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Biomedical subjects

M S Alexander

Publications and source records attributed to M S Alexander.

At least 19 recordsLinked to original sources
PubMed2005

Autoregulation of CCL26 synthesis and secretion in A549 cells: a possible mechanism by which alveolar epithelial cells modulate airway inflammation.

Eotaxins (CCL11, CCL24, CCL26) originating from airway epithelial cells and leukocytes have been detected in bronchoalveolar lavage of asthmatics. Although the alveolar epithelium is the destination of uncleared allergens and other inflammatory products, scanty information exists on their contribution to the generation and regulation of the eotaxins. We envisioned a state whereby alveolar type II cells, a known source of other inflammatory proteins, could be involved in both the production and regulation of CCL24 and CCL26. Herein, we demonstrated that all three eotaxins are constitutively expressed in A549 cells. IL-4 and IL-13 stimulated a concentration-dependent secretion of CCL24 and CCL26. The cytokines did not act synergistically. Cycloheximide and actinomycin D abrogated IL-4- and IL-13-dependent CCL26 but not CCL24 secretion. Both IL-13 and IL-4 stimulated CCL26 synthesis that was inhibited in a concentration-dependent manner by CCL26 but not CCL24. Only CCL26 reduced expression of CCR3 receptors by 30-40%. On the other hand, anti-CCR3 pretreatment reduced IL-4+IL-13-dependent CCL26 secretion, implying autoregulation. A CCR3-specific antagonist (SB-328437) significantly decreased IL-4-dependent synthesis and release of CCL26. Eosinophils treated with medium from IL-4-stimulated A549 cells preincubated with anti-CCL26 showed a marked decrease of superoxide anion production compared with anti-CCL24 treated. These results suggest that CCL26 is a major eotaxin synthesized and released by alveolar epithelial cells and is involved in autoregulation of CCR3 receptors and other eotaxins. This CCL26-CCR3 ligand-receptor system may be an attractive target for development of therapeutics that limits progress of inflammation in airway disease.

Cell Line↗
PubMed2001

Isolated bilateral trochlear nerve palsy as the first clinical sign of a metastatic [correction of metastasic] bronchial carcinoma.

PURPOSE: To report a case with isolated, nontraumatic bilateral fourth nerve palsy as the first clinical sign of a metastatic lung carcinoma. METHODS: Case report. A 56-year-old man presented with isolated, nontraumatic bilateral fourth nerve palsy. Magnetic resonance imaging (MRI) of the brain and orbits and, subsequently, chest x-ray and a computer tomographic (CT)-scan of the thorax, the abdomen, and the pelvis were performed. RESULTS: Magnetic resonance imaging confirmed the presence of a midline brain stem lesion in the region of decussation of the trochlear nerves. Computed tomographic scan of the chest revealed that the lesion was caused by a metastatic lung carcinoma. CONCLUSION: The findings of isolated bilateral fourth nerve palsy in the absence of trauma should alert the clinician to the possibility of a posterior fossa lesion in the region of the trochlear nerves. Besides urgent scanning of the dorsal midbrain, investigations should be directed to search for the primary tumor.

Brain Neoplasms↗
PubMed2000

Expediting the method development and quality control of reversed-phase liquid chromatography electrospray ionization mass spectrometry for pharmaceutical analysis by using an LC/MS performance test mix.

Mass spectrometry combined with liquid chromatography (LC/MS) has become an important analytical methodology in both pharmaceutical and biomolecule analyses. LC/MS, especially with reversed-phase HPLC (RP-LC), is extensively used in the separation and structural identification of pharmaceutical samples. However, many parameters have to be considered when a new LC/MS method is developed for either separation and structural analysis of unknown mixtures or quantitative analysis of a set of known compounds in an assay. The optimization of a new LC/MS method can be a time-consuming process. A novel kit-LC/MS performance test mix-composed of aspartame, cortisone, reserpine, and dioctyl phthalate has been developed to accelerate the process of establishing a new RP-LC/MS method. The LC/MS mix makes the evaluation and validation of an LC/MS method more efficient and easier. It also simplifies the quality control procedure for an LC/MS method in use.

Chromatography, High Pressure Liquid↗
PubMed1995

Synthesis and anticonvulsant activity of enaminones. 3. Investigations on 4'-, 3'-, and 2'-substituted and polysubstituted anilino compounds, sodium channel binding studies, and toxicity evaluations.

In a continuing evaluation of the aniline-substituted enaminones, the synthesis of additional para-substituted analogs has been made in an attempt to further quantify the electronic (sigma) and lipophilic (pi) requirements for anticonvulsant activity in this series. In addition, meta- and ortho-substituted and polysubstituted compounds have been synthesized and evaluated for anticonvulsant activity. In the para-substituted series, 4-cyano analogs (32 and 33) (+ sigma, - pi), which were highly active via intraperitoneal (ip) injection in mice, were inactive on oral (po) administration in rats. The para-substituted trifluoromethoxy (+ sigma, + pi) analog (8) had significant potency by both routes. Meta substitution limited the activity due to steric factors. Bromo and iodo substituents produced active para-substituted analogs (5 and 17) but were inactive when substituted in the meta position (37 and 41, respectively). Ortho substitution provided no clear relationship due to nonparametric deviations. Neither 1, the prototype enaminone, nor 2, the putative metabolite, produced significant nephrotoxicity or hepatotoxicity. Sodium channel binding of 1 and 8 indicated that 8 displayed relatively potent sodium channel binding but 1 showed weaker effects with IC50 values of 489 and 170 microM respectively against [3H]batrachotoxinin A 20 alpha-benzoate ([3H]BTX-B).

Animals↗
PubMed1994

Nuclear magnetic resonance studies of anticonvulsant enaminones.

1H nuclear magnetic resonance (NMR) spectra of enaminones were determined and compared to the anticonvulsant activity of the compounds. Although the precise employment of the NMR data to predict anticonvulsant activity of the enaminones could not be established, general inferences were made. The NMR data confirmed that the enaminones existed predominantly in the amino tautomer, and no evidence was found for the imino tautomer. The ketamine form of the enaminones was supported by the observed spin-spin splittings of the NH with the alpha-protons on certain enaminones. The NH of secondary enaminones was very important in conferring anticonvulsant activity to the enaminones. The peak for the NH proton which could be seen between delta (ppm) 4.50 and 9.70 was present in all of the active enaminones. The tertiary enaminones, which were devoid of the NH proton, were uniformly inactive. It appeared that a combination of steric and electronic effects, lipophilicity, and hydrogen bonding were necessary for the anticonvulsant activity of the enaminones. The cyclic enaminones existed in the trans-S-trans fixed conformation, and the NMR data supported our hypothesis that enantioselectivity is retained in synthesizing enaminones from cyclic, diasteriomeric 1,3-diketones. In addition, the AB system and many unique features were observed in some enaminones. The para, meta, and ortho substituted patterns were observed for monosubstituted phenyl protons, and the NMR patterns for di- and trisubstituted phenyl groups were elucidated.

Anticonvulsants↗
PubMed1992

Impaired left lower lobe ventilation in patients with cardiomegaly. An isotope study of mechanisms.

Reduced left lower lobe ventilation (V) in patients with enlarged hearts has been commonly observed on routine isotope ventilation-perfusion lung scanning, and there is evidence to show that this reduction is dependent on posture. Clinically, it may have a role in posture-dependent dyspnea and postoperative left lower lobe changes in cardiomegaly. Previous studies have shown improvement in left lower lobe V in the prone compared with the supine position. In 11 patients showing this phenomenon in krypton 81m V scanning, a mean relative reduction in V of 53 percent occurred at the left base. No significant change in perfusion or in the signal from preinjected technetium 99m macroaggregated albumin was observed between the two positions. No significant change in ventilatory turnover (measured with intravenous xenon 133) was seen either, suggesting that no air trapping takes place. By combining the data from the intravenous 133Xe (which gives the ratio, V/lung volume) and continuously inhaled 81mKr (which reflects regional V), an index of relative volume between the two sides was derived and shown to be significantly reduced at the left base on moving from the prone to supine positions (a mean reduction of 40 percent; p less than 0.02 by Wilcoxon signed rank test). Thus, the mechanism of postural left lower lobe hypoventilation in cardiomegaly is predominantly a regional loss of alveolar volume.

Cardiomegaly↗
PubMed1991

The use of radionuclide imaging in the evaluation of suspected biliary damage during laparoscopic cholecystectomy.

Laparoscopic cholecystectomy offers a reliable and effective alternative to the standard operative cholecystectomy with reduced morbidity and patient recovery time. We report three cases in which radionuclide hepatobiliary imaging was utilized to evaluate the integrity of the extrahepatic biliary ducts following suspected biliary damage during the procedure, documenting bile leakage in two of the patients.

Adult↗
PubMed1990

Incidence of pulmonary embolism in elderly patients newly admitted to an acute geriatric unit: a prospective study.

To study the incidence of pulmonary embolism (PE) in elderly patients newly admitted to an acute geriatric unit, the authors carried out ventilation perfusion scans on 33 patients, 25 women and 8 men, mean age 79 years, consecutively admitted to the geriatric wards. The first scan was done within 5 days of admission and repeated between days 10 and 20. Where possible, patients with a positive second scan had a repeat scan at 2-3 months. Six (18%) patients were found to have a high probability of PE, 4 (12%) at the time of admission and two (6%) after admission. Three patients (9%) were considered to suffer from chronic pulmonary artery disease. Mortality was 5 for the whole group (15%) and 1 of 6 (17%) with a high probability of PE; this patient was suffering from carcinomatosis. The only patient who was anticoagulated suffered serious side effects. In no patient was PE clinically suspected. The authors conclude that PE is common in sick elderly patients newly admitted to acute geriatric wards, that rehabilitation with mobilization may precipitate new PE, and that nonanticoagulated PE does not seem to appreciably shorten the prognosis for life. Treatment with anticoagulants may be more dangerous than not treating PE in this older age group.

Aged↗
PubMed1989

Dysphagia after fast neutron therapy to the head and neck.

Nine patients presenting with dysphagia following successful treatment for head and neck cancer with neutron radiotherapy are reviewed. Combined clinical and videofluoroscopic investigation is used to analyse their deficits and provide indications for management. All patients show impairment of both the oral and pharyngeal phases of the swallow, with the exception of one subject who shows signs of focal neurological damage. It is suggested that fibrosis is the underlying cause of dysphagia in the remainder.

Adult↗
PubMed1986

Spontaneous subarachnoid hemorrhage and negative cerebral panangiography. Review of 140 cases.

One hundred and forty consecutive patients who sustained proven spontaneous subarachnoid hemorrhage (SAH) with negative cerebral panangiography were studied retrospectively. Attention was directed to the presence, amount, and distribution of subarachnoid blood on computerized tomography (CT) scans. It was determined that the finding of blood on CT had a significant association with clinical grade, loss of consciousness, ventricular ratio, fixed ischemic deficit, and total of all complications, but not with epilepsy, hypertension (previously known or detected on admission), treated hydrocephalus, rebleeding, angiographic spasm, and eventual outcome (which was generally excellent on follow-up examination). The distribution of blood, predominantly around the basal cisterns, suggests leakage from ventriculostriate and thalamoperforating vessels as the cause of SAH, and closer study of these vessels is suggested.

Adolescent↗
PubMed1985

Interspecies variation in ritodrine metabolism.

The metabolism of ritodrine has been studied in the rat, both in vitro and in vivo, and in the in vivo pregnant baboon, with the use of tritium-labeled drug as a probe. Combined enzymatic degradation and radiochromatography of the radioactive components of bile and urine show that ritodrine undergoes significant Phase l metabolism in addition to conjugation to both sulfate and glucuronide, as previously reported. The presence of more than one conjugate is shown, and evidence for major interspecies variation in patterns of metabolism and conjugation is presented, with comments on the applicability of results to human clinical use.

Animals↗
PubMed1985

Metabolism and disposition of ritodrine in a pregnant baboon.

Relatively little is known about the detailed metabolism of ritodrine. The aim of this study was to examine ritodrine metabolism and pharmacokinetics in the maternal and fetal baboon. A fetal-maternal model was made with use of Papio anubis at 144 days of gestation. Tritiated ritodrine was injected as an intravenous bolus into the mother. Maternal and fetal blood samples, amniotic fluid, and maternal urine were collected at time intervals. Samples were analyzed by a combination of high-pressure liquid chromatography and radiochromatography. Conjugated metabolites were recovered and characterized by cleavage studies with use of beta-glucuronidase and sulfatase. The distribution half-life of ritodrine in the mother was 6 minutes and the elimination half-life was 61 minutes. Metabolites were found in both fetal serum and amniotic fluid. The concentrations of ritodrine and its metabolites in fetal serum were at or above the concentrations in maternal serum at 2 hours after maternal intravenous injection. The principal metabolite identified was the sulfate conjugate. The fetus appears to accumulate metabolites. These data indicate that ritodrine crosses the placenta and, in the baboon, achieves levels in the fetus equal to or higher than those in the mother.

Amniotic Fluid↗