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Biomedical subjects

J S Stillman

Publications and source records attributed to J S Stillman.

At least 19 recordsLinked to original sources

Skeletal muscle lipids and glycogen mask substrate competition (Randle cycle).

The glucose-free fatty acid (FFA) cycle (Randle) was examined in soleus muscle, a red muscle with a high lipid oxidation rate, and extensor digitorum longus (EDL) muscle, a white muscle with a low lipid oxidation rate, using a carnitine palmethyltransferase (CPT-I) inhibitor as a probe. Exogenous palmitate by itself had little if any effect on glycolysis or glycogen accumulation in the two muscle types. The CPT-I inhibitor markedly decreased glycogen accumulation in both muscles (from fed rats), but increased glycolysis (lactate formation) and glucose oxidation to carbon dioxide only in the red muscle. When the muscles were made more dependent on FFA oxidation by prior fasting or exercise, the CPT-I stimulatory effect on glycolysis and glucose oxidation in white muscle was unmasked. In conclusion, the competition between lipid and carbohydrate utilization (Randle cycle) is easily demonstrated in both red and white muscle using a CPT-I inhibitor as a probe. The difficulties encountered in showing this competition in other studies using exogenous FFA may be explained by a combination of factors, including (1) low tissue lipid oxidation rates, (2) competition between exogenous and endogenous lipids such that provision of exogenous lipids fails to increase overall lipid oxidation, and (3) preferential utilization of exogenous glucose with glycogen sparing in the presence of FFA.

Animals↗

Evidence for dissociation of gluconeogenesis stimulated by non-esterified fatty acids and changes in fructose 2,6-bisphosphate in cultured rat hepatocytes.

In order to examine the role of fructose 2,6-bisphosphate (Fru-2,6-P2) in non-esterified-fatty-acid-stimulated gluconeogenesis, Fru-2,6-P2 levels were measured in cultured rat hepatocytes under conditions mimicking the fasted state. After addition of either 1.5 mM-palmitate or 10 nM-glucagon, [U-14C]lactate incorporation into glucose increased 2-fold, but only glucagon suppressed Fru-2,6-P2. Prevention of palmitate oxidation with a carnitine palmitoyltransferase-I inhibitor (2-bromopalmitate) diminished glucose production and Fru-2,6-P2 levels. Addition of exogenous glucose to the media increased Fru-2,6-P2 in a dose-related manner, which was further augmented by addition of palmitate. When Fru-2,6-P2 levels were examined in cells cultured under conditions mimicking the fed state (significantly higher basal Fru-2,6-P2 levels and lower glucose production), palmitate oxidation was associated with a significant fall in Fru-2,6-P2. In conclusion, the present studies have demonstrated a dissociation between fatty-acid-stimulated gluconeogenesis and changes in Fru-2,6-P2 in cultured rat hepatocytes. Further experiments suggest that the accumulation of intracellular hexose 6-phosphate as a result of fatty-acid-stimulated gluconeogenesis masks a putative inhibitory effect of fatty acids on Fru-2,6-P2 concentrations.

Animals↗

The effect of hyperosmolarity on muscle glycogen accumulation.

Soleus (red) and extensor digitorum longus (white) muscles from Sprague Dawley rats were incubated with 6-14C-labelled glucose in normal and in hyperosmotic media. Hyperosmolarity decreased 6-14C-glucose incorporation into muscle glycogen in a dose dependent manner and increased glycolysis and glucose oxidation. Increased glycogenolysis rather than decreased glycogenesis was responsible for the reduction in labelled glycogen accumulation.

Animals↗

The history of pediatric rheumatology in the United States.

Children were afflicted uncommonly by the rheumatic diseases so that one physician's experience was obviously limited. In the latter half of the nineteenth century a few physicians began to study several of the diseases systematically in hospitals. Slow progress continued in the twentieth century but was accelerated by the grants in the 1950s which made possible the establishment of well-staffed centers for the treatment of these patients and their long-term clinical and laboratory study. Teaching of medical students and resident staffs was improved. A serious medical problem was getting the attention it deserved.

History, 20th Century↗

Lymphocytotoxic antibodies. HLA antigen associations, disease associations, and family studies.

Lymphocytotoxic antibodies (LCTAB) were sought in sera of patients with rheumatic diseases and in family members. Patients with SLE and cutaneous necrotizing venulitis and family members of JRA patients had an increased frequency of LCTAB; JRA patients and family members of SLE patients did not. The only association between LCTAB and the HLA phenotype of persons with LCTAB was a decreased frequency of LCTAB in individuals with HLA-B27.

Antilymphocyte Serum↗

Inherited deficiency of the second component of complement. Rheumatic disease associations.

The prevalence of homozygous and heterozygous deficiency of the second component of complement (C2) was determined in patients with rheumatic disease including 137 with systemic lupus erythematosus (SLE), 274 with juvenile rheumatoid arthritis, and 134 with rheumatoid arthritis. 1 C2 homozygous deficient and 19 possible heterozygous deficient individuals were identified by using both immunochemical and functional assays to determine C2 levels. Of the 20, 8 had SLE (5.9%), 10 had juvenile rheumatoid arthritis (3.7%), and 2 had rheumatoid arthritis (1.4%), the homozygous deficient individual having SLE. The prevalence of C2 deficiency in the SLE and juvenile rheumatoid arthritis patients was significantly increased (P = 0.0009 and P = 0.02, respectively) when compared with controls, 6 (1.2%) of 509 blood donors having C2 levels consistent with heterozygous deficiency. 15 of the 20 C2 deficient patients were HLA typed and found to have antigens A10(Aw25), B18, or both. The patients with C2 deficiency and SLE had earlier age of onset of disease and less antinuclear antibody when compared with the C2 normal SLE patients. 11 families of the propositi were studied and found to have one or more C2 heterozygous deficient individuals. The family members had an equal distribution of rheumatic disease and antinuclear antibody in the C2 deficient and C2 normal groups. C2 deficient individuals were found to have significantly lower levels of properdin Factor B (242 mug/ml+/-54) when compared with the non-C2 deficient family members (282 mug/ml+/-73). These data support the concept that inherited deficiency of C2 is significantly associated with both SLE and juvenile rheumatoid arthritis.

Adult↗

Re-examination of histocompatibility antigens found in patients with juvenile rheumatoid arthritis.

One hundred and twenty-three patients with juvenile rheumatoid arthritis and a similar number of controls were tissue typed for 30 HL-A antigens to determine if there were any associations between particular HL-A antigens and the disease. None were found. However, HL-A7 was found more frequently in patients with juvenile rheumatoid arthritis demonstrating tenosynovitis than in the population with juvenile rheumatoid arthritis as a whole. These observations fail to support the contention of others that HL-A-W27 is found more frequently than expected in such patients.

Adolescent↗

Photochemical reactions of horseradish peroxidase compounds I and II at room temperature and 13 degrees K.

Some photochemical reactions of horseradish peroxidase compounds I and II (HRP-I and HRP-II, respectively) have been studied by electronic absorption spectroscopy over the temperature range 297 degrees K-10 degrees K. In glassy matrices below 80 degrees K HRP-I is rapidly converted to hrp-ii when irradiated with low power white light. The native enzyme and HRP-II are not photochemically active at these temperatures with low power irradiation. At room temperature the spontaneous decay of both HRP-I and HRP-II is catalyzed by irradiation with white light. It is shown that the photolysis is dependent upon light in the region 450-320 nm. It is concluded that the HRP-I and HRP-II conformations are closely related with only a low transition energy in the presence of electrons generated by the light. The conversion of HRP-II to HRP is accompanied by large conformational changes and so is inhibited at low temperatures.

Freezing↗

Ocular manifestations of juvenile rheumatoid arthritis.

We followed 210 cases of juvenile rheumatoid arthritis closely for eleven years. Thirty-six of the 210 patients (17.2%) developed iridocyclitis. Iridocyclitis was seen most frequently in young female patients (0 to 4 years) with the monoarticular or pauciatricular form of the arthritis. However, 30% of the patients developed uveitis after 16 years of age. Although 61% of patients had a noncontributory ocular history on entry, 42% had active uveitis on entry. Our approach was effective in detecting uveitis in new cases and exacerbations of uveitis in established cases. Forty-four percent of patients with uveitis had one or more identifiable signs or symptoms, such as red eye, ocular pain, decreased visual acuity, or photophobia, in order of decreasing frequency. Even after early detection and prompt treatment, 41% of cases of uveitis did not respond to more than six months of intensive topical treatment with corticosteroids and mydriatics. Despite this, there was a dramatic decrease in the 50% incidence of blinding complications of uveitis cited in earlier studies. Cataract and band keratopathy occurred in only 22 and 13% of our group, respectively. We used chloroquine or hydroxychloroquine in 173 of 210 cases and found only one case of chorioretinopathy attributable to these drugs. Systemically administered corticosteroids were used in 75 of 210 cases; a significant number of posterior subcapsular cataracts was found. Typical keratoconjunctivitis sicca developed in three of the uveitis cases. This association with uveitis and JRA was not noted previously. Surgical treatment of cataracts, band keratopathy, and glaucoma achieved uniformly discouraging results.

Adolescent↗

Osteoarthritis.

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Exercise Therapy↗

Characteristics of juvenile rheumatoid arthritis: its medical and orthopedic management.

The characteristics of juvenile rheumatoid arthritis have been presented and the important features of its medical and orthopedic management described. Surgical experience in a carefully studied group of 200 patients has been recounted. The increasing importance of reconstructive joint surgery is noted, preferably performed after growth has stopped.

Adolescent↗