Biomedical subjects

A Kay

Publications and source records attributed to A Kay.

At least 19 recordsLinked to original sources

PubMed1995

Individual differences in relationship between upper airway resistance and ventilation during sleep onset.

Sleep-induced hypoventilation is caused partly by inadequate compensation for elevated upper airway resistance (UAR). Some evidence suggests that the effect of UAR on ventilation may vary among individuals. The relationship between minute ventilation (VI) and UAR was examined in 26 healthy young men (average of 10.12 sleep onsets). Variables were analyzed over transitions between wakefulness (defined by alpha electroencephalographic activity) and sleep (theta electroencephalographic activity). Transitions to sleep were associated with increases in UAR in synchrony with reductions in VI, and equally rapid opposite changes occurred with awakenings. The relationship between the magnitudes of the changes in VI and UAR at transitions varied among subjects, accounting for 30% of the variance for alpha-to-theta transitions and 50% of the variance for theta-to-alpha transitions. Results indicated that, although ventilatory changes during sleep onset are partly a consequence of changes in UAR, alterations in UAR do not account fully for alterations in VI. Other factors that may contribute to ventilatory instability during sleep onset include state-related fluctuations in drive to the primary respiratory muscles and variability in compensatory mechanisms.

Adult↗

PubMed1994

Identification of major antigenic domains of duck hepatitis B virus pre-S protein by peptide scanning.

Neutralization epitopes of duck hepatitis B virus (DHBV) have been previously mapped within the N-terminal portion of the pre-S protein using monoclonal antibodies. However, the immune response of ducks to this region is not well characterized at the amino acid level. To this end, we have immunized adult Pekin ducks with either DHBV positive serum or bacterially expressed DHBpre-S polypeptide representing the N-terminal portion of the DHBV pre-S region. We have demonstrated that adult ducks inoculated with either antigen developed antibodies to the DHBV pre-S region starting 5 to 10 days postinjection. The sera of all ducks, irrespective of the immunogen used, exhibited a significant protective activity against DHBV, as assessed in vivo. To identify which pre-S domains bind antibodies from these duck sera, we have used the Pepscan methodology with overlapping octapeptides spanning the DHBV pre-S sequence from amino acids 1 to 145. Using this approach, five major antigenic domains, 7KSMDVRRI14, 22NQLAGRMIP30, 58TLQNQGAW65, 71RRVGLSNPT79, and 127GDDPLLGNQ135 were identified within the DHBV pre-S region.

Amino Acid Sequence↗

PubMed1994

Woodchuck hepatitis virus surface antigen produced in vitro fails to bind polymerized woodchuck serum albumin.

Using a plasmid (pSWS) similar to one that has been successfully used for large-scale production of hepatitis B virus (HBV) envelope protein particles (pSVS) but containing the corresponding woodchuck hepatitis virus (WHV) envelope gene sequences, we have stably transformed the rodent dihydrofolate reductase-deficient cell line CHO dhfr-. Although production of WHV envelope particles in CHO/pSWS cell lines was low, it was sufficient to test whether these particles could bind to polymerized serum albumin. Whereas binding of HBV particles produced in CHO/pSVS cells to polymerized human serum albumin could readily be detected, we found no evidence that the WHV envelope protein particles produced in vitro bind to either human or woodchuck polymerized serum albumin.

Animals↗

PubMed1994

Changes in airway resistance during sleep onset.

Ventilation is lower during sleep than wakefulness. An increase in airway resistance has been proposed as the critical factor. As the change in ventilation has been shown to occur abruptly at transitions between alpha and theta electroencephalogram activity, it was of interest to determine whether the increase in airway resistance between wakefulness and sleep also occurs at these transitions. Three young healthy male subjects were run for an average of 15 sleep onsets in each of three conditions. The three conditions were 1) an esophageal balloon was put in place to allow the measurement of airway resistance, 2) in addition to an esophageal balloon the nose was occluded, and 3) there was no esophageal balloon and the nose was not occluded. Ventilation and airway resistance were measured during sleep onset and analyzed as a function of arousal state. In those conditions of the experiment in which airway resistance was affected by state, the changes, like those in ventilation, occurred at transitions between alpha and theta electroencephalogram activity. However, in the three subjects studied, the magnitude of ventilatory changes at alpha-theta transitions and the extent to which changes in ventilation were associated with changes in airway resistance differed between subjects. It was concluded that although inspiratory airway resistance is a major component affecting the state-related changes in ventilation at sleep onset, the degree of its contribution may vary over individuals.

Adult↗

PubMed1993

Fine mapping of neutralization epitopes on duck hepatitis B virus (DHBV) pre-S protein using monoclonal antibodies and overlapping peptides.

To define the residues involved in duck hepatitis B virus (DHBV) neutralization at the amino acid level, we have used a procedure combining monoclonal antibodies (MAbs) and overlapping octapeptides (Pepscan). Two neutralizing MAbs (SD20 and 900), specific for the pre-S protein were shown to reduce DHBV infectivity in vivo by 75 and 90%, respectively, while complete protection of ducklings was achieved with a polyclonal antiserum raised against the bacterially expressed first 131 amino acids of the DHBV pre-S region (DHBpre-S). Using fusion polypeptides, the binding sites of these MAbs were localized between aa 77 and 100 on pre-S protein. We have used octapeptides spanning the pre-S sequence from aa 64 to 115 for fine mapping of these epitopes. Within the sequence scanned, the polyclonal anti-DHBpre-S antiserum recognized a region exclusively limited to the residues E82-K95, suggesting immunodominance of this region in the sequence aa 64-115. The epitope recognized by Mab 900 was mapped within the same region, whereas the epitope recognized by Mab SD20 was localized downstream from this region. To define the amino acids essential for binding to the highly neutralizing Mab 900, we have used single amino acid replacement and demonstrated that two residues Q87 and W88 were important for antibody recognition.

Amino Acid Sequence↗

PubMed1993

Duck hepatitis B virus (DHBV) as a model for understanding hepadnavirus neutralization.

The role of the immune response to the human hepatitis B virus (HBV) envelope proteins in neutralization of viral infectivity has been well documented. The similarity between HBV, prototype member of the hepadnavirus family, and the closely related duck hepatitis B virus (DHBV) has allowed, use of the latter as a convenient model for the study of molecular mechanisms of HBV replication and neutralization. In this brief review, we will examine the HBV and DHBV envelope proteins and their role as targets for virus neutralization.

Amino Acid Sequence↗

PubMed1993

Electrocardiography in epilepsy patients without cardiac symptoms.

Sudden unexpected death in epilepsy (SUDEP) has been ascribed to cardiac arrhythmia, possibly triggered by cerebral events. Young, noncompliant, substance-abusing males with convulsions may be at risk. EEG/ECG studies have not shown significant cardiac arrhythmias in these and other seizure patients. We reviewed resting ECGs in 75 epilepsy patients and compared ventricular rate, PR interval, QRS duration, and QT interval corrected for heart rate (QTC) with normal ECGs recorded in age-matched patients without cardiac or neurologic disorders. No potentially lethal arrhythmias were noted in the seizure patients. Patients who fit the previously-described profile of high risk of SUDEP had more abnormal ECGs and ventricular rate was faster in these patients than in other epileptics. Patients with complex partial and secondarily generalized seizures had faster ventricular rates than other epileptics. No differences were noted in QRS duration or PR interval. QT was longer in patients with complex partial seizures than in control ECGs or other epileptic patients. These findings suggest that resting ECG has low diagnostic yield in epilepsy patients without cardiac symptoms. The factors possibly predisposing to SUDEP may relatively increase resting heart rate, however, and relatively increased QT interval with complex partial seizures may indicate some differences, possibly neurally-mediated, in cardiac excitability which could contribute to SUDEP.

Adult↗

PubMed1992

Timing of pregnancy in relation to the onset of rheumatoid arthritis.

The interval between the onset of rheumatoid arthritis (RA) and the most recent pregnancy prior to RA onset in 88 women was determined. These data were compared with data obtained from a group of 144 age-matched normal women (controls) who had been assigned a "dummy date for RA onset" for the purposes of analysis. The frequency of disease onset during 3 time intervals within the period from conception to 1 year postpartum was compared with the frequency of disease onset outside this period. There was a reduction in the incidence of disease onset during pregnancy (adjusted odds ratio [OR] 0.30, 95% confidence interval [CI] 0.04-2.6) and a numerically greater increased risk of RA onset during the first 3 months postpartum (OR 5.6, 95% CI 1.8-17.6), which persisted for the subsequent 9 months (OR 2.6, 95% CI 0.8-7.9). A reduction in the incidence of disease onset was seen during all pregnancies; in contrast, the postpartum increase was greater in those with RA onset after the first pregnancy. The reduced incidence of RA onset during pregnancy, with the increased risk postpartum, mirrors the previously described suppression of disease activity during pregnancy and the subsequent flare postpartum in women with established RA. In addition, the increased postpartum risk after the first pregnancy might suggest that in susceptible women, either the hormonal changes or the exposure to the fetus's paternal HLA might represent a risk factor for disease causation.

Adult↗

PubMed1992

The effect of ammonium, phosphate, potassium, and hypotonicity on stored red cells.

The use of an experimental solution that maintained high ATP levels and produced greater than 70 percent viability of stored red cells (RBCs) for up to 18 weeks has been described by other investigators. This solution differed markedly from conventional storage media in that it lacked sodium; contained high concentrations of potassium, ammonium, and phosphate; and was hypotonic. It was not clear which feature or features were responsible for the observed effects. The effects of ammonium, phosphate, potassium, and hypotonicity on stored RBCs have been examined. It was determined that ammonium and phosphate were the important factors in ATP maintenance. The biochemical mechanism by which ammonium acts was studied. In fresh human blood samples, ammonium was found to relieve phosphofructokinase from inhibition by increased ATP concentrations, to have no significant effect on adenine phosphoribosyl transferase activity, and, unexpectedly, to increase the activity of AMP deaminase. Despite prolonged ATP maintenance by ammonium and phosphate-containing storage media, satisfactory viability of RBCs stored up to 77 days was not demonstrated in the rabbit transfusion model.

AMP Deaminase↗

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↗