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Biomedical subjects

M D Anderson

Publications and source records attributed to M D Anderson.

At least 19 recordsLinked to original sources

Comparison of two assay methods for activities of uroporphyrinogen decarboxylase and coproporphyrinogen oxidase.

Uroporphyrinogen decarboxylase (UROD) and coproporphyrinogen oxidase (copro'gen oxidase) are two of the least well understood enzymes in the heme biosynthetic pathway. In the fifth step of the pathway, UROD converts uroporphyrinogen III to coproporphyrinogen III by the decarboxylation of the four acetic acid side chains. Copro'gen oxidase then converts coproporphyrinogen III to protoporphyrinogen IX via two sequential oxidative decarboxylations. Studies of these two enzymes are important to increase our understanding of their mechanisms. Assay comparisons of UROD and copro'gen oxidase from chicken blood hemolysates (CBH), using a newly developed micro-assay, showed that the specific activity of both enzymes is increased in the micro-assay relative to the large-scale assay. The micro-assay has distinct advantages in terms of cost, labor intensity, amount of enzyme required, and sensitivity.

Animals↗

Using QuickTime virtual reality objects in computer-assisted instruction of gross anatomy: Yorick--the VR Skull.

QuickTime virtual reality (QTVR) is a software technology that creates, on a normal computer screen, the illusion of holding and turning a three-dimensional object. QTVR is a practical photo-realistic virtual reality technology that is easily implemented on any current personal computer or via the Internet with no special hardware requirements. Because of its ability to present dynamic photo-quality images, we reasoned that QTVR can provide a more realistic presentation of anatomic structure than two-dimensional atlas pictures and facilitate study of specimens outside the dissection lab. We created QTVR objects, using portions of the skull, and incorporated them into an instructional program for first-year medical students. To obtain images, the bones of the skull were mounted on a rotating table, and a digital camera was positioned on a swinging arm so that the focal point remained coincident with the rotational center of the object as the camera was panned through a vertical arc. Digital images were captured at intervals of 10 degrees rotation of the object (horizontal pan). The camera was then swung through an arc with additional horizontal pan sequences taken at 10 degrees intervals of vertical pan. The images were edited to place the object on a solid black background, then assembled into a linear QuickTime movie. The linear movie was processed to yield a QTVR object movie that can be manipulated on vertical and horizontal axes using the mouse. QTVR movies were incorporated into an interactive environment that provided labeling, links to text-based information and self-testing capabilities. This program, Yorick-the VR Skull, has been used in our first-year medical and graduate gross anatomy courses for the past two years. Results of student evaluation of the program indicate that this QTVR-based program is an effective learning tool that is well received by students.

Anatomy↗

Effect of androgen administration during puberty on hepatic CYP2C11, CYP3A, and CYP2A1 expression in adult female rats.

This biochemical and pharmacokinetic investigation was undertaken to evaluate the effects of androgen administration during puberty on sex-dependent cytochrome P450 (CYP or P450) enzyme expression in adult female rats. Hepatic testosterone 2alpha-hydroxylase activity and CYP2C11 and CYP3A protein levels were elevated in prepubertally ovariectomized rats injected subcutaneously with testosterone enanthate at 35-49 days of age and killed 41 days after discontinuation of treatment. In contrast, testosterone 6beta- and 7alpha-hydroxylase activities and CYP2A1 protein content were not affected. The increase in CYP2C11 and CYP3A was likely not due to circulating testosterone because plasma testosterone was undetectable. The calculated elimination half-life was 51 +/- 6 hr (mean +/- SE) after testosterone enanthate administration. By 80 days after treatment, CYP2C11 and CYP3A levels were no longer increased. To determine if CYP2C11 expression was responsive to a more periodic pattern of androgen release, ovariectomized rats were injected subcutaneously once or twice daily with unesterified testosterone (elimination half-life was 2.0 +/- 0.3 hr, mean +/- SE). Once- or twice-daily dosing (5 or 2.5 micromol/kg/injection, respectively) during days 35-49 of age did not increase the mean CYP2C11 expression in 90-day-old female rats, although testosterone 2alpha-hydroxylase activity and CYP2C11 protein content were elevated in three of the eight rats injected twice daily. Neither dosing regimen increased CYP3A or decreased CYP2A1 expression. In summary, the results indicate that treatment with testosterone enanthate during puberty resulted in a prolonged but reversible increase in hepatic expression of CYP2C11 and CYP3A.

Animals↗

Effect of ovariectomy and androgen on phenobarbital induction of hepatic CYP2B1 and CYP2B2 in Sprague-Dawley rats.

The purpose of this study was to investigate the impact of prepubertal ovariectomy and postpubertal administration of testosterone on inducibility of rat hepatic CYP2B1 and CYP2B2 by phenobarbital. Intact adult male and female Sprague-Dawley rats were injected ip with sodium phenobarbital (10 mg/kg) or saline (control) once daily on days 129-135 of age and sacrificed one day after the last dose. Hepatic microsomal androstenedione 16beta-hydroxylase activity, benzyloxyresorufin O-dealkylase activity, pentoxyresorufin O-dealkylase activity, and CYP2B1 protein levels were lower in phenobarbital-treated female rats than in phenobarbital-treated male rats. In contrast, there was no sex difference in inducibility of CYP2B2. The lesser inducibility of CYP2B1 in adult female rats was attributed to the presence of an intact ovary because prepubertal ovariectomy (day 25 of age) resulted in increased induction of CYP2B1 and its associated activities (androstenedione 16beta-hydroxylase, benzyloxyresorufin O-dealkylase and pentoxyresorufin O-dealkylase) by phenobarbital. By comparison, postpubertal administration of testosterone enanthate (5 micromol/kg sc once daily on days 80-94 of age) did not enhance the inducibility of CYP2B1 or its associated activities in prepubertally ovariectomized adult (136-day-old) rats administered phenobarbital (10 mg/kg/day on days 129-135 of age). However, the androgen treatment did increase CYP2C11-dependent testosterone 2alpha-hydroxylase activity in the same microsomal samples. Overall, the results show a sex difference in phenobarbital induction of hepatic CYP2B1 but not CYP2B2 in adult Sprague-Dawley rats. They also indicate that prepubertal ovariectomy enhances the effect of phenobarbital on CYP2B1, whereas administration of testosterone enanthate postpubertally does not influence the inducibility of either CYP2B1 or CYP2B2 in prepubertally ovariectomized adult rats.

Animals↗

CPOM: alleviating the demand for ICU beds.

Technology is adapting to health care's changing environment as more acutely ill patients, including those with respiratory risks, are being placed on the general care units. Centralized noninvasive pulse oximetry, a method to measure oxygen saturation, provides a relatively inexpensive, efficient means to serve a broader spectrum of patients.

Central Supply, Hospital↗

Retrobulbar neuritis complicating acute Epstein-Barr virus infection.

A 19-year-old man presented with retrobulbar neuritis and was initially suspected to have neurosyphilis because of a positive microhemagglutination assay for Treponema pallidum (MHA-TP). However, a Venereal Disease Research Laboratory assay was negative, and the patient was subsequently diagnosed with infection due to Epstein-Barr virus (EBV) by heterophile antibody assay and serology for EBV. A biological false-positive MHA-TP has been reported in association with EBV infection. Physicians need to be aware that both retrobulbar neuritis and a biological false-positive MHA-TP can be seen in association with EBV infection.

Adult↗

Crystallographic characterization of tetanus toxin fragment C.

The C-terminal fragment from tetanus toxin has been crystallized. The 50 kDa protein forms prismatic crystals with an orthorhombic unit cell of dimensions a = 64.03 A, b = 76.31 A and c = 135.3 A. The space group is P2(1)2(1)2(1). Assuming one molecule per asymmetric unit, the solvent occupies 63% of the unit cell.

Crystallization↗

Iontophoresis and chloride-containing compounds: parameters required for killing.

Fungi, and gram-positive and gram-negative organisms were susceptible to iontophoretic killing in simple media. Iontophoresis did not depend on electrode type but did require chloride-containing compounds in the medium. All organisms could be killed efficiently if chloride-containing compounds (for example sodium chloride and calcium chloride) were present in physiological concentrations. Effectiveness of iontophoretic killing could be reduced by nonphysiologically elevated concentrations of other substances (for example creatinine and albumin). The data suggest that iontophoresis should function well in urine, since chloride-containing compounds are present in adequate concentrations even if some naturally occurring compounds, such as creatinine or albumin, are elevated.

Calcium Chloride↗

Crossover of human immunodeficiency virus-infected patients from aerosolized pentamidine to trimethoprim-sulfamethoxazole: lack of hematologic toxicity and relationship of side effects to CD4+ lymphocyte count.

Trimethoprim-sulfamethoxazole (TMP/SMZ) was given in a crossover study to 130 human immunodeficiency virus-infected patients who had been receiving aerosolized pentamidine; 86 (66%) successfully crossed over to TMP/SMZ without hypersensitivity reactions or hematologic toxicity. No significant changes occurred in mean hemoglobin concentration, leukocyte count, or platelet count between study enrollment and 12-month follow-up. Predominant side-effects, in 41 patients (33.8%), were fever and maculopapular rashes, which resolved promptly with discontinuation of TMP/SMZ. The mean time to first side effect was 12.3 days, and 86% of side effects developed within 30 days. Three patients experienced toxicity serious enough to warrant hospitalization. Of patients with < or = 200 CD4+ lymphocytes/mm3, 57% developed rashes after the cross-over compared with only 27% of patients with higher CD4+ cell counts. Many patients currently receiving aerosolized pentamidine can be safely crossed over without hematologic toxicity or hypersensitivity reactions.

Adult↗

Electrode and bacterial survival with iontophoresis in synthetic urine.

Urinary catheters, especially in patients with long-term catheter requirements, frequently are a source of infection. Iontophoresis has been proposed as a method to decrease or eliminate such infections. Several types of material were examined for their potential use as electrodes in an iontophoretic catheter system. Silver, copper and nickel electrodes did kill microorganisms but did not show longevity. Carbon and gold electrodes showed longevity and killing of microorganisms. Gold proved to be somewhat better than carbon in killing Klebsiella pneumoniae in a broth. Few organisms survived iontophoresis. Those few that survived (mainly Klebsiella in broth), when rechallenged by iontophoresis, did not show any striking resistance to iontophoresis. Our data support the proposition that inclusion of electrodes, depending on the electrode type, in a catheter probably will decrease or eliminate a bacterial population in urine and, thus, may help prevent catheter-related infections and their sequelae.

Bacteria↗

Iontophoresis generates an antimicrobial effect that remains after iontophoresis ceases.

Iontophoresis required chlorine-containing compounds in the medium for effective microbial population reduction and killing. After iontophoresis ceased, the antimicrobial effect generated by iontophoresis remained but slowly decreased. Antimicrobial effects of iontophoresis may be related to the generation of short-lived chlorine-containing compounds.

Candida albicans↗

Serum and urinary immunoglobulin in the rat model of acute urinary tract infection.

Total levels of urine and serum immunoglobulin IgM, IgG and IgA, and the E. coli-specific bacterial immunoglobulin response were determined by enzyme-linked immunosorbent assay (ELISA) in a rat model of acute urinary tract infection. High levels of urinary IgM were detected as early as day 3 post infection and then decreased to statistically insignificant levels. Peak levels of IgG occurred in the serum and urine on day 14. Urine and serum IgA levels remained low throughout the study period. The results demonstrate that in the rat model of acute urinary tract infection, IgM appears first in the urine and serum, and rapidly decreases. IgG then appears in the serum and urine followed by a late E. coli-specific immunoglobulin serum and urine response. Also, a non-specific component of the immunoglobulin response was noted in both the serum and urine. In the rat, IgA appears to play little or no role in the urine or in the serum response to the infection.

Acute Disease↗

Urothelial hyperplasia and neoplasia. III. Detection of nitrosamine production with different bacterial genera in chronic urinary tract infections of rats.

Various agents have been implicated in inducing urothelial cancer. Although drugs, occupational and environmental carcinogens are more widely accepted as playing a major role as urothelial carcinogens, several investigations suggest that bacteria may play a role. The mechanism of how bacteria may interact with the host to augment the development of urothelial carcinoma is not well understood. Clinically, investigators have linked the development of infection, urinary stones and indwelling catheters with urothelial cancer. Other investigators have suggested that the mechanism may be related to the production of carcinogenic compounds (nitrosamines) which can be detected during urinary tract infection. In our laboratory, we showed that rats with chronic urinary tract infections produced increasing urinary levels of N,N dimethylnitrosamine over a 24 week period and that the production correlated with hyperplasia and early neoplasia of the bladder epithelium. Three bacterial genera were used and two of these (Escherichia coli and a protein sp.) showed production of increasing levels of urinary nitrosamine and correlated with infection. The purpose of this current study is to determine if other bacterial genera and strains can also produce similar increasing nitrosamine levels in the rat model of chronic urinary tract infection and thus provide evidence that a number of bacterial genera and strains can produce nitrosamines in vivo. Also, the histology of the chronically infected bladder was examined for hyperplasia and neoplasia.

Animals↗