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Biomedical subjects

J R Kent

Publications and source records attributed to J R Kent.

At least 19 recordsLinked to original sources
PubMed2005

The cellular response to herpes simplex virus type 1 (HSV-1) during latency and reactivation.

In order to learn more about the cellular response to viral gene activity during latency and reactivation of herpes simplex virus type 1 (HSV-1), the authors have employed microarray analysis. On an array of about 1200 cellular genes, approximately 56 genes were found to be differentially regulated in infected trigeminal ganglia of mice, compared to uninfected mice, during latency and reactivation. Of these genes, 10 were examined more closely using quantitative real-time polymerase chain reaction (PCR) to confirm the microarray results. Genes involved in interferon and other signaling pathways appeared to predominate in response to a latent or reactivating HSV infection. Interestingly, some genes found to be differentially regulated in latently infected ganglia are neuronal-specific genes (pro-opiomelanocortinin; zinc finger proteins of the cerebellum 1 and 2). During reactivation, the involvement of several cell signaling molecules that may be important for the initiation of an HSV infection was observed, including various receptors and molecules involved in cell-cell spread.

Animals↗
PubMed2004

During lytic infection herpes simplex virus type 1 is associated with histones bearing modifications that correlate with active transcription.

Herpes simplex virus type 1 (HSV-1) is a large (150-kb) double-stranded DNA virus that forms latent infections in neuronal cells of the human peripheral nervous system. Previous work determined that the HSV-1 genome is found in an ordered nucleosomal structure during latent infection. However, during lytic infection, it was unclear whether viral DNA was in a chromatin state. We examined HSV-1 during lytic infection using micrococcal nuclease digestion and chromatin immunoprecipitation. The HSV-1 genome is at least partially nucleosomal, although apparently not in a regular repeating structure. Analysis of histones associated with HSV-1, within both the promoter and the transcribed regions, revealed covalent amino tail modifications similar to those associated with active host mammalian genes. Certain of the modifications were detected in the temporal order expected of the immediate-early, early, and late gene classes. These data suggest that productive infection may be accompanied by acquisition of a permissive chromatin state.

Base Sequence↗
PubMed1991

Diabetic amyotrophy without pain. A puzzling clinical picture.

A patient with weight loss and weakness presents a diagnostic challenge. Drs Moeser and Kent describe an unusual case of diabetic amyotrophy that required extensive workup to arrive at the diagnosis and rule out more serious disease. Symptoms were dramatic, and recovery was spontaneous following conservative treatment.

Aged↗
PubMed1985

Reactions of the intervening sequence of the Tetrahymena ribosomal ribonucleic acid precursor: pH dependence of cyclization and site-specific hydrolysis.

During self-splicing of the Tetrahymena rRNA precursor, the intervening sequence (IVS) is excised as a unique linear molecule and subsequently cyclized. Cyclization involves formation of a phosphodiester bond between the 3' end and nucleotide 16 of the linear RNA, with release of an oligonucleotide containing the first 15 nucleotides. We find that the rate of cyclization is independent of pH in the range 4.7-9.0. A minor site of cyclization at nucleotide 20 is characterized. Cyclization to this site becomes more prominent at higher pHs, although under all conditions examined it is minor compared to cyclization at nucleotide 16. The circular IVS RNAs are unstable, undergoing hydrolysis at the phosphodiester bond that was formed during cyclization. We find that the rate of site-specific hydrolysis is first order with respect to hydroxide ion concentration, with a rate constant 10(3)-10(4)-fold greater than that of hydrolysis of strained cyclic phosphate esters. On the basis of these results, we propose that circular IVS RNA hydrolysis involves direct attack of OH- on the phosphate at the ligation junction, that particular phosphate being made particularly reactive by the folding of the RNA molecule. Cyclization, on the other hand, appears to occur by direct attack of the 3'-terminal hydroxyl group of the linear IVS RNA without prior deprotonation.

Animals↗
PubMed1985

Sequence requirements for self-splicing of the Tetrahymena thermophila pre-ribosomal RNA.

The sequence requirements for splicing of the Tetrahymena pre-rRNA have been examined by altering the rRNA gene to produce versions that contain insertions and deletions within the intervening sequence (IVS). The altered genes were transcribed and the RNA tested for self-splicing in vitro. A number of insertions (8-54 nucleotides) at three locations had no effect on self-splicing activity. Two of these insertions, located at a site 5 nucleotides preceding the 3'-end of the IVS, did not alter the choice of the 3' splice site. Thus the 3' splice site is not chosen by its distance from a fixed point within the IVS. Analysis of deletions constructed at two sites revealed two structures, a hairpin loop and a stem-loop, that are entirely dispensable for IVS excision in vitro. Three other regions were found to be necessary. The regions that are important for self-splicing are not restricted to the conserved sequence elements that define this class of intervening sequences. The requirement for structures within the IVS for pre-rRNA splicing is in sharp contrast to the very limited role of IVS structure in nuclear pre-mRNA splicing.

Base Sequence↗
PubMed1984

A labile phosphodiester bond at the ligation junction in a circular intervening sequence RNA.

The excised intervening sequence of the Tetrahymena ribosomal RNA precursor mediates its own covalent cyclization in the absence of any protein. The circular molecule undergoes slow reopening at a single phosphodiester bond, the one that was formed during cyclization. The resulting linear molecule has 5'-phosphate and 3'-hydroxyl termini; these are unusual products for RNA hydrolysis but are typical of the other reactions mediated by this molecule. The reopened circle retains cleavage-ligation activity, as evidenced by its ability to undergo another round of cyclization and reopening. The finding that an RNA molecule can be folded so that a specific phosphate can be strained or activated helps to explain how the activation energy is lowered for RNA self-splicing. The proposed mechanisms may be relevant to several other RNA cleavage reactions that are RNA-mediated.

Animals↗
PubMed1983

Endemic goiter in Vietnam.

Endemic goiter involves about 15% of the population of Vietnam. To define the role of various factors which contribute to endemic goiter in Vietnam, we surveyed 935 people in Vancon, a lowland commune with goiter appearing only in the past decade, and 619 people in Dich Giao, a highland commune with endemic goiter treated erratically with iodized salt. In Dich Giao, cassava, a goitrogenic food, constitutes half of the dietary caloric intake. The prevalence of goiter was 45% in Vancon and 28% in Dich Giao. Laboratory studies were carried out in a subgroup of 63 subjects in Vancon, 52 subjects in Dich Giao, and a control group of 46 women in Hanoi. The mean serum TSH levels were 1.4 +/- 0.1 (+/- SE) microU/ml in Hanoi, 3.6 +/- 0.5 microU/ml in Vancon (P less than 0.001), and 2.4 +/- 0.2 microU/ml in Dich Giao (P less than 0.05). The mean serum T4 concentrations were similar in the three groups, but the mean free T4 concentration was low in Vancon. Serum T3 levels and the T3 to T4 ratios were significantly elevated in the goitrous regions. The mean serum thyroglobulin (Tg) concentrations were 27 +/- 3 ng/ml in Hanoi, 101 +/- 20 ng/ml in Vancon (P less than 0.01), and 44 +/- 5 ng/ml in Dich Giao (P less than 0.01). The 4-h thyroid uptake was higher in Vancon than in Hanoi. The urinary iodine concentration was low in both goitrous regions, and urinary thiocyanate was increased in Dich Giao, reflecting the ingestion of cassava. For all regions combined, there was a direct correlation between serum TSH and T3 and between serum TSH and Tg. In Vancon, where iodine deficiency was more severe, there was an inverse correlation between thyroid uptake and the urinary iodine concentration; thyroid uptake correlated directly with serum T3, the T3 to T4 ratio, and serum Tg. In Dich Giao, there was no correlation between urinary thiocyanate and thyroid uptake or urinary iodine levels. The data show that low iodine intake is a major factor in the causation of goiter in Vancon, where iodine deficiency had not been suspected. The ingestion of cassava in Dich Giao did not cause a major change in thyroid hormone economy even though iodine intake was marginally low; the data suggest that the goitrogenic effect of cassava is easily overcome by supplementary iodine, even when it is ingested irregularly.

Adolescent↗
PubMed1977

Immunosuppression by sex steroid hormones. The effect upon PHA- and PPD-stimulated lymphocytes.

Progesterone, estradiol, testosterone, cortisol, and 11-desoxycortisol (compound S) were added to cultures of human lymphocytes stimulated with phytohaemagglutinin (PHA) and purified protein derivative (PPD). The immunosuppressive effect of cortisol was verified and the three sex-steroid hormones also were found to inhibit lymphocyte transformation although at concentrations higher than for cortisol. Compound S, a steroid of low biological potency, also had immunosuppressive activity. At concentrations (0-01-1-0 microng/ml), progesterone, oestrogen, testosterone, and Compound S augmented the transformation response to PPD but not to PHA. Marked variation from individual to individual in the suppressive effects of all the steroids were noted. The clinical implications of immunosuppression by the sex steroid hormones are discussed.

Cortodoxone↗
PubMed1971

Myocardial infarction and carbohydrate metabolism relating to diabetes mellitus.

Fifteen non-obese males with acute myocardial infarction and no diabetic history were evaluated for diabetes. During infarction, results of oral glucose tolerance tests were "diabetic" or "probably diabetic" in 10 of the 15 patients (67 percent). The plasma immuno-reactive insulin response in 12 patients (80 percent) was of a pattern observed in patients with maturity-onset diabetes. Six months after infarction, follow-up glucose tolerance tests in 12 surviving patients were diabetic or probably diabetic in three cases (25 percent). In seven of twelve patients (58 percent) had delay in the peaking of the plasma insulin response to an oral glucose tolerance test, a phenomenon that is observed in patients with maturity-onset diabetes. Glucose tolerance tests were abnormal in one of fourteen control subjects (7 percent). There was a delayed plasma insulin response to an oral glucose test in two of fourteen controls (14 percent). Patients with myocardial infarction have an increased incidence of diabetes mellitus.

Adult↗