Histologic and morphometric study of chronic gastritis in alcoholic patients.

The effect of chronic alcohol ingestion on the gastric mucosa was determined in 96 patients in whom gastroscopy was performed because of upper gastrointestinal symptoms. Seventy-two patients were classified as alcoholics and 24 patients as nonalcoholics. In all cases biopsy specimens were taken from the fundus and antrum. The diagnoses of chronic superficial and atrophic gastritis were based on conventional histologic criteria and a morphometric technique utilizing quantitation of the chronic inflammatory cells in the lamina propria. Alcoholic patients were found to have a higher incidence of chronic gastritis of the antrum than nonalcoholics (p less than 0.001). Fundic involvement was also more common, probably accounting for the decreased gastric acid output described in chronic alcoholic patients. Finally, gastritis was more severe in the alcoholics; below 45 years of age chronic atrophic gastritis was seen only in alcoholics. We conclude that chronic gastritis develops more frequently in alcoholic patients and evolves into chronic atrophic gastritis at an earlier age than in nonalcoholic subjects.     

Detection of Antibodies in Human Sera to Streptococcal Groups A and C Carbohydrates by a Radioimmunoassay

The human lymphokine, leucocyte migration-inhibitory factor (LIF), appears to be a serine esterase and protease by virtue of its susceptibility to the irreversible enzyme inhibitor, phenylmethylsulfonyl fluoride (PMSF), and by the ability of arginine esters and amides to protect LIF against PMSF-induced inactivation. In this paper, three methods are described by which putative substrates for LIF may be investigated. Thus, molecules satisfying the substrate specificities of this lymphokine should (1) protect LIF against inactivation by PMSF, (2) reduce LIF activity in vitro on polymorphonuclear leucocytes, and (3) reduce the esterolytic activity of purified LIF-rich supernatants. The first two reactions were tested by means of the leucocyte migration agarose technique; the third reaction was tested by a sensitive enzyme assay using tritiated tosyl arginine methyl ester as substrate. Guanosine 3',5'-cyclic monophosphoric acid, which is capable of protecting LIF against PMSF-induced inhibition, also inhibited the esterolytic activity of the purified LIF preparation. Four synthetic oligopeptide substrates for trypsin, thombin and plasmin were investigated. Only one, the thrombin- and trypsin-specific benzoyl-phenylalanyl-valyl-agarine-p-nitroanilide, possessed high affinity for the LIF molecule and may therefore prove to be a potent substrate for this lymphokine.     

Exposure of melanoma cells to dacarbazine results in enhanced tumor growth and metastasis in vivo.

PURPOSE: In recent years, the incidence of cutaneous melanoma has increased more than that of any other cancer. Dacarbazine is considered the gold standard for treatment, having a response rate of 15% to 20%, but most responses are not sustained. Previously, we have shown that short exposure of primary cutaneous melanoma cells to dacarbazine resulted in the upregulation of interleukin-8 (IL-8) and vascular endothelial growth factor (VEGF). The purpose of the present study was to determine how long-term exposure of melanoma cells to dacarbazine would affect their tumorigenic and metastatic potential in vivo. MATERIALS AND METHODS: The primary cutaneous melanoma cell lines SB2 and MeWo were repeatedly exposed in vitro to increasing concentrations of dacarbazine, and dacarbazine-resistant cell lines SB2-D and MeWo-D were selected and examined for their ability to grow and metastasize in nude mice. RESULTS: The dacarbazine-resistant cell lines SB2-D and MeWo-D exhibited increased tumor growth and metastatic behavior in vivo. This increase could be explained by the activation of RAF, MEK, and ERK, which led to the upregulation of IL-8 and VEGF. More IL-8, VEGF, matrix metalloproteinase-2 (MMP-2), and microvessel density (CD-31) were found in tumors produced by SB2-D and MeWo-D in vivo than in those produced by their parental counterparts. No mutations were observed in BRAF. CONCLUSION: Our results have significant clinical implications. Treatment of melanoma patients with dacarbazine could select for a more aggressive melanoma phenotype. We propose that combination treatment with anti-VEGF/IL-8 or MEK inhibitors may potentiate the therapeutic effects of dacarbazine.     

A fully human antimelanoma cellular adhesion molecule/MUC18 antibody inhibits spontaneous pulmonary metastasis of osteosarcoma cells in vivo.

PURPOSE: The melanoma cellular adhesion molecule, also known as MUC18, is highly expressed on several tumors, including bone sarcomas. The level of MUC18 expression has been found to correlate directly with tumor progression and metastatic potential. These observations have established MUC18 as a candidate mediator of tumor growth and metastasis, and suggest that blockade of MUC18 might be a potential target for immunotherapy against several MUC18-expressing tumors, including human bone sarcomas. EXPERIMENTAL DESIGN: To investigate whether blockade of MUC18 might be a potential target for immunotherapy against osteosarcoma, we have recently developed a fully human anti-MUC18 antibody, ABX-MA1. We studied the effect of ABX-MA1 on growth, adhesion, invasion, and metastasis of human osteosaroma cells both in vitro and in vivo. RESULTS: MUC18 was widely expressed on both osteosarcoma and Ewing's sarcoma cells. ABX-MA1 had no effect on the proliferation of osteosarcoma cells in vitro, nor did it significantly inhibit the growth of KRIB human osteosarcoma cells when they were orthotopically implanted into the tibias of nude mice. However, after 6 weeks, significantly fewer ABX-MA1-treated mice developed spontaneous pulmonary metastases than did IgG-treated control mice. Additionally, ABX-MA1 decreased the invasion of osteosarcoma cells through Matrigel-coated filters and disrupted homotypic adhesion between osteosarcoma cells and their heterotypic interaction with human vascular endothelial cells. CONCLUSIONS: Our findings demonstrate that MUC18 plays a central role in the metastasis of osteosarcoma and suggest that targeted inhibition of this antigen by ABX-MA1 may be a novel immunotherapeutic approach in the management of this tumor.     

Advances in computer-assisted single-photon emission computed tomography (SPECT) for epilepsy surgery in children

Epilepsy surgery has emerged as an important option in the treatment of children with epilepsy that is refractory to antiepileptic drug management. The cornerstone of successful surgery is accurate localization of the brain region of seizure onset. Traditional techniques of seizure onset localization, e.g. surface electroencephalography (EEG) recording and magnetic resonance imaging (MRI), allow accurate localization in a significant number of patients. When the focus of seizure onset is not apparent from these non-invasive techniques, other methods of localization, e.g. intracranial EEG recording, may be needed before resection of the focus. Single-photon emission computed tomography (SPECT) is a nuclear medicine blood-flow technique that has been used to identify a region of epileptogenic brain associated with low blood flow in the resting state (interictal SPECT) or increased blood flow at the time of seizure activity (ictal SPECT). This report describes the validation and utility of a computer-assisted method of subtracting the interictal from the ictal SPECT scans and co-registering the difference image on the MRI. This method, called subtraction ictal SPECT co-registered on MRI (SISCOM), is used in guiding the location and the extent of intracranial electrode implantation, or in obviating the need for the implantation in some cases.     

Female circumcision (female genital mutilation): a problem for brachytherapy in cervical cancer

Female circumcision is a traditional practice common in African countries. It involves partial or total removal of external female genitalia. It has led to many complications, in particular, the scarring of the external genitalia. The consequence is a very narrow introitus making the intracavitary brachytherapy treatment component difficult when these women develop cancer of cervix. We present two such cases from our institution. Our aim is to make the radiation and gynecological oncologists, both in developed and developing countries, aware of this practice and the problems they can encounter in the management of such cases. Intracavitary brachytherapy is an important component in the potentially curative role of radiation therapy for cervical cancer. Every effort should be made to ensure that the sequelae of genital mutilation does not deprive these women of the same standard of care as the general population.     

A benign congenital myopathy in an inbred Samaritan family.

We describe a novel form of myopathy in a mother and her two daughters from an inbred Samaritan family. The patients displayed severe neonatal hypotonia, lethargy and dysmorphic features. Motor milestones were delayed; however, the hypotonia and muscle weakness gradually improved during the first 2 years of life and independent walking was achieved by 18 months. The mother at the age of 23 years shows myopathic facies and minimal proximal weakness. Her intelligence is normal. Her muscle biopsy revealed central nuclei and disruption of the intermyofibrillary network with moth eaten and spiral fibers. Mutations in SMN, MTM1 and the myotonic dystrophy genes were excluded. We suggest this is a new benign form of congenital myopathy. Inheritance is probably autosomal recessive.