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Biomedical subjects

J Waters

Publications and source records attributed to J Waters.

At least 55 records · Page 3Linked to original sources
PubMed1993

Ultrastructural neuropathology in murine trisomy 16 hippocampal grafts.

Trisomy 21, Down syndrome individuals demonstrate Alzheimer's disease-associated neuropathology at post mortem. The amyloid precursor protein, one of the pathological proteins is encoded for on chromosome 21. Mouse chromosome 16 is syntenic to human chromosome 21 for the region spanning the amyloid gene. We have previously reported the appearance of Alzheimer's disease-associated neuropathological proteins in cortical grafts derived from Trisomy 16 mice at 4-6 months survival. This paper reports the ultrastructural observations of large and multiple deposits of intracellular lipofuscin within these trisomic grafts at 12 months survival along with increased numbers of free ribosomes, extended Golgi apparatus and endoplasmic reticulum, membrane degeneration and abnormal axonal profiles. Similar but less severe neuro-degeneration is occasionally observed within 18-month-old normal, mouse hippocampal tissue and rarely observed in age-matched control grafts.

Aging↗
PubMed1991

A recombinant vaccinia virus expressing hepatitis A virus structural polypeptides: characterization and demonstration of protective immunogenicity.

A recombinant vaccinia virus containing most of the P1 region of hepatitis A virus (HAV) was constructed. Cell lysates of cultures infected with the virus contained HAV proteins detectable by radioimmunoassay. Western blot analysis revealed the presence of a single protein of Mr 60K to 62K, bearing epitopes from structural polypeptides VP4, -3 and -2, and the N terminus of VP1. The size of the protein suggests that at least some of the vaccinia virus thymidine kinase is also expressed. Inoculation of tamarin monkeys with the recombinant virus resulted in the development of a specific anti-HAV immune response which was protective against challenge with a virulent strain of HAV. Recombinant viruses expressing the above region of HAV or the proteins expressed by such viruses may be useful in the development of a vaccine suitable for use in man.

Animals↗
PubMed1990

Vaccine-induced escape mutant of hepatitis B virus.

In southern Italy, 44 contacts of hepatitis B virus carriers, including infants of carrier mothers, became HBsAg positive despite passive and active immunisation according to standard protocols. In 32 of these vaccinees infection was confirmed by the presence of additional markers of viral replication. In 1 infant, serious disease occurred. The virus from this patient is an escape mutant with a different sequence from that of the isolate from the mother. A point mutation from guanosine to adenosine at nucleotide position 587 resulted in an aminoacid substitution from glycine to arginine in the highly antigenic a determinant of HBsAg. This mutation is stable: it is present in an isolate from the child 5 years later. In some of these patients, including this child, the a determinant, to which a large part of the vaccine-induced immunity is directed, has been partly lost. Binding to HBsAg of a monoclonal antibody, previously mapped to the region of the mutation, was reduced in the child relative to that of the mother.

Biomarkers↗
PubMed1990

A submicroscopic homozygous deletion at the D3S3 locus in a cell line isolated from a small cell lung carcinoma.

We have used 14 DNA probes, which detect 19 different restriction enzyme length polymorphisms, to search for heterozygosity on chromosome 3 in five cell lines isolated from patients with small cell lung carcinoma. The cell lines on karyotype analysis did not show the deletion in chromosome 3 characteristic of this disease. Our objective was to determine if allelic loss had occurred by some chromosomal mechanism other than deletion. Two of the cell lines are consistent with allelic loss having occurred by whole chromosome loss and reduplication. The third may have lost only the short arm due to i(3q) formation. The fourth cell line has an i(3q) chromosome, together with a translocation product involving the distal portion of the short arm of chromosome 3. Lack of evidence of heterozygosity for this distal portion of 3p suggests that a copy of the 3p homologue is involved in the translocation and therefore does not explain allelic loss of of the other homologue. The fifth, while also likely to have lost one chromosome homologue, has a submicroscopic deletion on all chromosome 3s, only detectable by RFLP analysis. Such homozygous deletions have recently proved useful in the isolation of tumour suppressor genes.

Alleles↗
PubMed1990

Visual analogue scales distinguish between low urinary flow rates due to impaired detrusor contractility and those due to bladder outflow obstruction.

In patients with symptoms suggestive of bladder outflow obstruction and a free flow rate less than 12 ml/s a visual analogue scale was used to measure the response to the question "Compared to 5 years ago, how thick is your stream when you pass urine?". The visual analogue scale compared favourably with cystometry in distinguishing between low flow rates resulting from impaired detrusor contractility and low flow rates due to bladder outflow obstruction. A visual analogue scale may serve to alert the surgeon to the presence of impaired detrusor contractility and the need for a fuller urodynamic assessment in patients with a low urinary flow rate prior to consideration for prostatectomy.

Aged↗
PubMed1989

Frequency and extent of allelic loss in the short arm of chromosome 3 in nonsmall-cell lung cancer.

DNA was prepared from tumour and normal tissue from 48 patients representing all common histological types of nonsmall-cell lung cancer. Using eight DNA probes, which detect nine restriction enzyme fragment length polymorphisms (RFLP) on chromosome 3, we established that among the 44 informative patients 32 had lost alleles on the short arm of one of their copies of chromosome 3. Of these 32, at least 13 had also lost alleles on the long arm of chromosome 3, suggesting that the whole chromosome might be lost. For one patient, cytogenetic analysis indicated that the mechanism of allelic loss was reciprocal translocation followed by chromosomal loss of one of the reciprocal products. Two patients with allelic loss distal to the D3S3 locus (which maps to 3p13-14) retained heterozygosity at that locus. These results indicate that loss of alleles on the short arm of chromosome 3 is a common event in lung tumours of the nonsmall-cell type, that this loss occurs by a variety of chromosomal mechanisms, and that the minimally deleted region is 3p13-14----3pter.

Alleles↗
PubMed1989

Adults with Prader-Willi syndrome: abnormalities of sleep and behaviour.

A survey of 32 adult females and 31 adult males with Prader-Willi syndrome (PWS) shows that sleep disorders (including excessive day and night time sleep) and behavioural abnormalities, (temper tantrums and deliberate picking of sores) are common. These abnormalities are not related to the degree of obesity or to each other. Speech disorders also occur. Intelligence quotients are often within the normal range.

Adolescent↗
PubMed1988

Virus-host interaction in chronic hepatitis B virus infection.

The clearance of HBV-infected cells from the liver is probably dependent on an interplay between the interferon system and the cellular limb of the host immune response. Although the importance of the nucleocapsid proteins as targets for sensitized cytotoxic T cells is established in chronic HBV infection, further studies are needed during the early phase of acute HBV infection. The relative importance of pre S sequences as inducers and targets of the virus neutralizing humoral immune response is becoming established, but their precise place will await the development of in vitro models of hepadnavirus infection and precise definition of the mechanism of viral uptake. Our understanding of the mechanisms underlying the development of chronic HBV infection is still incomplete. When this occurs in adult life, deficient production of alpha interferon and suppression of the ability of the host to respond to interferon are probably important factors, and the role of suppression of the humoral response remains to be determined. In the neonate, specific suppression of the cell-mediated immune response, perhaps because of exposure to soluble HBe antigen or to modulating quantities of maternally derived antinucleocapsid antibodies at a time when the immune system is "immature," may be involved. In each of these postulated mechanisms the virus has neutralized one important host defense. Increasing the response rate to therapy with interferon or synthetic antiviral compounds will depend on identifying the cause in each patient and devising specific therapies to reverse the host-virus balance in favor of the host defenses.

Acute Disease↗
PubMed1988

Staff satisfaction in short stay wards.

Two Short Stay Wards (SSWs) have been opened in a large teaching hospital in Sydney's outer Western suburbs, as a means of overcoming budget constraints and a shortage of nurses prepared to work conventional rosters. This paper reports a survey of the attitudes of medical and nursing staff using these two SSWs. Overall, medical personnel were found to hold positive attitudes to the SSWs and reported higher patient turnover as a result of their opening. Identified barriers to usage of the wards included scheduling of operating suite time, and lack of flexibility in the booking, admission and movement of SSW patients. Nurses who work in the SSWs have chosen to work under these special nursing conditions. They were found to be particularly satisfied with their work hours, rapport with patients and other staff, the high patient turnover and varied case mix. Sources of dissatisfaction included Friday night duty and deployment, and the administrative procedures practised by medical staff, including difficulties in contacting them.

Attitude of Health Personnel↗
PubMed1988

The T-ALL specific t(11;14)(p13;q11) translocation breakpoint cluster region is located near to the Wilms' tumour predisposition locus.

A breakpoint cluster region (T-ALLbcr) has been previously described on 11p13 for T-ALL carrying t(11;14)(p13;q11). One further T-ALL breakpoint is described bringing to 5 out of 6 such translocations which are found to break within a maximum of 6.7 kb on chromosome 11p13. Studies of somatic cell hybrids derived from t(11;14)(p13;q11) T-ALL placed the T-ALLbcr between the genes for catalase (CAT) and the beta-subunit of follicle stimulating hormone (FSHB). This suggested a link between the T-ALLbcr and the Wilms' tumour predisposition locus (WT) since constitutional 11p13 deletions predispose to Wilms' tumour. Utilising somatic cell hybrids from patients with Wilms' tumours and aniridia, we show that while the T-ALLbcr maps distal to the catalase gene at 11p13, it maps outside the shortest region of overlap of a series of 11p13 deletions associated with Wilms'-Aniridia. The data suggest the order of genes at 11p13 to be: centromere-CAT-T-ALLbcr-WT-aniridia-FSHB-telomere. Therefore, the T-ALLbcr must lie very close to but may be distinct from the Wilms' predisposition locus at 11p13.

Aniridia↗
PubMed1987

Cytotoxic T-cell responses to the nucleocapsid proteins of HBV in chronic hepatitis. Evidence that antibody modulation may cause protracted infection.

The nucleocapsid antigens (HBc and HBe) are present on the membranes of HBV-infected hepatocytes from HBV carriers. In autologous cytotoxicity experiments we demonstrate that cytotoxic T cells sensitised to the nucleocapsid proteins of hepatitis B are present in HBe antigen-positive HBV carriers with chronic hepatitis and can be blocked by monoclonal anti-HBc and anti-HBe. Passive immunisation of chimpanzees with monoclonal anti-HBc and anti-HBe offers no protection against HBV infection but in both cases leads to an unusually prolonged hepatitis probably by modulation of HBc and HBe antigen display on the hepatocytes. High-titre anti-HBc in the circulation of HBe antigen-positive patients probably modulates the former protein making HBe the important target antigen for cytotoxic T cells mediating liver damage in chronic carriers. These data also support the hypothesis that passive transfer of IgG anti-HBc across the placenta may be one major factor promoting development of persistent infection in neonates infected from carrier mothers.

Animals↗
PubMed1986

Virus-neutralizing antibodies to hepatitis B virus: the nature of an immunogenic epitope on the S gene peptide.

Using a murine monoclonal antibody (RF-HBs-1) which has been shown to be capable of neutralizing both ad and ay subtypes of hepatitis B virus (HBV), we have devised a competitive inhibition assay to measure the presence of virus-neutralizing antibodies in the sera of patients who have recovered from acute type B hepatitis. The majority of patients have this antibody in their serum. We also show that this antibody inhibits the binding of polymerized human serum albumin (pHSA) to the pHSA receptor site of the HBV particle, which has been proposed as an important site for the entry of HBV into liver cells. We have demonstrated that the epitope recognized by this antibody is dependent on the linkage of 24,000 and 28,000 mol. wt. polypeptides via a disulphide bond. This conformational determinant in the coat of the virus which is part of or near to the pHSA binding site is important in evoking a virus-neutralizing response.

Antibodies, Monoclonal↗