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Biomedical subjects

C Watts

Publications and source records attributed to C Watts.

At least 109 records · Page 6Linked to original sources
PubMed1994

Antigen processing and class II MHC peptide-loading compartments in human B-lymphoblastoid cells.

The peptide/class II major histocompatibility complex (MHC) complexes recognized by CD4+ T cells have been characterized at the structural and biochemical levels and studies on the transport and maturation of class II MHC indicate that specialized sites may be involved in peptide acquisition. Here we report the characterization of the compartments involved in antigen processing and class II MHC loading relative to distinct functional domains of the endocytic pathway in antigen-specific human B lymphocytes. Peroxidase-mediated crosslinking analysis in intact cells demonstrates that peptide loading of class II MHC takes place in a compartment accessible to membrane immunoglobulin but not to transferrin receptors, although processing may be initiated within the latter domain. The density of membrane vesicles carrying newly assembled class II MHC complexes was distinct from early and late endosomes and dense lysosomes. Endocytosed antigen-gold complexes enter a class II MHC-rich compartment morphologically very similar to that described previously and within the time frame of biochemically detectable peptide loading.

B-Lymphocytes↗
PubMed1994

Professional presentation of antigen by activated human T cells.

Activated human T cells express class II molecules, but their capacity to present soluble antigens and stimulate T cells has been repeatedly questioned. Two lines of evidence indicate that T cells may indeed function as professional antigen-presenting cells. First, T cells that have been recently activated can efficiently capture, process and present tetanus toxoid to class II-restricted T cell clones. This capacity correlates with the rate of class II synthesis. Second, activated T cell clones express high levels of B7, are powerful stimulators in mixed lymphocyte reactions, and their stimulatory capacity is inhibited by soluble CTLA4 or anti-B7 antibody. Furthermore, expression of B7 can be detected in vivo on T cells from biopsies of patients with liver disease. Presentation of soluble antigen by activated T cells may play a role in the amplification of the specific response, and possibly in immunopathological states.

Antigen-Presenting Cells↗
PubMed1994

AIDS knowledge and high risk behaviors in the chronic mentally ill.

Chronic mentally ill adults are a high risk group for AIDS. In the present study, we used a questionnaire to assess AIDS knowledge, attitudes, and risk behaviors in 54 men and women who were clients at a "drop in" center for mentally ill adults. Most of the subjects were suffering from schizophrenia and about one-third of them had co-existing drug problems. Results showed widespread misunderstandings about AIDS transmission, high risk groups, and practices. Many of the subjects had been treated for STDs such as syphilis and gonorrhea and were engaging in behaviors that increased their vulnerability to AIDS. These include casual sex, anal sex, sex with an IV drug user, or sex in exchange for money, drugs, or a place to sleep. Subjects expressed a moderately high level of concern about acquiring AIDS/HIV, and 15% of those tested (5/33) said they already had the illness. We observed a significant correlation between misinformation about AIDS and the frequency of high risk behaviors. We also detected ambivalence about using condoms and i.v. drugs. Although males and females did not differ in AIDS knowledge or risk behaviors, the AIDS knowledge of both groups was significantly lower than a comparison sample of public high school students. Taken together, the results underscore the immediate need for comprehensive AIDS assessment, education, and prevention in this segment of the population.

Acquired Immunodeficiency Syndrome↗
PubMed1994

The coated pit and macropinocytic pathways serve distinct endosome populations.

Clathrin-coated vesicle endocytosis and macropinocytosis are distinct endocytic pathways demonstrable in several cell types including human epidermoid A431 cells (West, M.A., M.S. Bretscher, and C. Watts. 1989. J. Cell Biol. 109:2731-2739). Here we analyze the extent of mixing of macropinocytic endosome (macropinosome) content with that of conventional endosomes served by coated vesicle endocytosis. Using laser scanning confocal fluorescence microscopy we detected very little delivery of macropinosome content to either early or late endosomes-lysosomes as defined by labeling with transferrin or with LDL. Mixing of the contents of the macropinosomes and conventional endosomes was not induced by the addition of brefeldin A. Moreover, the morphology of macropinosomes was not grossly altered in the presence of brefeldin A, whilst in the same cells there were dramatic tubulation effects on conventional endosomes as reported by others. Although refractory to fusion with conventional endosomes, macropinosomes were nonetheless dynamic structures which sometimes exhibited vesiculo-tubular morphology in living cells and were capable of fusing with each other. We suggest that different endocytic mechanisms can give rise to distinct endosome populations.

Brefeldin A↗
PubMed1994

Daily prognostic estimates for critically ill adults in intensive care units: results from a prospective, multicenter, inception cohort analysis.

OBJECTIVE: To develop daily prognostic estimates for individual patients treated in adult intensive care units (ICU). DESIGN: Prospective, multicenter, inception cohort analysis. SETTING: Forty-two ICUs at 40 U.S. hospitals with > 200 beds including 20 ICUs in tertiary care centers with major teaching activities. PATIENTS: A consecutive sample of 17,440 ICU admissions. MEASUREMENTS AND MAIN RESULTS: A series of multivariate equations were developed using the patient's primary reason for ICU admission, age, chronic health status, treatment before ICU admission, admission Acute Physiology Score, current day Acute Physiology Score, and change between the current and previous day's Acute Physiology Score. The equations were used to create daily risk predictions and cross-validated within the 17,440-patient sample. The single most important factor determining daily risk of hospital death during each of the initial 7 days of ICU care was the current day's Acute Physiology Score of the Acute Physiology and Chronic Health Evaluation (APACHE) III score. The admission Acute Physiology Score and change from previous to current day's Acute Physiology Score were also important, as were ICU admission diagnosis, age, chronic health status, and treatment before ICU admission. Equations incorporating these risk factors had receiver operating characteristics areas ranging from 0.9 on the first ICU day to 0.84 for patients remaining in the ICU for 7 days. The percent of cases with cross-validated predicted risks over 90% increased from 2.3% (n = 406) of cases on day 1 to 9% of all patients remaining in the ICU on ICU day 7 (n = 218). The 1,033 patients who had a daily risk estimate of > 90% during any of their initial 7 ICU days had a 90% mortality rate and represented 47% of all ICU deaths and 31% of the total number of hospital deaths. CONCLUSIONS: Equations using initial and repeated physiologic measurements provide a high degree of explanatory power for subsequent hospital mortality rate. These daily prognostic estimates deserve evaluation for their potential role in improving the process and outcome from clinical decision-making.

Adult↗
PubMed1993

Suppressive effect of antibody on processing of T cell epitopes.

Immunoglobulins drive efficient antigen capture by antigen presenting cells for processing and presentation on class II MHC-molecules. High affinity antibody/antigen interactions are stable at endosomal/lysosomal pH thus altering the substrate for antigen processing. We show that this can result in strong suppression of presentation of some T cell epitopes. This effect was observed when the antibody specificity was a B cell surface Ig, or formed part of an immune complex. In the latter case the presence of the suppressing antibody boosts presentation of other T cell epitopes through enhanced uptake into Fc receptor bearing cells. The influence of bound antibodies on the outcome of antigen processing may influence with T cell epitopes dominate T cell responses and may change the focus of the response with time.

Antibodies↗
PubMed1993

Risks and cost-effectiveness of sublaminar wiring in posterior fusion of cervical spine trauma.

A report on the use of sublaminar wiring in the fusions of 34 patients with cervical spine injuries is given. No neurologic deficits were incurred in the use of this technique. There were no wire failures nor clinically significant complications. When compared with other forms of instrumentation to achieve similar results, the use of sublaminar wire is the most cost-effective.

Adolescent↗
PubMed1992

Irreversible association of peptides with class II MHC molecules in living cells.

Functional, morphological and biochemical evidence indicates that class II major histocompatibility complex (MHC) molecules associate with processed peptides during biosynthesis. Peptide/MHC complexes in living cells have been reported to be less stable than similar complexes generated in vitro, which has led to the suggestion that there may be a peptide exchange mechanism operating in vivo. Although this could increase the capacity for binding incoming antigens, it would reduce the efficacy of processed antigenic peptides by exchanging these for self peptides. Here we measure the half-life of peptide/class II complexes in human antigen-presenting cells and find that it is very similar to the half-life of class II molecules themselves, indicating that peptides are bound irreversibly under physiological conditions. Thus class II MHC retains long-term 'memory' of past encounters with antigen to maximize the opportunity for T cell/antigen-presenting cell interaction.

Antigen-Presenting Cells↗
PubMed1992

Osmotic blood-brain barrier disruption and chemotherapy in the treatment of high grade malignant glioma: patient series and literature review.

In the past, chemotherapeutic treatment of patients with high grade malignant gliomas following surgery and radiation has not added significantly to the 12-14 month median survival rate. Over four years, 37 patients with high grade malignant gliomas underwent 246 treatment procedures with a combination of methotrexate, cyclophosphamide, and procarbazine given in association with hyperosmolar mannitol-induced transient breakdown of the blood-brain barrier. These patients have demonstrated a median survivorship of 22 months after considering age, Karnofsky Performance Score, and necrosis by the Cox Proportional Hazards model. The study group had a mean age of 43 years, and mean Karnofsky Performance Score of 67%. Sixty-five percent of the procedures had well-documented barrier disruption. Sixteen percent remained in complete remission while 24 patients (65%) had partial or temporary remission. Progression-free intervals after blood-brain barrier disruption/chemotherapy ranged from 1-47 (mean 15) months. Neurotoxicity has been minimal with one peri-procedural mortality and five patients suffering an increase in neurologic deficit after a procedure. The results of this study are consistent with and further extend the reported literature on this method of brain tumor therapy as described in other centers. Chemotherapy in conjunction with osmotic disruption of the blood-brain barrier may provide the pharmacokinetic advantage sufficient to significantly improve survival in patients with high grade malignant glioma.

Antineoplastic Combined Chemotherapy Protocols↗