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Biomedical subjects

J D Wagner

Publications and source records attributed to J D Wagner.

At least 73 records · Page 4Linked to original sources
PubMed1996

Effects of 17 alpha-dihydroequilenin sulfate on atherosclerotic male and female rhesus monkeys.

OBJECTIVES: Our purpose was to determine the effects of 17 alpha-dihydroequilenin on plasma lipid and lipoprotein, glucose, and insulin concentrations; coronary artery vasomotor function; and reproductive organ and mammary gland proliferation in atherosclerotic male and female rhesus macaques. STUDY DESIGN: Fifty adult female and 33 adult male rhesus macaques were randomized to treatment by lifetime dietary cholesterol exposure and ratio of total plasma cholesterol to high-density lipoprotein cholesterol. The female treatment groups were intact female controls (n = 9), ovariectomized controls (n = 16), ovariectomized plus 0.3 mg/kg/day 17 alpha-dihydroequilenin (n = 17) and ovariectomized plus subcutaneous estradiol (n = 7). The male treatment groups were control (n = 16) and 1.25 mg/kg/day 17 alpha-dihydroequilenin (n = 17). Treatment lasted 5 weeks. Longitudinal assessments of plasma lipid and lipoprotein and glucose and insulin concentrations were performed. Coronary artery vasomotor function was assessed by quantitative coronary angiography 1 week after initiation of treatment. Morphologic and immunohistochemical assessments of proliferation index values of reproductive organs and mammary glands were done at necropsy. RESULTS: 17 alpha-Dihydroequilenin prevented endothelium-dependent vasoconstriction in males (p < 0.05) and ovariectomized females (p < 0.08). 17 alpha-Dihydroequilenin treatment increased plasma apolipoprotein A-1 concentrations (p < 0.05) and lowered fasting insulin concentrations (p < 0.05) without changing fasting plasma glucose concentrations in males. 17 alpha-Dihydroequilenin had no other effects on plasma lipid and lipoprotein concentrations in either males or females. It had no trophic effects on uterus, endometrium, or breast. There was no effect on either prostatic or testicular weight. CONCLUSION: 17 alpha-Dihydroequilenin may represent a single-agent hormone therapy for reduction of ischemic hear disease risk for both menopausal women and men. It has no apparent trophic effects on reproductive organs or mammary glands of female and male rhesus macaques.

Animals↗
PubMed1996

Repair of midline vertical lower lip deficiency after mandible reconstruction.

BACKGROUND: When lower lip incisions are combined with anterior oromandibular resection and composite flap reconstruction, increased potential exists for abnormal healing of the lower lip. The aim of this study is to describe these deformities and operative techniques for their correction. METHODS: A retrospective review of all patients undergoing oromandibular reconstruction with osteocutaneous free tissue transfer at Indiana University Medical Center and Affiliated Hospitals during the 5-year period between January 1991 and 1996 was performed. Patients requiring secondary lower lip revision or repair were identified. Patient characteristics, lip deformities, and operative correction techniques were detailed. RESULTS: Sixty patients underwent 62 free tissue transfers for oromandibular reconstructions. Five patients (7.1%) required reoperation for lower lip deformities related to abnormal wound healing. All affected patients had lower lip split incisions for access to the oropharynx and composite anterior floor of mouth and mandibular resection and reconstruction. Each patient had successful repair of the lower lip deformity and correction of related functional deficits using lower lip tissue. CONCLUSION: Lower lip deformities occur in a subset of patients undergoing anterior mandibular reconstruction. Horizontally redundant lower lip tissue can be mobilized to repair the secondary aesthetic and functional deficits.

Humans↗
PubMed1996

The effects of hormone replacement therapy on carbohydrate metabolism and cardiovascular risk factors in surgically postmenopausal cynomolgus monkeys.

Controversy exists regarding the effects of estrogen and estrogen/progestin replacement therapies on glucose tolerance and insulin resistance. Also unknown are whether changes in glucose tolerance and insulin resistance with hormone therapy affect arterial glycation and atherosclerosis. We studied ovariectomized female monkeys fed a lipid-lowering diet and given either no hormone replacement therapy (n = 25) or conjugated equine estrogens (CEE) alone (n = 22) or combined with medroxyprogesterone acetate ([MPA] n = 21) for 30 months. Monkeys receiving combined hormone replacement had significantly higher fasting glucose and insulin levels and higher insulin responses to a glucose challenge compared with controls or those given estrogen alone. Monkeys given estrogen-only therapy had lower body weights, lower measures of abdominal adiposity, and decreased serum androgen concentrations. However, due to the effective dietary lipid decrease, there was no additional effect of hormone treatment on atherosclerosis. Also, there was no correlation between either arterial glycation or insulin levels and atherosclerosis extent. Thus, although there were adverse effects of combined hormone replacement therapy on carbohydrate metabolism, we were unable to determine whether these effects altered the extent of atherosclerosis.

Adipose Tissue↗
PubMed1996

Wegener's granulomatosis followed by development of sarcoidosis.

Although both Wegener's granulomatosis and sarcoidosis are considered granulomatous disorders, their clinical courses differ markedly, and typically patients with these two diseases are readily distinguishable. We report an unusual case in which the patient presented with a systemic vasculitis consistent with Wegener's granulomatosis that remitted with therapy and then, months later, developed sarcoidosis. This is the first case report of the sequential development of the two diseases. We review the relationship of vasculitis to sarcoidosis and speculate on the etiopathogenesis that might link the two.

Adult↗
PubMed1996

Histoplasma capsulatum necrotizing myofascitis of the upper extremity.

Necrotizing myofascial fungal infections of the upper extremity is a rare event even in immunocompromised hosts. We report the course of a renal transplant patient who developed extensive necrotizing myofascial infection of an upper extremity secondary to Histoplasma capsulatum. Initial, functional, upper limb salvage was achieved after aggressive surgical debridement and high doses of amphotericin B. The patient ultimately succumbed to systemic fungal sepsis. The etiology and treatment of these infections are discussed.

Amphotericin B↗
PubMed1996

Extraction of nuclei from sonchus yellow net rhabdovirus-infected plants yields a polymerase that synthesizes viral mRNAs and polyadenylated plus-strand leader RNA.

Although the primary sequence of the genome of the plant rhabdovirus sonchus yellow net virus (SYNV) has been determined, little is known about the composition of the viral polymerase or the mechanics of viral transcription and replication. In this paper, we report the partial isolation and characterization of an active SYNV polymerase from nuclei of SYNV-infected leaf tissue. A salt extraction procedure is shown to be an effective purification step for recovery of the polymerase from the nuclei. Full-length, polyadenylated SYNV N and M2 mRNAs and plus-strand leader RNA are among the products of the in vitro polymerase reactions. Polyadenylation of the plus-strand leader RNA in vitro is shown with RNase H and specific oligonucleotides. This is the first report of a polyadenylated plus-strand leader RNA for a minus-strand RNA virus, a feature that may reflect adaptation of SYNV to replication in the nucleus. Analysis of the SYNV proteins present in the polymerase extract suggests that the N, M2, and L proteins are components of the transcription complex. Overall, the system we developed promises to be useful for an in-depth characterization of the mechanics of SYNV RNA synthesis.

Base Sequence↗
PubMed1996

Esterified estrogens with and without methyltestosterone decrease arterial LDL metabolism in cynomolgus monkeys.

Although both epidemiological and experimental evidence suggests that estrogen replacement therapy reduces the risk of coronary heart disease, the mechanisms for this beneficial effect are largely unknown. Furthermore, the addition of progestins or androgens to estrogen replacement therapy is of concern. The objective of this study was to examine the effects of esterified estrogens alone or in combination with an androgen on arterial LDL metabolism and early atherogenesis in ovariectomized female cynomolgus monkeys. Arterial LDL metabolism was assessed by using dual-labeled LDL that was injected 24 hours before necropsy. Arterial LDL degradation was reduced by 64% to 84% and cholesteryl ester content was decreased by approximately 50% in the thoracic aorta in both treatment groups compared with controls. In addition, aortic lipid peroxidation products, as assessed by thiobarbituric acid reaction, were significantly lower in animals treated with esterified estrogens, with a similar trend for combined estrogen-androgen treatment. Both treatments also reduced plasma concentrations of apoB-containing lipoproteins, reduced LDL particle size, and increased total-body LDL catabolism. The combination of decreased arterial LDL metabolism, decreased arterial lipid peroxidation, and improved plasma lipoprotein metabolism may explain some of the protective effects of estrogens on coronary heart disease and indicate that beneficial actions extend to a combination of estrogen and androgen.

Animals↗
PubMed1996

Islet amyloid and islet amyloid polypeptide in cynomolgus macaques (Macaca fascicularis): an animal model of human non-insulin-dependent diabetes mellitus.

To further characterize spontaneous diabetes mellitus in cynomolgus macaques (Macaca fascicularis) as a model for human non-insulin-dependent diabetes mellitus (NIDDM), we evaluated the morphologic characteristics of the endocrine pancreas of 4 diabetic and 12 age-matched nondiabetic cynomolgus macaques. In addition, the cDNA-predicted amino acid sequence for islet amyloid polypeptide (IAPP) of this species was determined. Islet amyloid deposits exhibiting typical congophilia and green birefringence were found in 4/4 diabetic animals and in 8/12 nondiabetics. Islet amyloid deposits were significantly more extensive in the diabetic macaques (P = 0.001), in which they occupied a mean of 60% of the islet area. In contrast, in the nondiabetic group the maximum islet area occupied by amyloid was 24% (group mean = 6.8%), with four animals having no detectable islet amyloid. Amyloid deposits consistently showed immunoreactivity for IAPP but not for insulin. Comparisons between group means for diabetic versus nondiabetic macaques showed significantly greater islet area (P = 0.01, 85,390 versus 36,540 microns 2) and significantly greater islet area fraction (P = 0.02, 0.065 versus 0.032) for the diabetic group. The cDNA-predicted amino acid sequence for cynomolgus IAPP was identical to that previously reported for pig-tail macaques (M. nemestrina) and had 92%, 86%, and 84% amino acid sequence identity with human, domestic cat, and murine IAPPs, respectively. These findings support the use of cynomolgus macaques as an animal model of human NIDDM.

Amino Acid Sequence↗
PubMed1996

Increased glycation of plasma lipoproteins in diabetic cynomolgus monkeys.

Hyperglycemia associated with diabetes mellitus increases glycation of hemoglobin and serum proteins in human and nonhuman primates. It also has been documented that numerous other circulating proteins may be glycated. In this study we found that most of the major subclasses of lipoproteins (low-density, very low-density, and high-density) from diabetic cynomolgus monkeys were significantly more glycated than were lipoproteins from age- and sex-matched controls. Correlations between levels of glycemic control and glycation of lipoproteins also were significant. Because glycation of lipoproteins has been shown to affect their normal metabolism, this animal model may be useful in determining the interaction between lipoproteins, diabetes mellitus, and the increased risk of atherosclerosis.

Animals↗
PubMed1996

Diabetes mellitus and islet amyloidosis in cynomolgus monkeys.

Six 15- to 20-year-old obese cynomolgus monkeys were determined to have diabetes mellitus. These monkeys were hyperglycemic and hypertriglyceridemic, yet remained nonketotic for several years before requiring clinical intervention. A significant decrease in glucose disappearance and an increased area under the glucose disappearance curve were found in response to intravenous glucose tolerance testing. Basal hyperinsulinemia was found in three animals that, in response to glucose stimulation, had a blunted insulin response, resulting in an overall decrease in the area under the insulin curve. Two animals died during the study and had extensive amyloid infiltration of pancreatic islets. The combined findings of old age, obesity, hyperinsulinemia, improvement in response to caloric restriction, and islet amyloidosis are consistent with type 2 diabetes mellitus.

Adipose Tissue↗
PubMed1995

Critical analysis of results of craniofacial surgery for nonsyndromic bicoronal synostosis.

We retrospectively assessed the intermediate and long-term results of craniofacial surgery in 22 consecutive patients with nonsyndromic bicoronal synostosis to determine the outcome of corrective surgery. The study population consisted of 13 males and 9 females whose ages ranged from 6 weeks to 24 months (mean, 5.6 months) at the time of initial surgery. All patients had been assigned a diagnosis of nonsyndromic bicoronal synostosis. Each patient underwent resection of both coronal sutures and frontal orbital advancement with cranial vault remodeling using a floating forehead technique. Age at initial operation was 5 months or less in 13 patients and 6 months or more in 9. Complications occurred in 5 patients (23%), and 1 patient with an associated metabolic disorder died from respiratory arrest postoperatively. Follow-up ranged from 6 to 168 months (mean, 53.2 months). Results were graded according to the need for and extent of reoperation. Residual aesthetic deformities were documented in 12 patients (55%). Three patients (14%) required calvarial recontouring or cranioplasty to achieve satisfactory forehead contour or bony continuity. Total reoperation for recurrent deformity was required at a mean age of 29.7 months in 8 patients (36%) and is pending in another (4%). Four patients (18%) required a third operation (two total reoperations and two cranioplasties) to achieve satisfactory results. Eight of 13 patients (62%) operated on at 5 months of age or younger required total reoperation compared with 1 of 9 (11%) operated at 6 months of age or older. When analyzed alone, age of operation was a statistically significant determinant of the need for reoperation (p < 0.03). However, when subjected to multivariate analysis, neither age at operation nor the presence of an associated anomaly or positive family history had a significant effect on outcome.

Age Factors↗
PubMed1995

Matrix modulates uptake of calcium oxalate crystals and cell growth of renal epithelial cells.

Handling of urinary crystals by renal epithelial and medullary interstitial cells may play an important role in the pathogenesis of renal stones and associated renal scarring. We examined the effects of calcium oxalate monohydrate (CaOM) crystals on the proliferative activity of renal tubular cells (opossum kidney) and renal medullary interstitial cells in culture. We also studied the impact of altered extracellular matrix on cell proliferation as well as on uptake of crystals by epithelial cells. Epithelial cells incubated with CaOM showed greater (p < 0.05) growth when compared with untreated cells (control, 10.5 +/- 1.1 versus CaOM, 16.6 +/- 1.6 x 10(6) cells per dish). the CaOM crystal-cell interaction also enhanced proliferation of interstitial cells (at 48 hours, control, 3.3 +/- 0.2 versus CaOM, 4.2 +/- 0.1 x 10(6) cells per dish, p < 0.02; at 72 hours, control, 3.6 +/- 0.3 versus 5.5 +/- 0.4 x 10(6) cells per dish, p < 0.01). Collagen, a constituent of extracellular matrix, inhibited (p < 0.01) proliferation of epithelial cells. Semiconfluent epithelial cells grown on collagen gels showed greater (p < 0.01) uptake of 45CaOM crystals when compared with uptake by cells grown on either uncoated (control) or albumin-coated plastic dishes (control, 979.9 +/- 51.1, albumin, 876.4 +/- 28.3, collagen gel, 1502.5 +/- 103.8 cpm per well). Epithelial cells grown to confluence on collagen gels also showed enhanced (p < 0.05) uptake of 45CaOM crystals. Reflectance microscopy as well as ultrastructural studies revealed intracellular localization of CaOM crystals. These results indicate that CaOM crystals stimulate the growth of both epithelial and interstitial cells. Enhanced growth of interstitial cells may also lead to increased synthesis of extracellular matrix. The latter may further modulate crystal uptake as well as cell growth of adjacent epithelial cells. These findings may be important in the development of nephrolithiasis and associated interstitial scarring.

Animals↗
PubMed1995

What is known about the health of rural homeless families?

Families represent the fastest-growing subgroup of the homeless population. Most of the research has focused on urban homeless families and not on rural homeless families. The purpose of this study was to describe the characteristics and health of rural homeless families in Ohio. A descriptive cross-sectional design was used to study 76 families who had 125 children under 12 years of age. An interview schedule, the Denver Developmental Screening Test (DDST), the Child Behavior Checklist (CBCL), and the SCL-90-R were used to collect data. The majority of the mothers perceived themselves and their children as having no physical health problems. Twenty-four of the children were behind on their immunizations. Forty-four (52%) of the children under 6 years of age had DDST scores that indicated they might have developmental lags and 15 of the children over 4 years of age had CBCL scores that indicated they might have behavioral problems. The reported use of illegal drugs, alcohol, and cigarettes was high for this group of mothers. Strategies are included that nurses can use in working with rural homeless families.

Adolescent↗
PubMed1995

Effect of time of day of dialysis shift on serum biochemical parameters in patients on chronic hemodialysis.

It is unknown whether predialysis serum biochemical parameters may differ among chronic hemodialysis patients depending on the shift during which they are dialyzed. We studied 115 patients on chronic hemodialysis in our institution for 3 consecutive months and compared clinical and biochemical parameters based on the shift during which they were dialyzed. Predialysis serum potassium was found to be progressively higher for patients dialyzed on later as compared with earlier dialysis shifts, and phosphate was significantly higher for patients dialyzed during the evening shift as well. Regression analysis suggested that higher of potassium and phosphate levels were related to the time of day these sessions and not to patient age, amount of dialysis given or diet. By contrast, serum albumin, creatinine, sodium, and chloride levels were found to differ depending on dialysis shift, though these differences appeared to be accounted for by patient age. We concluded that the time of day of the beginning of the dialysis shift appears to mildly influence the levels of serum predialysis biochemical parameters which are important in monitoring patients on chronic hemodialysis, in particular potassium and phosphate. Further insight into the mechanism of this observed effect might improve our ability to interpret and treat derangements of these serum biochemical parameters in patients on chronic hemodialysis.

Case-Control Studies↗
PubMed1995

Accelerated cholesteryl ester transfer and altered lipoprotein composition in diabetic cynomolgus monkeys.

To determine whether nonhuman primates demonstrate the same alterations in transport of cholesteryl ester (CE) in plasma observed in diabetic humans, cholesteryl ester transfer (CET) was measured in cynomolgus monkeys with chronic spontaneous diabetes mellitus (glycated hemoglobin: diabetics 10.7 +/- 4.1%; controls 3.8 +/- 0.8%, P < 0.005). Among the plasma lipids, only triglycerides were significantly increased in diabetic monkeys (diabetics 303 +/- 294 mg/dl; controls 85 +/- 34 mg/dl; P < 0.05); total plasma, LDL, HDL2, and HDL3 cholesterol concentrations did not differ significantly from those of control animals. Similar to human beings with insulin-dependent and non-insulin-dependent diabetes mellitus, CET estimated both as the mass of cholesteryl ester transferred from HDL to the apoB-containing lipoproteins (VLDL + LDL) and as the loss of radiolabeled cholesteryl ester from HDL was significantly greater (P < 0.001) in diabetic compared to control monkeys. Glycated hemoglobin levels in the combined control and diabetic groups correlated directly with both the mass of cholesteryl ester transferred at 2 h (r = 0.75; P < 0.001) and the isotopic transfer (k) (r = 0.64; P < 0.005). The mass of cholesteryl ester transfer protein (CETP) tended to be higher in the diabetic animals (diabetic 4.06 +/- 0.73 microgram/ml versus control 3.05 +/- 0.93; P < 0.1).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Hemodialyzability of sertraline.

Sertraline is an antidepressant which selectively inhibits the neuronal uptake of serotonin in the central nervous system. The pharmacokinetics of sertraline in end-stage renal disease (ESRD) and the effect of hemodialysis on sertraline clearance is unknown. A dose of 100 mg sertraline was administered to two anuric hemodialysis patients after hemodialysis. During the next hemodialysis session, simultaneous pre- and post dialyzer blood samples were obtained at the start of and hourly throughout dialysis until completion. All spent dialysate was collected hourly, quantified and an aliquot retained. Additional blood samples were obtained approximately 20 hours after dialysis and prior to the next treatment. Serum and dialysate were assayed for sertraline by gas chromatography-mass spectroscopy. Initial sertraline serum concentrations were similar to those observed in subjects with normal renal function given the same sertraline dose, implying unaltered absorption and distribution. Sertraline was not detected in any dialysate sample. The elimination half-life was 42-92 h (normally 24-36 h), suggesting impaired clearance. Smaller doses of sertraline may be required in ESRD patients, yet post-hemodialysis supplementation is unnecessary.

1-Naphthylamine↗
PubMed1994

Sequence analysis of the trailer region of sonchus yellow net virus genomic RNA.

The sequence of the 5' terminus (or the "trailer" region) of the minus-sense RNA genome of sonchus yellow net virus (SYNV) was determined by dideoxynucleotide termination sequencing of purified viral RNA and cloned cDNAs. The 5'-terminal nucleotide was identified by nuclease P1 digestion of 32P-end-labeled genomic RNA followed by polyethyleneimine cellulose chromatography. The trailer sequence occupies positions 13,561 to 13,720 relative to the 3' end of the genomic RNA and is composed of 160 nucleotides (nt) adjacent to a dinucleotide forming a portion of the "gene junction" sequence at the terminus of the L protein gene. The trailer sequence is longer than the 144-nt plus-strand leader RNA transcribed from the 3' end of the genomic RNA and is the longest trailer sequence yet reported among the nonsegmented negative-strand viruses. As is characteristic of other rhabdovirus genomes, the 3' and 5' termini of the SYNV genome are complementary and are capable of forming a panhandle structure involving 16 of the 18 terminal nucleotides. However, there is no obvious direct nucleotide sequence relatedness between the SYNV trailer sequence and those of animal rhabdoviruses and paramyxoviruses. The existence of a minus-strand leader RNA of the same polarity as the trailer sequence could not be detected in nucleic acid extracted from infected plants under hybridization conditions suitable for detection of the plus-strand leader RNA. In this regard, SYNV differs from vesicular stomatitis virus and is similar to other rhabdoviruses which also fail to accumulate detectable minus-strand leader RNAs.

Base Sequence↗