Nucleotide sequence of the phoP gene encoding PhoP, the response regulator of the phosphate regulon of Bacillus subtilis.
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Alkaline Phosphatase↗
Biomedical subjects
J W Lee
Publications and source records attributed to J W Lee.
An evaluation of the effect of food on the oral bioavailability of sustained-release morphine sulfate tablets (ORAMORPH SR) after multiple doses.
The effect of food on the oral bioavailability of sustained-release morphine sulfate tablets (ORAMORPH SR; Roxane Laboratories, Inc., Columbus, OH; OSR) was examined in an open-label, randomized, two-period crossover study. Healthy male volunteers received a 30-mg OSR tablet orally every 12 hours for seven doses during both the fasted and fed states. Dosing periods were separated by a 14-day washout. Volunteers in the fasted group received all doses either 2 hours before or after meals. Volunteers in the fed group received all doses immediately after meals. All meals were standardized. Serial blood samples were collected for analysis of plasma morphine concentration by radioimmunoassay. Pharmacokinetic parameters were calculated using plasma concentration data collected after the last dose at 72 hours of each dosing period. The two one-sided t analysis indicated confidence intervals between 80% and 120% for maximum peak plasma concentration (Cmax), AUC72-84hr, Cavg, and Cmin. The relative bioavailability of OSR administered after meals was 90.2% of that administered in the fasted state. As compared with the fasted condition, morphine bioavailability was essentially unchanged when multiple oral doses of 30-mg OSR tablets were given after meals.
Administration, Oral↗
Fragmentation of dimyristoylphosphatidylcholine vesicles by apomyoglobin.
Previously we have reported results of a preliminary study on the micellization of phosphatidylcholine vesicles by apomyoglobin at pH 4 (J. W. Lee and H. Kim, 1988, FEBS Lett. 241, 181-184). The micellization study has been extended here to investigate the effect of the lipid to protein ratio, temperature, size of vesicles, and pH. The pH-dependent study indicated that micellization occurs when the protein assumes either a molten globular or random coil structure. Time-dependent hydrophobic labeling by 3-(trifluoromethyl)-3-(m-[125I]iodophenyl)-diazirine showed that there is an initial increase in contact between the protein and hydrophobic acyl chain of lipid followed by a decrease in the interaction. This may be explained as the initial stage of vesicle aggregation which is subsequently superseded by the fragmentation. These reactions are discussed in term of protein unfolding at low pH.
Amino Acid Sequence↗
Evaluation of dexamethasone for reduction of postsurgical sequelae of third molar removal.
Sixty patients with bilaterally symmetrical impacted third molars participated in this double-blind, within-subject study to quantify the effects of 4 mg of dexamethasone on reducing postsurgical sequelae. Each patient's surgery was staged by mouth side and completed in two appointments 5 to 6 weeks apart. A preoperative dose of dexamethasone given intravenously was randomized to mouth side and surgical appointment; sterile water served as a control. Major areas assessed in this study were facial swelling, pain, and trismus. No difference in swelling and daily pain was noted. However, trismus and global pain were significantly affected by the steroid. Patients had a daily postsurgical increase in incisal opening of 4 to 6 mm over the control side during the examination period. Patients evaluated pain by choosing the least painful side. By a greater than 4:1 margin, patients chose the steroid side as the least painful side. No increase in the rate or type of complications was detected between control and steroid sides.
Adolescent↗
Safety and pharmacokinetics of fluconazole in children with neoplastic diseases.
To evaluate the safety, tolerance, and pharmacokinetics of fluconazole in children with neoplastic diseases, we studied fluconazole in 26 children, aged 5 to 15 years, with normal renal function who were receiving treatment for cancer. The patients received fluconazole, 2, 4, or 8 mg/kg per day for 7 days intravenously for a 2-hour period. Patients had no nausea or vomiting related to fluconazole; three patients had an asymptomatic rise in hepatic aminotransferase values after four to six doses (one patient at 2 mg/kg per day and two patients at 8 mg/kg per day), which returned to normal within 2 weeks after discontinuation of the drug. Fluconazole showed linear first-order kinetics over the dosage range tested and during multiple dosing. After the first dose, mean clearance was 22.8 +/- 2.3 ml/min, volume of distribution 0.87 +/- 0.06 L/kg, and terminal elimination half-life 16.8 +/- 1.1 hours. Similarly, after the last dose, clearance was 19.4 +/- 1.3 ml/min, volume of distribution 0.84 +/- 0.04 L/kg, and terminal elimination half-life 18.1 +/- 1.2 hours. Patients receiving their first fluconazole dose of 8 mg/kg achieved peak serum levels of 9.5 +/- 0.4 microgram/ml and trough levels of 2.7 +/- 0.5 microgram/ml 24 hours later, and an area under the serum concentration-time curve from time zero to infinity of 186 +/- 16 micrograms.hr per milliliter. Renal clearance of fluconazole was 65% +/- 5% of total clearance and demonstrated the predominantly renal excretion of this drug. We suggest that the shorter serum half-life and the higher frequency of aminotransferase elevations in comparison with those of adults warrant careful investigation of fluconazole in controlled clinical trials.
Child↗
Vascular catheter-associated fungemia in patients with cancer: analysis of 155 episodes.
We reviewed all 155 episodes of central venous catheter-associated fungemia among inpatients at the National Cancer Institute during a 10-year period. Candida species accounted for 98% of episodes. Fungemia was documented by culture of blood drawn through catheters in 50% of cases and by culture of both catheter-drawn and peripheral blood in 39%; mortality and the rate of dissemination were similar for these two groups. Four management strategies were used: catheter removal, antifungal therapy (with amphotericin B), both, or neither; indications for the use of both modes of treatment included fever, neutropenia, long-term indwelling catheterization, positive cultures of both catheter-drawn and peripheral blood, isolation of Candida tropicalis, and fungal isolation from two or more blood cultures. Disseminated fungal infection was documented in 82% of cases with these features but also in 35% of the less severe cases treated only with catheter removal. In addition, nine (82%) of 11 cases managed only with antifungal therapy had a negative outcome (either death from disseminated infection or the recurrence of fevers and/or fungemia), a finding suggesting that intravascular catheters should be removed in fungemia. Virtually all cases of catheter-associated fungemia in patients with cancer are clinically significant and require prompt therapy with amphotericin B.
Adolescent↗
Experimental antifungal chemotherapy in granulocytopenic animal models of disseminated candidiasis: approaches to understanding investigational antifungal compounds for patients with neoplastic diseases.
Disseminated candidiasis is the most common life-threatening invasive fungal infection in granulocytopenic patients. A review of recent approaches to pre-clinical laboratory investigation of promising antifungal compounds, which may have potential utility in granulocytopenic patients is presented. A particularly useful strategy is the study of persistently granulocytopenic rabbit models of acute, subacute, and chronic forms of disseminated candidiasis. When the antifungal triazoles (fluconazole, itraconazole, and SCH 39304 [SCH 42427]) were each evaluated for use as preventive, early treatment, or delayed treatment in the different models, the triazoles were consistently more active when used for preventive and early treatment than for delayed treatment. These triazoles were as active as amphotericin B plus flucytosine (AB + FC) when used for early treatment but were less active than AB + FC when used for delayed treatment. Several lipid formulations of amphotericin B demonstrate reduced nephrotoxicity at higher safely achievable dosages in comparison to those of deoxycholate amphotericin B in several models of disseminated candidiasis. When administered to follow non-linear saturable Michaelis-Menten-type plasma pharmacokinetics, the antifungal activity of the echinocandin compound cilofungin was significantly augmented. Thoughtfully designed and carefully conducted laboratory investigations in appropriate animal models of disseminated candidiasis can provide a scientific foundation and guide for development of clinical protocols investigating new approaches to prevention and treatment of invasive candidiasis in granulocytopenic patients.
Agranulocytosis↗
Experimental Trichosporon infection in persistently granulocytopenic rabbits: implications for pathogenesis, diagnosis, and treatment of an emerging opportunistic mycosis.
Disseminated Trichosporon infection, an uncommon but emerging opportunistic mycosis due to Trichosporon beigelii, is frequently difficult to diagnose, refractory to treatment, and associated with a high attributable mortality. Models of disseminated and gastrointestinal Trichosporon infection were developed in persistently granulocytopenic rabbits. The patterns of infection resembled those of clinical disease, including cutaneous lesions, chorioretinitis, renal infection, pulmonary infection, and antigenemia cross-reactive with cryptococcal capsular polysaccharide. Antigenemia, an early manifestation of disseminated Trichosporon infection, originated in vivo from a fibrillar extracellular matrix. Trichosporon organisms disseminated from the gastrointestinal tract to visceral tissue in colonized immunosuppressed rabbits, whereas there was no dissemination from the gastrointestinal tract of otherwise normal rabbits. The antifungal triazoles, fluconazole and SCH 39304, were most active; maximum tolerated doses of amphotericin B and liposomal amphotericin B were ineffective. Trichosporon antigenemia declined in response to antifungal therapy. These findings contribute to improved understanding of the pathogenesis, diagnosis, and treatment of disseminated Trichosporon infection.
Agranulocytosis↗
Recent progress and current problems in management of invasive fungal infections in patients with neoplastic diseases.
Patients with neoplastic diseases are predisposed to develop invasive fungal infections as the result of impairments of host defense mechanisms due principally to pharmacologic immunosuppression resulting from intensive cytotoxic chemotherapy, ablative radiation therapy, and corticosteroids. Candida species, Aspergillus species, and emerging opportunistic fungal pathogens comprise the principal etiologic agents of opportunistic mycoses in cancer patients. This paper reviews the recent progress, particularly during the year of 1991, in management of invasive fungal infections and the current problems of invasive mycosis, which confront patients with neoplastic diseases.
Antifungal Agents↗
Pharmacokinetics and milk residues of butorphanol in dairy cows after single intravenous administration.
The pharmacokinetics of butorphanol tartrate were investigated following intravenous administration of 0.25 mg/kg of body weight to six healthy non-lactating Jersey cows. Three lactating Holstein cows also received 0.045 mg of butorphanol/kg of body weight intravenously to determine the extent and duration of drug transfer into milk. A radioimmunoassay technique was used to measure butorphanol concentrations in plasma and milk. The disposition of butorphanol following intravenous administration was characterized by rapid and extensive distribution followed by a slower elimination phase. Apparent volume of distribution was 4.178 +/- 1.145 (mean +/- SD) 1/kg, mean elimination half-life was 82 min, and clearance was 34.6 +/- 7.7 ml/min/kg. Trace quantities of butorphanol were detected in the cow's milk for up to 36 h following administration. These pharmacokinetic data were compared with pharmacokinetic and pharmacodynamic data for butorphanol in other species and for three other potent opioids in related ruminant species.
Animals↗
Thyroid hormone receptor dimerization function maps to a conserved subregion of the ligand binding domain.
Thyroid hormone receptors (TRs) bind as dimers to specific DNA response elements. We have used a genetic approach to identify amino acid sequences required for dimerization of the TR beta isoform. Bacteria expressing a chimeric repressor composed of the DNA binding domain of the bacteriophage lambda cl repressor fused to the TR beta ligand binding domain are immune to lambda infection as a consequence of homodimerization activity provided by the receptor sequences. The phenotypes of deletions and point mutations of the TR beta sequences map dimerization activity to a subregion of the ligand binding domain that is highly conserved among all members of the nuclear hormone receptor superfamily. These results confirm and extend previous findings indicating that this subregion plays an important role in the dimerization of TR beta and other superfamily members.
Amino Acid Sequence↗
MELAS syndrome with mitochondrial tRNA(Leu)(UUR) mutation: correlation of clinical state, nerve conduction, and muscle 31P magnetic resonance spectroscopy during treatment with nicotinamide and riboflavin.
We report a patient with mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes treated with riboflavin and nicotinamide for 18 months, during which time previously frequent encephalopathic spells ceased. To confirm clinical benefit, we withdrew treatment and monitored response with muscle 31P magnetic resonance spectroscopy (MRS) and sural nerve conduction studies. Of three prospectively chosen MRS variables, two changed coincidentally with clinical end points; phosphocreatine (PCr)/adenosine triphosphate recovery rates fell in parallel with sural nerve sensory amplitudes, and a drop in muscle bioenergetic efficiency (relationship of inorganic phosphate/PCr to the accelerating force of contracting muscle) coincided with development of encephalopathy. Investigations revealed a deficiency of respiratory complex I and mutation of the mitochondrial tRNA(Leu)(UUR). We suggest that a defective cellular energy state in mitochondrial disease may be partially treatable and that changes seen in appropriate muscle spectroscopy studies may parallel improvement in brain and peripheral nerve function.
Adult↗
Pyogenic arthritis of the hip due to Campylobacter fetus--a case report.
Septic arthritis of the hip caused by Campylobacter fetus subsp. fetusis very rare. The authoris isolated C. fetus subsp. fetus from a specimen of the left hip. The patient was a 53-year old man with a history of heavy drinking, diabetes, and chronic hepatitis, and had been suffering from avascular necrosis of both femoral heads. It was considered that the organism invaded already damaged tissue of the joint. The patient was treated with intravenous antibiotics and later received successful total hip replacement.
Arthritis, Infectious↗
Basic FGF in adult rat brain: cellular distribution and response to entorhinal lesion and fimbria-fornix transection.
Basic fibroblast growth factor (bFGF) is a potent trophic factor for neurons and astrocytes and recently has been implicated in the pathology of Alzheimer's disease. In order to better understand the role of bFGF in normal brain function and during pathology, we have analyzed its anatomical distribution and its response to injury in the CNS. Double-staining immunohistochemistry showed that bFGF immunoreactivity was localized in astrocytes, in select neuronal populations, and occasionally in microglial cells throughout the normal rat brain. Neuronal populations that showed bFGF immunoreactivity included septohippocampal nucleus, cingulate cortex, subfield CA2 of the hippocampus, cerebellar Purkinje cells, cerebellar deep nuclei, facial nerve nucleus, and the motor and spinal subdivisions of the trigeminal nucleus and facial nerve nucleus. The pattern of bFGF immunoreactivity in the hippocampus was examined following entorhinal cortex lesion, or fimbria-fornix transection. After entorhinal cortex lesion, bFGF immunoreactivity increased in the outer molecular layer of the dentate gyrus ipsilateral to the lesion. The lesion effect on bFGF immunoreactivity was expressed as an increase in the number of bFGF astrocytes, as an increase in the intensity of bFGF immunoreactivity within astrocytes, and as an increase of bFGF immunoreactivity in the surrounding extracellular matrix, relative to the contralateral side. The time course and pattern of reorganization paralleled the sprouting of septal cholinergic terminals in response to the same type of lesion, suggesting that bFGF may play an important role in lesion-induced plasticity. After transection of the fimbria-fornix, chronic infusion of bFGF appeared to preserve NGF receptors on neurons within the medial septal complex and, as previously reported, prevent the death of medial septal neurons. Therefore, it appears that bFGF infusion, which has been shown to increase the synthesis of NGF by astrocytes (Yoshida and Gage, 1991), also helps enable neurons to respond to NGF. This suggests that after injury bFGF may participate in a cascade of neurotrophic events, directly and indirectly facilitating neuronal repair and/or promoting neuronal survival.
Animals↗
Continuous intravenous infusion and simultaneous pharmacokinetic monitoring in ambulatory rabbits with a programmable micropump and dual subcutaneous Silastic central venous catheters.
We describe a newly developed method of continuous intravenous infusion and simultaneous monitoring of plasma levels of investigational compounds in ambulatory untethered rabbits. Continuous infusion was administered by means of a portable programmable external micropump which permitted adjustable dosing. Simultaneous plasma pharmacokinetic monitoring during infusion was accomplished by dual silastic central venous catheters. The potential applications of the micropump infusion system as an alternative to current methods of continuous infusion in other species and in other studies are further discussed. This method provided a safe, reliable, and well-tolerated method of adjustable continuous intravenous infusion and simultaneous sampling of central venous blood in rabbits.
Animals↗
Multipartite structure of a negative regulatory element associated with a steroid hormone-inducible promoter.
The steroid hormone-inducible promoter from mouse mammary tumor virus is associated with a distal negative regulatory element that represses its inherent basal activity. Deletion analysis localized the sequences required for repression to 64 base pairs of DNA between -427 and -364 with respect to the transcription initiation site. Transient transfection experiments with a series of linker scanning and small internal deletion mutations revealed two mutation-sensitive domains separated by a region of relative resistance to sequence alterations. DNase I footprinting and gel electrophoresis mobility shift experiments with crude nuclear extracts identified at least one protein-binding site within each of the two mutation-sensitive regions. An oligonucleotide corresponding to one of these sites is able to repress transcription, but only when linked to the promoter in multiple copies. This negative regulatory element functions synergistically with a promoter proximal negative element to mediate efficient promoter repression, selectively affecting basal relative to steroid hormone-induced transcription and thus increasing the ratio of promoter activity observed in the presence and absence of hormone.
Animals↗
Sensitive and specific radioimmunoassays for opiates using commercially available materials. I: Methods for the determinations of morphine and hydromorphone.
Sensitive and specific radioimmunoassay (RIA) methods for the analysis of morphine and hydromorphone in human plasma samples using commercially available materials were developed. The limit of quantitation was 0.3 ng/mL of plasma for morphine and 50 pg/mL of plasma for hydromorphone. An extraction step preceding the RIA quantitatively removed morphine, leaving 99% morphine-3-glucuronide (M3G) and 95% hydromorphone-3-glucuronide (H3G) in the aqueous phase. The specificity of the morphine RIA method for the analysis of clinical samples was confirmed by HPLC quantitation. The antiserum used in the hydromorphone RIA method cross reacted slightly with H3G at 0.66%. However, analysis of clinical samples using the direct versus the extraction RIA showed that the extraction step was necessary for the specific determination of hydromorphone in pharmacokinetic studies. After extraction, only 0.033% of the H3G present in plasma samples would be observed as interference for the free hydromorphone. The RIA methods were shown to be accurate and reproducible with almost 100% recovery of morphine and hydromorphone. They offer convenient alternatives to chromatographic methods for pharmacokinetic studies.
Antibody Specificity↗
Computer analysis of physiologic signals in a cardiovascular research laboratory.
A comprehensive computer program which provides immediate computation and feedback has been developed for data acquisition and analysis of signals in a cardiovascular animal laboratory. The system is based on a microcomputer equipped with analog-to-digital converter and supports function modules which digitize, filter, and differentiate up to 8 simultaneously sampled cardiovascular signals. The program detects, analyses, and plots incoming and averaged beats. Beat-by-beat signal averaging for each channel is performed and cardiac cycles are partitioned automatically. For each cardiac and average cycle the amplitude at 6 physiologic fiducial markers are measured and derived calculations are made. Channel vs channel plots and loop area measurements are also computed and displayed. The computer algorithms have been shown to give accurate, precise, and reproducible results when tested on canine cardiovascular data. Also, it has been demonstrated that signal averaging is an appropriate analysis technique for cardiovascular signals.
Algorithms↗