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Biomedical subjects

J L Martin

Publications and source records attributed to J L Martin.

At least 253 records · Page 14Linked to original sources

College report analyzes recent Medicare data.

The growth in Medicare payments to physicians continues to be a major concern for federal policymakers. In order to gain a better understanding of the trends in Medicare spending for surgical services, the College obtained Medicare Part B claims data for the years 1986 through 1988, which were analyzed and published in a report that was issued in December 1990. The following article describes the federal activity that prompted the College to commission this report on Medicare Part B spending trends, and presents some of the significant results of the analysis.

Fee Schedules↗

Comparison of the binding of glucose and glucose 1-phosphate derivatives to T-state glycogen phosphorylase b.

The binding of T-state- and R-state-stabilizing ligands to the catalytic C site of T-state glycogen phosphorylase b has been investigated by crystallographic methods to study the interactions made and the conformational changes that occur at the C site. The compounds studied were alpha-D-glucose, 1, a T-state-stabilizing inhibitor of the enzyme, and the R-state-stabilizing phosphorylated ligands alpha-D-glucose 1-phosphate (2), 2-deoxy-2-fluoro-alpha-D-glucose 1-phosphate (3), and alpha-D-glucose 1-methylenephosphonate (4). The complexes have been refined, giving crystallographic R factors of less than 19%, for data between 8 and 2.3 A. Analysis of the refined structures shows that the glucosyl portions of the phosphorylated ligands bind in the same orientation as glucose and retain most of the interactions formed between glucose and the enzyme. However, the phosphates of the phosphorylated ligands adopt different conformations in each case; the stability of these conformations have been studied by using computational methods to rationalize the different binding modes. Binding of the phosphorylated ligands is accompanied by movement of C-site residues, most notably a shift of a loop out of the C site and toward the exterior of the protein. The C-site alterations do not include movement of Arg569, which has been observed in both the refined complex with 1-deoxy-D-gluco-heptulose 2-phosphate (5) [Johnson, L. N., et al (1990) J. Mol. Biol. 211, 645-661] and in the R-state enzyme [Barford, D. & Johnson, L. N. (1989) Nature 340, 609-616]. Refinement of the ligand complexes has also led to the observation of additional electron density for residues 10-19 at the N-terminus which had not previously been localized in the native structure. The conformation of this stretch of residues is different from that observed in glycogen phosphorylase a.

Animals↗

Autoradiographic analysis of the distribution of vasoactive intestinal peptide binding sites in the vertebrate central nervous system: a phylogenetic study.

The distribution of vasoactive intestinal peptide (VIP) binding sites in the brain of several vertebrate species was examined by in vitro autoradiography on slide-mounted sections. This study included fish, frog, snake, pigeon, rat, mouse, guinea pig, cat and monkey brain. A fully characterized, monoiodinated form of vasoactive intestinal peptide (M-125I-VIP), which maintains the biological activity of the native peptide in the central nervous system (CNS), was used throughout the study. Among the lower vertebrate species, no significant specific binding was found in the fish brain, whereas in the frog and snake brain, specific VIP binding sites were observed, mainly in the telencephalon. In the pigeon brain, high densities of VIP binding sites were localized in the hyperstriatum, neostriatum, archistriatum, hippocampal area, dorsolateral cortical area and in the optic tectum. Ectostriatum and paleostriatum augmentatum displayed lower densities of specific binding. In mammals, the highest concentrations of VIP binding sites were observed in the rodent brain. In the rat, mouse and guinea pig brain, high densities were detected in the olfactory bulb, external layers of the cerebral cortex, dentate gyrus, midline thalamic nuclei, geniculate nuclei, some hypothalamic nuclei, superior colliculus and locus coeruleus. Intermediate densities were found in amygdala, caudate-putamen, septum and nucleus accumbens, CA1-CA3 fields of the hippocampus and central gray. The cerebellum of these species presented high densities of VIP binding sites, with species to species differences in their localization. The non-specific binding was, however, increased in the rodent cerebellum. Lower densities of VIP binding sites were observed in the cat and monkey CNS. In these two species, the non-specific binding was considerably higher than in the lower mammals brain. In the cat and monkey brain, as in the lower mammals, the highest densities were revealed in the neocortex, dentate gyrus, thalamic nuclei and some midbrain structures including substantia nigra and locus coeruleus. In all the species studied, the white matter was never labeled with M-125I-VIP. This study suggests that VIP binding sites appear relatively early in the evolution of the vertebrate CNS. The most important densities of specific VIP binding sites are observed in the pigeon and rodent brain, whereas the cat and monkey present a marked increase in non-specific binding. It is interesting to note that the distribution of VIP binding sites as revealed by autoradiography is quite conservative in terms of evolution and indicates an association, although non-exclusive, of VIP receptors with brain regions involved in the processing of specific sensory inputs.

Animals↗

Purification and properties of a novel insulin-like growth factor-II binding protein from transformed human fibroblasts.

We have purified an insulin-like growth factor (IGF) binding protein from culture medium conditioned by the SV40-transformed human fibroblast line AG 2804. This protein (TFBP), of apparent Mr = 34,000 on gel electrophoresis, binds IGF-II with an affinity constant of 3 x 10(11) liters/mol, 100-fold higher than its affinity for IGF-I. Amino-terminal sequencing indicated no structural relationship to any previously characterized IGF binding protein or receptor. Like a protein in cerebrospinal fluid with selective affinity for IGF-II, TFBP does not bind IGF-I lacking the amino-terminal tripeptide. In contrast with binding proteins produced by normal human fibroblasts, TFBP does not cross-react in radioimmunoassays for the plasma protein IGFBP-3 or the amniotic fluid protein IGFBP-1; however, after affinity labeling with IGF-II, it is immunoprecipitable by an anti-IGFBP-3 antiserum. The cerebrospinal fluid binding protein is not precipitable by this antiserum and appears smaller than TFBP. TFBP reacts with wheat germ agglutinin, but not with concanavalin A, or with the acid-labile subunit of the high molecular weight serum IGF binding protein complex. Furthermore, since RNA from transformed fibroblasts does not hybridize with an IGFBP-3 cDNA probe, TFBP is not derived from the IGFBP-3 gene. We conclude that, although TFBP appears to share an epitope with IGFBP-3, it is distinctly different from any previously described IGF binding protein.

Amino Acid Sequence↗

The influence of social support on AIDS-related grief reaction among gay men.

This paper examines the relationships between instrumental and emotional social support and the experience of grief reaction in a sample of 180 gay men who had lost a lover or close friend to AIDS during the first 5 years of the epidemic. Structured, face-to-face interviews were conducted in mid-1985. Grief reaction was assessed through a newly developed 12-item scale (alpha = 0.85). Availability and adequacy of instrumental and emotional support were assessed with reference to the tasks of caretaking and emotional pain experienced during the lover's or close friend's illness with AIDS. The findings indicate that gay men who lost a lover or close friend to AIDS experienced symptoms of grief similar to those reported in studies of bereaved spouses and parents. The intensity of these grief reactions appears to be influenced by a number of factors. First, more intense grief reactions were observed among those who had taken care of their lover or close friend during his illness compared with those who did not act as caretakers. Second, while the simple availability of instrumental and emotional support was unrelated to grief reactions, the perceived adequacy of both types of support was strongly related to the level of grief. Respondents who had received inadequate help with caretaking responsibilities experienced more intense symptoms of grief subsequent to the death compared with those who reported receiving adequate caretaking support. Similarly, respondents who did not obtain adequate emotional support for the pain they experienced during the course of the illness reported more intense symptoms of grief compared with those who felt they had received adequate support.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗

Drug use and unprotected anal intercourse among gay men.

Conducted a longitudinal study of 604 New York City gay men to examine the link between unprotected insertive and receptive anal intercourse and drug use with sex. Data spanning four 12-month periods from 1980 to 1987 indicated that the link between drug use and high-risk sex diminished as the acquired immunodeficiency syndrome (AIDS) epidemic progressed. Strong and significant cross-sectional associations (average r = .30, p less than .0001) were found between drug use with sex and both types of anal intercourse in the year prior to the onset of AIDS. By 1987 the magnitude of these associations was markedly reduced (average r = .09, p less than .05). Longitudinal results indicate that, although cessation of drug use with sex is associated with subsequent lower rates of unprotected anal intercourse, initiation of drug use with sex is not associated with subsequent increases in this sexual activity. These findings support both causal and noncausal interpretations of the link between substance use and high-risk sex among gay men.

HIV Infections↗

Production of an insulin-like growth factor (IGF)-inducible IGF-binding protein by human skin fibroblasts.

Neonatal human skin fibroblasts produce insulin-like growth factor-binding proteins (IGFBPs) that have the potential to modulate the actions of the growth factors. We have examined the IGFBPs secreted by monolayer cultures of neonatal fibroblasts by ligand blotting with [125I]IGF-II and immunoblotting with antisera raised against three well characterized IGFBPs: IGFBP-1, IGFBP-2, and IGFBP-3. As detected by ligand blotting, medium from untreated fibroblasts contained IGFBP-3, a second IGFBP which appeared as a doublet of 29-31 K, and a smaller protein of 22 K. Within 10 h of the addition of 50 ng/ml IGF-I, a markedly increased level of production of the 29-31 K IGFBP doublet was detectable, with levels increasing 8- to 9-fold by 24 h compared to that in untreated samples. IGF-I was approximately twice as potent as IGF-II at inducing 29-31 K IGFBP, with a half-maximal response at 15.4 +/- 2.7 ng/ml IGF-I and 26.6 +/- 1.6 ng/ml IGF-II (n = 3). Insulin tested at 1 microgram/ml did not induce 29-31 K IGFBP. Neither GH nor the acid-labile subunit of the circulating high mol wt IGFBP complex induced 29-31 K IGFBP or affected its induction by IGF-I or IGF-II. Immunoblotting demonstrated that IGF-inducible IGFBP did not react with antibodies to IGFBP-1, IGFBP-2, or IGFBP-3. These results indicate that IGF-I and IGF-II induce an IGFBP that is different from previously characterized human IGFBPs.

Cell Transformation, Neoplastic↗

Antibody assays for the detection of patients sensitized to halothane.

Sera from patients with a clinical diagnosis of halothane hepatitis have been shown to contain antibodies that react with liver microsomal proteins (100, 76, 59, 57, and 54 kDa) covalently altered by the trifluoroacetyl (TFA) halide metabolite of halothane. In the present study, rapid and sensitive enzyme-linked immunosorbent assays for the detection of these antibodies have been evaluated. A recently described method that utilizes TFA-rabbit serum albumin as test antigen was studied employing a large population of halothane hepatitis and control patients. Several problems were discovered with the assay that were not previously recognized. The assay was then compared directly with methods that utilize as test antigens either liver microsomes or purified TFA proteins from halothane-treated rats. Sixty-seven percent of patients with a clinical diagnosis of halothane hepatitis tested positive for antibodies when the test antigens were either TFA-rabbit serum albumin or liver microsomes. This value was increased to 79% when the purified TFA-57 kDa, TFA-76 kDa, and TFA-100 kDa proteins were used as test antigens. These results indicate that the specificity and sensitivity of enzyme-linked immunosorbent assay methods for the detection of patients' antibodies may be increased significantly by utilizing the purified TFA microsomal proteins as test antigens.

Animals↗

Behavioural changes in intravenous drug users in Geneva: rise and fall of HIV infection, 1980-1989.

In the early 1980s, more than 90% of intravenous drug users (IVDUs) shared needles and syringes in Geneva. The prevalence of antibodies to HIV in the sera of outpatient IVDUs increased from 6% in 1981 to 38% in 1983; it was, however, still only 37% in 1988. IVDUs starting methadone maintenance in 1987-1989 had a seroprevalence rate of 22%. In 1989 the percentage of IVDUs exchanging syringes and needles fell to only 5% of seropositive addicts. Only one seroconversion was observed in 1094 patient-months of observation in 1988-1989, which was probably due to sexual contact. The evidence suggests that, in the IDVUs studied, transmission of HIV has diminished since the early 1980s.

Adolescent↗

Involvement of the carboxyl-terminal propeptide of beta-glucuronidase in its compartmentalization within the endoplasmic reticulum as determined by a synthetic peptide approach.

The proenzyme form of beta-glucuronidase is compartmentalized in large quantities within the endoplasmic reticulum by binding to the esterase, egasyn. Also, the propeptide of the proenzyme form of beta-glucuronidase is likely located at the carboxyl terminus. We have, therefore, tested if this carboxyl-terminal peptide is important in binding to egasyn. A polyclonal antibody to a 30-mer synthetic peptide, corresponding to the carboxyl-terminal 30 amino acids of pro-beta-glucuronidase, provided evidence that egasyn binds to the carboxyl terminus of beta-glucuronidase. This antibody interacted with proenzyme beta-glucuronidase-egasyn complexes in which one, two, or three egasyn molecules were bound to the beta-glucuronidase tetramer, but not with those complexes (M4) which contained four egasyn molecules. We interpret these results as indicating that all available carboxyl termini of the beta-glucuronidase proenzyme tetramer are shielded by egasyn in the M4 complexes. The same antibody did not recognize the mature lysosomal form of beta-glucuronidase, indicating that only the proenzyme form of microsomal beta-glucuronidase contains the original carboxyl terminus. Also, the synthetic 30-mer was found to be a specific and potent inhibitor (50% inhibition at 1.3 microM) of the esterase activity of purified egasyn but exhibited little inhibitory activity toward other purified esterases including a rat trifluoroacetylated esterase or egasyn esterase from another species. Together, these data describe a potent interaction of the exposed carboxyl terminus of precursor glucuronidase with the esterase catalytic site of egasyn, which in turn results in the specific localization of glucuronidase within the lumen of the endoplasmic reticulum.

Amino Acid Sequence↗

High molecular weight insulin-like growth factor binding protein complex. Purification and properties of the acid-labile subunit from human serum.

In the human circulation, the insulin-like growth factors (IGFs) circulate as part of a growth hormone-dependent 125- to 150-kDa complex. This complex has been postulated to contain, in addition to IGFs and one or more IGF-binding proteins, an acid-labile subunit (ALS) which does not itself bind IGFs. In this study, the ALS has been purified 1600-fold from human serum, and its binding properties have been examined. Fresh serum was fractionated on DEAE-Sephadex, and active fractions (determined by radioimmunoassay) were purified by affinity chromatography on an IGF-agarose column saturated with the plasma IGF-binding protein BP-53. After further high performance anion exchange chromatography, an ALS preparation was obtained which contained only an 84-86-kDa protein doublet, converting to a single 70-kDa band on N-glycanase treatment, and having an amino-terminal sequence unrelated to IGF-binding proteins or receptors. Pure ALS formed a complex with BP-53 (Ka approximately 5 x 10(8) M-1), immunoprecipitable by anti-BP-53 antiserum, only in the presence of IGF-I or IGF-II. This complex appeared at approximately 150 kDa on high performance gel chromatography. Pure ALS had no intrinsic IGF-binding activity and no effect on the binding of IGF-I or IGF-II to BP-53. These studies suggest that formation of the high molecular weight IGF-binding protein complex requires ALS, BP-53, and IGF.

Carrier Proteins↗

Barbara Snell Dohrenwend memorial lecture. The impact of AIDS on a gay community: changes in sexual behavior, substance use, and mental health.

This report describes progress made to date on a study of the impact of the AIDS epidemic on the gay community of New York City. Using a model of the life stress process described by Barbara Dohrenwend and her colleagues, the AIDS epidemic was conceptualized as a community stressor resulting in two key stress-inducing events: death of loved ones due to AIDS and potential illness and death of oneself due to infection with human immunodeficiency virus (HIV). It was hypothesized that these stressors would be significantly related to three domains of health outcomes: sexual behavior, drug and alcohol use, and psychological distress. Descriptive trends over time are provided for both the health outcome variables and the stressor variables. Cross-sectional analyses for 3 years of data provide evidence in support of the main hypothesis. The implications of these findings are discussed from the standpoints of methodology, public health, and the psychology of stress processes in community settings.

Acquired Immunodeficiency Syndrome↗

Recognition of ovulatory/anovulatory cycle pattern in adolescents by mucus self-detection.

The high frequency of anovulation during adolescence raises the question of whether a method for the recognition of ovulation by self-detection of cervical mucus patterns is useful in teenagers. We performed a secondary analysis of 1049 completely recorded cycles of 235 teen women 15-17 years of age with a gynecologic age from less than 1 to 7 years. These subjects had learned to monitor their fertility patterns using the Billings Ovulation Method. The cycles were analyzed by the length of the mucus and luteal phases and recorded "peak symptom." Ovulatory cycles were grouped by the length of the luteal phase, short (4-8 days) and average (8-18 days), and plotted against gynecologic age. The frequency of anovulatory cycles was comparable to Vollman's age-stratified monophasic cycle groups. Ovulatory patterns were found at gynecologic ages of 1 year, 49%; 2 years, 60%; 3 years, 72%; 4 years, 61%; 5 years, 86%; and 6 years, 71%. The study proved that teen-age women can distinguish patterns of ovulation and anovulation by self-detection of cervical mucus.

Adolescent↗

Pharmacological studies of voltage-sensitive Ca2+-channels involved in the release of vasoactive intestinal peptide evoked by K+ in mouse cerebral cortical slices.

Three types of voltage-sensitive Ca2+-channels, denominated T, N and L, have recently been identified in the nervous system. This classification is based on both the electrophysiological and pharmacological properties of each type of channel. The increase in free intracellular Ca2+ concentration that results from the opening of voltage-sensitive Ca2+-channels triggers various cellular processes. One such process is the depolarization-induced release of neurotransmitters. Owing to the rather selective sensitivity of each type of voltage-sensitive Ca2+-channel to certain antagonists, attempts have recently been carried out to determine which of the T, N or L channels mediates neurotransmitter release. In the present study we have applied such a strategy to the study of the release of vasoactive intestinal peptide from mouse cerebral cortical slices. The release of vasoactive intestinal peptide evoked by K+ 20 mM is inhibited in a concentration-dependent manner by Co2+, Ni2+ and Mn2+ while it remains unaffected by diltiazem 20 microM, nifedipine 10 microM, omega-conotoxin 1 microM and Cd2+ up to 100 microM. Such a pharmacological profile indicates that voltage-sensitive Ca2+-channels of the N and L types are not involved in the release of vasoactive intestinal peptide. These observations are in contrast to what has been described for amine release in the central nervous system, which appears to be mediated by voltage-sensitive Ca2+-channels of the N type.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Binding proteins for the insulin-like growth factors: structure, regulation and function.

Binding proteins for the insulin-like growth factors (IGF-I and IGF-II) are increasingly being recognized as modulators of IGF actions in both inhibitory and stimulatory ways. At least three distinct classes of binding protein are thought to exist, differing in their primary structures and binding characteristics, although all are able to bind both IGF-I and IGF-II. This review outlines the purification and characterization of the binding proteins that have been identified to date, and describes the regulation of their production and of their levels in the circulation. Current views on their potential biological roles are also discussed.

Amino Acid Sequence↗