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Biomedical subjects

J Reed

Publications and source records attributed to J Reed.

At least 163 records · Page 9Linked to original sources
PubMed1985

Circular dichroic evidence for an ordered sequence of ligand/binding site interactions in the catalytic reaction of the cAMP-dependent protein kinase.

A limiting requirement for substrate specificity of the cAMP-dependent protein kinase is the presence of one or two basic residues located to the N-terminal side of the target substrate serine. Furthermore, circular dichroic (CD) studies have shown that binding of protein substrate involves a series of at least two independent conformational changes in the enzyme, each of which is initiated by a recognition signal on the substrate protein. The present study attempts to elucidate further the complete sequence of enzyme/ligand interactions by using the synthetic substrate peptide Kemptide and analogues differing from it at crucial points in the sequence: the Ala-peptide, where alanine is substituted for the target serine, and D-Ser-Kemptide, where the target serine is in the D rather than the L configuration. Examination of the effects of binding of these substrates on the intrinsic UV CD of the enzyme and the induced CD in the presence of Blue Dextran has revealed a third step in the substrate/enzyme binding interaction. Although sections of the conformational change at the active site are dependent on the basic subsite and the serine hydroxyl group on the peptide, respectively, the complete conformational change requires that the substrate be bound in random coil conformation. Where this does not occur, the kinetics show that the peptide will not act either as substrate or as inhibitor of the enzyme. Further, the interaction between the serine hydroxyl group and an enzyme tyrosine residue, previously observed, appears to be dependent on the correct orientation as well as the mere presence of the target -OH group.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1985

Pseudohyponatremia in acute hyperlipemic pancreatitis. A potential pitfall in therapy.

Six patients had apparent hyponatremia associated with hyperlipidemia and acute pancreatitis. To our knowledge, only one such patient with acute pancreatitis has previously been described, although the association of hyperlipidemia with "pseudohyponatremia" had been well documented. One of the above patients, whose condition was hemodynamically unstable on admission, developed dangerous symptoms of hyperosmolarity and cerebral dysfunction following aggressive resuscitation with hypertonic saline solution. The pseudohyponatremia results from displacement of water in the serum by the lipids, with sodium existing only in the aqueous phase. This volume displacement results in errors of sodium measurement when the latter is determined by flame photometry or indirect potentiometry, but not when determined by ultracentrifugation and direct potentiometry.

Acute Disease↗
PubMed1985

Prenatal stress and prepuberal social rearing conditions interact to determine sexual behavior in male rats.

The two major categories of factors known to influence adult sexual behavior potentials are the relative amounts of androgen present during specific stages of perinatal ontogeny and adequate social stimulation during prepuberal development. The possible interaction between these two was evaluated by characterizing the ejaculatory and lordotic behavior potentials of prenatally stressed and control male rats that had been weaned at 16 days of age and raised either in total social isolation or with a same-age female, a control male, or a prenatally stressed male. The decrement in male sexual behavior produced by prenatal stress was attenuated by raising the male with either a female or a control male. Social isolation alone or in combination with stress resulted in severely deficient male behavior. Peripheral skin shock promoted ejaculatory behavior in many previously noncopulating prenatally stressed males raised with other stressed males, but it was ineffective in most isolated animals. The high lordosis potential characteristic of prenatally stressed male rats was slightly lower in the group with a female cagemate and was markedly decreased by social isolation. These results support and extend the finding by Dunlap, Zadina, and Gougis (1978) that prenatal hormonal events and prepuberal rearing conditions can interact to attenuate or accentuate the effects that either treatment alone has on the development of adult sexual behavior potentials.

Animals↗
PubMed1985

Natural killer cytotoxic factor induction by K562 cells in patients with advanced cancer: correlation with production of interferon.

Advanced cancer patients were studied for their ability to produce natural killer cytotoxic factor (NKCF). Of 23 patients with advanced epithelial cancers, 8 showed deficient natural killer (NK) activity, as measured in a standard 51Cr release assay. Lymphocytes from these patients did not generate NKCF (nonproducers) in the presence of K562 cells. In addition, 7 other patients whose NK activity was in the normal range did not generate NKCF. Thus the deficiency in NKCF production was only partially correlated with the level of NK activity. Supernatants generated for NKCF were also assayed for antiviral activity. Mean interferon (IFN) titer of supernatants generated from peripheral blood lymphocytes (PBL) of cancer patients was significantly lower than that of supernatants generated by PBL from normal donors. Supernatants from 10 of 15 NKCF nonproducers contained no detectable IFN, whereas the remaining 5 contained up to 100 U IFN. NKCF was never generated in the absence of IFN. The defect in NKCF production by PBL from cancer patients could be corrected by the incubation of effector cells with exogenous IFN-alpha or IFN-alpha inducers, such as other tumor cells or viruses. The relationship among NKCF, IFN, and NK activities is discussed.

Adult↗
PubMed1985

Multicentric giant lymph node hyperplasia, Kaposi's sarcoma, and lymphoma.

We studied two cases of a recently recognized systemic lymphoproliferative disease with morphological features of Castleman's disease: multicentric giant lymph node hyperplasia. Both patients developed Kaposi's sarcoma and had laboratory evidence of immune abnormalities, including reversed T4 to T8 ratios. One patient's disease had a subacute course with fevers of unknown origin, mucocutaneous candidiasis, and progressive thrombocytopenia, while the other patient's disease had a fulminant course with anemia, thrombocytopenia, and splenic lymphoma. Both patients were elderly, and both died of complications of multicentric giant lymph node hyperplasia.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Postoperative thyroid storm after lithium preparation.

Lithium carbonate is a known antithyroid agent that acts primarily to inhibit the release of preformed thyroid hormone. Lithium was chosen for preoperative preparation in a noncompliant patient with Graves' Disease who was not able to tolerate any other antithyroid agents. Despite excellent preoperative control, postoperative thyroid storm developed. This is the first reported case of the use of lithium for preoperative preparation. Since it is possible that surgical manipulation caused the demonstrated release of preformed hormone and subsequent postoperative storm, caution in the sole use of this agent for preoperative preparation seems warranted.

Adolescent↗
PubMed1984

Near- and far-ultraviolet circular dichroism of the catalytic subunit of adenosine cyclic 5'-monophosphate dependent protein kinase.

The circular dichroism spectrum of the catalytic subunit of cAMP-dependent protein kinase was measured in the far-UV (190-240 nm) and near-UV (250-300 nm) region. Data from the far-UV spectra were processed with the CONTIN program for estimation of globular protein secondary structure [ Provencher , S. W. (1982) CONTIN (Version 2) User's Manual, European Molecular Biology Laboratory, Heidelberg, West Germany]. The composition of the protein determined by this method was 49 +/- 2% alpha-helix, 20 +/- 4% beta-sheet, and 31 +/- 3% remainder. This composition changes when the protein is allowed to bind Kemptide , a synthetic peptide substrate, with more than half of the disordered portion of the protein taking the form of beta-sheet. A certain portion of the alpha-helical structure also appears to move into a beta-sheet form. The near-UV CD spectrum of catalytic subunit shows changes in aromatic amino acid dichroism associated with substrate binding. These changes can be ascribed with a fair degree of certainty to alterations in the orientation of a tyrosine residue at the surface of the protein. These findings are discussed in terms of previous work on induced dichroism in this enzyme with regard to control mechanisms operating at the active site.

Amino Acid Sequence↗
PubMed1984

Ligand binding site interaction in adenosine cyclic 3',5'-monophosphate dependent protein kinase catalytic subunit: circular dichroic evidence for intramolecular transmission of conformational change.

Blue Dextran has been shown to interact specifically with the nucleotide binding site of the catalytic subunit of cAMP-dependent protein kinase. By observing changes in the induced dichroism associated with the absorbance of the bound chromophore, one can monitor conformational changes in the immediate vicinity of the ATP binding site. With this technique, it has been possible to demonstrate that attachment of ligand at the protein substrate binding site of the enzyme results in a conformational change at the ATP binding site. This alteration takes place in at least two steps, one of which appears to be dependent on the presence of a phosphorylatable hydroxyl group on the substrate and the other being triggered by the "basic subsite" (usually one or more arginine residues) to the N-terminal side of the target serine or threonine. Competition experiments suggest that the change induced results in closure over the substrate protein after the initial electrostatic binding; the movement initiated by the presence of a serine hydroxyl group may also involve interaction with a tyrosine residue at the surface of the ATP binding site.

Adenosine Triphosphate↗
PubMed1984

Trauma to the bones of small infants from passive exercise: a factor in the etiology of child abuse.

Four infants, three premature and one term, developed serious bony injury from parent- or caretaker-administered passive exercises. In the three infants born prematurely, the exercise program was prescribed by neonatal intensive care unit staff before discharge; in the fourth infant, the babysitter initiated the program. In each case the passive exercise was begun to diminish actual or presumed muscle tightness. When these infants were presented to the physician with a serious traumatic injury between the ages of 4 and 10 months, the presumptive diagnosis of child abuse was made after radiologic assessment revealed multiple bone injuries. The several traumatic injuries to bones resulting from the home-administered physical therapy were most impressive. Passive exercise in three of the four infants was a significant factor in the cause of their injuries. Caution must be used in prescribing this form of "therapy" in small infants.

Bone and Bones↗
PubMed1983

Isolation and elucidation of some functional properties of the "mute" catalytic subunit of cAMP-dependent protein kinase.

A mute isoenzyme of type II cAMP-dependent protein kinase from rat muscle has been reported that is released from the regulatory subunit by cAMP but remains inactive until combination with heat- and acid-stable modulator has occurred. This enzyme has now been obtained in isolation free of the normal catalytic subunit using affinity chromatography with both an ATP analog (Blue Dextran/Sepharose) and a protein substrate analog (Kemptide/CH-Sepharose). Separation can be effected in both cases before activation of the mute enzyme. Affinity of the mute enzyme for Blue Dextran--a ligand specific for the dinucleotide fold in this kinase--is somewhat higher than that of the normal enzyme. Conversely, before reaction with the modulatory protein the mute enzyme will not bind at all to Kemptide/CH-Sepharose, where the normal enzyme elutes at 50 mM KCl. When pretreated with the modulatory protein and so activated, mute enzyme binds to Kemptide with a very high affinity and can only be eluted using a natural substrate (phosphorylase kinase), up to 500 mM salt being ineffective. The modulator thus appears to act through alteration of the protein substrate binding site on the enzyme.

Animals↗
PubMed1983

Recurrence of macular corneal dystrophy within grafts.

Two patients (a 41-year-old woman and a 40-year-old man) with macular corneal dystrophy developed significant visual impairment from recurrent disease within corneal grafts. One patient required regrafting 18 years after a penetrating keratoplasty, and the second patient underwent a penetrating graft 19 years after a lamellar corneal graft. In both cases the typical histochemical and electron-microscopic features of macular dystrophy were evident within donor tissue from the original grafts. The patient who originally underwent penetrating keratoplasty had recurrent disease in the corneal endothelium and within Descemet's membrane. Although the explanation of this observation is uncertain, endothelial cells of the recipient human cornea may resurface Descemet's membrane after penetrating keratoplasty, contrary to current belief. An alternative possibility is that involvement of both the corneal endothelium and Descemet's membrane in macular dystrophy is a secondary phenomenon, and that the abnormal storage product of this dystrophy is an abnormal metabolite rather than a normal compound with a defective catabolic enzyme as previously suspected.

Adult↗
PubMed1983

Studies of gaze during induced conflict in families with a hypertensive father.

Three modified replications (N = 32, 46, and 32) investigated verbal and nonverbal interactions during role playing of family conflict by family groups of father, mother, and one child. Half the fathers had essential hypertension and half were normotensive. Nonverbal but not verbal behavior differed between families with hypertensive vs. normotensive fathers. Hypertensive fathers and their normotensive wives and children looked at each other less (gaze aversion), both while listening and speaking, than did the members of normotensive families. The difference in duration of gaze aversion occurred more prominently during emotionally negative verbalizations. The results suggest a pattern of conflict avoidance in families with a hypertensive father.

Adolescent↗
PubMed1983

Predicting alcoholism manpower needs.

In response to the needs both to develop new, nonduplicative alcoholism services and to contain cost, and in order to plan for the labor-intensive alcoholism treatment system, planning techniques are needed to assist in the rational planning for and allocation of manpower. Using data from the 1980 National Drug and Alcoholism Treatment Utilization Survey, it is possible to analyze the staffing patterns of various modalities of alcoholism treatment. Two regression equations were developed to identify key variables for predicting manpower needs in various facilities. Budget, service type, and treatment capacity were statistically significant predictions of direct-care FTE staff in inpatient/residential units. The best predictive ability for direct-care FTE staff in detoxification and longer-term residential facilities was obtained with a general regression model which was based on all types of services (e.g., detoxification, longer-term residential, and outpatient). For outpatient settings, however, direct-care FTE staff was best predicted by considering budgets and treatment capacities within outpatient settings only. Based on this study, a planner can predict, with reasonable confidence, FTE direct-care staff by varying the values of the independent variables in the regression equation to reflect the various characteristics of the services being planned.

Alcoholism↗