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Biomedical subjects

J L Martin

Publications and source records attributed to J L Martin.

At least 235 records · Page 13Linked to original sources
PubMed1992

Medicare Part B spending.

In its continuing effort to identify and examine the trends in Medicare spending for surgical services, the College obtained copies of the Medicare procedure code files for the years 1986 through 1989. The results from analysis of these data files were presented in a report entitled Trends in Medicare Part B Spending 1986-1989, issued by the College in September 1991. This article describes the federal activity that prompted the College to commission the report, and presents some of the significant results of the analysis.

Data Interpretation, Statistical↗
PubMed1992

High pressure liquid chromatographic determination of the new non-steroidal anti-inflammatory agent butibufen.

High performance liquid chromatography (HPLC) method for the determination and validation of a new non-steroidal anti-inflammatory agent, butibufen (CAS 55837-18-8), microencapsulated butibufen and its pharmaceutical forms--tablets, sachets (microencapsulated butibufen with excipients), microemulsion and cream--is described. Acetonitrile proved to be the best solvent for the extraction of butibufen from its pharmaceutical forms. The results submitted in this paper suggest that the HPLC method for the quantitative determination of butibufen is linear, accurate, precise and sensitive.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1992

Leukoedema: a review of the literature.

Leukoedema, a grayish-white lesion of the oral mucosa in humans, was once thought to be a probable precursor to leukoplakia. Clinical examination differentiates leukoedema from leukoplakia, lichen planus, white sponge nevus, and pathomimia morsicatio buccarum. Prevalence rates vary greatly in different countries and in different ethnic groups. For many years, leukoedema was alleged to occur only in adult populations until Martin and Crump found this lesion in children and youth. There is a definite predilection for this lesion in black Americans. Although the etiology is unknown, it has been suggested that leukoedema develops in areas of local irritation. This article reviews the literature related to the prevalence of leukoedema and correlates the independent findings, which might pertain to its etiology.

Black or African American↗
PubMed1991

Glucose analogue inhibitors of glycogen phosphorylase: the design of potential drugs for diabetes.

The T-state crystal structure of the glucose-phosphorylase b complex has been used as a model for the design of glucose analogue inhibitors that may be effective in the regulation of blood glucose levels. Modeling studies indicated room for additional atoms attached at the C1-beta position of glucose and some scope for additional atoms at the C1-alpha position. Kinetic parameters were determined for alpha-D-glucose: Ki = 1.7 mM, Hill coefficient n = 1.5, and alpha (synergism with caffeine) = 0.2. For beta-D-glucose, Ki = 7.4 mM, n = 1.5, and alpha = 0.4. More than 20 glucose analogues have been synthesized and tested in kinetic experiments. Most were less effective inhibitors than glucose itself and the best inhibitor was alpha-hydroxymethyl-1-deoxy-D-glucose (Ki = 1.5 mM, n = 1.3, alpha = 0.4). The binding of 14 glucose analogues to glycogen phosphorylase b in the crystal has been studied at 2.4-A resolution and the structure have been refined to crystallographic R values of less than 0.20. The kinetic and crystallographic studies have been combined to provide rationalizations for the apparent affinities of glucose and the analogues. The results show the discrimination against beta-D-glucose in favor of alpha-D-glucose is achieved by an additional hydrogen bond made in the alpha-glucose complex through water to a protein group and an unfavorable environment for a polar group in the beta pocket. The compound alpha-hydroxymethyl-1-deoxy-D-glucose has an affinity similar to that of glucose and makes a direct hydrogen bond to a protein group. Comparison of analogues with substituent atoms that have flexible geometry (e.g., 1-hydroxyethyl beta-D-glucoside) with those whose substituent atoms are more rigid (e.g., beta-azidomethyl-1-deoxyglucose or beta-cyanomethyl-1-deoxyglucose) indicates that although all three compounds make similar polar interactions with the enzyme, those with more rigid substituent groups are better inhibitors. In another example, alpha-azidomethyl-1-deoxyglucose was a poor inhibitor. In the crystal structure the compound made several favorable interactions with the enzyme but bound in an unfavorable conformation, thus providing an explanation for its poor inhibition. Attempts to utilize a contact to a buried aspartate group were partially successful for a number of compounds (beta-aminoethyl, beta-mesylate, and beta-azidomethyl analogues). The beta pocket was shown to bind gentiobiose (6-O-beta-D-glucopyranosyl-D-glucose), indicating scope for binding of larger side groups for future studies.

Deoxyglucose↗
PubMed1991

Direct observation of vibrational coherence in bacterial reaction centers using femtosecond absorption spectroscopy.

It is shown that vibrational coherence modulates the femtosecond kinetics of stimulated emission and absorption of reaction centers of purple bacteria. In the DLL mutant of Rhodobacter capsulatus, which lacks the bacteriopheophytin electron acceptor, oscillations with periods of approximately 500 fs and possibly also of approximately 2 ps were observed, which are associated with formation of the excited state. The kinetics, which reflect primary processes in Rhodobacter sphaeroides R-26, were modulated by oscillations with a period of approximately 700 fs at 796 nm and approximately 2 ps at 930 nm. In the latter case, at 930 nm, where the stimulated emission of the excited state, P*, is probed, oscillations could only be resolved when a sufficiently narrow (10 nm) and concomitantly long pump pulse was used. This may indicate that the potential energy surface of the excited state is anharmonic or that low-frequency oscillations are masked when higher frequency modes are also coherently excited, or both. The possibility is discussed that the primary charge separation may be a coherent and adiabatic process coupled to low-frequency vibrational modes.

Bacterial Chromatophores↗
PubMed1991

Resistance to ddI and sensitivity to AZT induced by a mutation in HIV-1 reverse transcriptase.

Serial human immunodeficiency virus type-1 (HIV-1) isolates were obtained from five individuals with acquired immunodeficiency syndrome (AIDS) who changed therapy to 2',3'-dideoxyinosine (ddI) after at least 12 months of treatment with 3'-azido-3'-deoxythymidine (zidovudine, AZT). The in vitro sensitivity to ddI decreased during the 12 months following ddI initiation, whereas AZT sensitivity increased. Analysis of the reverse transcriptase coding region revealed a mutation associated with reduced sensitivity to ddI. When this mutation was present in the same genome as a mutation known to confer AZT resistance, the isolates showed increased sensitivity to AZT. Analysis of HIV-1 variants confirmed that the ddI resistance mutation alone conferred ddI and 2',3'-dideoxycytidine resistance, and suppressed the effect of the AZT resistance mutation. The use of combination therapy for HIV-1 disease may prevent drug-resistant isolates from emerging.

Acquired Immunodeficiency Syndrome↗
PubMed1991

A metabolite of halothane covalently binds to an endoplasmic reticulum protein that is highly homologous to phosphatidylinositol-specific phospholipase C-alpha but has no activity.

When the inhalation anesthetic halothane was administered to rats, a 58 kDa protein in the liver became covalently labeled by the trifluoroacetyl chloride metabolite of halothane. The amino acid sequences of the N-terminal and of several internal peptide fragments of the protein were 99% homologous to that of the deduced amino acid sequence of a cDNA reported to correspond to phosphatidylinositol-specific phospholipase C-alpha. The purified trifluoroacetylated 58 kDa protein or native 58 kDa protein, however, did not have phosphatidylinositol-specific phospholipase C activity. We conclude that the reported cDNA of phosphatidylinositol-specific phospholipase C-alpha may encode for a microsomal protein of unknown function.

Amino Acid Sequence↗
PubMed1991

Ligand binding and protein relaxation in heme proteins: a room temperature analysis of NO geminate recombination.

Ultrafast absorption spectroscopy is used to study heme-NO recombination at room temperature in aqueous buffer on time scales where the ligand cannot leave its cage environment. While a single barrier is observed for the cage recombination of NO with heme in the absence of globin, recombination in hemoglobin and myoglobin is nonexponential. Examination of hemoglobin with and without inositol hexaphosphate points to proximal constraints as important determinants of the geminate rebinding kinetics. Molecular dynamics simulations of myoglobin and heme-imidazole subsequent to ligand dissociation were used to investigate the transient behavior of the Fe-proximal histidine coordinate and its possible involvement in geminate recombination. The calculations, in the context of the absorption measurements, are used to formulate a distinction between nonexponential rebinding that results from multiple protein conformations (substates) present at equilibrium or from nonequilibrium relaxation of the protein triggered by a perturbation such as ligand dissociation. The importance of these two processes is expected to depend on the time scale of rebinding relative to equilibrium fluctuations and nonequilibrium relaxation. Since NO rebinding occurs on the picosecond time scale of the calculated myoglobin relaxation, a time-dependent barrier is likely to be an important factor in the observed nonexponential kinetics. The general implications of the present results for ligand binding in heme proteins and its time and temperature dependence are discussed. It appears likely that, at low temperatures, inhomogeneous protein populations play an important role and that as the temperature is raised, relaxation effects become significant as well.

Binding Sites↗
PubMed1991

Vasoactive intestinal peptide binding sites and fibers in the brain of the pigeon Columba livia: an autoradiographic and immunohistochemical study.

The distribution of vasoactive intestinal peptide (VIP) binding sites in the pigeon brain was examined by in vitro autoradiography on slide-mounted sections. A fully characterized monoiodinated form of VIP, which maintains the biological activity of the native peptide, was used throughout this study. The highest densities of binding sites were observed in the hyperstriatum dorsale, archistriatum, auditory field L of neostriatum, area corticoidea dorsolateralis and temporo-parieto-occipitalis, area parahippocampalis, tectum opticum, nucleus dorsomedialis anterior thalami, and in the periventricular area of the hypothalamus. Lower densities of specific binding occurred in the neostriatum, hyperstriatum ventrale and nucleus septi lateralis, dorsolateral area of the thalamus, and lateral and posteromedial hypothalamus. Very low to background levels of VIP binding were detected in the ectostriatum, paleostriatum primitivum, paleostriatum augmentatum, lobus parolfactorius, nucleus accumbens, most of the brainstem, and the cerebellum. The distribution of VIP-containing fibers and terminals was examined by indirect immunofluorescence using a polyclonal antibody against porcine VIP. Fibers and terminals were observed in the area corticoidea dorsolateralis, area parahippocampalis, hippocampus, hyperstriatum accessorium, hyperstriatum dorsale, archistriatum, tuberculum olfactorium, nuclei dorsolateralis and dorsomedialis of the thalamus, and throughout the hypothalamus and the median eminence. Long projecting fibers were visualized in the tractus septohippocampalis. In the brainstem VIP immunoreactive fibers and terminals were observed mainly in the substantia grisea centralis, fasciculus longitudinalis medialis, lemniscus lateralis, and in the area surrounding the nuclei of the 7th, 9th, and 10th cranial nerves. The correlation between the distribution of VIP binding sites and immunoreactive fibers and terminals was assessed in a restricted number of regions. A qualitatively good matching was found in the area corticoidea dorsolateralis, hyperstriatum dorsale, hyperstriatum accessorium, nucleus septi lateralis, nuclei dorsomedialis and dorsolateralis thalami, and in some hypothalamic areas. A striking mismatch occurred in the hyperstriatum ventrale, neostriatum, tectum opticum (high to moderate density of binding sites but only few immunoreactive profiles), and in the tuberculum olfactorium, median eminence, and spinal cord (lower density of binding sites but abundant immunoreactive profiles). The paleostriatum, lobus parolfactorius, and ectostriatum were virtually devoid of both binding sites and immunoreactive profiles. The results are discussed in relation to the known actions of VIP in the rodent and avian brain and are compared with previous observations on the distribution of VIP binding sites in the central nervous system of other vertebrates.

Animals↗
PubMed1991

Tissue acylation by the chlorofluorocarbon substitute 2,2-dichloro-1,1,1-trifluoroethane.

Hydrochlorofluorocarbons (HCFCs) are being developed as substitutes for ozone-depleting chlorofluorocarbons (CFCs); because widespread human exposure to HCFCs may be expected, it is important to evaluate their toxicities thoroughly. Here we report studies on the bioactivation of the CFC substitute 2,2-dichloro-1,1,1-trifluoroethane (HCFC-123) to an electrophilic intermediate that reacts covalently with liver proteins. HCFC-123 and its analog halothane (2-bromo-2-chloro-1,1,1-trifluoroethane) were studied in rats by 19F NMR spectroscopy, and we found that a trifluoroacetylated lysine adduct was formed with liver proteins. Also, the pattern of proteins immunoreactive with hapten-specific anti-trifluoroacetylprotein antibodies was identical in livers of HCFC-123- and halothane-exposed rats. Because halothane causes an idiosyncratic, and sometimes fatal, hepatitis that is associated with an immune response against several trifluoroacetylated liver proteins, the present findings raise the possibility that humans exposed to HCFC-123 or structurally related HCFCs may be at risk of developing an immunologically mediated hepatitis.

Acylation↗
PubMed1991

Towards time-resolved diffraction studies with glycogen phosphorylase.

Laue diffraction with high intensity, broad-spectrum synchrotron radiation sources allows three-dimensional data sets on protein crystals to be recorded in seconds or milliseconds and opens the way for time-resolved studies on dynamic events in crystals. This chapter briefly reviews the field and describes progress towards time-resolved studies with glycogen phosphorylase. Methods for the synchronization of the start of reaction with the start of data collection have been developed for the phosphorolytic reaction of glycogen phosphorylase. The compound 3,5-dinitrophenylphosphate is photolabile, yielding Pi and the by-product, 3,5-dinitrophenol, which is non-reactive with the enzyme. Spectroscopic studies show that the compound has good quantum yield and that photolysis is rapid (greater than 1000 s-1). Release of the dinitrophenylate anion, following a pulse of light from a xenon flash lamp, has been monitored with a diode array spectrophotometer specially adapted for measurements on crystals. In a laboratory X-ray experiment with crystals of glycogen phosphorylase b, release of Pi and formation of the enzyme-product complex have been demonstrated. The way is now open for Laue diffraction studies on the catalytic reaction in the crystal.

Crystallography↗
PubMed1991

Differential distribution of somatostatin receptor subtypes in rat brain revealed by newly developed somatostatin analogs.

Somatostatin receptor subtypes were labeled with the somatostatin analogs [125I]CGP 23996 and [125I]MK 678 and the distribution of these receptors in rat brain was investigated using quantitative autoradiographic techniques. [125I]CGP 23996 and [125I]MK 678 specifically label different populations of somatostatin receptors in rat brain. In a number of brain regions striking differences in the distribution of the somatostatin receptor subtypes labeled by each peptide were observed. High levels of binding sites for both [125I]CGP 23996 and [125I]MK 678 were present in the cerebral cortex, CA1 region and subiculum of the hippocampus. In contrast, high levels of [125I]MK 678 binding were found in the dentate gyrus of the hippocampus while few [125I]CGP 23996 binding sites were observed in this brain region. [125I]CGP 23996 binding was detected in the central region of the interpeduncular nucleus whereas the dorsal and lateral subnuclei of this brain area expressed mainly somatostatin receptors with high affinity for MK 678. The locus coeruleus and regions of the superior colliculus and hypothalamus selectively express [125I]MK 678-sensitive somatostatin receptors. Furthermore, limbic structures such as the lateral septum, the nucleus accumbens and ventromedial striatum had much higher levels of [125I]MK 678 binding sites than [125I]CGP 23996 binding sites. Differences in the expression of the somatostatin receptor subtypes were also detected in the substantia nigra. [125I]CGP 23996 binding was present in the pars reticulata but not the pars compacta whereas the reverse distribution for [125I]MK 678 binding sites was observed. The differential distribution of [125I]CGP 23996 and [125I]MK 678 binding sites in rat brain supports the hypothesis that these peptides selectively label different somatostatin receptor subtypes in the central nervous system.

Animals↗
PubMed1991

A rapid-afterloading vaginal cylinder for 137Cs brachytherapy.

A small diameter, single-step afterloading vaginal cylinder has been developed for 137Cs brachytherapy of the vaginal cuff and walls. The Lucite cylinder has an interior slot of rectangular cross section running along its length and opening to the outside of the patient. A single rectangular Lucite insert, containing preselected sources, fits into the slot. Two short sources in the tip form a T with the sources along the vaginal canal and provide a high, uniform dose rate across the spherical tip of the applicator. A catalog of 30 precalculated loadings provides surface dose rates at the tip which vary from 140 to 230 cGy/hr for standard source strengths, as well as a variety of dose rate profiles along the vaginal wall. The applicator is tapered at the base for comfortable and secure placement, and the single-step insertion reduces both patient discomfort and personnel radiation exposure for this procedure.

Brachytherapy↗
PubMed1991

Transforming growth factor-beta stimulates production of insulin-like growth factor-binding protein-3 by human skin fibroblasts.

Human neonatal fibroblasts in monolayer culture produce insulin-like growth factor-binding protein-3 (IGFBP-3), the IGF-binding subunit of the circulating 140-kDa IGFBP complex. We now report that transforming growth factor-beta (TGF beta) is a potent stimulator of IGFBP-3 production by fibroblasts. After 72-h incubation with 1 ng/ml TGF beta, the levels of IGFBP-3 in conditioned medium were increased 5.8 +/- 1.2-fold (mean +/- SE; n = 9). Half-maximal stimulation of IGFBP-3 production was seen at 0.4 +/- 0.05 ng/ml TGF beta (n = 4). Coincubation of fibroblasts with TGF beta and either IGF-I or IGF-II at 50 ng/ml enhanced IGFBP-3 production 1.5- to 2-fold compared to TGF beta alone. As previously reported, fetal calf serum (FCS) stimulated IGFBP-3 production 5- to 6-fold; 1 ng/ml TGF beta increased the stimulated production of IGFBP-3 by FCS a further 2.5- to 3.5-fold. Acidification of FCS before addition enhanced the stimulation of IGFBP-3 compared to that caused by untreated FCS, but decreased further potentiation by TGF beta. This effect of acidified FCS was reversed by a neutralizing antibody to TGF beta. Similarly, the stimulation of IGFBP-3 levels by human serum or conditioned serum-free fibroblast medium was significantly increased by acidification of serum or medium before addition and was reversed by TGF beta antibody. These observations are consistent with acid-mediated activation of latent TGF beta added in serum or secreted by fibroblasts. Since IGFBP-3 is known to regulate IGF activity in fibroblasts, these results raise the possibility that TGF beta may modulate IGF actions in these cells by stimulating the production of IGFBP-3.

Animals↗