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Biomedical subjects

P Henning

Publications and source records attributed to P Henning.

At least 19 recordsLinked to original sources
PubMed2006

Decreased immune reactivity towards a knobless, affibody-targeted adenovirus type 5 vector.

In this study, a prototype Adenovirus type 5 (Ad5) vector deleted of the fiber knob domain and carrying an Affibody molecule as the targeting ligand showed decreased susceptibility to human pre-existing antibodies. This vector, Ad5/R7-Z(taq)Z(taq), has short fibers carrying seven shaft repeats, a non-native trimerization signal and an affibody molecule (Z(taq)) reactive to Taq polymerase. Ad5/R7-Z(taq)Z(taq) could be specifically targeted to 293 cells stably expressing membrane-bound anti-Z(taq) idiotypic affibody called Z(ztaq) (293Z(ztaq)). Sera from 50 blood donors were analyzed for neutralization activity (NA) against the parental Ad5/Fiwt vector and knobless Ad5/R7-Z(taq)Z(taq) on 293Z(ztaq) cells. Twenty-three sera had NA titers (> or =1:64) against Ad5/Fiwt (46%) and only two against Ad5/R7-Z(taq)Z(taq) (4%). Characterization of sera with NA titers showed that the knob domain is one of the targets of the antibodies. Neutralization assays using sera pre-adsorbed on knob and hexon proteins showed that the NA of the sera was carried mainly by anti-knob and anti-hexon antibodies, but in certain sera the anti-hexon antibodies represent the major population of the neutralizing antibodies (NAbs). Our results suggested that a combination of knob deletion and hexon switching could be an effective strategy for Ad vectors to better evade the anti-Ad NAbs.

Adenoviruses, Human↗
PubMed2005

[Abdominal pain in emergency service--what should I not forget?].

Abdominal pain for the General Practitioner (GP) is an important problem and presents as a significant challenge since the complaint emerges to the primary care provider as one of the 3 most important complaints. This paper serves as a facilitator and guide in helping the General Practitioner differentiate between the so-called normal abdominal pain versus severe abdominal pain which should be referred to a specialist. One of the most important messages the paper attempts to convey is that patients have to be seen and personally examined by the General practitioner. This is a paramount feature in establishing course of severity and outcome. Since approximately 25% of all presenting abdominal pain complaints are unclear, even to the experienced specialist, the authors attempt to direct a focused exam by means of a thorough history and physical examination and then to formulate a decision tree regarding the question of referral or continued primary care by the provider.

Abdominal Pain↗
PubMed2005

Tumor cell targeted gene delivery by adenovirus 5 vectors carrying knobless fibers with antibody-binding domains.

Most human carcinoma cell lines lack the high-affinity receptors for adenovirus serotype 5 (Ad5) at their surface and are nonpermissive to Ad5. We therefore tested the efficiency of retargeting Ad5 to alternative cellular receptors via immunoglobulin (Ig)-binding domains inserted at the extremity of short-shafted, knobless fibers. The two recombinant Ad5's constructed, Ad5/R7-Z(wt)-Z(wt) and Ad5/R7-C2-C2, carried tandem Ig-binding domains from Staphylococcal protein A (abbreviated Z(wt)) and from Streptococcal protein G (C2), respectively. Both viruses bound their specific Ig isotypes with the expected affinity. They transduced human carcinoma cells independently of the CAR pathway, via cell surface receptors targeted by specific monoclonal antibodies, that is, EGF-R on A549, HT29 and SW1116, HER-2/neu on SK-OV-3 and SK-BR-3, CA242 (epitope recognized by the monoclonal antibody C242) antigen on HT29 and SW1116, and PSMA (prostate-specific membrane antigen) expressed on HEK-293 cells, respectively. However, Colo201 and Colo205 cells were neither transduced by targeting CA242 or EGF-R nor were LNCaP cells transduced by targeting PSMA. Our results suggested that one given surface receptor could mediate transduction of certain cells but not others, indicating that factors and steps other than cell surface expression and virus-receptor interaction are additional determinants of Ad5-mediated transduction of tumor cells. Using penton base RGD mutants, we found that one of these limiting steps was virus endocytosis.

Adenoviruses, Human↗
PubMed2002

Genetic modification of adenovirus 5 tropism by a novel class of ligands based on a three-helix bundle scaffold derived from staphylococcal protein A.

The use of adenovirus (Ad) as an efficient and versatile vector for in vivo tumor therapy requires the modulation of its cellular tropism. We previously developed a method to genetically alter the tropism of Ad5 fibers by replacing the fiber knob domain by an extrinsic trimerization motif and a new cellular ligand. However, fibers carrying complex ligands such as single-chain antibody fragments did not assemble into functional pentons in vitro in the presence of penton base, and failed to be rescued into infectious virions because of their inability to fold correctly within the cytoplasm of Ad-infected cells. Here we show that the coding sequence for a disulfide bond-independent three-helix bundle scaffold Z, derived from domain B of Staphylococcal protein A and capable of binding to the Fc portion of immunoglobulin (Ig) G1, could be incorporated into modified knobless Ad fiber gene constructs with seven shaft repeats. These fiber gene constructs could be rescued into viable virions that were demonstrated to enter 293 cells engineered for IgG Fc surface expression but not unmodified 293 cells, via a mechanism that could be specifically blocked with soluble Fc target protein. However, the tropism modified viruses showed a slightly impaired cellular entry and a lower infectivity than wildtype (WT) virus. In addition, we generated recombinant fibers containing an IgA binding Affibody ligand, derived from combinatorial specificity-engineering of the Z domain scaffold. Such fiber constructs also showed the expected target specific binding, indicating that the affibody protein class is ideally suited for genetic engineering of Ad tropism.

Adenoviridae↗
PubMed2002

Neural mechanisms of saccadic suppression.

In normal vision our gaze leaps from detail to detail, resulting in rapid image motion across the retina. Yet we are unaware of such motion, a phenomenon known as saccadic suppression. We recorded neural activity in the middle temporal and middle superior temporal cortical areas during saccades and identical image motion under passive viewing conditions. Some neurons were selectively silenced during saccadic image motion, but responded well to identical external image motion. In addition, a subpopulation of neurons reversed their preferred direction of motion during saccades. Consequently, oppositely directed motion signals annul one another, and motion percepts are suppressed.

Animals↗
PubMed2001

Nationwide study of haemolytic uraemic syndrome: clinical, microbiological, and epidemiological features.

AIMS: To establish the incidence and aetiology of haemolytic uraemic syndrome (HUS) in Australia and compare clinical and microbial characteristics of sporadic and outbreak cases. METHODS: National active surveillance through the Australian Paediatric Surveillance Unit with monthly case notification from paediatricians, July 1994 to June 1998. Children under 15 years presenting with microangiopathic haemolytic anaemia, thrombocytopenia, and acute renal impairment were identified. RESULTS: Ninety eight cases were identified (incidence 0.64 per 10(5) children <15 years/annum and 1.35 per 10(5) children <5 years/annum). Eighty four were associated with diarrhoea (64 sporadic, 20 constituting an outbreak) and 14 were atypical. Shiga toxin producing Escherichia coli (STEC) O111:H- was the most common isolate in sporadic HUS and caused the outbreak. However O111:H- isolates from outbreak and sporadic cases differed in phage type and subtyping by DNA electrophoresis. STEC isolates from sporadic cases included O26:H-, O113:H21, O130:H11, OR:H9, O157:H-, ONT:H7, and ONT:H-. STEC O157:H7 was not isolated from any case. Only O111:H- isolates produced both Shiga toxins 1 and 2 and possessed genes encoding E coli attaching and effacing gene (intimin) and enterohemolysin. Outbreak cases had worse gastrointestinal and renal disease at presentation and more extrarenal complications. CONCLUSIONS: Linking national surveillance with a specialised laboratory service allowed estimation of HUS incidence and provided information on its aetiology. In contrast to North America, Japan, and the British Isles, STEC O157:H7 is rare in Australia; however, non-O157:H7 STEC cause severe disease including outbreaks. Disease severity in outbreak cases may relate to yet unidentified virulence factors of the O111:H- strain isolated.

Adolescent↗
PubMed2000

Low to high spin-state transition induced by charge ordering in antiferromagnetic YBaCo2O5

The oxygen-deficient double perovskite YBaCo2O5, containing corner-linked CoO5 square pyramids as principal building units, undergoes a paramagnetic to antiferromagnetic spin ordering at 330 K. This is accompanied by a tetragonal to orthorhombic distortion. Below 220 K orbital ordering and long-range Co(2+)/Co(3+) charge ordering occur as well as a change in the Co2+ spin state from low to high spin. This transition is shown to be very sensitive to the oxygen content of the sample. To our knowledge this is the first observation of a spin-state transition induced by long-range orbital and charge ordering.

Journal Article↗
PubMed1998

Venous access via the renal vein: a technical innovation.

A patient with difficult venous access is described in whom both haemodialysis and parenteral nutrition were required. To minimize the impact on transplant prospects, the renal veins were used for vascular access. The technique and rationale for this novel approach are presented.

Catheters, Indwelling↗
PubMed1997

High-resolution ultrasonography in the differential diagnosis of cystic diseases of the kidney in infancy and childhood: preliminary experience.

Autosomal recessive polycystic kidney disease, autosomal dominant polycystic disease, and glomerulocystic disease may all appear in the perinatal period as bilaterally enlarged echogenic kidneys. Current ultrasonographic equipment can better demonstrate the underlying pathologic state and assist in the differentiation of these conditions. The primary abnormality in autosomal recessive polycystic kidney disease is at the level of the collecting ducts, which are dilated and saccular. The nephrons remain normal. These dilated ectatic tubules are seen in their usual distribution as a radial array, with major ducts being perpendicular to the renal capsule, in both the renal cortex and the medulla. The peripheral renal cortex does not normally contain collecting ducts and remains unaffected in patients with mild disease. Autosomal dominant polycystic disease is characterized by cystic changes involving both the nephron and the collecting ducts. The nephron may become cystic at any point. Multiple discrete cysts of varying sizes are seen in both the renal cortex and the medulla in the severely affected infant. Subcapsular cysts are seen regularly. Glomerulocystic disease is an unusual sporadic condition characterized by the cystic dilation of the space of Bowman and the proximal convoluted tubule. On ultrasonographic examination tiny, isolated cysts, usually smaller than those occurring in autosomal dominant polycystic kidney disease, are seen in the echogenic renal cortex and may extend to the periphery of the kidney. No cysts are seen in the renal medulla. Correlation between pathologic findings and sonographic images is of value in correctly diagnosing these conditions.

Biopsy↗
PubMed1994

Stopping treatment for end-stage renal failure: the rights of children and adolescents.

Dialysis and transplantation have been of obvious benefit to children with renal failure. Yet this is not always so. End-stage treatment can also create physical and mental suffering, for both patients and their families. For this reason, the availability of life-saving treatment creates difficult ethical and legal dilemmas concerning when it can morally and lawfully be rejected. These dilemmas are explored through a general account of the doctrine of informed consent and its application to the refusal of such therapy. Clinical and parental duties of care are outlined for young and adolescent children. For young children, the rights of parents are evaluated, recognising the significance of parental involvement and support for treatment for renal failure to be successful. It is further argued that adolescents who are deemed to be competent to give informed consent have the moral right to choose to die rather than to continue treatment. To minimise this prospect, the importance of effective counselling and peer group support is made clear, along with a partnership model of clinical negotiation.

Adolescent↗
PubMed1988

Isolation, characterization and microsequence analysis of a small basic methylated DNA-binding protein from the Archaebacterium, Sulfolobus solfataricus.

DNA-binding proteins have been extracted from the thermoacidophilic archaebacterium Sulfolobus solfataricus strain P1, grown at 86 degrees C and pH 4.5. These proteins, which may have a histone-like function, were isolated and purified under standard, non-denaturing conditions, and can be grouped into three molecular mass classes of 7, 8 and 10 kDa. We have purified to homogenity the main 7 kDa protein and determined its DNA-binding affinity by filter binding assays and electron microscopy. The Stokes radius of gyration indicates that the protein occurs as a monomer. The complete amino-acid sequence of this protein contains 14 lysine residues out of 63 amino acids and the calculated Mr is 7149. Five of the lysine residues are partially monomethylated to varying extents and the methylated residues are located exclusively in the N-terminal (positions 4 and 6) and the C-terminal (positions 60, 62 and 63) regions only. The protein is strongly homologous to the 7 kDa proteins of Sulfolobus acidocaldarius with the highest homology to protein 7d. Accordingly, the name of this protein from S. solfataricus was assigned as DNA-binding protein Sso7d.

Amino Acid Sequence↗
PubMed1988

Long term outcome of treatment of end stage renal failure.

The most common causes of end stage renal failure in 46 children (mean age 11 years, range 4-14) treated between January 1972 and June 1977 were: reflux nephropathy (n = 12), cystinosis (n = 7), focal and segmental glomerulosclerosis (n = 6), and Schönlein-Henoch disease (n = 5). The quality of life, degree of renal function, and height attainment of the 31 survivors were assessed in June 1985, when their mean age was 22 years (range 14-27), using hospital records and a questionnaire designed to highlight social and psychological problems. Twenty six patients had a functioning transplanted kidney. Average growth during treatment for all survivors was normal, but most were disappointed with their 'final height'. Though five patients had some form of disabling bone disease, all 31 could walk and 27 could run. Sixteen (67%) were in full or part time employment and nine were living independently. A group of 32 patients with juvenile onset diabetes treated at this hospital for at least five years were also asked to complete the questionnaire and of these, 17 responded. On average, their data could usefully be compared with those of cases of end stage renal failure. More of the diabetics had jobs, but most sexually mature patients with renal disease were concerned about their physical appearance and had not achieved any stable long term sexual relationships. We suggest that a poor body image resulting in low self esteem may be responsible for the deficiency and believe that further study in this group is warranted.

Adolescent↗