Biomedical subjects
Publications and source records attributed to M Arnold.
By means of a longitudinal study in which only tablet fluoridation was applied the carioprotective effect of complement measures in comparison to a test group has been investigated. A further reduction of caries increase of over 60% occurs by complex preventive programmes.
A spontaneous murine mammary carcinoma, designated SP1, grew more aggressively in the mammary gland than in the subcutis exhibiting a 10-fold lower 50% lethal tumor dose and the ability to metastasize spontaneously from the orthotopic mammary gland site. The appearance of metastasis could be abrogated by resection of the primary tumor up to 21 days postinjection, arguing against the possibility that metastasis occurred due to trauma of the injection and/or healing processes. In addition, tumor cells recovered from lung metastases exhibited an increased ability to metastasize when reinjected into either the s.c. or mammary sites. Tumor cells from lung metastases showed low levels of Class I major histocompatibility (MHC) antigens, like the parental SP1 cells, but were found to express differentiation markers typical of normal basal and luminal mammary epithelium. SP1 tumors expressed increased Class I MHC antigens, as well as high levels of basal and luminal breast epithelial markers, within 7 days of implantation into the mammary gland. On the other hand, SP1 tumors growing in the subcutis never expressed increased Class I MHC levels and expressed the epithelial marker antigens at lower levels and not until at least 21 days of growth. Removal of host epithelium by cauterization of the mammary bud at 3 weeks had no effect on the increased growth, metastasis and acquired heterogeneity of MHC and epithelial associated antigens, suggesting that the mammary gland stroma was responsible for the observed phenomenon. These findings suggest that the mammary gland either selects distinct tumor subpopulations, or induces a phenotypic change leading to tumor progression and the generation of metastatic subpopulations.
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The use of gas chromatography and mass spectrometry with selected ion monitoring detected tuberculostearic acid (TBSA) in 10 of 12 formalin fixed, paraffin wax embedded nasopharyngeal and head and neck biopsy specimens from patients with confirmed tuberculosis and carcinoma, and in one of 50 control specimens (giving a sensitivity of 83% and a specificity of 98%). The two false negative cases had very small tissue fragments and the patient with a false positive result may have had pulmonary tuberculosis. Tuberculostearic acid (TBSA) was also detected in nine of 16 specimens from the head and neck region with non-caseating granulomas suspected, but not confirmed, to be tuberculosis. It is concluded that nasopharyngeal tuberculosis is relatively common in Hong Kong and should be considered when biopsy specimens show granulomas. The detection of TBSA in tissue biopsy specimens is a useful, rapid method for the diagnosis of tuberculosis and other mycobacterial infections, and can be conveniently performed within two days on formalin fixed and paraffin wax embedded material.
Rheumatoid arthritis is the most common form of severe inflammatory arthropathy affecting patients at a relatively early age. Although there are a number of drugs which significantly reduce pain and swelling, few alter the development of erosions and progression of joint destruction. A significant number of patients with rheumatoid arthritis develop this progressive disability and will require treatment with corticosteroids or immunosuppressive agents. In this article the use of immunosuppressive drugs and corticosteroids in the treatment of aggressive rheumatoid arthritis is reviewed. Controlled clinical trials have shown that a number of these drugs can play a significant role in reducing pain and swelling and might possibly alter the disease course in rheumatoid arthritis. Side effects of these agents, including the potential for oncogenesis, still pose major problems in their long term use. The risks and benefits of immunosuppressive and corticosteroid drug therapy must be balanced in each patient to whom they are prescribed and reviewed at frequent intervals.
The hypereosinophilia syndrome with cardiac involvement, as an incidental autopsy finding in a 50-yr-old male, is reported. A review of the literature on the clinical manifestations, pathologic findings, differential diagnosis, associated conditions, pathogenesis of the cardiac involvement, and the role of palliative treatment is presented.
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In a study of 23 consecutive thymectomies from patients with myasthenia gravis (MG), 10 (43.5%) were thymomas, 8 (34.8%) were thymic lymphoid hyperplasia (TLH), and 5 (21.7%) were normal/involuted thymuses. The incidence of thymoma in MG appears to be considerably higher in Hong Kong than in similar series from Western countries. Six patients from this group were examined for the presence of Epstein-Barr virus (EBV) genome by Southern blot, as were a thymoma from a patient without MG, a patient with TLH in the absence of MG, and 3 normal control thymuses. All 3 thymomas (2 of 2 with MG, 1 of 1 without MG), 2 of 4 TLH with MG, and 1 of 1 TLH without MG were positive for EBV genome. Thymoma should be included, along with nasopharyngeal carcinoma and malignant lymphoepithelial lesions of the salivary gland, as EBV-related epithelial tumors, all of which are prevalent in this region.
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The relationship between expression of cell surface glycoproteins encoded by the major histocompatibility complex (MHC) and immunogenicity of a recently obtained spontaneous murine mammary adenocarcinoma (designated CBA.SP1) was examined. Immunogenic and nonimmunogenic variant clones were isolated from a subclone of the parent tumor after treatment with the mutagen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) or the DNA hypomethylating agent and "gene activator," 5-aza-2'-deoxycytidine (5-aza-dCyd). All clones from the untreated tumor population were tumorigenic in normal syngeneic recipients. In contrast, immunogenic variant clones, isolated at high frequencies after drug treatment [ranging from 5% (5-aza-dCyd treated) to greater than 90% (MNNG treated)], were rejected in normal syngeneic mice but grew progressively in T-cell deficient nude mice. Consistent with our previous report (J. Natl. Cancer Inst., 75: 291, 1985), all 5-aza-dCyd induced immunogenic clones expressed elevated levels of class I (particularly Dk) MHC antigens. However some (three out of nine) nonimmunogenic clones also showed enhanced class I MHC expression, implying that not all high MHC expressors were immunogenic. In contrast to 5-aza-dCyd induced variants, only 50% of MNNG induced immunogenic variants showed elevated levels of Dk or Dk and Kk antigens in vitro. Strong augmentation of class I MHC antigens in situ was observed on all immunogenic, but not nonimmunogenic, clones following transplant into syngeneic mice; no increase in MHC expression on variants during progressive growth in athymic nude mice occurred. Although no class II (Ak or Ek) antigens were detected on the parent line or any of the immunogenic variants, a strong infiltration of host I-A bearing cells occurred during immune rejection of SP1 variants. These results are consistent with the hypothesis that induction of class I MHC antigen expression on certain low MHC expressing tumors, although not the sole requirement for immunogenicity, can facilitate immune rejection of the SP1 tumor and, conversely, that the reduced level of MHC observed in certain clinical cancers may significantly affect the immunological aspects of the tumor-host relationship.
A 44 year-old Chinese male presented with lymphoid blast crisis of chronic myeloid leukemia, in which the blast cells exhibited a pre-pre-B cell phenotype (B4+B1-J5+12+smIg-). There was a phenotypic transition during the course of the disease to a more mature B cell phenotype (B4+B1+J5+12+smIgG lambda+). The maturation of blast crisis cells may be related to the chemotherapeutic agents used in the treatment of the disease.
The purpose of this investigation was to determine if the inhibition of the serine proteases, thrombin and plasmin, by heparin and epsilon-aminocaproic acid (EACA) would improve endothelial cell retention on synthetic grafts. Endothelium was harvested from the external jugular veins of mongrel dogs using an enzymatic technique. The cells were grown in tissue culture for 3-4 weeks, labeled with 111In oxine, inoculated (2000 cells/mm2) into fibronectin-coated 4 mm-diameter tubes of polyester elastomer (PE, Hytrel 4056, DuPont), and cultured for 18 hr. Each animal received iv heparin (100 U/kg) prior to implantation, and a 4 X 30-mm segment of the culture-lined PE was interposed in the dog's own carotid artery. After 6 hr of flow the grafts were perfusion fixed; the percentage of endothelial retention was determined by 111In counting, and the surfaces of the grafts were analyzed by scanning electron microscopy. Six experiments were performed in each of three treatment groups. Animals in Group I received no additional drugs. Group II animals received a continuous infusion of heparin at 30 U/kg/hr. Group III animals received a bolus of 200 mg/kg of EACA with the initial heparin dose and a continuous infusion of heparin at 30 U/kg/hr and EACA at 200 mg/kg/hr. Group I grafts retained an average of 36.1 +/- 23.3% of the cells; Group II retained 67.5 +/- 24.9%; and Group III retained 83.4 +/- 9.8%. Although continuous heparin infusion resulted in a trend (P = 0.067) toward better retention, a combined infusion of heparin and EACA resulted in significantly better retention (P = 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)
Approximately 90% of endothelial cells that are seeded or cultured onto vascular prostheses are lost from the flow surface within 24 hours of implantation. To determine the contribution of leukocytes to endothelial cell loss, 111In-labeled, cultured canine jugular venous endothelial cells were grown to confluence on fibronectin-coated polyester elastomer tubes measuring 4 mm inner diameter and 30 mm in length. Autogenous cell-lined tubes were implanted as bilateral carotid replacement grafts in six dogs made leukopenic by cyclophosphamide. Similar unilateral grafts were placed in 12 control dogs. Grafts were removed and perfusion-fixed from six control animals after 2 hours of in vivo arterial perfusion and from the other six animals after 6 hours of perfusion. One graft was removed and perfusion-fixed from each leukopenic animal after 2 hours of implantation and the other after 6 hours. Attachment of endothelial cells to the grafts was measured by indium-labeling technique. Retention of endothelium on grafts removed after 2 hours was measured by planimetric counting with scanning electron microscopy and on those removed after 6 hours by radioisotope quantification. Endothelial cell retention after 2 hours was 37.6% +/- 27.0% in control dogs and 97.0% +/- 3.4% in leukopenic animals (p less than 0.0007). After 6 hours retention was 35.9% +/- 23.2% in control animals and 86.5% +/- 6.0% in leukopenic animals (p less than 0.0009). Leukocyte surface activity was present in less than 1% of the leukopenic dogs compared with 8.5% of the other in vivo midgrafts after 2 hours. These results suggest that leukocytes play a significant role in the loss of seeded endothelium from vascular prostheses.
Problems in studying pharmacokinetic interactions with digoxin were evaluated using as a test model the examination of a possible interaction between digoxin and ethmozine in a group of 11 patients with cardiac disease. A single-blind, placebo-controlled, nonrandomized protocol design was used. Considerable intrapatient variability in day-to-day serum digoxin levels was documented that could not be accounted for by laboratory variability in digoxin assay measurements (mean coefficient of variation 10.1%) or alterations in blood urea nitrogen (BUN), serum creatinine, or body weight during the course of the study. No consistent, statistically significant alteration of mean serum digoxin levels occurred when the baseline, placebo, and ethmozine phases were compared, although the study design would have permitted detection of a 0.29-ng/ml alteration in mean serum digoxin levels. A discussion of the sources of variability in digoxin levels is provided.