The possible role of c-fos expression in rheumatoid joint destruction

At present, although the etiology of rheumatoid arthritis (RA) remains unknown, most investigators believe that it is primarily an inflammatory disease of the synovial membrane of the joints. However, we have recently focused on the pathology of the early changes in articular cartilage and subchondral bone in RA patients, and have shown that RA involves articular cartilage and subchondral bone, not synovia. This research direction may lead to the development of a new specific treatment for the disease.     

Erythema nodosum leprosum: a possible cause of oral destruction in leprosy.

Apart from vague statements and speculative remarks, the role of ENL in the oral cavity has not been considered in the recent English language literature. A case of oral ENL is reported, and we postulate that ENL plays a prominent role in the intra-oral destruction noted in leprosy. Information gathered from the literature and from our own experience with a series of 37 leprosy patients with oral lesions support this postulation.     

Hypertension management: The computer as a participant

A computerized system called ARTEMIS has been taking part in the management of a referral hypertension clinic since September 1975. From January 1, 1976 to January 1, 1979, 3,624 patients' records were set up and updated, all of them accessible on line. The mean rate of response to 17 questions with obligatory answers concerning patients' past history was 97.6 per cent. The 10 routine laboratory tests included in the initial in-hospital work-up were registered in over 92 per 100 of the 2,651 hospital records examined. Negative responses were registered with the same accuracy as positive ones, when the computerized questionnaires were appropriately drafted. Standardized collection of information insured homogeneity of the medical staff and has already made possible epidemiologic studies. ARTEMIS has detected strategical errors such as the lack of yearly programmed tests for cardiovascular risk-factors associated with hypertension. The computer has helped to achieve a high rate of patient compliance at one year (81.3 per cent), by providing patients up-dated editions of their personal summary reports as well as sending periodical letters of recall to them and to their physicians. At a total annual cost of 11 dollars per patient, the computer provides continuous information on process and outcome, for each patient and physician, and for the entire population followed up at the clinic. It facilitates physician adherence to predefined protocols and reinforces follow-up continuity by creating a communications network between the referral clinic, the patient and the general practitioner.     

Activation of oxidative and arachidonic acid metabolism in neutrophils by respiratory syncytial virus antibody complexes: possible role in disease

The effect of respiratory syncytial virus (RSV) antibody complexes on the metabolism of human neutrophils was determined by examining the generation of luminol-dependent chemiluminescence, superoxide, and thromboxane B2. Incubation of neutrophils with RSV antibody complexes resulted in a significant increase in the production of chemiluminescence. The increase in chemiluminescence appeared to be due to (1) active phagocytosis of RSV antibody complexes as evidenced by 70% inhibition with cytochalasin B (P less than 0.001) or (2) increased superoxide production as evidenced by 40% inhibition with superoxide dismutase (P less than 0.001). The generation of superoxide was confirmed by specific analysis in a superoxide dismutase-inhibitable ferricytochrome c reduction assay. Of particular importance was the observation that RSV antibody complexes induced the release of significant quantities of thromboxane B2 from neutrophils as determined by radioimmunoassay. Oxygen radicals and/or products of arachidonic acid metabolism may, in part, mediate the pathogenesis of RSV infection through direct tissue damage and bronchoconstriction.     

The participant effect: mortality in a community-based study compared to vital statistics

The 20-year mortality experience of the community-based Evans County Heart Study population is compared to local, regional and national vital statistics. Deficit mortality occurred in the study population at younger ages while at older ages mortality was similar to or greater than vital statistics. This was particularly true for white and nonwhite males, whose mortality patterns were statistically significantly different from Evans Co. vital statistics (P less than 0.005). Nonwhite/white mortality ratios in the study were close to those observed in local vital statistics, particularly for males. Sex mortality ratios in the study population were lower than in vital statistics due to a stronger participant effect (lower mortality) in males. Evans Co. was an area of particularly high mortality for whites in the period 1960-1980 compared to other parts of Georgia and the U.S. Results of this study are similar to other reports of participant effects in epidemiologic follow-up studies; implications for bias in estimates of population levels of disease and of disease/exposure relationships are discussed.     

Amoxicillin-clavulanic acid and oral anticoagulants: a possible dangerous association

We describe a 68-year-old male patient, treated with amoxicillin-clavulanic acid for 18 days and oral anticoagulants. He developed a cholestatic hepatitis with conjugated bilirubin of 11 mg/dL and a concomitant overdose of oral anticoagulants (INR 7). Nausea, vomiting, jaundice and large ecchymoses occurred 41 days after treatment with amoxicillin-clavulanic acid; the clinical manifestations resolved within 1 week and the liver tests returned to normal 48 days after therapy withdrawal. The mechanism of the amoxicillin-clavulanate-induced hepatitis is probably immunoallergic; this complication occurs mainly in subjects with a metabolic and/or immunologic idiosyncrasy. The pharmacokinetics of this antibiotic, which is not directly metabolized by cytochrome P450, may be affected by the concomitant use of drugs under cytochrome P450 control. When using amoxicillin-clavulanic acid, one should take into account its potential hepatic toxicity and possible interaction with oral anticoagulants. However, it appears to be crucial to follow the correct indications for both drugs. In fact, in the patient described above amoxicillin-clavulanic acid was wrongly administered as prophylaxis after a cutaneous biopsy of the nose. The same occurred with the oral anticoagulants prescribed to the patient for a single episode of paroxysmal atrial fibrillation which had occurred one year previously.     

Plasma-free eicosapentaenoic acid/arachidonic acid ratio: a possible new coronary risk factor

Seventy-six effort angina patients who had typical angina on exertion documented by treadmill stress test with evidence of ischemic ST-segment depression and 78 healthy volunteers in urban Japan were investigated in this study. Plasma free fatty acids (FFA) in both groups were determined using high-performance liquid chromatography. The relationships between the total cholesterol, high-density lipoprotein (HDL), triglycerides in plasma, and the genesis of coronary heart disease were also examined. The ratio (0.08 +/- 0.08) of eicosapentaenoic acid (EPA)/arachidonic acid (AA) in plasma FFA was significantly lower in effort angina patients than that (0.15 +/- 0.12) in healthy volunteers. The lower ratio was due to significantly lower levels of EPA in the patients than in normals. In 42% of angina patients, the ratio is below 0.03. In all age subgroups except the age 30-39 subgroup, the ratio of EPA/AA was significantly lower in patients than in normals, when divided into four subgroups by using a 10-year age interval. Though the total cholesterol and triglycerides were not significantly different between the two groups, HDL was significantly lower and total cholesterol/HDL ratio was significantly higher in effort angina patients than in healthy volunteers. However, there was no correlation between EPA/AA ratio and HDL in individuals in either group. From these results, it could be concluded that lower EPA/AA ratio is a new coronary risk indicator other than HDL.     

Cigarette smoking and lung destruction. Accumulation of neutrophils in the lungs of cigarette smokers

It has been hypothesized that lung destruction in persons with emphysema associated with cigarette smoking is mediated by elastase released by neutrophils that have migrated to the alveolar structures in response to cigarette smoke. To directly evaluate this hypothesis, cell suspensions, isolated from bronchoalveolar lavage fluid and from open lung biopsies of nonsmokers and cigarette smokers with normal lung parenchyma and from open lung biopsies of nonsmokers and cigarette smokers who have sarcoidosis were evaluated for the presence of neutrophils. A significantly increased number of neutrophils was present in the cell suspensions isolated from bronchoalveolar lavage fluid and from open lung biopsies of both normal and sarcoid cigarette smokers compared with that in the nonsmokers (p less than 0.01, each comparison). Evaluation of the alveolar macrophages present in lavage fluid suggested a mechanism by which neutrophils may be attracted to the lungs of cigarette smokers: alveolar macrophages of cigarette smokers release a chemotactic factor for neutrophils, whereas alveolar macrophages of nonsmokers do not. In addition, alveolar macrophages of nonsmokers, after exposure to cigarette smoke, in vitro, are stimulated to release this chemotactic factor. These studies demonstrate that an increased number of neutrophils are present in the lungs of cigarette smokers compared with that in nonsmokers and suggest that cigarette smoke may attract neutrophils to the lung by stimulating alveolar macrophages to release a potent chemotactic factor for neutrophils.     

Leishmania mexicana: destruction of isolated amastigotes by amino acid esters

Amino acid esters can destroy intracellular as well as isolated amastigotes of Leishmania mexicana amazonensis. In the present study we examined, using a tetrazolium reduction assay, the toxicity of the esters for amastigotes isolated from mouse lesions. Parasite killing by the "prototype" compound L-leucine methyl ester at 1 mM concentration and at pH 7.3 took place within 15-30 min. Time-lapse cinematographic observations showed that the amastigotes rounded up and became less phase-dense before they rapidly broke down. Ammonium chloride, ethylamine or monensin, known to raise the intracellular pH, reduced the sensitivity of the amastigotes to L-Leu-OMe. This finding suggests that an acidified compartment is involved in the destruction of the parasites. The leishmanicidal activity of a series of L-amino acid esters was also investigated. The ED50 (concentration for half maximal effect) for methyl esters was (in mM): Leu (0.62), Trp (0.96), Met (1.13), Glu (2.0), Phe (2.5), and Tyr (3.8). In contrast, the methyl esters of Ile, Val, Ala, beta Ala, Gly, Ser, His, and Pro were either inactive or weakly active at 15 mM. Benzyl esters were more active than their methyl homologs: the ED50 of the benzyl esters of Leu, Val, Ile, Gly, Ala, beta Ala, and Pro were, respectively, 0.07, 0.20, 0.22, 0.88, 1.5, 2.3, and 6.7 mM. Ranks of leishmanicidal activity may reflect differences in the rates of ester uptake and trapping by the amastigotes, in the specificity of the relevant hydrolytic enzyme(s), in the accumulation and metabolic fate of the released amino acids, or in the toxicity of the amino acid or alcohol released within the amastigotes.     

Clinical investigation of serum deoxyribonuclease: II. Clinical studies of serum deoxyribonuclease activity in pancreatic disease

Serum Deoxyribonuclease (DNase) of normal persons and of patients with chronic pancreatitis, pancreatic cancer, Diabetes Mellitus, or other malignant diseases was determined with (32P) DNA as substrate. Serum DNase activity was much lower in patients with chronic pancreatitis, pancreatic cancer, or other malignant diseases than in control subjects, and serum DNase activity was almost normal in patients with Diabetes Mellitus. There was no correlation between serum DNase and serum amylase, but there was a good correlation between serum DNase and DNase I output in duodenal juice. There was an inverse correlation between serum DNase and serum RNase. These results imply that in the diagnosis of possible pancreatic disorders serum DNase may be a good indicator and thus may be useful for the detection of malignant diseases.     

Hemolytic property of some carbohydrases; their possible role in red cell destruction

-glucuronidase, in concentration above the normal level in the blood, hemolyzed human red blood cells after a latent period of 10 to 12 hours. Erythrocytessensitized by specific antibodies are lysed in the presence of -glucuronidase inphysiologic concentrations (approximately 200 Fishman units per 100 ml. ofserum). Other enzymes, such as hyaluronidase and lysozyme, are hemolytic also.Similarity between these enzymes and the lysins found in pre-incubated tissueextracts is pointed out. It is suggested that -glucuronidase and hyaluronidaseplay some role in the destruction of red blood cells under certain pathologic conditions. The inhibition of the lytic action of -glucuronidase by D-glucosaccharicacid and by small concentration of silver nitrate is shown. Inhibitors of -glucuronidase lysis could be of some value in the treatment of some hemolyticdisorders.

Submitted on October 8, 1954 Accepted on May 30, 1955     

Analysis of antibody to neutrophils associated with autoimmune neutropenia: possible recognition of Fc-receptor-related molecules

The serum of a 50-year-old male with neutropenia and a bout of bacterial infection was studied. Anti-neutrophil IgG antibody was detected by indirect immunofluorescence using a laser flow cytometry system. Purified IgG from our patient's serum did not inhibit chemotaxis of neutrophils, but inhibited rosette formation of neutrophils with ox red blood cells (ORBC) coated with anti-ORBC rabbit IgG dose-dependently. Surface iodination of neutrophils followed by their immunoprecipitation by purified IgG and sodium dodecylsulfate polyacrylamide gel electrophoresis showed a single band that corresponded to 45 kilodaltons. Possibly the IgG antibody in our patient's serum recognizes molecules related to Fc receptors.