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Biomedical subjects

C C King

Publications and source records attributed to C C King.

52 records · Page 3Linked to original sources
PubMed1992

Viral infection of the thymus.

We have examined infection of the thymus during congenitally acquired chronic lymphocytic choriomeningitis virus (LCMV) infection of mice, a classic model of antigen-specific T-cell tolerance. Our results show that (i) infection starts at the fetal stage and is maintained throughout adulthood, and (ii) this chronic infection of the thymus can be eliminated by transfer of virus-specific cytotoxic T lymphocytes (CTL) that infiltrate the thymus and clear all viral products from both medullary and cortical regions. Elimination of virus from the thymus results in abrogation of tolerance. During the fetal stage, the predominant cell type infected is the earliest precursor of T cells with a surface phenotype of Thy1+ CD4- CD8- J11d+. In the adult thymus, infection is confined primarily to the cortisone-resistant thymocytes present in the medullary region. The infected cells are CD4+ and J11d+. The presence of J11d, a marker usually associated with immature thymocytes, on infected single positive CD4+ "mature" thymocytes is intriguing and suggests that infection by this noncytolytic virus may affect development of T cells. There is minimal infection of the CD8+ medullary thymocytes or of the double positive (CD4+ CD8+) cells present in the cortex. Infection within the cortex is confined to the stromal cells. Interestingly, there is infection of the double negative (CD4- CD8-) thymocytes in the adult thymus, showing that even during adulthood the newly developing T cells are susceptible to infection by LCMV. Virus can be eliminated from the thymuses of these carrier mice by adoptive transfer of medullary region first and then from the thymic cortex. This result clearly shows the need to reevaluate the widely held notion that mature T cells are unable to reenter the thymus. In fact, in our experiments the donor T cells made up to 20 to 30% of the total cells in the thymus at 5 to 7 days after the transfer. The number of donor T cells declined as virus was eliminated from the thymus, and at 1 month posttransfer, the donor T cells were hardly detectable. The results of this study examining the dynamics of viral infection and clearance from the thymus, the primary site of T-cell development, have implications for understanding tolerance induction in chronic viral infections.

Aging↗
PubMed1991

Fractal and chaotic dynamics in nervous systems.

The chaotic aspects of brain structure and dynamics have been discussed. The relation of chaos to fractal processes in the brain from the neurosystems level down to the molecule has been explored. It is found that chaos appears to play an integral, though not necessarily exclusive role in function at all levels of organization from the neurosystems to the molecular and quantum levels. An interesting consequence involving the possible interface between chaotic dynamics and quantum physics has been discussed because of its potential significance is resolving several of the most intractable conceptual problems to do with computability, the brain and the mind (Blakemore and Greenfield, 1987; Hooper and Teresi, 1987; Rose, 1973; Searle, 1979; Penrose, 1986, 1989).

Action Potentials↗
PubMed1991

[Changing seroepidemiology pattern of hepatitis B virus infection among elementary and junior high school children in Keelung, Taiwan, 1988].

A large-scale seroepidemiologic study of 20816 (35.6% of total) elementary and junior high school children (grades 1-9) in Keelung, Taiwan was conducted in April-May 1988. The study was to investigate the current status of hepatitis B virus (HBV) infection and to plan the extension of the present HBV prevention program to other age groups. Two HBV markers, hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (anti-HBs), were determined by enzyme immunoassay. The overall seropositivity rates of HBsAg and anti-HBs were 19.0% and 25.6%, respectively. Only 0.4% of the children studied were concurrently positive for both HBsAg and anti-HBs and 55.8% of them were negative for these two markers. It is noteworthy that the seropositivity rate of HBsAg increased with increasing age, from 15.4% in grade 1 (ages 6) to 23.7% in grade 9 (ages 15). This rate of HBsAg was not higher than the 1986 findings (14.0-25.5%) screened from children (4-13 years old) in Keelung, by comparing each age cohort strata, even though the age of study population was two years older. These data indicate that the current hepatitis control strategies have resulted in the reduction of the hepatitis B carrier rate among children from more than 20% to 15% at age 6 (grade 1) in Keelung, but the reduction is still higher than in Taipei children (10%). The seropositivity rate of anti-HBs was also increased with increasing age, from 13.5% (grade 1) to 44.1% (grade 9) and was similar to previous findings in Taiwan.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Did membrane electrochemistry precede translation?

The discovery of RNA-based enzymes, such as ribonuclease-P, has stimulated new interest in the idea that catalytic functions of RNA preceded the use of coded enzymes during an era loosely termed 'the RNA world'. This paper examines various lines of evidence which support the idea that electrochemical processes associated with the membrane may have preceded the development of coded protein enzymes and may have provided a basis for the phosphorylation energy of the RNA world.

Biological Evolution↗
PubMed1990

In vivo selection of lymphocyte-tropic and macrophage-tropic variants of lymphocytic choriomeningitis virus during persistent infection.

This study demonstrates cell-specific selection of viral variants during persistent lymphocytic choriomeningitis virus infection in its natural host. We have analyzed viral isolates obtained from CD4+ T cells and macrophages of congenitally infected carrier mice and found that three types of variants are present in individual carrier mice: (i) macrophage-tropic, (ii) lymphotropic, and (iii) amphotropic. The majority of the isolates were amphotropic and exhibited enhanced growth in both lymphocytes and macrophages. However, some of the lymphocyte-derived isolates grew well in lymphocytes but poorly in macrophages, and a macrophage-derived isolate replicated well in macrophages but not in lymphocytes. In striking contrast, the original wild-type (wt) Armstrong strain of lymphocytic choriomeningitis virus that was used to initiate the chronic infection and from which the variants are derived grew poorly in both lymphocytes and macrophages. These three types of variants also differed from the parental virus in their ability to establish a chronic infection in immunocompetent hosts. Adult mice infected with the wt Armstrong strain cleared the infection within 2 weeks, whereas adult mice infected with the variants harbored virus for several months. These results suggest that the ability of the variants to persist in adult mice is due to enhanced replication in macrophages and/or lymphocytes. This conclusion is further strengthened by the finding that the variants and the parental wt virus grew equally well in mouse fibroblasts and that the observed growth differences were specific for cells of the immune system.

Animals↗
PubMed1989

High-dose cisplatin with diethyldithiocarbamate (DDTC) rescue therapy: preliminary pharmacologic observations.

Diethyldithiocarbamate (DDTC), a chelating agent that is a major metabolite of disulfuram, has been proposed as a potential rescue agent to reduce toxicity following high-dose cisplatin (HDCP) therapy. In the present study, we examined the pharmacologic interaction of HDCP and DDTC given as rescue therapy. Total plasma platinum and ultrafiltrate platinum pharmacokinetics and DDTC levels were determined in six patients with advanced malignancies who received a total of 11 cycles of HDCP with DDTC rescue. HDCP therapy (200 mg/m2 per cycle) consisted of 100 mg/m2 reconstituted in 250 cc 3% saline and infused over 3 h on days 1 and 8 of each 28-day cycle. DDTC rescue at a dose of 4 gm/m2 was given by an i.v. infusion (duration 1.5-3.5 h), beginning 45 min after the completion of cisplatin infusion. Peak total and ultrafiltrate levels and cisplatin pharmacokinetics in this study were indistinguishable from those of previous studies using the same HDCP regimen without DDTC rescue. Ultrafiltrate or unbound plasma platinum was less than 10% of total plasma platinum concentrations and demonstrated a biphasic pattern of elimination. Levels of DDTC predicted to be chemoprotective (greater than 400 microM) were achieved with the dose and schedule used in this study. These data demonstrate that DDTC can be targeted to protective plasma concentrations without significantly altering plasma cisplatin pharmacokinetics and support the potential usefulness of DDTC as a rescue agent following HDCP therapy.

Cisplatin↗
PubMed1989

Community-wide epidemiological investigation of a typhoid outbreak in a rural township in Taiwan, Republic of China.

An outbreak of typhoid fever occurred in Chu-Tung township, Taiwan, with dates of onset from 6 July to 8 August, 1983. Fifty-four cases were hospitalized, of which 52 were laboratory confirmed. A chloramphenicol-resistant strain of Salmonella typhi was isolated from patients' blood samples. A community survey of 2772 people selected from 490 households by stratified systematic cluster sampling, presented an attack rate of 9.4 per 1000 and a case reporting rate of 10%. The attack rate was higher in males than females for persons younger than ten years, but was greater in females than in males aged 40 years and older. The only consistent characteristic of the early outbreak cases was drinking of tapwater (10/10, 100% versus 319/490, 65% of the controls). None of the early cases but 36% (13/36) of the late cases had drunk stream or river water. Households of early cases had better hygienic conditions than those of late cases. Laboratory examination of environmental specimens indicated Escherichia coli contamination of tapwater, well water and all stream foci associated with human activities. The epidemiological data combined with laboratory results suggested that the epidemic might be due to repeated contamination of some common source (such as municipal tapwater) and/or a variety of other vehicles.

Adolescent↗
PubMed1987

Virus-lymphocyte interaction: T cells of the helper subset are infected with lymphocytic choriomeningitis virus during persistent infection in vivo.

The lifelong persistence of lymphocytic choriomeningitis virus (LCMV) in neonatally or congenitally infected mice is accompanied by a suppression of virus-specific T-cell responses. In this study, we identified the subset of T cells infected with LCMV during persistent infection in vivo. Using specific monoclonal antibodies to separate the different lymphocyte cell populations and employing both an infectious center assay and immunofluorescence to detect the virus, we found that infection is confined primarily to T cells of the helper subset (L3T4+ Lyt2-), with minimal involvement of cytotoxic T cells (Lyt2+ L3T4-) and mature B cells. About 0.54 to 1.1% of L3T4+ T cells were producing the virus, as determined by the infectious center assay. In contrast, 9.1 to 12.2% of these L3T4+ T cells contained viral antigen, as shown by immunofluorescence studies. This finding suggested that, at any given time, a substantial number of infected T cells were not producing infectious virus. This infection of T helper cells may be involved in the suppression of LCMV-specific T-cell responses observed in persistently infected mice.

Animals↗
PubMed1985

A model for transposon-based eucaryote regulatory evolution.

This paper presents a compact model of the role of transposable elements in eucaryote evolution which, although forward looking, is consistent with both experimental results and theories of gene regulation. The model postulates that a principal factor in the emergence of the eucaryotes was the development of a symbiotic relationship between reverse transcribing transposable elements and RNA based gene regulation, which we will call structural symbiosis. Thus, although transposable elements follow their own evolutionary protocol, structural homologies between "cellular" and "viral" genomes result in selective mutagenesis, a situation where transposon mutations are permitted because they can result in phenotypic mutations of the regulatory process with reduced probability of deleterious mutation of structural genes. The incorporation of this scheme into the life cycle of higher organisms results in two forms of integral evolution. Exogenous, in which differing species in an ecosystem share genetic information through viral transfer, and endogenous in which somatically induced regulatory mutations can be mapped back into the germ line.

Biological Evolution↗
PubMed1982

A model for the development of genetic translation.

Several models have been advanced, both in this journal and others, for the development of the genetic code and translation apparatus. Eigen in particular has put forward a detailed model based on the hypercycle. This paper uses some of these previous ideas to develop a new model of the code and translation in which the pairs AU and GC play complementary roles, and in which tRNAs develop from a molecule with two loops which stacks in repetitive patterns without the need for a messenger RNA. Thus a bridge is provided between random, (or autocatalytic) polymerization, and coded translation. In addition, alternative postulates to several of Eigen's ideas are tested by computer simulation.

Base Composition↗
PubMedDate not supplied

Governance challenges for managed care organizations. Interview by Ann C. Bartling.

When Healthcare Executive asked managed care organization CEOs and board chairs to identify governance challenges, they found the question so easy that it was difficult to limit their responses. while all the healthcare leaders interviewed pointed to the need to--and challenge of--staying ahead of the changes affecting the healthcare field, many identified challenges that were more specific to their organizations, markets, or patient population. Some also pointed out that while their challenges may be shared by hospitals and other provider organizations, there were aspects of each that were particularly relevant to managed care organizations, which often offer a variety of products in a number of different of markets.

Community-Institutional Relations↗
PubMedDate not supplied

Effect of major dietary modifications on immune system in patients with breast cancer: a pilot study.

A pilot study was conducted to evaluate the effect of diet on immune function in nine premenopausal, post-therapy patients with breast cancer. The patients were instructed on following the American Cancer Society dietary guidelines and were told to do so from day 0 to day 28. These guidelines recommend a high-fiber, low-fat diet. On day 29, the patients continued the diet but included fish high in omega-3 fatty acids until day 56. Twenty-four-hour urine and blood samples, and 3-day diet records were obtained on days 0, 28, and 56. The following parameters were monitored: lymphocyte subsets, T-cell function (proliferation and cytolytic response), and urinary prostaglandin E2 (PGE2). Results throughout the study suggested a benefit from decreasing dietary fat intake, and increasing fish intake. Helper T-cell (CD4) percentage increased from day 0 to days 28 and 56 (P = 0.048). Cytotoxic/suppressor T-cell (CD8) percentage decreased from day 0 to days 28 and 56 (P = 0.002). The CD4/CD8 cell ratio increased by days 28 and 56 (P = 0.0004). The proliferation of CD4 cells increased from day 0 to days 28 and 56 (P = 0.005). Significant changes were not found in the cytolytic activity of T cells, natural killer cells, total T and B cells, or urinary prostaglandin E2. Results suggest that patients with breast cancer may benefit from following American Cancer Society dietary guidelines and consuming cold-water ocean fish.

Adult↗