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Biomedical subjects

A Hayman

Publications and source records attributed to A Hayman.

17 recordsLinked to original sources
PubMed2006

NS1 proteins of avian influenza A viruses can act as antagonists of the human alpha/beta interferon response.

Many viruses, including human influenza A virus, have developed strategies for counteracting the host type I interferon (IFN) response. We have explored whether avian influenza viruses were less capable of combating the type I IFN response in mammalian cells, as this might be a determinant of host range restriction. A panel of avian influenza viruses isolated between 1927 and 1997 was assembled. The selected viruses showed variation in their ability to activate the expression of a reporter gene under the control of the IFN-beta promoter and in the levels of IFN induced in mammalian cells. Surprisingly, the avian NS1 proteins expressed alone or in the genetic background of a human influenza virus controlled IFN-beta induction in a manner similar to the NS1 protein of human strains. There was no direct correlation between the IFN-beta induction and replication of avian influenza viruses in human A549 cells. Nevertheless, human cells deficient in the type I IFN system showed enhanced replication of the avian viruses studied, implying that the human type I IFN response limits avian influenza viruses and can contribute to host range restriction.

Amino Acid Sequence↗
PubMed2005

Variation in the ability of human influenza A viruses to induce and inhibit the IFN-beta pathway.

We investigated the ability of a selection of human influenza A viruses, including recent clinical isolates, to induce IFN-beta production in cultured cell lines. In contrast to the well-characterized laboratory strain A/PR/8/34, several, but not all, recent isolates of H3N2 viruses resulted in moderate IFN-beta stimulation. Through the generation of recombinant viruses, we were able to show that this is not due to a loss of the ability of the NS1 genes to suppress IFN-beta induction; indeed, the NS1 genes behaved similarly with respect to their abilities to block dsRNA signaling. Interestingly, replication of A/Sydney/5/97 virus was less susceptible to pre-treatment with IFN-alpha than the other viruses. In contrast to the universal effect on dsRNA signaling, we noted differences in the effect of NS1 proteins on expression of interferon stimulated genes and also genes induced by a distinct pathway. The majority of NS1 proteins blocked expression from both IFN-dependent and TNF-dependent promoters by an apparent post-transcriptional mechanism. The NS1 gene of A/PR/8/34 NS1 did not confer these blocks. We noted striking differences in the cellular localization of different influenza A virus NS1 proteins during infection, which might explain differences in biological activity.

Animals↗
PubMed2004

Meconium staining of amniotic fluid correlates with intestinal peel formation in gastroschisis.

Several studies in animal models demonstrate that peel formation in gastroschisis is due to the accumulation and activation of intestinal waste products (IWP) in the amniotic fluid. We reviewed our recent experience with gastroschisis and asked the following questions: First, does staining of the bowel and amniotic fluid with IWP correlate with intestinal peel formation? Second, what prenatal ultrasound findings indicate that peel formation is occurring in utero? Over two years, 16 neonates were treated for gastroschisis; twelve had been diagnosed by prenatal ultrasound and followed closely. Patients were grouped based on the presence of IWP in the amniotic fluid at the time of delivery (staining or no staining), and outcomes were reviewed. All neonates in the staining group (n=7) had a fibrinous peel present at the time of birth whereas a peel was absent in all neonates in the no-staining group (n=9). Matting of the bowel was seen by prenatal ultrasound in four patients in the staining group (0/8 in the no-staining group) and correlated with peel formation (Fisher's exact test p =0.007). Primary closure was done in 14 of the infants, and two required silo closure. In neonates with gastroschisis, staining of the amniotic fluid and bowel serosa with IWP correlated with intestinal peel formation. The ultrasound findings of matting correlated with both peel formation and staining with IWP. These results suggest that spillage of IWP into the amniotic fluid is one of the factors in peel formation in gastroschisis. Identification of matting of the bowel by prenatal ultrasound indicates formation of a peel.

Amniotic Fluid↗
PubMed2001

Phylogenetic analysis of multiple heterosexual transmission events involving subtype b of HIV type 1.

Between 1996 and 1999 thirteen cases of HIV infection were detected in Doncaster, a small town in the north of England (population approximately 250,000). A complex network of shared sexual histories involving local nightclubs linked these cases, with the only known risk factor being heterosexual intercourse. A series of frozen blood samples was collected in 1998-1999 and amplified by PCR to generate full-length gp120 clones. Sequencing demonstrated that all the transmission events in this heterosexual group involved the B subtype of HIV-1. When relationships between the samples were assessed it became clear that these 13 cases represented at least three separate strains of HIV-1, indicating that HIV is well established in this community. Eleven of the 13 cases were related, forming two distinct groups. Further investigation revealed that one group contained five patients whose general health was good and who were not receiving HAART. In contrast, the second group of six patients, including the putative index case, were symptomatic, receiving HAART, and may have been infected with a CXCR-4-utilizing virus. Several of the cases that were linked by genetic criteria were not linked by contact tracing, implying that further undiagnosed cases may exist in this community. To our knowledge, this is the largest outbreak of HIV studied within the heterosexual community in the United Kingdom to date, suggesting that this route of infection is becoming more common within the United Kingdom.

Disease Outbreaks↗
PubMed2000

False-negative HIV antibody test results.

Ideally HIV antibody tests have to be both extremely sensitive and able to recognize all known HIV subtypes. Three patients whose sera failed to react with a synthetic oligopeptide-based HIV antibody test are described in this report. The patients were a Pakistani male infected recently, an Australian male infected for several years, and a Ugandan woman with AIDS. The presence of anti-HIV antibodies was confirmed by means of a standard algorithm with different assay formats. All three sera failed to react in one antiglobulin enzyme-linked immunosorbent assay (ELISA) (Bioelisa HIV-1+2, Biokit SA). No single underlying reason could be identified for the assay failure in the three cases. The first patient, probably infected recently when first tested, was strongly positive by the same assay a year later, confirming the relative insensitivity of oligopeptide assays reported previously for detecting the early antibody response. The other two patients appear to have been infected for several years. Although unlikely to have been infected with a non-clade B virus, the sample from patient 2 lacked detectable antibody to the transmembrane glycoprotein (gp41), the site of the synthetic oligopeptides. Patient 3, of Ugandan origin, was found to be infected with a non-clade B virus. Although her serum reacted strongly to subtype B gp41 in Western blot, it failed to react in the antiglobulin ELISA. Since there appears to be no single common explanation for these three failures there is little opportunity to identify prospectively those situations where testing using assays employing synthetic oligopeptides on the solid phase is likely to fail.

AIDS Serodiagnosis↗
PubMed1994

Some remarks about the 'controversial discussions'.

In 1943-44, the British Psycho-Analytical Society held the 'Controversial Discussions' in an attempt to resolve various disagreements then current in the theory, practice and teaching of psychoanalysis. This paper selects and assesses in some detail some of the arguments that emerged around the concepts of 'unconscious phantasy' and 'unconscious conflict'. Inter alia, they included arguments about assumed early events, about ways of interpreting and assessing evidence, about modes and different levels of conceptualisation, about interpretations of Freud and about changes in psychoanalyic theory. Attempts to achieve mutual understanding existed side by side with total and sometimes rancorous disagreement. Attention is given to sometimes irresolvable communicative and conceptual difficulties that arose and still arise, from differences in meaning that different psychoanalytic thinkers assigned and still assign to each of the two conceptual terms, 'unconscious phantasy' and 'unconscious conflict'.

Fantasy↗
PubMed1993

Quantitative analysis of the lipophilic doxorubicin analogue annamycin in plasma and tissue samples by reversed-phase chromatography.

A rapid and sensitive HPLC method was developed to detect and quantitate the lipophilic doxorubicin analogue annamycin (Ann) and its metabolites in biological samples. Reversed-phase chromatography coupled with fluorescence detection was used. The emission and excitation wavelengths of the fluorescent detector were set at 550 and 472 nm, respectively. The optimal mobile phase was acetonitrile:methanol:water at a 115:95:90 ratio (v/v/v). The lower limit of detection was 0.35 ng of Ann (7 ng/mL). The retention times of 4-demethoxyadriamycinone (Anone) and Ann were 2.6 and 4.3 min, respectively, and their resolution was 1.3. The precision of the determination of Ann and Anone were 0.5 +/- 0.3 and 0.8 +/- 0.7%, respectively. Ann dissolved in methanol was stable under the determination conditions. With chloroform, 60-90% of Ann was extracted from biological samples. Apart from Anone, two Ann metabolites (retention times 3.4 and 6.0 min) were detected in plasma and tissues from C57BL/6 mice bearing subcutaneous B16 tumors 6 h after intravenous administration of a 5-mg/kg suspension of Ann. No peaks were detected in blank tissues and plasma.

Animals↗
PubMed1992

Pathological left-handedness and preserved function associated with a slowly evolving brain tumor.

The authors report the serial neuropsychological evaluations of a patient with acquired left-handedness who had a massive brain tumor that infiltrated the entire temporal and posterior parietal lobes of the left hemisphere. Although the patient had pre-operative impairment of non-verbal memory, follow-up assessment 31 and 66 months after the tumor was resected revealed cognitive functions to be in the high-average to superior range. This case demonstrates the sparing of neuropsychological functions that can be seen with a slowly evolving lesion. The authors suggest that such functional sparing may be due to transfer of function rather than to the residual function of tumor-infiltrated neuronal tissue. Possible mediators of functional preservation include slow lesion growth, the patient's youth at disease onset and the large size of the lesion.

Adult↗
PubMed1992

Case report: acquired antisocial personality disorder associated with unilateral left orbital frontal lobe damage.

We report on our analysis of a patient who developed personality changes which strongly resembled an antisocial personality disorder after surgical resection of a pituitary tumor. Despite behavioral changes that were obvious to friends, family and health care professionals, formal neuropsychological and personality testing revealed no specific cognitive deficits or psychopathology. We hypothesize that damage to a circumscribed region of the left orbitofrontal cortex, illustrated by magnetic resonance imaging, underlies these personality alterations. In contrast to previous reports, which ascribe such personality changes to bilateral frontal lobe injury, we suggest that unilateral frontal lobe damage alone may have resulted in the development of this syndrome.

Adenoma↗
PubMed1989

What do we mean by 'phantasy'?

The term 'phantasy' may be used by psychoanalysts to mean an imaginative fulfillment of frustrated wishes, conscious or unconscious. This approximately condenses what is generally seen as Freud's main use of the term. It may also be used, inter alia, to denote the primary content of unconscious mental processes, as the mental representative and corollary of instinctual urges, and as based on or identical with Freud's postulated 'hallucinatory wish-fulfillment' and his 'primary introjection', which reflects Melanie Klein's extension of Freud's concept. The differences between the two notions were first clearly aired during the Controversial Discussions conducted by the British Psycho-Analytical Society during the war. This paper gives a necessarily abbreviated and incomplete account of some of the points made then, to give some detail of how widely the two notions differed. It then notes how the term 'phantasy' is still used for such widely differing notions: to indicate the problems that must exist, of what we mean and of how to communicate our ideas, if different people mean such different things by one technical term that is in constant use.

Anxiety↗