Leif Athlin

Helicobacter pylori Infection: Independent Risk Indicator of Gastric Adenocarcinoma

BACKGROUND Helicobacter pylori has been implicated as a possible etiologic factor in gastric cancer. This case control study was performed to determine the association between H. pylori and gastric cancer, taking into account the possibility of confounding by other background factors. METHODS Sera were collected from 112 incident case patients with gastric cancer and 103 control patients with nongastroenterological diseases, who were frequency-matched with respect to age and sex. Immunoglobulin G antibodies to H. pylori were identified using the HM-CAP immunoassay (Enteric Products Inc., Wesbury, NY). RESULTS The prevalence of H. pylori seropositivity was significantly higher (P = 0.002) among case patients than control patients. The odds ratio (OR) was 2.60 (95% confidence interval, 1.35-5.02). The increased OR associated with H. pylori infection was confined to tumors with a noncardia location (OR, 3.06) and men (OR, 4.27). OR increased with decreasing age at cancer diagnosis to reach 9.33 in patients < 60 years of age. Multivariate logistic regression analysis was used as control for potential confounding, but the elevated OR associated with H. pylori infection remained significantly increased. CONCLUSIONS The results support the hypothesis of H. pylori infection as an independent risk indicator of gastric cancer.

Isolation of functionally active intraepithelial lymphocytes and enterocytes from human small and large intestine.

A mild purification method has been developed for the isolation of human intraepithelial lymphocytes (IEL) and enterocytes from the same individual. The isolation procedure includes mechanical disruption of the mucosal layer, treatment with reducing agent and sedimentation followed by Percoll gradient centrifugation. Finally, epithelial cells are removed from the IEL fraction using magnetic beads coated with the anti-epithelial antigen monoclonal antibody (mAb) BerEP4. Leucocytes are removed from the enterocyte fraction using magnetic beads coated with mAbs directed against common leucocyte antigen (CD45). Using this procedure IEL and enterocytes have been isolated from apparently normal jejunal, ileal and colonic tissue specimens. Recoveries of IEL were 7 x 10(5), 4 x 10(5) and 1 x 10(5)/cm2 mucosa from jejunum, ileum and colon respectively. 1-2 x 10(6) enterocytes/cm2 mucosa were recovered from small intestine while the corresponding value for colonic biopsies was approximately 2 x 10(5) enterocytes/cm2. The IEL fraction was pure as judged by the low percentages of B cells, macrophages and BerEP4 positive cells (less than 4%) present in the purified fraction. The enterocyte fraction contained less than 2% CD45+ cells. The two cell fractions were viable and expanded in vitro. Enterocytes expanded spontaneously while IEL required initial stimulation with mitogens. The isolation procedure described here will make it possible to study the function of human IEL, interactions between IEL and enterocytes and the role of both cell types in local immunity.

The phagocytosis of yeast cells by blood monocytes. Effects of therapeutic concentrations of vinca alkaloids

SummaryThe role of cytoplasmic microtubules in the phagocytosis of yeast cells by blood monocytes was studied by means of therapeutic concentrations of the Vinca alkaloids vincristine, vinblastine, and vindesine.Phagocytosis was measured in a monolayer of glass-adherent monocytes fed with fluorescein-labelled yeast cells.Phagocytosis was composed of two sequential processes, yeast cell adherence to the monocyte and yeast cell engulfment by the monocyte.Monocyte phagocytosis was significantly inhibited by the Vinca alkaloids, mainly due to inhibition of engulfment but probably also due to inhibition of adherence.Since the Vinca alkaloids are microtubule antagonists it is reasonable to assume that monocyte phagocytosis, both adherence and engulfment, are partially microtubule-dependent processes.It is suggested that Vinca alkaloid inhibition of monocyte phagocytosis is of value in the treatment of type II–III autoimmune disorders, such as idiopathic thrombocytopenic purpura and autoimmune haemolytic anaemia.

Effect of therapeutic concentrations of anthracyclines on monocyte phagocytosis of yeast cells

SummaryThe effect of therapeutic concentrations of doxorubicin, epirubicin, and mitoxanthrone on mature leukocyte function has been examined by measuring phagocytosis of yeast cells by surface-bound monocytes, using a fluorescence-quenching method. There was a 10% inhibition of monocyte phagocytosis by doxorubicin, but epirubicin and mitoxanthrone had no effect on monocyte phagocytosis. Anthracyclines may have a major immunosuppressive effect due to bone marrow depression. The lack of interference with mature monocyte function by epirubicin and mitoxanthrone provides a potential advantage in comparison with the parent compounds.

A cytostatic drug (taxol) which does not inhibit monocyte phagocytosis

Taxol is a new cytotoxic agent which arrests cell division in the G2 and the M phases, due to its unique property of inhibiting microtubule function by stabilization. In contrast to other microtubule antagonists except griseofulvin, taxol did not inhibit monocyte phagocytosis. It is suggested that lack of interference with the function of mature leukocytes may reduce the immunosuppression induced by a cytotoxic agent.

Therapeutic Concentrations of Griseofulvin Do Not Affect Yeast Cell Phagocytosis by Monocytes

The effect of griseofulvin on monocyte phagocytosis was assessed by studying the uptake of fluorescent yeast cells by glass-adherent monocytes (a fluorescence-quenching technique). In contrast to other microtubule antagonists, griseofulvin did not inhibit monocyte phagocytosis. It is suggested that the lack of griseofulvin interference with essential leukocyte functions is a possible explanation for the fact that the microtubule antagonist griseofulvin serves as a comparatively safe and harmless drug.

Low Field Magnetic Resonance Imaging of Focal Hepatic Masses at 0.02 T

The diagnostic utility of extremely low field magnetic resonance (MR) imaging was evaluated in 25 patients with focal hepatic masses, including 17 with primary (n=7) or secondary (n= 10) malignant neoplasms and 8 with benign lesions (6 hemangiomas). The findings were compared with the results of computed tomography (CT). Out of 16 patients with malignant tumors demonstrated by both modalities, the diagnostic information from MR imaging was equal to or better than that from CT in 6 patients and inferior to CT in 10. Shortcomings of MR were mainly due to low signal-to-noise ratio and poor spatial resolution, resulting in an image quality inferior to that obtained at higher field strengths. Considering these facts, together with the long imaging times required, low field MR cannot be recommended for general use in the evaluation of hepatic masses. On the other hand, our results indicate that this technique may be useful in establishing the diagnosis of hepatic hemangioma.

Therapeutic concentrations of melphalan do not affect yeast cell phagocytosis by monocytes

The effect of melphalan on monocyte phagocytosis was assessed by studying the uptake of fluorescent yeast cells by glass-adherent monocytes (a fluorescence-quenching technique). In contrast to several other cytotoxic agents, melphalan did not inhibit monocyte phagocytosis. Although the main immunosuppressive side effect of most cytotoxic drugs appears to be due to bone marrow depression with reduction of leukocyte counts, it is reasonable to assume that lack of interference with the function of mature leukocytes is a favourable feature of an antineoplastic drug.

Ultra-low field MR imaging of hepatic hemangiomas (at 0.02 and 0.04 T)

Twelve patients with cavernous hemangiomas of the liver were studied with computed tomography (CT) and ultra-low field magnetic resonance imaging (MRI). Seven patients were examined at a field strength of 0.02 T and 5 patients at 0.04 T, while 3 patients were studied at both field strengths. On T2-weighted images all hemangiomas had the same characteristic appearance of a homogeneous high signal intensity that has been described at higher field strengths. Signal characteristics of the hemangiomas were the same at 0.02 and 0.04 T, but the higher field strength provided better signal-to-noise (S/N) ratio and hence improved image quality. Homogeneous contrast enhancement was seen in three hemangiomas examined after intravenous administration of gadopentetate dimeglumine. Our results indicate that ultra-low field MRI can be useful in the differential diagnosis of hepatic hemangiomas.