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Biomedical subjects

J A Block

Publications and source records attributed to J A Block.

54 records · Page 3Linked to original sources

Heterogeneity of keratan sulfate substituted on human chondrocytic large proteoglycans.

Newly synthesized 35S-labeled chondrocytic keratan sulfate chains were generated by chondrocytes of human chondrosarcoma cell line 105KC and were analyzed for heterogeneity of regional substitution, hydrodynamic size, and charge density. After isolation of the high density large chondrocytic proteoglycans and sequential digestions with chondroitinase ABC, L-1-tosylamido-2-phenylethyl chloromethyl ketone-treated trypsin, and alpha-chymotrypsin, followed by Superose 6 chromatography, two populations of keratan sulfate-containing proteoglycan fragments were identified and pooled separately. Keratan sulfate chains from each of the regions were compared after release by Pronase digestion, and differences in substitution patterns were observed; keratan sulfate chains of greater polydispersity, as well as a population of larger hydrodynamic size, were present in only one of the two regions. Alkaline/borohydride treatment confirmed both the existence of a population of uniquely large keratan sulfate chains and its restriction to a single region of proteoglycan fragments. In addition to heterogeneity of hydrodynamic size, the keratan sulfate chains exhibited regional heterogeneity of charge density and hence, of sulfation patterns. Analysis by Mono Q chromatography identified distinct groups of keratan sulfate that segregated by charge density and whose proportionate composition differed between the proteoglycan regions. Furthermore, the most highly charged species were unique to a single region and encompassed the chains of larger hydrodynamic size. This suggests that there may be regional heterogeneity of keratan sulfate chains substituted along a single class of proteoglycans and identifies a novel population of large, highly sulfated chondrocytic keratan sulfate chains.

Cartilage↗

The effects of long term monolayer culture on the proteoglycan phenotype of a clonal population of mature human malignant chondrocytes.

Articular cartilage chondrocytes maintain biosynthetic heterogeneity in cell culture, but undergo irreversible dedifferentiation of their proteoglycan phenotype, as defined by keratan sulfate content. A recently described cell line of malignant human chondrocytes, 105KC, was the first to maintain a differentiated keratan sulfate-proteoglycan phenotype in long-term culture. A clone of 105KC, labeled KC2H3, is currently described and represents a distinct and metabolically more homogeneous population of mature chondrocytes than 105KC. KC2H3 cells universally express keratan sulfate biosynthesis, as defined by indirect immunofluorescence. In addition, KC2H3 expresses a more mature proteoglycan phenotype than 105KC, as demonstrated by the keratan sulfate content: 24% of glycosaminoglycan content of the aggregating proteoglycans of KC2H3 versus 13% for 105KC. Further reported are the effects of long term monolayer culture on the proteoglycan phenotype expressed by KC2H3. After more than 16 months in continuous monolayer, KC2H3 cells remained morphologically indistinguishable from those maintained in suspension alternating with monolayer. In addition, the proteoglycan phenotype remained mature, without a tendency towards dedifferentiation. The flattened morphology adopted by chondrocytes while in monolayer has been considered a stimulus of dedifferentiation; the present study is the first to examine the direct effects of physical state on a homogeneous and stable population of chondrocytes.

Chondroitin Sulfates↗

Synthesis of chondrocytic keratan sulphate-containing proteoglycans by human chondrosarcoma cells in long-term cell culture.

Keratan sulphate is an integral component of the large aggregating proteoglycans of mature human articular cartilage. The keratan sulphate content of chondrocytic proteoglycans increases during maturation, and it is a useful marker of mature-type chondrocytic proteoglycans. Ordinarily, in cell culture, chondrocytes from non-neoplastic tissues dedifferentiate, diminish or cease to synthesize aggregating proteoglycans with the same amount of keratan sulphate as those formed in vivo, and do not maintain their in vivo phenotype. In tissue culture, this down-regulation of synthesis of keratan sulphate is irreversible. The study of the metabolism of mature human chondrocytes has been hampered by the absence of stable models. We report a cell-line, 105KC, derived from a human chondrosarcoma, that has maintained a stable proteoglycan phenotype during more than three years of culture. Analysis with immunofluorescence suggested that 105KC cells continued to synthesize keratan sulphate in long-term culture. Biochemical analysis demonstrated that 105KC cells maintained the production of chondrocytic large-aggregating proteoglycans and that keratan sulphate composed 13 per cent of their glycosaminoglycan content. To our knowledge, 105KC represents the first model to have maintained the post-fetal chondrocytic proteoglycan phenotype in stable culture. This study documents the feasibility of the development of mature chondrocytic cell-lines and sheds light on the biological characteristics of chondrosarcomas.

Cartilage↗

The effect of chemonucleolysis on serum keratan sulfate levels in humans.

Sensitive measurements of serum keratan sulfate (KS), a glycosaminoglycan found in large quantities in the proteoglycans of human cartilage, can be obtained using an enzyme-linked immunosorbent-inhibition assay. Patients who are undergoing chemonucleolysis (CN) provide a clinical opportunity to monitor the large-scale proteolytic degradation of cartilage. By measuring serum KS levels both pre- and post-CN, we have demonstrated that serum KS levels rise predictably after CN, in a manner that reflects major catabolic events of cartilage.

Adult↗

A community hospital payment experiment outperforms national experience. The Hospital Experimental Payment program in Rochester, NY.

Since January 1980, the hospitals in the Rochester, NY, area have been operating under a community-wide revenue cap. This prospective payment system features local administration and control and is the first time a group of hospitals have committed themselves to a comprehensive regional financing system. This system differs from other prospective payment programs in that it covers both inpatient and outpatient care and offers incentives for ambulatory treatment whenever clinically appropriate. In the first five years of this program, the increase in Rochester area hospital expenses was 46%, compared with 52% for New York State hospitals and 68% for US hospitals at large. Further, the financial position of the Rochester hospitals improved, showing an operating margin of 2.6%, compared with a figure of-15.8% for New York State hospitals at large. A community-wide assessment showed no evidence of a reduction in the quality of or access to care. This community system for hospital payment and planning merits serious consideration for areas wishing to realize high-quality care at an affordable cost through a balanced combination of self-regulation, cooperation, and competition.

Boston↗

Histones and histone phosphorylation during quail myogenesis in vitro.

Cultured quail myoblasts were labelled with 32Pi and nuclear proteins extracted before and after myoblast fusion. Histones H1, H4 and the H1-H2B-H2A complex were all phosphorylated in proliferating prefusion cultures, while histone phosphorylation was absent in B1-arrested postfusion cultures except for minor phosphorylation of the H3-H2B-H2A complex. Postfused cultures were distinguished by the appearance of the histone-like protein whch migrated slightly faster than H1. Histone phosphorylation is therefore correlated with cell proliferation, while the appearance of the new histone-like protein is associated with G1 arrest and the absence of cell division.

Animals↗

Imapct of a primary care group practice on emergency room utilization at a community hospital.

This paper reports the effects on a community hospital's emergency room utilization that were brought about by the development of a primary care group practice. The practice, which has replaced the hospital's traditionally structured outpatient clinics, employs full-time, salaried physicians and provides evening office hours and 24-hour coverage. The primary care group appears to have effected a substantial reduction in pediatric emergency room use. To a lesser extent, utilization by former clinic users among the adult atients was also reduced. These reductions, however, created only modest impact in the context of the hospital's total emergency room use, owed in part to the relatively small size of the patient population who formerly had depended upon the hospital for primary care.

Adult↗

A study of consumer attitudes about health care: the control, cost, and financing of health services.

The delivery of health care had emerged as one of the most important political issues of the 1970's, yet public attitudes about health issues remains a relatively unexplored subject. Little is known about the public's opinion of who should control the delivery of health care, about how the costs of health care are perceived, or about how the delivery of care should be financed. This paper relates respondent attitudes on these subjects to attitudes about criteria that determine the respondent's choice of ambulatory care facility and to socioeconomic, political, and other demographic characteristics. The data are derived from a survey (N=521) of households representative of the area of Rochester, New York.

Adolescent↗

An emergency room's patients: their characteristics and utilization of hospital services.

Utilization of the emergency room at an urban community hospital is studied in a format designed to accomplish three complementary objectives: 1) to characterize a sample of individual patients, rather than an unweighted sample of visits, 2) to estimate the number of individuals served during a specified period and the magnitude of the relationship between these patients and the utilization of other hospital services, and 3) to introduce the patient's "frequency-of-visit" as an important variable in the analysis of emergency room utilization. Some specific findings are: 1) the vast majority of patients who used the emergency room did so very infrequently; 46,527 visits were made in one year by an estimated 34,286 different patients; 2) an estimated 2,586 patients made three or more visits during the year; a disproportionately large number of these "high-frequency" users were black, low-income, and from inner-city areas; a relatively small percentage of their visits were for accidental injury, 3) approximately 53 per cent of the hospital's inpatient admissions and 68 per cent of the inpatient days were generated by patients who also made at least one emergency room visit during the year studied.

Accidents↗