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Biomedical subjects

J Frazier

Publications and source records attributed to J Frazier.

At least 37 records · Page 2Linked to original sources
PubMed1993

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↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1987

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↗
PubMed1986

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↗
PubMed1985

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↗
PubMed1984

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↗
PubMed1982

Electromyographic gait analysis before and after operative treatment for hemiplegic equinus and equinovarus deformity.

Gait electromyograms were obtained before and after tendon transfer, lengthening, or release in twenty-seven hemiplegic patients with equinus or equinovarus deformities. Abnormal patterns of muscle activity almost always were present preoperatively in the gastrocnemius, soleus, tibialis posterior, flexor hallucis longus, flexor digitorum longus, peroneus brevis, and tibialis anterior muscles in these patients. The surgical procedures to correct the foot deformities altered the gross patterns of activity of most of the muscles operated on by very little. Of particular importance to the surgeon was the finding that the pattern of activity of the muscles whose tendon was transferred, lengthened, or released was not altered after operation. This finding makes the preoperative gait electromyogram a useful means of determining the appropriate surgical plan, since it is an indication of the type of muscle activity to expect postoperatively.

Adult↗
PubMed1978

Infrared spectroscopy of polynucleotides in the carbonyl region in H2O solution: A.U systems.

Strong absorbance of water at 1645 cm-1 has previously prevented dependable observation of infrared spectra of H2O solutions in the carbonyl region. We have obtained reliable spectra in pure water and in alcohol-water mixtures in this region and used them to study A.U polynucleotide interaction. Spectra in pure water were obtained by computer subtraction of solvent from that of solution measured in short path length cells. Mixed solvents, by diluting the water, permit use of longer cells and standard double-beam compensation methods. Poly(adenylic acid) in H20 solution has a strong NH2 deformation band at 1659 cm-1 coupled to an A ring vibration at 1605 cm-1. Poly(uridylic acid) has a broad band at approximately 1695 cm-1, predominantly C2 carbonyl stretch, an unresolved CR carbonyl band (probably near 1660 cm-1), and a ring vibration at approximately 1636 cm-1. The large changes these spectra undergo when helical structures are formed are discussed and compared with changes observed in D2O.

Adenosine Monophosphate↗
PubMed1976

Poly(2-aminoadenylic acid): interaction with poly(uridylic acid).

Poly(2-aminoadenylic acid) forms both double and triple helices with poly(uridylic acid) [poly(U)]. The 2-amino group forms a third hydrogen bond, elevating the 2 leads to 1 transition temperature by 33 degrees C. The third strand, however, has about the same stability as poly(A)-2poly(U), as measured by Tm 3 leads to 2. This selective stabilization of the two-stranded helix results in a much greater resolution of the differnt thermal transitions than that observed in analogous polynucleotide systems. In contrast to other A, U systems 3 leads to 1 and 2 leads to 3 transitions are not observed under any conditions, and the triple helix always undergoes a 3 leads to 2 transition even at very high ionic strength. A 1:1 mixture of poly(2NH2A) and poly(U) exhibits no transient formation of 1:2 complex, unlike similar mixtures of poly(A) with poly(U) and poly(T). This difference is evidently due to a more rapid displacement reaction: [poly(2NH2A) + poly(2NH2A)-2poly(U) leads to 2 poly(2NH2A)-poly(U)] With poly(2NH2A) than with poly(A). We describe a method for establishing the combining ratios of polynucleotide complexes which used a computer to calculate the angles of intersection of mixing curves as explicit and continuous functions of the wavelength. The wavelength dispersions of the angles of intersection determine optimum wavelengths for establishing stoichiometry and can also provide reliable negative evidence that presumably plausible complexes are not formed. Analogous computer procedures have been developed to determine wavelengths which are selective for the formation of both 1:1 and 1:2 complexes. Infrared spectra of the 1:1 and 1:2 complexes resemble those of other A, U homoribopolynucleotide helices in having two and three strong bands, respectively, in the region of carbonyl stretching vibrations. CD spectra of the two complexes are unusual in having negative first extrema of moderate intensity. We attribute these extrema to intrastrand interactions of strong, well-resolved transitions at 278 nm (B2u) of the 2-aminoadenine residues. The CD spectra are correlated with those of other polynucleotide helices.

Autoanalysis↗