Evidence that tolerance to cultured thyroid allografts is an active immunological process. Protection of third-party grafts bearing new antigens when associated with tolerogenic antigens.

We studied the tolerance phenomenon that develops in long-term recipients of cultured thyroid allografts. Allogeneic mouse thyroids were cultured under hyperbaric oxygen or acidic conditions and then transplanted beneath the kidney capsule of C57BL/6 recipients. Donors differed from the recipients in minor antigens alone, major histocompatibility complex antigens alone, or both. At 35-77 weeks after the first cultured graft, recipients received two more cultured grafts under the capsule of the opposite kidney and were immunized with donor spleen cells (SC). At 5 weeks after the second transplantation, we observed that whereas second grafts carrying new antigens alone were rejected, second grafts carrying new antigens in association with antigens in the first graft were significantly protected. In another set of experiments, normal mice became tolerant to cultured allografts after 2 weeks in parabiosis with tolerant individuals. Tolerant mice showed reduced specific in vivo and in vitro cytotoxic T lymphocyte responses. However, the frequency of CTL precursors of tolerant mice was the same as in normal mice. The reduced in vitro CTL responses were restored to normal levels by the addition of a lymphokine rich medium. Also, we observed that the injection of specifically activated immune SC caused the rejection of cultured allografts in normal but not in tolerant recipients. We conclude that the tolerance that develops in recipients of cultured allografts is an active immunological process that affects the activation and effector function of CTL.     

Cancer risk in farmers: Results from a multi-site case-control study in north-eastern italy

The relationship between farming and cancer risk was investigated in an integrated series of case-control studies conducted from 1985 to 1991 in the Friuli Venezia Giulia region, north-east Italy. Patients with cancer of the oral cavity and pharynx, larynx, oesophagus, colon and rectum, pancreas, breast, thyroid gland, kidney and urinary tract, bladder, prostate, soft-tissue sarcomas, Hodgkin's diseases, non-Hodgkin's lymphomas and multiple myelomas, and controls admitted to hospital for acute, non-neoplastic conditions, were interviewed. For males, a significantly elevated relative risk was seen for oral cavity and pharynx. Farming, however, was associated with a significant protection against cancer of the colon and rectum and bladder. In females, only one significant association emerged, for multiple myeloma. A few significant interactions between cancer risk and year of birth (i.e., before 1930 or 1930 and after) were observed. The risk of cancer of the larynx was significantly elevated in younger male farmers but not in older ones. Our multi-site case-control study confirms that farmers have, for some cancer sites, a distinctive pattern. Excesses of cancer of the oral cavity and pharynx in farmers are characteristic of the present study area and, possibly, of similar European rural populations who have in common high levels of alcohol consumption and, at least in the past, unbalanced diets.     

Female hormone utilisation and risk of hepatocellular carcinoma.

The relationship between female hormone use and primary liver cancer was analysed using data from a case-control study conducted between 1984 and 1992 in Milan on 82 female incident cases with histologically or serologically confirmed hepatocellular carcinoma and 368 controls admitted to hospital for acute non-neoplastic, non-hormone-related diseases. An elevated relative risk (RR) or primary liver cancer was observed in oral contraceptive (OC) users (RR 2.6, for ever versus never users, 95% confidence interval, CI 1.0-7.0). The RR was directly related to duration of use (RR 1.5 for < or = 5 years and 3.9 for > 5 years) and persisted for longer than 10 years after stopping use (RR 4.3%, 95% CI 1.0-18.2). The RR were below unity, although not significantly, for women ever using oestrogen replacement therapy (RR 0.2, 95% CI 0.03-1.5) and female hormones for indications other than contraception and menopausal therapy (RR 0.4, 95% CI 0.1-1.5). The long-lasting, association between risk of hepatocellular carcinoma and OC use has potential implications on a public health scale, since primary liver cancer is a relatively rare disease among young women, but much more common at older ages. This study provides limited but reassuring evidence on the possible relationship between oestrogen replacement treatment and subsequent risk of hepatocellular carcinoma.     

Exclusive radiotherapy in the treatment of carcinoma of the portio cervicis, stage IIB FIGO]

From January 1970 through December 1987, 135 patients with cervical cancer in stage IIB (FIGO criteria) were treated by means of exclusive radiotherapy in the Istituto del Radio of the Brescia University. Thirty cases were treated by exclusive external-beam radiotherapy (RTT), 39 by brachytherapy (CU) plus external-beam radiotherapy, 24 by combined RTT and CU, 41 by RTT + CU + RTT, and 1 case by CU alone. Crude survival at 5 years is 52.4%, and NED survival is 50%. The differences between the values of crude and NED survival by radiotherapy technique were statistically significant (p 0.05), ranging from 69.8% in the RTT + CU group to 35.5% in the RTT alone group. Twenty-four cases (18%) failed to obtain complete remission, and 24 more cases recurred in the pelvis. Sequelae were evaluated by the French-Italian glossary; they were present in 62 cases (46%), but in 12 cases only (9%) they were severe. The incidence of sequelae was highest in the groups of patients treated with the combined techniques (RTT and CU) which allowed best disease control.     

Bilateral internuclear ophthalmoplegia in a patient with Wernicke's encephalopathy.

The most common cause of bilateral internuclear ophthalmoplegia is multiple sclerosis. Wernicke's encephalopathy has been reported as a cause of unilateral internuclear ophthalmoplegia but not of bilateral internuclear ophthalmoplegia. In this report, we present the case of a patient with a history of alcohol abuse and acute onset of bilateral internuclear ophthalmoplegia whose clinical course and diagnostic studies are most consistent with a diagnosis of Wernicke's encephalopathy.     

Loss of endogenous androgen receptor protein accelerates motor neuron degeneration and accentuates androgen insensitivity in a mouse model of X-linked spinal and bulbar muscular atrophy

Human Molecular     

Les hibiscus, tradition et modernité

In his 2005 dissertation,Les Malvacées en-Phytothérapie (The Malvaceae in Phytotherapy), the author reviews the traditional uses and the most recent studies about the Malvaceae family. In the extract below, the author summarizes the data concerning plants of the Hibiscus genus.     

Incomplete pregnancies and ovarian cancer risk.

The role of spontaneous and voluntary abortions was assessed in a case-control study conducted in Milan, northern Italy on 953 cases of epithelial ovarian cancer (median age, 54) and 2500 control subjects (median age, 52) in hospital for acute diseases other than malignant, gynecological, or hormonal disorders. Overall the inverse relationship between total number of incomplete pregnancies and ovarian cancer risk was statistically significant, estimated relative risks (RRs) being, respectively, 0.9 (95% confidence interval (CI), 0.7-1.1) for one abortion and 0.8 (95% CI, 0.6-1.0) for two or more as compared to none. Furthermore, the protections afforded by spontaneous and voluntary abortions were well comparable (RRs 0.7 and 0.8 for > or = 2 spontaneous and voluntary abortions, respectively, versus none). While the protective effect of incomplete pregnancy was not explicable in terms of other characteristics of women nor significantly different across strata of reproductive factors or oral contraceptive use, it seemed more marked in women whose ovarian cancer occurred below age 50. Etiologically, these findings suggest that interrupted pregnancy per se and not predisposition to spontaneous abortion affects ovarian cancer risk.