Biomedical subjects
P Adams
Publications and source records attributed to P Adams.
Ocular copper deposition associated with benign monoclonal gammopathy and hypercupremia.
The deposition of copper on Descemet's membrane and the anterior and posterior lens capsule with extreme hypercupremia and IgG hypergammaglobulinemia has been previously described with multiple myeloma and pulmonary carcinoma. A 66-year-old man presenting with blurred vision was found to have bilateral golden-brown metallic dust-like deposits on the central region of Descemet's membrane and the anterior and posterior lens capsule. Laboratory investigations revealed an elevated serum copper level 10 times the normal level associated with a monoclonal gammopathy and a normal ceruloplasmin level. Copper binding to the serum proteins was investigated by three biochemical methods. The results demonstrated that the major copper binding fraction in the serum was IgG. N-terminal amino acid analysis of the IgG did not find the sequence of Asp-Ala-His, which has been shown to be a copper binding site in albumin. This is the first report of benign monoclonal gammopathy being associated with the ocular deposition of copper.
Characterization of IMT1, myo-inositol O-methyltransferase, from Mesembryanthemum crystallinum.
A full-length transcript, Imt1, encoding myo-inositol O-methyltransferase (EC 2.1.1.X) from the halophyte Mesembryanthemum crystallinum was expressed in Escherichia coli. The enzyme, IMT1, uses S-adenosyl-L-methionine to methylate myo-inositol to form D-ononitol. IMT1 with a monomeric mass of 41,000 was isolated by ammonium sulfate fractionation, gel filtration and ion exchange chromatography to apparent purity on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The N-terminal amino acid sequence of the purified recombinant enzyme was identical to that encoded by the cDNA sequence. The apparent Km for S-adenosylmethionine was 0.18 mM with a Vmax of 1550 pkat/mg protein. The Km for myo-inositol was 1.32 mM. The reaction became substrate-inhibited by concentrations of S-adenosylmethionine greater than 0.5 mM. Inositol methyltransferase was competitively inhibited 50% with 0.01 mM S-adenosyl-homocysteine, while 1 mM homocysteine, homoserine, or adenosine did not inhibit. The enzyme exhibited a pH optimum of 7.8 and a temperature optimum of 37 degrees C. Activity of the isolated inositol methyltransferase was stable when stored at 4 degrees C.
Avalanches and Slow Relaxation: Dynamics of Ultrathin Granular Superconducting Films in a Parallel Magnetic Field.
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Is the comorbidity between social phobia and panic disorder due to familial cotransmission or other factors?
BACKGROUND: We previously reported significantly elevated rates of social phobia in relatives of probands with panic disorder compared with relatives of other proband groups. This study further investigates the relationship between social phobia and panic disorder. METHOD: This sample is from a family study that included 193 probands from four mutually exclusive groups (patients with panic disorder, patients with panic disorder and major depression, patients with early-onset major depression, and normal controls) and 1047 of their adult first-degree relatives. Best-estimate diagnoses were completed using DSM-III-R criteria. RESULTS: Social phobia and agoraphobia aggregate in the families of probands with panic disorder without major depression. Social phobia frequently co-occurs with panic disorder in relatives, but the risk for comorbidity does not vary across proband groups. CONCLUSIONS: The familial aggregation of social phobia with panic disorder may be explained by the aggregation of panic disorder in relatives of probands with panic disorder combined with the tendency for panic disorder to occur comorbidly with social phobia in individuals.
Social work in pediatric oncology: a family needs assessment.
When a child is diagnosed with cancer, the family is confronted with meeting both the physical and psychosocial needs of the child and maintaining normal family functioning. This study assessed the perceived psychosocial needs of 77 families who have a child diagnosed with cancer. Preliminary results suggest practical application for social work interventions in specific areas such as the development of an informal support network, enhancement of communication within families concerning the disease, the need for adequate information at various stages of the disease, and continued supportive services for the family.
The best medicine. Interview by Jim Montague.
Laughter can be crucial to patient care, but physician and clown Patch Adams, M.D., sees nothing funny about the greed he finds in the nation's health care system and in current reform plans. Adams has spent almost 25 years infusing practitioners with a sense of humor. This philosophy extends into his work as founder of the not-for-profit Gesundheit Institute, which is trying to build an "ultimate fantasy" hospital on 310 acres in rural West Virginia. So far, he's raised $1.1 million, built one of three main buildings, and broken ground on a second. However, millions of dollars still need to be raised. Adams sees the very notion of his dream hospital as a necessary pie in the face of the traditional health care system. Besides speaking and performing, Adams takes groups of clowns to Russia, where they perform in hospitals, orphanages, prisons and on the street. Adams has co-authored a book about his philosophies, Gesundheit, and sold the rights to a Hollywood studio. He spoke recently with staff editor Jim Montague.
LABMAN and LINKMAN: a data management system specifically designed for genome searches of complex diseases.
Two programs have been developed to manage linkage analysis data. The first program, LABMAN, is a comprehensive laboratory data management system organizing pedigrees, blood DNA samples, DNA markers, Southern blot or polyacrylamide gels, autoradiographs, and marker-allele typings generated from these samples. Output includes mendelization checks for genetic incompatibilities in typings and formatted files ready for linkage analysis. LABMAN can also compress highly polymorphic allele systems into smaller allele systems facilitating analysis of large systems. The second program, LINKMAN, provides data management for lod score output from linkage analyses. It reads linkage analysis output files, calculates lod scores by family, associates lod scores with specific marker and family identifiers, and stores these data in a database where they can be combined with lod scores from previous analyses. LINKMAN easily incorporates any of a wide variety of genetic models. It produces formatted output of lod scores by user-specified criteria for reports or as ASCII files for input to other programs. If desired, tests of homogeneity of linkage across families can be run via the HOMOG program [Ott, 1991] and their output included in reports. The programs include features critical for conducting genome searches of complex diseases: They are easy-to-use, well-tested, and reliable. Data from multicenter investigations can be easily combined for analysis. Moreover, they include extensive error-checking capabilities, and they are specifically set up to protect blindness between laboratory workers and data analysts. LABMAN and LINKMAN are currently available free of charge under DOS.
The familial aggregation of panic disorder by source of proband ascertainment.
Estimates of familial aggregation of psychiatric disorder obtained from relatives of probands ascertained in treatment settings may differ from estimates obtained from relatives of probands ascertained from the general population. In this paper we investigate this hypothesis for panic disorder, by comparing the degree of familial aggregation of panic disorder in relatives of probands with panic disorder ascertained from either a specialty anxiety clinic, a specialty depression clinic or a population survey, respectively. Results for panic disorder do not suggest that familial rates are associated with source of proband ascertainment. Results show that the rates of panic disorder in relatives were similar by proband source. This suggests that familial rates of panic disorder are not associated with proband ascertainment and that selecting probands from treatment clinics rather than from the general population does not necessarily lead to greater estimates of familial aggregation of panic disorder. Further research is needed to determine if this finding can be generalized to other psychiatric disorders.
Therapy-related acute myeloid leukaemia following immunosuppression with azathioprine for polymyositis.
A 52-year-old man developed therapy-related acute myeloid leukemia (AML) following prolonged immunosuppression with azathioprine for polymyositis. Karyotypic analysis showed deletions of the short arm of chromosome 7 and the long arm of chromosome 5. The importance of recognizing this potential complication while treating benign rheumatological and immunological diseases with purine analogues like azathioprine is emphasized. Therapy-related AML is a poor prognostic group that does not respond favourably to standard induction therapy.
(S)-3-methyl-5-(1-methyl-2-pyrrolidinyl) isoxazole (ABT 418): a novel cholinergic ligand with cognition-enhancing and anxiolytic activities: I. In vitro characterization.
A diversity of nicotinic acetylcholine receptor (nAChR) subtypes has been identified in mammalian brain using recombinant DNA technology. Alterations in the activity of these acetylcholinegated ion channels have been implicated in a number of central nervous system disorders including Alzheimer's disease (AD). The potential therapeutic usefulness of (-)-nicotine [(S)-3-(1-methyl-2-pyrrolidinyl) pyridine], the prototypic agonist at nAChRs, is severely limited by side effects that are the result of activation of both cholinergic and noncholinergic pathways in the central and peripheral nervous systems. This study sought to determine the in vitro selectivity of (S)-3-methyl-5-(1methyl-2-pyrrolidinyl)isoxazole (ABT 418), a novel analog of (-)-nicotine in which the pyridine ring was replaced with an isoxazole bioisotere, to activate nAChRs. ABT 418 was a potent inhibitor of [3H]-cytisine binding to nAChR in rat brain (Ki = 3 nM) but was inactive (Ki > 10,000 nM) in 37 other receptor/neurotransmitter-uptake/enzyme/transduction system binding assays, including those for alpha-bungarotoxin, muscarinic and 5-hydroxytryptamine3 receptors. In PC12 cells, patch-clamp studies indicated that ABT 418 was an agonist with an EC50 value of 209 microM, a potency to activate cholinergic channel currents some 4-fold less than that of (-)-nicotine (52 microM). Channel current responses elicited by ABT 418 were prevented by the cholinergic channel blocker, mecamylamine. ABT 418 was also approximately 10-fold less potent (EC50 value = 380 nM) than (-)-nicotine (40 nM) in increasing [3H]-dopamine release from rat striatal slices, an effect that was blocked by the nAChR antagonist, dihydro-beta-erythroidine (10 microM).2+ In contrast, ABT 418 appeared equipotent with (-)-nicotine in enhancing 86Rb+ flux from mouse thalamic synaptosomes. ABT 418 demonstrated an in vitro pharmacological profile of cholinergic channel activation that was robust at some nAChR, but not others. The reasons for this are unclear. However, a nAChR subtype selectivity may account for the in vitro potency differences of ABT 418 on various neurotransmitter systems, and the substantial separation between the cognitive enhancement/anxiolytic benefits, and the reduced central nervous system side-effect liabilities seen in vivo. ABT 418 represents the first neuronal nAChR ligand that differentiates the toxicities/liabilities and other negative aspects normally associated with liabilities and other negative aspects normally associated with (-)-nicotine from the potential pharmacological benefits of selective cholinergic channel activation.
(+/-)-Epibatidine elicits a diversity of in vitro and in vivo effects mediated by nicotinic acetylcholine receptors.
(+/-)-Epibatidine, exo-2-(6-chloro-3-pyridyl)-7-azabicyclo-[2.2.1] heptane, is a novel, potent analgesic agent that acts through nicotinic acetylcholine receptor (nAChR) mechanisms. This study sought to establish whether (+/-)-epibatidine, like (-)-nicotine, also displays a wide diversity of behavioral responses that are known to be elicited by nAChR activation or whether it demonstrates subtype selectivity for its interactions with nAChRs.(+/-)-Epibatidine displaced [3H](-)-cytisine binding to the alpha 4 beta 2 nAChR subtype in rat brain membranes with high affinity (Ki, 43 pM). The compound was approximately 5000-fold less potent (Ki = 230nM) in the displacement of [125I] alpha-bungarotoxin binding from the alpha-bungarotoxin-sensitive nAChR subtype present in rat brain but was a potent inhibitor (Ki, 2.7 nM) of [125I] alpha-bungarotoxin binding to the nAChR subtype in Torpedo electroplax, which is similar to that present in the neuromuscular junction. Functionally, (+/-)-epibatidine enhanced 86Rb+ flux in IMR 32 cells with an EC50 value of 7 nM. It was some 3000-fold more potent than (-)-nicotine (EC50 value, 21,000 nM) and was approximately 150-fold more potent (EC50 value, 0.4 nM) than (-)-nicotine (EC50 value = 60 nM) in increasing [3H]dopamine release from rat striatal slices. Remarkably, (+/-)-epibatidine was 40% to 50% more efficacious than (-)-nicotine in both functional assays. Both functional effects were blocked by the nAChR channel blocker, mecamylamine (100 microM). (+/-)-Epibatidine was 300 to 1000 times more potent than (-)-nicotine in the reduction of body temperature and locomotor activity in mice.(ABSTRACT TRUNCATED AT 250 WORDS)
Anion exchange separation and pulsed amperometric detection of inositols from flower petals.
A rapid and specific method for the separation of cyclic sugar alcohols by anion exchange HPLC and subsequent detection by pulsed amperometry is presented. The cyclitols include the inositols and O-methyl inositols. Although examples use plant extracts the method has general application and is suitable for detecting as little as 10 pmol of substance. Carbohydrates are weak acids with pKa values typically above 12. While separation of most monosaccharides on high-performance anion exchange columns in aqueous NaOH is adequate, the ionization of inositols and O-methyl inositols is weak and their separation is poor. Use of a high-capacity anion exchange column separated the inositols well but the more ionized sugars were tightly retained. Automatic switching of the inositol fraction eluting from the lower-capacity column onto the high-capacity column with subsequent detection by pulsed amperometry gave specific and rapid separations of the inositols with a turnaround time of 16 min. As an example of application, we chose the separation and identification of cyclic and acyclic sugar alcohols in flower petals from a variety of plants. There was an apparent correlation between the postharvest longevity of flowers and the content of inositols, particularly D-pinitol.
Heparin-binding fibroblast growth factors and prostate cancer.
Studies of model rat prostate tissue and derived cells indicate the insulin-like (IGF), epidermal growth factor (EGF), transforming growth factor beta (TGF-beta) and heparin-binding fibroblast growth factor (HBGF) families and their receptors may play important roles in regulation of normal prostate cell growth. Tumor cells at different levels in the progression from slow-growing, hormone-dependence to fast-growing, hormone-independence exhibit distinct alterations in expression of specific growth factors and their receptor phenotype. Distinct IGF-I and HBGF mRNAs are constitutively expressed in the mesenchymal cells of slow-tumors, but alteration in HBGF receptor phenotype occurs in the epithelial cells. Fast-tumors exhibit even higher constitutive expression of multiple HBGFs. Splice variants in cDNA for the HBGF receptor in fast-tumors suggest constitutive expression of an intracellular receptor, that together with intracellular HBGFs, may constitute an intracellular autocrine system that is independent of exogenous hormones and growth factors.
Naltrexone in autistic children: behavioral symptoms and attentional learning.
OBJECTIVE: To assess critically the short-term efficacy and safety of naltrexone in autistic children and its effects on discrimination learning in the laboratory. METHOD: A parallel group design was employed. After a 2-week placebo baseline period, children were randomly assigned either to naltrexone or to placebo for a period of 3 weeks followed by a one-week posttreatment placebo period. Multiple raters and rating scales were employed in a variety of conditions. Forty-one children, all inpatients, ages 2.9 to 7.8 years, completed the study. Naltrexone reduced hyperactivity and had no effect on discrimination learning in the laboratory. There was a suggestion that it had a beneficial effect on decreasing self-injurious behavior. Untoward effects were mild and transient. CONCLUSION: In the present study, naltrexone significantly reduced only hyperactivity, and no serious untoward effects were observed. The effectiveness of naltrexone in the treatment of autism and self-injurious behavior requires additional assessment in a sample of children with moderate to severe self-injurious behavior.
Maternal paroxysmal supraventricular tachycardia treated with adenosine.
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