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Biomedical subjects

J Frazier

Publications and source records attributed to J Frazier.

At least 19 recordsLinked to original sources

Mania in children with pervasive developmental disorder revisited.

OBJECTIVE: Although a small literature of case reports suggests that mania co-occurs with pervasive developmental disorder (PDD), little is known about this overlap. The authors systematically investigated the overlap between mania and PDD in a consecutive sample of referred youths, examining its prevalence and correlates. It was hypothesized that children with PDD plus manic features have both disorders. METHOD: Subjects were consecutively referred children meeting diagnostic criteria on structured interview for PDD without mania (n = 52), the comorbid condition PDD + mania (n = 14), and mania without PDD (n = 114). All subjects were evaluated using a comprehensive diagnostic battery that included assessment of psychopathology (structured diagnostic interview and Child Behavior Checklist), cognition, and functioning. RESULTS: Of the 727 referred children, 52 met criteria for PDD, 114 met criteria for mania, and 14 met criteria for both. The 14 children with both PDD + mania represented 21% of the PDD subjects and 11% of all manic subjects. Clinical characteristics of PDD were similar in PDD subjects with and without mania, and manic features were similar in manic children with and without PDD. CONCLUSIONS: Children with PDD and mania may suffer from two disorders. Comorbid mania among patients with PDD may be more common than previously thought. Identification of the comorbid condition may have important therapeutic and scientific implications.

Bipolar Disorder

Complex and rapid-cycling in bipolar children and adolescents: a preliminary study.

26 subjects aged 7-18 years were studied. Diagnoses of bipolar disorders were established using the Kiddie-Schedule for Affective Disorders and Schizophrenia-Present Episode Version-1986 modified for DSM-III-R criteria and for rating the number and duration of manic and hypomanic episodes. Complex cycling patterns were observed. These included numerous brief episodes suggesting continuous rapid-cycling in 80.8% of cases. Mean age of onset was early (8.5 +/- 4.4 years). Psychotic phenomena, suicidality, hyperactivity and 'mixed mania' were highly prevalent. Data in this report provide support for complex and rapid-cycling patterns in childhood onset bipolar disorder.

Adolescent

A novel DNA duplex. A parallel-stranded DNA helix with Hoogsteen base pairing.

We show here for the first time that a stable parallel double helix with Hoogsteen pairing can exist independently of the triple helix of which it is a component part. The experiments employ DNA oligonucleotides with mixed sequences of normal bases. These duplexes are distinct from previously reported ribopolynucleotide helices containing bulky substituents which prevent Watson-Crick pairing as well as from parallel duplexes with Donohue, or reversed Watson-Crick, pairing. Stoichiometry is established by mixing curves and gel electrophoresis. Tm depends linearly upon pH, increasing with acidity because of the need to protonate N3 of C. The Tm of the 20-mer studied here is 52 degrees C at pH 5.2 and 0.1 M NaCl. At pH above 6, the molecule rearranges to form an antiparallel duplex with imperfect Watson-Crick pairing and loops, and the Tm is then independent of pH. The CD spectrum of the parallel duplex is very similar to that of the corresponding triple helix but quite different from that of the Watson-Crick helix. The infrared spectrum in the double bond region closely resembles that of the triple helix but, as with the CD, is quite different from that of the Watson-Crick duplex. The infrared spectra of the duplex and triple helix are also nearly identical in the region form 800 to 1000 cm-1, which is sensitive to backbone conformation. The only symmetry element present is a pseudorotational axis coincident with the helix axis of the parallel duplex as well as with the axis of the corresponding triple helix.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Composition

Fowlpox virus host range restriction: gene expression, DNA replication, and morphogenesis in nonpermissive mammalian cells.

Fowlpox virus (FPV), type species of the Avipoxvirus genus, causes a slow-spreading pox disease of chickens. Following infection of mammalian cells there is no evidence of productive replication of FPV although cytopathic effects are induced and FPV recombinants have been shown to express foreign genes from vaccinia virus early/late promoters. Here we report results of a study to investigate the expression of FPV genes, the replication of FPV genomic DNA, and any ultrastructural changes in mammalian cells infected by wild-type virus, undertaken as a first step in elucidating the nature of the block (or blocks) to productive replication of FPV in mammalian cells. Early and late gene expression as well as genomic DNA replication was observed in fibroblast-like cell lines of monkey and human origin. Furthermore, viral morphogenesis was observed in monkey cells, with the production mainly of immature particles though smaller numbers of apparently mature virus particles were observed.

Animals

Extended survival and function of peripheral nerve allografts after cessation of long-term cyclosporin administration in rats.

To determine whether survival and function of peripheral nerve allografts are possible after cessation of long-term cyclosporin (CsA) treatment, we grafted 4.25 cm Lewis rat peripheral nerve allografts (n = 22) into tibial nerve gaps in recipient brown Norway rats. Allograft groups received CsA (15 mg/kg) subcutaneously every day for 20 days and then biweekly for either 5 or 8 months after transplantation. The control group, brown Norway rats with isografts from brown Norway donor rats (n = 2), also received identical CsA treatment. Semimonthly electrophysiologic studies were done from postoperative week 13 until the animals were killed (up to 79 weeks). The corresponding CsA levels in the nerve and blood were recorded from cessation of CsA up to 58 weeks after surgery. No electrophysiologic signs of rejection were observed in any of the 22 allograft recipients treated with CsA for up to 8 months or in 17 of the 22 observed for up to 58 weeks after cessation of CsA. Overall, 5 of 22 allografts were rejected in the first 8 weeks after discontinuation of CsA. Signs of rejection occurred only in the 5-month treatment group and followed the large initial drop in CsA blood level (from 1010 ng/ml to < 25 ng/ml) that occurred within the first 6 weeks after CsA cessation. The two isograft controls demonstrated no electrophysiologic signs of rejection up to 58 weeks after surgery. Peripheral nerve allografts in the rat can regenerate and function on long-term CsA; after cessation of CsA, they can function for extended periods of time without signs of rejection if trace amounts of CsA are present.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials

Structure of d(T)n.d(A)n.d(T)n: the DNA triple helix has B-form geometry with C2'-endo sugar pucker.

The polynucleotide helix d(T)n.d(A)n.d(T)n is the only deoxypolynucleotide triple helix for which a structure has been published, and it is generally assumed as the structural basis for studies of DNA triplexes. The helix has been assigned to an A-form conformation with C3'-endo sugar pucker by Arnott and Selsing [1974; cf. Arnott et al. (1976)]. We show here by infrared spectroscopy in D2O solution that the helix is instead B-form and that the sugar pucker is in the C2'-endo region. Distamycin A, which binds only to B-form and not to A-form helices, binds to the triple helix without displacement of the third strand, as demonstrated by CD spectroscopy and gel electrophoresis. Molecular modeling shows that a stereochemically satisfactory structure can be build using C2'-endo sugars and a displacement of the Watson-Crick base-pair center from the helix axis of 2.5 A. Helical constraints of rise per residue (h = 3.26 A) and residues per turn (n = 12) were taken from fiber diffraction experiments of Arnott and Selsing (1974). The conformational torsion angles are in the standard B-form range, and there are no short contacts. In contrast, we were unable to construct a stereochemically allowed model with A-form geometry and C3'-endo sugars. Arnott et al. (1976) observed that their model had short contacts (e.g., 2.3 A between the phosphate-dependent oxygen on the A strand and O2 in the Hoogsteen-paired thymine strand) which are generally known to be outside the allowed range.(ABSTRACT TRUNCATED AT 250 WORDS)

Chemical Phenomena

Intensive, focused utilization management in a teaching hospital. An exploratory study.

A 3-month study was performed in a teaching hospital to determine the impact of intensive, focused utilization management on the average length of stay and average total charges in a carefully defined group of indigent patients. Prompt admission review was performed, the treatment plan ascertained, and a physician advisor notified. The attending physician was informed by a physician advisor of the patient's financial class, and assistance with expediting patient care and discharge planning was offered. Daily concurrent review monitored the treatment and discharge plans. The study compared 73 patients with a control group of 191 patients of similar financial class and diagnosis related groups (DRGs) for the immediately preceding 3 months. Compared with the control patients, the study patients experienced a 23% decrease in average length of stay and 16% decrease in average total charges. This study indicates that an intensive utilization management effort in a teaching hospital can be effective without compromising the quality of care.

Hospital Bed Capacity, 500 and over

Poly(2-amino-8-methyldeoxyadenylic acid): contrasting effects in deoxy- and ribopolynucleotides of 2-amino and 8-methyl substituents.

Poly(2-amino-8-methyldeoxyadenylic acid) interacts readily with pyrimidine polynucleotides to form double helices only slightly less stable than those in which the purine polymer lacks the 8-Me group. In the ribo series, by contrast, complexes formed with poly(2-amino-8-methyladenylic acid) are very strongly destabilized by the 8-Me group, despite a larger stabilizing effect of the 2-NH2 group in the ribo series. These results are interpreted in terms of a smaller steric interference of the 8-Me group with 2'-CH2 than with 2'-CHOH, leading to a smaller population of syn structures in the deoxy chain and a consequent lower interference with homopolymer duplex formation. UV, circular dichroism (CD), and IR spectra of the new polymer and its complexes are reported and related to structural and energetic characteristics of the molecules. Since direct synthesis of 2-amino-8-methyldeoxyadenosine was not feasible, the corresponding riboside was prepared, the 3'- and 5'-positions were protected with a disilyloxy group, and a 2'-[(imidazol-1-yl)thiocarbonyl] group was introduced. Reduction with tributyltin hydride followed by deprotection gave the nucleoside, which was then converted to the triphosphate by standard methods. The homopolymer was prepared with terminal deoxynucleotidyl transferase.

Amines

Transition metal-binding proteins from three Chesapeake Bay fish species.

Three species of Chesapeake Bay fish were collected, and endogenous levels of metal binding protein (MBP) were determined. In addition, the induction of metal-binding proteins by cadmium was studied. Livers from freshly caught fish were extracted and chromatographed on Sephadex G-75 to resolve MBP in the 5 to 20 kdalton range. All species studied exhibit measurable but varied levels of endogenous MBPs in the molecular weight range investigated, mostly as a copper protein complex. Upon induction with cadmium, the total MBP content increased in both catfish (Ictalurus punctatus) and striped bass (Morone saxatilis), with significant amounts of cadmium bound to the protein. In white perch (Morone americana), induction of MBPs with cadmium could not be demonstrated due to the large amount of constitutive Cu-BP present, although significant quantities of cadmium were bound to MBP. Electrophoresis in polyacrylamide gel was used to further identify these MBPs. Electrochemical analysis of the MBPs by polarography indicated that the wave properties of the fish MBPs resemble that of rat metallothionein. In conclusion, these studies indicate that: MBPs are present in estuarine fish from the Chesapeake Bay; concentrations of MBPs and their inducibility by exogenous cadmium vary with species, and fish MBPs may be related to mammalian metallothionein.

Animals

Ancrod: normalization of fibrinolytic enzyme abnormalities in patients with systemic lupus erythematosus and lupus nephritis.

Ancrod is a thrombinlike enzyme from Malayan pit viper (Agkistrodon rhodostoma) venom that has a selective enzyme substrate specificity for fibrinogen. Unlike thrombin, it splits only fibrinopeptide A from the fibrinogen molecule and does not activate factor XIII. Simultaneously with the occurrence of hypofibrinogenemia there is a reduction of plasma plasminogen and a rise in fibrin degradation products, suggesting secondary recruitment of the fibrinolytic enzyme system. Ancrod was given to 18 patients with systemic lupus erythematosus and glomerular and vascular microthrombi. Before treatment vascular plasminogen activator (VPA) was low or unmeasurable in 14, an inhibitor of urokinase-induced plasminogen activation (IPA) was elevated in 18, and an inhibitor of plasmin (PI) was elevated in five. Ancrod treatment resulted in prompt normalization of IPA levels in 13 patients; they were classified as fibrinolysis responders. In five patients IPA levels remained elevated throughout treatment with ancrod; they were classified as fibrinolysis nonresponders. In these five the PI level was elevated before treatment and decreased slowly toward the normal range during ancrod administration. The PI did not appear related to the nonspecific serine protease inhibitors, and was shown to be identical with alpha 2-antiplasmin. In the fibrinolysis responders serial histologic studies showed a striking decrease of disappearance of microvascular thrombosis; in the fibrinolysis nonresponders microvascular thrombosis persisted. The action of ancrod is discussed.

Adult

Poly(8-bromodeoxyadenylic acid): properties of the polymer and contrast with the ribopolynucleotide analogue.

Introduction of the bulky 8-bromo substituent into adenine residues of polynucleotides has strikingly different consequences in the deoxy- and ribopolynucleotide series. Poly(r8BrA) was found in earlier studies to form a very stable double-helical self-structure but not to undergo interaction with potentially complementary polynucleotides. We find that poly(d8BrA), in contrast, does not form an ordered self-structure in 0.1 M Na+ but appears to exist as an electrostatically expanded rigid rod with unusual circular dichroism (CD) properties at very low ionic strength. The deoxy polymer, moreover, readily forms double helices with either deoxy or ribo pyrimidine polynucleotides, studied by UV, CD, and IR spectroscopy. These complexes are destabilized, relative to those formed by poly(dA), possibly because energy is needed to convert the purine residues from a more stable syn to an anti conformation, required for heteroduplex formation. The CD spectrum of (d8BrA)n X (dT)n is similar to that of B DNA. The deoxy-ribo hybrids (d8BrA)n X (rU)n and (d8BrA)n X (rBrU)n have CD spectra resembling those of A DNA or RNA. Unlike other deoxy-deoxy pairs (d8BrA)n X (dBrU)n, however, has a CD spectrum resembling RNA and other helices having the A form.

Chemical Phenomena