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Biomedical subjects

R Wright

Publications and source records attributed to R Wright.

At least 109 records · Page 6Linked to original sources
PubMed1989

Evidence for specificity in the encapsidation of Sindbis virus RNAs.

We investigated the interaction of the capsid protein of Sindbis virus with Sindbis viral RNAs and defined a region of the genome that is required for binding in vitro and for packaging in vivo. The binding studies were performed with purified capsid protein immobilized on nitrocellulose and 32P-labeled RNAs transcribed in vitro from viral and nonspecific cDNAs. Genomic and defective interfering (DI) RNAs bound capsid protein significantly better than either the subgenomic (26S) RNA or nonspecific RNAs. Transcripts prepared from either truncated or deleted cDNAs were used to define the segment required for binding. This segment, which is represented twice in DI RNA, lies between nucleotides 746 and 1226 of the genomic RNA and is within the coding region of the nonstructural protein nsP1. Insertion of a domain covering these sequences into a nonviral RNA was able to convert it from a background level of binding to an activity that was 80% that of the Sindbis virus DI RNA. We analyzed DI RNA transcripts in detail because they could be studied not only for the ability to bind capsid protein in vitro but also for the ability to be replicated and packaged in vivo in the presence of helper virion RNA. The results obtained with three DI RNAs are reported. One (CTS14), which has one copy of the binding domain, bound efficiently to capsid protein in vitro and was packaged in vivo as measured by amplification on passaging. In contrast, a DI RNA (CTS1) which lacked this region did not bind to capsid protein and was not detected on passaging. By using lipofectin (P. L. Felgner, T. R. Gadek, M. Holm, R. Roman, H. W. Chan, M. Wenz, J.P. Northrop, G. M. Ringold, and M. Danielson, Proc. Natl. Acad. Sci. USA 84:7413-7417, 1987) to enhance RNA uptake, we were able to demonstrate that CTS1 RNA was replicated in the transfected cells. It was replicated to the same level as another DI RNA (CTS253) which has only the 3' 279 nucleotides of the binding domain and these are located near the 3' terminus of the RNA. CTS253 bound capsid protein to an intermediate level but was amplified on passaging. The binding studies and the in vivo packaging data, taken together, provide strong support for the conclusion that there is a specific capsid recognition domain in Sindbis virus RNA that plays a role in nucleocapsid assembly.

Capsid↗
PubMed1989

Cirrhosis in partial lipodystrophy.

A patient with partial lipodystrophy, fatty liver and cirrhosis, and autoimmune thyroid disease is described. Treatment with thyroxine led to partial improvement in the hepatic abnormality.

Adult↗
PubMed1989

Research note: parallel reactions in rape victims and rape researchers.

In a recent study, several nurse researchers assisted in a case record review on 1,215 rape crisis center records to determine demographic predicators of sexual abuse. Despite the relatively impersonal nature of the method used in collection of data, researchers experienced highly subjective responses to the often sketchy case records both during and after the study. Some of the reactions reported by data collectors included: anger, dreams, fear of physical injury, and sleep disorders. These responses closely parallel those reported in the literature on rape victims. This research note (1) describes the reactions of the five different data collectors, (2) compares these reactions to those reported for rape victims, (3) suggests some implications for those engaged in research on potentially distressing topics, and (4) offers suggestions on how to best prepare data collectors and others for research in emotionally charged areas.

Crisis Intervention↗
PubMed1988

Antithymocyte globulin hypersensitivity in bone marrow failure patients.

We evaluated the predictive value of immediate epicutaneous (prick) skin testing in 36 patients receiving a heterologous protein of equine origin, antithymocyte globulin (ATG), for bone marrow failure. Three of the 36 patients had positive epicutaneous test results. Two of these three received ATG treatment; one died of anaphylaxis while the other was desensitized successfully. Intradermal skin tests revealed positive wheal-flare reactions to progressively increasing dilutions of ATG in 96% of patients tested. None of these patients suffered any anaphylactic symptoms during treatment. Nine patients who had received ATG were evaluated subsequently for the possible development of immediate epicutaneous reactions three to 12 months after treatment; one of the nine patients developed a positive epicutaneous skin test reaction. We recommend that all patients who are to be treated or re-treated with heterologous antisera should be tested using the epicutaneous technique and that patients with positive reactions should be desensitized.

Adolescent↗
PubMed1988

The neglect of data-gathering instruments in behavior therapy practice.

Although the Willoughby Personality Questionnaire and the Fear Survey Schedule are demonstrably valuable aids to the practice of behavior therapy of neurosis, it is evident that many behavior therapists do not use them. In order to determine the extent of their neglect, we sent a questionnaire to all Clinical Fellows of the Behavior Therapy and Research Society. The 134 replies we received revealed that the Willoughby was routinely used by only 19% and the Fear Survey Schedule by only 42%. This seems to be manifestation of a wide-spread but indefensible homogenized view of neuroses. It is a sad reflection on the quality of behavior therapy training programs.

Attitude of Health Personnel↗
PubMed1988

Allergy and the chronic fatigue syndrome.

The chronic fatigue syndrome is a heterogeneous disorder characterized by easy fatigability, feverishness, diffuse pains, and depression. Many patients also report inhalant, food, or drug allergies. This article reviews the clinical features of the syndrome and hypotheses of its pathogenesis, especially those regarding the Epstein-Barr virus and cellular immune mechanisms. Also summarized are recent studies of the validity of atopic complaints in the syndrome. The results of epicutaneous skin testing demonstrated a high correlation with history in 24 patients. Atopy coexists with the chronic fatigue syndrome in greater than 50% of patients.

Chronic Disease↗
PubMed1988

Cold culture of different stage mouse embryos in bicarbonated and bicarbonate-free media.

Mouse embryos of different stages of development were cultured to expanded blastocysts following storage (1 to 8 d) at 4 degrees C in the presence or absence of HCO(3)(-). The effect of oxygen tension on the cold storage of one- and two-cell mouse embryos at 4 degrees C was evaluated by 37 degrees C culture and transfer to pseudopregnant recipients. Survival at 4 degrees C of early, one- to four-cell mouse embryos was improved with HCO(3)(-) in the medium. The presence of HCO(3)(-) was not of benefit for morulae or blastocyst survival following cold storage. Reducing the oxygen atmosphere from 20 to 5% O(2) improved survival of one-cell mouse embryos stored at 4 degrees C. The survival of two- and four-cell embryos, morulae and blastocysts at 4 degrees C was similar in 90% N(2), 5% CO(2) and 5% CO(2) in air, but it was significantly poorer in air alone. The collapse of morulae and blastocysts during cold storage up to 5 d was reduced with HCO(3)(-) in the storage medium. Blastocysts stored for 6 d at 4 degrees C failed to survive following immediate transfer to pseudopregnant recipients. Blastocyst survival was improved compared to controls (direct transfer of unstored blastocysts to recipients) when cultured for 36 h at 37 degrees C following 6 d of cold storage. This result suggests that cold-stored mouse blastocysts may require a metabolic period of readjustment to survive following transfer to synchronized recipients.

Journal Article↗
PubMed1988

Effect of endotoxin on release of reactive oxygen intermediates by rat hepatic macrophages.

Reactive oxygen intermediates released by activated hepatic macrophages have been implicated in the pathogenesis of a rat model of liver injury induced by sequential administration of Corynebacterium parvum and endotoxin. In this model, C. parvum causes extensive infiltration of the liver with activated macrophages, but severe liver injury occurs only after subsequent exposure to endotoxin. We have therefore investigated the effects of endotoxin on the release of reactive oxygen intermediates by C. parvum-activated hepatic macrophages. After in vitro exposure to zymosan, opsonized zymosan, or phorbol myristate acetate, hepatic macrophages isolated from C. parvum- and endotoxin-treated rats demonstrated significantly (1.5-2-fold) increased release of superoxide and oxidation of [1-14C]glucose via the hexose monophosphate shunt compared with hepatic macrophages isolated from C. parvum- and saline-treated control rats. These results indicate that endotoxin enhances the state of activation of hepatic macrophages already partially activated by C. parvum. We suggest that the increased release of reactive oxygen intermediates by these cells promotes liver injury in this model.

Animals↗
PubMed1988

Increased amounts of HMG-CoA reductase induce "karmellae": a proliferation of stacked membrane pairs surrounding the yeast nucleus.

Overproduction of the enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase in yeast resulted in striking morphological effects on the structure of intracellular membranes. Specifically, stacks of paired membranes closely associated with the nuclear envelope were observed in strains that over-produced the HMG1 isozyme, one of two isozymes for HMG-CoA reductase in yeast. These nuclear-associated, paired membranes have been named "karmellae." In strains that overproduced the HMG1 isozyme, HMG-CoA reductase was present in the karmellar layers. At mitosis, karmellae were asymmetrically segregated: the mother cells inherited all of the karmellae and the daughter cells inherited none. A membranous structure of different morphology was occasionally found in cells that overproduced the HMG2 isozyme. These observations further establish the existence of cellular mechanisms that monitor the levels of membrane proteins and compensate for changes in these levels by inducing synthesis of particular types of membrane.

Cell Nucleus↗
PubMed1987

Experience with a combined percutaneous and endoscopic approach to stent insertion in malignant obstructive jaundice.

A non-operative method of palliation in malignant obstructive jaundice was used in 14 patients in whom a biliary stent could not be placed endoscopically. A guide wire was manipulated through the obstructing lesion through the percutaneous transhepatic route and retrieved through an endoscope. The stent was then fed through the endoscope over the guide wire and across the biliary stricture. There were no early complications, and worth-while palliation was obtained in most cases. The success rate for placing an endoscopic stent increased in this unit from 69 to 97% with the introduction of this technique.

Aged↗
PubMed1987

Persistent measles virus genome in autoimmune chronic active hepatitis.

A radiolabelled 50-base oligonucleotide complementary with the measles virus gene encoding the nucleocapsid was used as a probe to identify persistent measles virus genome in the lymphocytes from patients with autoimmune chronic active hepatitis (AICAH). Positive hybrids were found in 12 of 18 patients, and correlated strongly with high antibody titres to measles. Among the 45 controls, positive hybrids were found in 1 patient with measles, 1 of 3 patients with systemic lupus erythematosus, and 2 of 4 patients with cryptogenic cirrhosis. Persistence of part of the measles virus genome in AICAH may have important implications in the pathogenesis of the liver disease, and possibly in other disorders such as systemic lupus erythematosus, multiple sclerosis, and Paget's disease where an abnormal immune response to measles has been observed.

Adult↗
PubMed1987

Reduction of ferricytochrome C may underestimate superoxide production by monocytes.

Superoxide production by stimulated phagocytes is commonly measured by reduction of ferricytochrome C, with specificity of the assay assumed if the reaction is inhibited by superoxide dismutase (SOD). Most preparations of ferricytochrome C contain a small proportion in the reduced (ferro) form, and this is also formed by the reaction of ferricytochrome C with superoxide. The generation of other reactive oxygen intermediates, such as hydrogen peroxide or hydroxyl radical, could cause oxidation of ferrocytochrome C and consequent underestimation of superoxide production. In support of this, it has been demonstrated that exogenous catalase enhanced the reduction of ferricytochrome C by phorbol myristate acetate (PMA)-stimulated human monocytes. Control experiments confirmed that this was due to enhanced detection rather than increased production of superoxide. In addition, SOD was found to promote oxidation of ferrocytochrome C by PMA-stimulated human monocytes, but this was also inhibited by catalase. These effects of catalase and SOD on ferricytochrome C reduction/ferrocytochrome C oxidation were also demonstrated when superoxide was produced independently of monocytes by a xanthine and xanthine oxidase generating system. It is concluded that the assay of superoxide, using 'SOD inhibitable' reduction of ferricytochrome C, underestimates superoxide production.

Catalase↗
PubMed1987

Food allergy and intolerance.

In summary, there has been a dramatic increase in our understanding of food allergy as a result of research in immune mechanisms and clinical studies over the last decade. The subject has been comprehensively reviewed in a major new publication (Brostoff and Challacombe, 1986).

Antibody Formation↗
PubMed1987

Patients with bone marrow failure demonstrate decreased cutaneous reactivity to human C5a.

In vivo studies have shown that human C5a, a potent complement-derived anaphylatoxin and chemoattractant, produces immediate inflammatory reactions following intradermal injection in human skin. At concentrations within its potential physiologic range, intradermal injection of C5a elicits immediate wheal and flare reactions, increased vascular permeability, mast cell degranulation, and neutrophil-rich infiltrates. To assess the relative contribution of interacting cellular elements to C5a-induced inflammation in normal human skin, purified human C5a was tested intradermally in 8 patients with bone marrow failure (BMF). Reactions to C5a in patients with BMF were compared with responses at identical test sites in healthy volunteers and other patients with cutaneous disorders. Patients with BMF demonstrated significantly less wheal and flare reactivity following intradermal injection of C5a than controls (p less than 0.05 and less than 0.02, respectively). In these studies, patients with the greatest cytopenia generally showed the least cutaneous reactivity to human C5a. Biopsies of C5a test sites in patients with BMF revealed an absence of leukocytes in marked contrast to neutrophil-rich infiltrates observed at test sites in healthy volunteers. Avidin-fluorescent and/or Giemsa staining of skin biopsies revealed no difference between the number of dermal mast cells in patients with BMF and samples of normal human skin. In addition, skin test studies with histamine (2 micrograms) and morphine (5 micrograms) performed to assess cutaneous vascular and mast cell responsiveness in patients with BMF, normal volunteers and controls with rhinitis revealed no significant differences in cutaneous reactivity to these pharmacologic agents. These in vivo studies demonstrate that patients with BMF specifically exhibit decreased cutaneous reactivity to human C5a and suggest that neutrophils make an important and an immediate contribution to inflammatory responses elicited by this anaphylatoxin.

Adolescent↗