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Biomedical subjects

A Kay

Publications and source records attributed to A Kay.

At least 55 records · Page 3Linked to original sources
PubMed1992

New assays for quantitative determination of viral markers in management of chronic hepatitis B virus infection.

We performed a quantitative study of serum hepatitis B virus (HBV) markers, including new parameters such as pre-S1 antigen (Ag), pre-S2 Ag, and anti-HBx, in 88 chronic hepatitis B surface antigen (HBsAg) carriers. New IMx assays for HBsAg and immunoglobulin M (IgM) anti-HBc detection were also used. The population studied was composed of 65 chronic hepatitis cases (40 positive for hepatitis B antigen [HBeAg] and 25 positive for anti-HBe) and 23 anti-HBe-positive, asymptomatic HBsAg carriers. Serum HBsAg levels detected by IMx were higher in HBeAg-positive than in anti-HBe-positive HBsAg carriers (all patient subgroups included) and correlated with the serum HBV DNA level (P = 0.0001). Both pre-S1 and pre-S2 Ags were detected by enzyme immunoassays in almost all HBsAg carriers. Both pre-S1 and pre-S2 Ag titers correlated positively with the serum HBsAg concentration (P = 0.0001), but only the pre-S1 Ag titer correlated with the level of serum HBV DNA (P = 0.02). The detection of low levels of IgM anti-hepatitis B core (anti-HBc) antibodies by IMx was associated with the presence of liver disease (P = 0.05) but not with the level of viral replication. The prevalence of anti-HBx antibodies detected by the enzyme immunoassay was slightly, although not significantly, higher in patients with high levels of HBV DNA (greater than 100 pg/ml) than in patients without detectable HBV DNA (P = 0.16). In anti-HBe-positive chronic HBsAg carriers, the quantitative detection of serum HBV DNA, pre-S Ag titers, and IgM anti HBc allowed us to predict which patients suffered from chronic liver disease and/or supported viral replication (P < 0.05). In a follow-up study of eight patients undergoing antiviral therapy, the clearance of both pre-S1 Ag and HBV DNA was associated with a subsequent clearance of HBV. Therefore, the quantitative determination of HBV DNA, pre-S Ags, IgM anti-HBc may prove useful for the decision to use and the monitoring of antiviral therapy, especially in anti-HBe-positive HBsAg carriers.

Carrier State↗
PubMed1992

Respiratory instability during sleep onset.

It has been hypothesized that regulatory control in the respiratory system is state dependent. According to this view respiratory instability during sleep onset is a consequence of repeated fluctuations in arousal state. However, these speculations are based primarily on measurements during stable sleep, not during sleep onset itself. The aim of the present study was to assess changes in ventilation and gas tensions during sleep onset as a function of arousal state. Twenty-one subjects (12 males and 9 females, mean age 20 yr) were assessed over an average of 11.3 sleep onsets. The subject's state was classified as alpha, theta, body movement, or stage 2 sleep, and expiratory tidal volume, minute ventilation, respiratory rate, and end-tidal CO2 and O2 were measured by means of a face mask, valve, and pneumotachograph on a breath-by-breath basis. Respiratory instability during sleep onset was found to be a result of two factors. The first factor was a between-state effect in which transitions from alpha to theta were associated with falls, and from theta to alpha with increases, in ventilation. The magnitude of the change was a positive function of metabolic drive at the time of the state change (as indicated by alveolar PCO2 and PO2 levels). The second was a within-state effect in which ventilation fell during consecutive alpha breaths and increased during consecutive theta breaths. These changes were due to the influence of the relative hyperventilation of the alpha state and the relative hypoventilation of the theta state on metabolic drive.

Adult↗
PubMed1992

Gaucher disease. Clinical, laboratory, radiologic, and genetic features of 53 patients.

We have reviewed our experiences with the clinical, laboratory, radiologic, and genetic features of 53 patients with Gaucher disease. Most were evaluated during early adult life, with a mean age of 33 years. Our patients were evaluated in a referral center, and therefore the data need to be interpreted with caution when applied to the general patient population, which includes a greater proportion of very mild cases. Thirty-nine patients were Ashkenazi Jews, 13 were non-Jewish and 1 was half-Jewish. The most common presenting symptom was bleeding related to splenomegaly and thrombocytopenia. The chronic symptoms, evaluated an average of 20 years after the diagnosis had been established, were mainly skeletal. Splenectomy had been performed in 43% of our patients and there was no evidence that this procedure accelerated the progression of liver and bone involvement. DNA from the patients was examined for 20 different mutations. The association between the 1226G/1226G genotype and a milder clinical course, and between the 1226G/84GG and 1226/1448C genotypes with more severe clinical manifestations, was confirmed. Repeated follow-up examinations in 29 patients revealed that in the majority of the patients, progression of the disease occurs during childhood, adolescence, or early adulthood with a marked tendency for stabilization thereafter. This observation suggests that Gaucher disease in most of the patients is not a relentless progressive disorder but a rather stable disorder during adulthood. The indications for the newly introduced intravenous enzyme replacement therapy as well as of future experimental treatments should be examined in the light of the natural history of the disease.

Adolescent↗
PubMed1991

Enzyme replacement therapy for Gaucher disease.

Four patients with moderately severe type I Gaucher disease were treated with commercially available mannose terminated glucocerebrosidase (Ceredase; Genzyme, Boston, MA) for up to 13 months. The enzyme was administered at the rate of three to four times weekly at one fourth the total recommended dosage, greatly decreasing the cost. Marked regression of hepatomegaly and improvement in liver function tests, peripheral blood counts, and serum angiotensin-converting enzyme levels were documented. The two patients with pulmonary involvement manifested improvement in pulmonary function tests. Skeletal disease remained unchanged.

Adult↗
PubMed1991

Sequence analysis of the simian foamy virus type 1 genome.

We have cloned the simian foamy virus type 1 genome (SFV1) and determined its nucleotide sequence. Analysis of this genome reveals, in addition to the usual genes encoding retroviral capsid, reverse transcriptase, and envelope protein (respectively, gag, pol, and env), two open reading frames (ORFs) between env and the long terminal repeat with partial homology to the human foamy virus (HFV) bel1 and bel2 genes. The first ORF could code for a polypeptide of 312 amino acids (aa) showing 40% homology with the HFV bel1 putative gene product. A more detailed analysis showed that the protein encoded by this ORF would have features characteristic of known trans-activating proteins. The second ORF could code for a polypeptide of 403 aa showing 38% homology with the putative HFV bel2 gene product. Moreover, the 5' extremity of the RNA genome can be folded into a secondary structure identical to the Tat-response element of human immunodeficiency viruses. A phylogenetic tree of retroviruses, including SFV1 and HFV, was constructed. It showed at the molecular level that Spumavirinae, previously classified on the basis of their morphology and their biological properties, constitute a separate group. The homology between SFV1 and HFV reaches 89% in the reverse transcriptase domain of the pol gene. but is much smaller in other parts of the genome.

Amino Acid Sequence↗
PubMed1991

Recognition of the N-terminal, C-terminal, and interior portions of HBx by sera from patients with hepatitis B.

We have cloned and expressed in Escherichia coli three different parts of the HBx open reading frame, the N- and C-termini and the interior or central portion, using two vector systems. The sera of 43 hepatitis B virus patients representing three clinical categories--asymptomatic carriers, chronic active hepatitis, and hepatitis B patients with cirrhosis--known to be anti-HBx positive, were tested for reactivity against these constructs by Western blotting. The great majority of sera, regardless of the clinical categories, clearly recognise all three parts of HBx, strongly suggesting that the normal mechanism of biosynthesis of the HBx gene product is a straight-forward translation of the open reading frame starting from the first ATG. However, asymptomatic carriers show a marked, often almost exclusive, preference for recognition of the central portion of HBx, while patients with chronic hepatitis and patients with cirrhosis generally recognise all three parts of HBx to a similar extent.

Amino Acid Sequence↗
PubMed1991

In vivo neutralization of duck hepatitis B virus by antibodies specific to the N-terminal portion of pre-S protein.

The neutralization of duck hepatitis B virus (DHBV) infection using antibodies directed against the N-terminal portion of the large surface protein was examined in vitro and in vivo. We demonstrate here that a monoclonal antibody, directed against an epitope mapped between aa 77 and aa 100 on the DHBV pre-S, exerts a similar neutralizing activity (77%) both in vivo and in vitro. Furthermore, we have found that a polyclonal antiserum raised against the bacterially expressed 131 first amino acids of the DHBV pre-S region abolished the infectivity of DHBV in ducklings. Therefore, antibodies against a peptide representing most of the DHBV pre-S region (1-131) or a monoclonal antibody specific to an epitope within this region neutralizes in vivo DHBV infectivity.

Animals↗
PubMed1991

Production of polyclonal antibodies against the S and preS2 regions of woodchuck hepatitis virus: lack of detectable low glycosylated preS2 protein (GP33) in sera from infected animals.

Polyclonal antibodies directed against the preS2 and S domains of the woodchuck hepatitis virus (WHV) envelope proteins were prepared using synthetic peptides and fusion polypeptides as immunogens. They were tested by immunoblotting and immunoprecipitation of infected woodchuck sera and lysates of a eukaryotic cell line expressing WHV envelope proteins. Only one anti-peptide serum directed against the preS2 domain was reactive with WHV envelope proteins, recognizing the preS2 and preS1 proteins by their preS2 epitopes. With recombinant fusion proteins we generated several anti-S sera, which recognized all envelope proteins, and anti-preS2 antisera, which recognized the preS proteins. Results obtained with our antisera showed that sera of infected woodchucks lack the low glycosylated form (GP33) of the preS2 protein, unlike human hepatitis B virus.

Animals↗
PubMed1990

The effect of postpartum lactation counseling on the duration of breast-feeding in low-income women.

We investigated the effectiveness of a program of intensive postpartum support for low-income, breast-feeding women and identified potential predictors of prolonged breast-feeding in this population. Ninety-seven low-income women were randomized to receive intensive postpartum education and support for breast-feeding or to receive only the routine assistance provided by the obstetrical nurses. Both groups were telephoned 6 weeks post partum to determine the method of infant feeding then, and those still breast-feeding were contacted monthly until complete weaning had occurred. No significant difference in breast-feeding duration between the two groups was noted. There was no association between duration of nursing and race, marital status, or the need to return to work or school. Earlier age at introduction of supplement, younger maternal age, and participation in prenatal classes predicted breast-feeding duration by logistic regression.

Breast Feeding↗
PubMed1990

Early and frequent detection of HBxAg and/or anti-HBx in hepatitis B virus infection.

To clarify the significance of the X gene of hepatitis B virus, we have tested for anti-HBx in the serum and HBxAg in the liver at different stages of the natural history of hepatitis B virus infection. Sera were screened by enzyme-linked immunosorbent assay and positive results confirmed by immunoblot. Purified recombinant MS2 Pol-HBx fusion protein was used as target for both assays. Among serial sera of patients with nonfulminant acute hepatitis, 24 of 64 patients (37.5%) were positive for anti-HBx. In fulminant cases, 15 of 36 patients (42%) had anti-HBx. In chronic hepatitis patients with high rates of hepatitis B virus replication, we found a significantly (p less than 0.01) higher prevalence of anti-HBx, 14 of 25 patients (56%), than in those with low replication, 14 of 66 patients (21%), or among asymptomatic HBsAg carrier blood donors (20 of 126 = 16%) without detectable hepatitis B virus replication (p less than 0.0001). The highest prevalence of anti-HBx was found in HBsAg carriers with cirrhosis (41 of 54 patients = 76%) and/or with hepatocellular carcinoma (18 of 33 patients = 54%). The findings suggest that anti-HBx appears as a common and early marker of hepatitis B virus infection, transient in self-limited hepatitis but persisting with progression to chronicity. In chronic hepatitis, the prevalence of anti-HBx correlated with the intensity and duration of hepatitis B virus replication but neither with the severity of the liver disease nor with malignant transformation per se.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1990

Behavioural and EEG responses to auditory stimuli during sleep in newborn infants and in infants aged 3 months.

Two studies were conducted in order to assess EEG and behavioural responsiveness to auditory stimuli as a function of sleep state in infants. The subjects in the first experiment were 11 infants aged 3 months, and in the second study the responsiveness of 8 infants aged 3 months was compared with that of 8 newborn infants. The stimuli ranged in intensity from 36 to 90 dB and were presented using a modification of the method of constant stimuli. The occurrence and intensity of behavioural responses were recorded by a trained observer. Electroencephalogram (EEG) responses were defined as EEG desynchronization and were identified by a Fast Fourier Transform algorithm. The results of the two studies showed that infants were more responsive during active sleep (AS) than during quiet sleep (QS) and gave behavioural responses at lower stimulus intensities than EEG responses. Behavioural responsiveness and EEG responsiveness during AS increased as a function of age, while EEG responsiveness during QS decreased. The marked suppression of EEG responsiveness during QS at 3 months of age is thought to be a consequence of developmental changes in sleep mechanisms--an effect which may have clinical implications.

Age Factors↗
PubMed1989

The district nurse.

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Community Health Nursing↗
PubMed1987

Finger flexion function in rheumatoid arthritis: the reliability of eight simple tests.

The inter- and intra-observer errors of eight tests of finger flexion function were estimated from the results obtained by three observers assessing 10 patients with rheumatoid hand involvement. Measurements of finger flexion and muscle power involved both conventional and novel techniques using simple and easily constructed apparatus. For each test, measurements were in agreement between observers and were reproducible on three occasions. These tests may now be used with confidence by other investigators.

Aged↗
PubMed1986

European League against Rheumatism study of adverse reactions to D-penicillamine.

An international multicentre study of adverse reactions to D-penicillamine was undertaken on 2879 patients exposed to the drug--1491 of them a prospective sample. The majority of patients were being treated for rheumatoid arthritis. Over a period of 18 months, 319 (21%) of patients in the prospective sample developed adverse reactions necessitating drug withdrawal; two thirds of these occurred during the first 3 months of treatment. The most frequently-occurring adverse reactions involved skin (6%), kidneys (4%), gastro-intestinal tract (4%) and haemopoiesis (3%). Adverse effects, considered to be serious by the reporting physician, included fever and leucopenia during the early weeks of treatment and, after some months of drug exposure, proteinuria, myasthenia gravis, dyspnoea and pemphigus. Two patients died, one of fulminating septicaemia and the other was found at autopsy to have had multiple lung abscesses following unexplained anaemia and hemiparesis.

Aged↗
PubMed1985

The HBV HBX gene expressed in E. coli is recognised by sera from hepatitis patients.

We have cloned the X gene (HBx) and the HBc antigen (HBc Ag) gene of human hepatitis B virus (HBV) in Escherichia coli as fusion products with beta-galactosidase. Both HBV genes are expressed in E. coli strain CSR 603. Expression is detected by u.v. irradiation of the bacteria, metabolic labelling and electrophoresis of the labelled extracts on SDS-polyacrylamide gels. The HBc Ag protein produced in bacteria can be recognised by anti-HBc sera and peptides derived from the protein are also recognised by anti-HBe sera. The HBx protein is recognised by some, but not all, sera which are anti-HBe positive. HBx Ag is also recognised by a woodchuck antibody similar to anti-HBe (anti-WHe). These results constitute the first proof that the open reading frame X is a true viral gene and is expressed during HBV (and WHV) infection and that an HBx/anti-HBx system, which may have important biological implications, can exist in parallel with the classic HBe/anti-HBe system.

Animals↗