia and blockade of the RAS prevent or delay diabetic kidney disease, and furthermore, may clarify the mechanism whereby high glucose promotes renal disease progression in diabetes.

Adult↗
PubMed1999

The northern exposure sign: a newly described finding in sigmoid volvulus.

OBJECTIVE: Previous studies of sigmoid volvulus have focused on the migration and dilatation of the sigmoid with respect to both fixed and mobile landmarks in the abdomen. None has specifically referred to the relationship of this colonic segment to the more proximal large intestine. We analyzed findings on abdominal radiographs, all of which had been obtained with the patient supine, of sigmoid volvulus, with particular attention to the juxtaposition of the sigmoid colon with the transverse colon. MATERIALS AND METHODS: The abdominal radiographs of 30 patients with clinically confirmed sigmoid volvulus were obtained from the teaching files of four hospitals and were retrospectively reviewed. These radiographs were compared with abdominal radiographs of 28 individuals, each of whom had a dilated colon but not sigmoid volvulus. All radiographs had been obtained with the patient in the supine position. RESULTS: The transverse colon was identified in 26 of the 30 patients with sigmoid volvulus. In each of these 26 patients, the sigmoid colon was cephalad to the transverse colon. Of the patients in the control group, the transverse colon was identified in 24 of the 28 patients. In none of these control group patients did the sigmoid colon extend rostral to the transverse colon. Thus, this sign had a sensitivity of 86% and a specificity of 100%. CONCLUSION: A dilated sigmoid colon that ascends cephalad to the transverse colon is a newly described and accurate finding of sigmoid volvulus on abdominal radiographs obtained with the patient supine.

Case-Control Studies↗
PubMed1999

Waxing and waning gynecomastia: an indication of noncompliant use of prescribed medication.

We present two cases of recurrent gynecomastia in men enrolled in a placebo-controlled trial evaluating the efficacy of finasteride in treating benign prostatic hyperplasia. When the pharmacologic records were examined, it was apparent that the breast tissue hyperplasia diminished when the patients become noncompliant with their study medication and then resumed therapy. Because of the difficulty in obtaining accurate data on an individual's ability to maintain a consistent pharmacologic regimen, we believe that observing such "waxing and waning gynecomastia" may provide the physician with a clue regarding a patient's actual compliance with certain medications.

5-alpha Reductase Inhibitors↗
PubMed1999

A reevaluation of the radiographically detectable complications of percutaneous venous access lines inserted by four subcutaneous approaches.

As a result of prior studies elucidating the potential complications associated with the use of central venous access lines, the Food and Drug Administration and the manufacturers themselves have published guidelines and warnings outlining these dangers and describing the safest insertion techniques. We will attempt to determine whether this improved education has altered the number and type of complications, comparing the results from different types of hospitals, among the various medical services and among operators with varying degrees of experience. This is a prospective analysis of all central venous pressure (CVP) and Swanz-Ganz catheters (SGCs) inserted between July 1, 1995, and February 30, 1996, at a regional Veteran's Affairs hospital and an inner city university medical center. Three hundred seventy-five inpatients underwent 417 new percutaneous venous catheter placements while in the medical or surgical intensive care units or in the general care wards. A portable chest radiograph was obtained immediately after each procedure, and the position of the catheter and any associated complications were recorded, initially by the radiology resident in the emergency suite and subsequently as confirmed by a chest radiology attending. CVP lines were considered malpositioned when the tip was not located in the superior vena cava, and SGCs were recorded as misplaced when the tip was not found within the main, left main, right main, or either lower lobe pulmonary artery within 2 cm of the cardiac border. For patients undergoing CVP line placement, the right atrium was the most frequent site of tip malposition with 38 of 69 total misplacements (55%), whereas for SGCs, 22 of 55 malplacements (40%) were too distal in a lower lobe pulmonary artery. Only 1 of 248 CVP lines resulted in a pneumothorax (PTX; 0.4%), whereas 6 of 169 SGC insertions caused a PTX (3.5%), a significant difference (P=0.019). Five of 192 catheters (2.6%) placed via an internal jugular approach resulted in PTX, whereas only 2 of 150 subclavian cannulations (1.3%) caused this complication, revealing a trend, but not reaching statistical significance (P=0.473). However, there was a significant decrease in the rate of catheter misplacements in the third part of the month compared with the first 20 days (35% versus 24%; P=0.031), and the Veteran's Affairs hospital displayed a trend toward more complications for SGC insertions than the university hospital (47% versus 32%), but not for CVP lines. In general, individual medical and surgical services displayed a similar frequency of complications (29-38%), except for CVP lines inserted in the medical intensive care unit. Venous access catheter tip malpositions are very common in all settings, but easily recognized by radiography, whereas PTXs are unusual. In contrast to most older studies, PTXs are more frequently observed with internal jugular as opposed to subclavian cannulations and with SGCs rather than CVP lines. However, our data support prior studies that the right atrium and distal right lower lobe pulmonary artery are the most common sites for CVP and SGC misplacement, respectively, and that there is an improvement in success rates with increasing operator experience.

Catheterization, Central Venous↗
PubMed1998

Monoclonal and polyclonal antibodies recognizing acetaldehyde-protein adducts.

Studies have investigated the hypothesis that metabolically derived acetaldehyde (AA) is capable of complexing with liver cell proteins to form AA-protein adducts that are capable of acting as antigens and inducing an immune response, as detected by the formation of unique antibodies. In an effort to better characterize and describe these adducts, mouse monoclonal and rabbit polyclonal antibodies specific for antigens prepared with AA under non-reducing (physiologic) and reducing (presence of sodium cyanoborohydride) conditions have been prepared. Two monoclonal antibodies were developed. The first antibody was RT1.1, which is specific to N-ethyl lysine (NEL); it is of the IgG2b isotype and recognizes all proteins modified with AA under reducing conditions. The other monoclonal antibody, NR-1, was of the IgG3 isotype; it recognizes proteins modified with AA under non-reducing conditions and cannot be inhibited by NEL. Affinity-purified and/or absorbed polyclonal antibodies were also produced to these epitopes. Using this panel of monoclonal and affinity-purified polyclonal antibodies, unique antigen-antibody binding occurred that: (1) detected only NEL; (2) reacted with the alpha-amino group on proteins prepared under reducing conditions; and (3) detected adducts on proteins prepared under non-reducing conditions. However, the only antibodies that recognized antigen(s) from alcohol-fed rat livers were those that were not specific to NEL or the alpha-amino group modified under reducing conditions. These data indicate that the relevant adduct in alcohol-fed rat livers is not NEL, and that it presumably is related to proteins modified with AA under non-reducing conditions.

Acetaldehyde↗
PubMed1998

Tn5/IS50 target recognition.

This communication reports an analysis of Tn5/IS50 target site selection by using an extensive collection of Tn5 and IS50 insertions in two relatively small regions of DNA (less than 1 kb each). For both regions data were collected resulting from in vitro and in vivo transposition events. Since the data sets are consistent and transposase was the only protein present in vitro, this demonstrates that target selection is a property of only transposase. There appear to be two factors governing target selection. A target consensus sequence, which presumably reflects the target selection of individual pairs of Tn5/IS50 bound transposase protomers, was deduced by analyzing all insertion sites. The consensus Tn5/IS50 target site is A-GNTYWRANC-T. However, we observed that independent insertion sites tend to form groups of closely located insertions (clusters), and insertions very often were spaced in a 5-bp periodic fashion. This suggests that Tn5/IS50 target selection is facilitated by more than two transposase protomers binding to the DNA, and, thus, for a site to be a good target, the overlapping neighboring DNA should be a good target, too. Synthetic target sequences were designed and used to test and confirm this model.

Amino Acid Sequence↗
PubMed1998

Association of malondialdehyde-acetaldehyde (MAA) adducted proteins with atherosclerotic-induced vascular inflammatory injury.

Atherosclerosis is a vascular injury characterized by elevated tissue levels of tumor necrosis factor-alpha (TNF-alpha), increased expression of endothelial cell adhesion molecules, and vascular wall inflammatory cell infiltration. Foam cells are associated with atherosclerotic plaque material, and low density lipoprotein (LDL) is a lipid component of foam cells. Malondialdehyde (MDA) is an oxidative product of unsaturated fatty acids and is also present in atherosclerotic lesions. MDA-modified (adducted) proteins, including MDA-modified LDL, are present in atherosclerotic human vascular tissue. Acetaldehyde (AA) is the major metabolic product of ethanol oxidation. Both MDA and AA are highly reactive aldehydes and will combine with proteins to produce an antigenically distinct protein adduct, termed the MAA adduct. This study demonstrates that proteins modified in the presence of high concentrations of MDA can produce MAA-modified proteins in vitro. In addition, MAA adducted proteins are capable of inducing rat heart endothelial cell cultures (rHEC) to produce and release TNF-alpha, and cause rHEC upregulation of endothelial adhesion molecule expression, including ICAM-1. These adhesion molecules are required for circulating inflammatory cells to adhere to endothelium which allows inflammatory cell tissue infiltration. Additionally, MAA modified proteins were defected in human atherosclerotic aortic vascular tissue but not in normal aortic tissue. Since atherosclerosis is associated with an inflammatory vascular injury characterized by elevated tissue TNF-alpha concentrations and inflammatory cell infiltration, these data suggest that MAA-adducted proteins may be formed in atherosclerotic plaque material and may be involved in the inflammatory reaction that occurs in atherosclerosis. These data further suggest that previous studies demonstrating MDA modified protein in atherosclerotic plaque may in fact have MAA modified proteins associated with them.

Acetaldehyde↗
PubMed1998

Locomotor advantages of Neandertal skeletal morphology at the knee and ankle.

We quantified Neandertal knee extensor and ankle plantarflexor moments to determine whether differences between Neandertal and recent human skeletal morphology represent important functional differences. Neandertal skeletal differences in the patella, tibial tuberosity, and calcaneus were used to modify a computer model of recent humans to calculate the moment arms and moments of Neandertal knee extensor and ankle plantarflexor muscles. We also conducted sensitivity studies on the effect of musculotendon parameters on the Neandertal moments. As expected, we found that Neandertal moment arms were greater than recent humans at the ankle (122-141%); however, the magnitude of the increase was not well-predicted from measurements of size differences between Neandertal and recent human skeletons. At the knee, Neandertal moment arms were greater than those of recent humans in the locomotor range (108%) but less so at more flexed knee angles (102%). Not all Neandertal skeletal adaptations at the knee contributed to increased moment arm. Knee extensor moments were enhanced in the Neandertal models in the locomotor range (111%), regardless of musculotendon parameters. At the ankle, however, Neandertal plantarflexor moment was greater than that of recent humans (149-200%) at all joint angles only if muscle fiber length increased proportionately with moment arm. Our results demonstrate that Neandertal skeletal morphology, compared to that of recent humans, generated greater moments at both the knee and ankle in the locomotor range but not at higher angles of knee flexion or ankle plantarflexion.

Animals↗
PubMed1998

Inhibition of vinyl carbamate-induced hepatotoxicity, mutagenicity, and tumorigenicity by isopropyl-2-(1,3-dithietane-2-ylidene)-2-[N-(4-methylthiazol-2- yl)carbamoyl]acetate (YH439).

Isopropyl-2-(1,3-dithietane-2-ylidene)-2-[N-(4-methylthiazol -2-yl)carbamoyl]acetate (YH439) is a novel dithioylidene malonate derivative developed for the treatment of hepatic injury. The compound has been found to down-regulate the expression of hepatic cytochrome P-450 2E1 (CYP2E1) at the transcriptional level (8). Certain organosulfur compounds present in garlic elicit protective effects on chemically induced carcinogenesis and mutagenesis and their chemopreventive activities are associated in part with inhibition of CYP2E1. As part of a program to determine the likely chemopreventive potential of YH439, we initially examined its effects on hepatotoxicity induced by vinyl carbamate (VC), a proximate carcinogen that is preferentially bioactivated by CYP2E1. A single i.p. injection of VC (125 mg/kg body wt) to male Sprague-Dawley rats resulted in severe hepatic lesions as demonstrated by elevated levels of serum enzymes such as alanine aminotransferase and aspartate aminotransferase. Histopathological evaluation of liver sections from VC-treated animals revealed that the hepatic damage mainly consisted of centrilobular necrosis with sinusoidal congestion. Oral administration of YH439 (200 mg/kg body wt) to male Sprague-Dawley rats 2 days, 1 day and 4 h prior to VC completely prevented the hepatic damage caused by this carcinogen. In another experiment, rat hepatic microsome-mediated bacterial mutagenicity of VC was suppressed by YH439 in a dose-related manner. Furthermore, pretreatment of female CD-1 mice with YH439 by gastric intubation resulted in diminution of VC-induced skin carcinogenesis.

Animals↗
PubMed1998

Chemopreventive effects of 2-(allylthio)pyrazine on hepatic lesion, mutagenesis and tumorigenesis induced by vinyl carbamate or vinyl carbamate epoxide.

2-(Allylthio)pyrazine (2-AP), synthesized for its possible use as a hepatoprotective agent, has been found to selectively inhibit rat hepatic cytochrome P450 2E1 (Kim et al., Biochem. Pharmacol., 53, 261-269, 1997), while it enhances the activities of phase II detoxification enzymes such as glutathione S-transferase and epoxide hydrolase. As part of a program in evaluating the chemopreventive potential of 2-AP, we have determined its effects on hepatotoxicity, mutagenicity and tumorigenicity of vinyl carbamate (VC), a prototypic hepatocarcinogen preferentially activated by P450 2E1 to the ultimate carcinogenic metabolite vinyl carbamate epoxide (VCO), which undergoes detoxification by glutathione conjugation and oxirane hydrolysis. Administration of 2-AP (100 mg/kg body wt) to male Sprague-Dawley rats by gavage, 2 days, 1 day and 4 h prior to VC or VCO, markedly ameliorated the hepatotoxicity of these compounds as determined by decreased serum aspartate aminotransferase and alanine aminotransferase activities. Furthermore, 2-AP pre-treatment significantly suppressed the VC-induced hepatocarcinogenesis in infant male B6C3F1 mice. In a separate experiment, the multiplicities of skin tumors formed in female ICR mice treated with 5.8 micromol of VC or VCO were inhibited 58 and 70%, respectively, by pre-treatment with 2-AP by oral administration. The mutational spectrum of ras-oncogene in papillomas was not altered by 2-AP pre-treatment. 2-AP also inhibited the mutagenicity of VC in the Salmonella-microsome assay. Taken together, these findings suggest that 2-AP is a potential chemopreventive agent.

Animals↗
PubMed1998

Delivery of ivermectin by injectable microspheres.

A bioabsorbable, injectable microsphere formulation containing ivermectin in poly-(lactide-co-glycolide) copolymer (PLA/PGA) was developed to provide long-lasting delivery of the drug for control of livestock pests. A solvent-evaporation technique was used to produce the spherical beads containing approximately 30% ivermectin and ranging in size from 25-250 microns. The pattern of delivery of the drug into the blood stream of Spanish goats was characterized for a 50:50 PLA/PGA, a 90:10 PLA/PGA copolymer formulation, and a PLA monomer formulation. When the 50:50 PLA/PGA formulation was used in cattle at the rate of 2 mg (AI)/kg body weight, 2 peaks of 45-50 ppb of ivermectin in serum were observed. The 1st peak was at approximately 1 wk after injection and the 2nd peak, which was broader than the 1st, occurred at approximately 6-7 wk after injection. Percentage of inhibition of estimated larvae for the lone star tick, Amblyomma americanum (L.), placed on treated cattle was 100% for the first 8 wk after injection and was 75, 57, 46 and 44% for wk 9, 10, 11, and 12, respectively. The treatment provided 98-100% control of larval horn flies, Haematobia irritans (L.), in the manure of treated cattle for 10 wk. The bioassay results against lone star ticks and larval horn flies were in agreement with the serum concentration data. The injectable microsphere formulation of ivermectin should be useful in a variety of other applications ranging from the control of Boophilus spp. ticks in south Texas to heartworms in pets.

Animals↗
PubMed1998

Predicting the rates of success and complications of computed tomography-guided percutaneous core-needle biopsies of the thorax from the findings of the preprocedure chest computed tomography scan.

The authors attempted to determine whether the anatomic characteristics of thoracic lesions and the surrounding lung field, as assessed by the preprocedure chest computed tomography (CT) scan, can assist in predicting the yield of complications or positive results of pathologic examination resulting from percutaneous core-needle biopsies (PCNB). The pathologic diagnoses and procedural complications of 50 consecutive thoracic PCNBs (43 men, age range 19-81 years) performed under the guidance of a single operator (J.A.M.) were recorded. Prebiopsy chest CT findings, including the size, depth, location, and border appearance of the lesion, as well as presence or absence of adjacent emphysema, interstitial fibrosis, bullae, pleural effusions, and the age and smoking history of the patient were correlated with the biopsy results and any ensuing complications. The pathologic analysis in 42 patients (84%) was specific enough to positively impact patient management, with 29 malignant and 13 benign entities. The imaging variables that predicted obtaining adequate tissue for pathologic diagnosis were most importantly large size (especially >35 mm), although irregular lesion margins and increased depth were significant as well. Seven patients (14%) experienced a pneumothorax, only one of which (2%) was symptomatic and required thoracostomy. All patients experiencing a pneumothorax had CT evidence of emphysema or interstitial fibrosis and all biopsied masses in these individuals had spiculated borders, with six (86%) in an anterior location and only one involving the pleural surface. We conclude that the preprocedure CT scan can delineate several characteristics of both the patient and the lesion to be biopsied that can assist in predicting the rates of successful tissue retrieval or pneumothorax during PCNBs.

Adult↗
PubMed1998

Benign fat necrosis simulating bilateral breast malignancy after reduction mammoplasty.

Fat necrosis follows many forms of trauma to the breast, including surgery. In unusual cases, it may be extensive enough to present as a palpable mass on physical examination with mammographic features suggestive of cancer. In these instances, regardless of patient age, surgical history, or multifocality, a biopsy must be done to exclude carcinoma. We describe a young woman who was evaluated for bilateral breast masses with highly suspicious imaging characteristics 2 years after having reduction mammoplasty.

Adult↗
PubMed1998

Factors related to family therapists' breaking confidence when clients disclose high-risks-to-HIV/AIDS sexual behaviors.

This national survey of 309 marriage and family therapists examined what therapists do when their HIV-positive clients disclose that they are engaging in high-risk sexual behavior. The participants were given vignettes in which a fictitious client told the therapist about engaging in unprotected sex. Although the basic situations were the same, the client variables of age, gender, race, sexual orientation, and HIV status were systematically varied. The participants were more likely to break confidence regarding unsafe sex practices when their clients were male, young, gay, or African American. Moreover, therapists who were more likely to disclose were older, female, had less experience with gay/lesbian populations, were Catholic, were very religious, and were more likely to practice in urban areas. The authors discuss the implications of these and other findings.

Adult↗