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Monkeys and mice were immunized with Rauscher murine leukaemia virus. Two types of leukaemia virus preparations were used as immunogens. One preparation was derived from viraemic plasma and was highly purified by density gradient ultracentrifugation. The other preparation of Rauscher virus was derived from spleen cells and was contaminated with cell membranes. Following immunization with each of these preparations sensitive techniques were utilized to measure antiviral and antileukaemia cell ('cytotoxic') antibody levels on aliquots of the same antiserums. Multiple serums from each animal were tested during the weeks of immunization in order to establish a parallelism or lack of parallelism in the changes in cytotoxic and antiviral antibody levels. In each antiserum the cytotoxic and antiviral titres were virtually the same. This was true whether the animal had been immunized with a purified or a non-purified virus preparation. The presence or absence of contaminating cell membrane material in the immunizing material did not result in an antiserum with increased or decreased cytotoxic to antiviral antibody ratio. This indicated that cytotoxic antibody is probably not the result of immunization against cell membrane antigens ('neoantigens') as distinguished from virus or virion subunit antigens. Conversely, we found that leukaemia cells containing relatively little virus did not lyse in the presence of cytotoxic antibody prepared against either membrane-rich or membrane-poor virus preparations. This finding suggests that virus and not independent neoantigen renders the leukaemia cell lysable by cytotoxic antibody. Our studies therefore minimize the significance and even question the presence of neoantigens in Rauscher leukaemia cells, since the cytotoxic capability of anti-Rauscher antiserum is dependent on the presence of virus and not neoantigen in the immunizing preparations, and since virus and not neoantigen renders the infected cell lysable by anti-Rauscher antibody. [ABSTRACT FROM AUTHOR]

Background: Diabetes mellitus is associated with a high risk of cardiovascular disease. Carotid intima-media thickness (CIMT) is increasingly used as a surrogate marker for atherosclerosis. Its use relies on its ability to predict future clinical cardiovascular end points., Methods: This review examines the evidence linking CIMT as a surrogate marker of vascular complications in people with type 1 and type 2 diabetes. We have also reviewed the various treatment strategies which have been shown to influence CIMT., Conclusions: CIMT measurement is an effective, noninvasive tool which can assist in identifying people with diabetes who are at higher risk of developing microvascular and macrovascular complications. It may also help to evaluate the effectiveness of various treatment strategies used to treat people with diabetes.

Endothelium plays a crucial role in the maintenance of vascular tone and structure. Endothelial dysfunction is known to precede overt coronary artery disease. A number of cardiovascular risk factors, as well as metabolic diseases and systemic or local inflammation cause endothelial dysfunction. Nitric oxide (NO) is one of the major endothelium derived vaso-active substances whose role is of prime importance in maintaining endothelial homeostasis. Low levels of NO are associated with impaired endothelial function. Asymmetric dimethylarginine (ADMA), an analogue of L-arginine, is a naturally occurring product of metabolism found in human circulation. Elevated levels of ADMA inhibit NO synthesis and therefore impair endothelial function and thus promote atherosclerosis. ADMA levels are increased in people with hypercholesterolemia, atherosclerosis, hypertension, chronic heart failure, diabetes mellitus and chronic renal failure. A number of studies have reported ADMA as a novel risk marker of cardiovascular disease. Increased levels of ADMA have been shown to be the strongest risk predictor, beyond traditional risk factors, of cardiovascular events and all-cause and cardiovascular mortality in people with coronary artery disease. Interventions such as treatment with L-arginine have been shown to improve endothelium-mediated vasodilatation in people with high ADMA levels. However the clinical utility of modifying circulating ADMA levels remains uncertain.

Context: Subclinical hypothyroidism (SCH) is associated with cardiovascular (CV) risk factors, and possibly CV disease. However, its management remains controversial. Endothelial progenitor cells (EPC), expressing both endothelial and stem cell markers, are known to offer a novel CV risk marker., Objective: The aim of the study was to ascertain whether EPC count or function is reduced in SCH and whether it improves with T(4) therapy., Design and Intervention: EPC were studied in peripheral blood by fluorescence-activated cell sorter and following in vitro cultures before and after T(4) together with CV risk factors in 20 SCH and healthy controls (HC)., Main Outcome Measure: EPC count was measured at baseline and after T(4) replacement in SCH., Results: EPC count was significantly reduced in SCH compared to HC: median (range)-CD133+/VEGFR-2+, 0.09 (0.02-0.44) vs. 0.47 (0.17-2.12), P < 0.001; CD34+/VEGFR-2+, 0.10 (0.04-0.46) vs. 0.39 (0.11-2.13), P < 0.001; whereas EPC function was similar. There was a significant positive correlation between CD133+/VEGFR-2+ with free T(4) levels (r = 0.38; P = 0.02); high-density lipoprotein cholesterol levels (r = 0.51; P = 0.001); and negative correlation with TSH concentrations (r = -0.64; P < 0.001). After adjustment for conventional CV risk factors, SCH predicted lower EPC count, beta coefficient/P value: CD133+/VEGFR-2+ (-0.77/<0.001), and CD34+/VEGFR-2+ (-0.71/<0.001). In SCH participants, EPC count increased and was similar to HC after T(4); CD133+/VEGFR-2+, 0.32 (0.03-0.94) vs. 0.09 (0.02-0.44), P < 0.001; and CD34+/VEGFR-2+, 0.26 (0.06-0.88) vs. 0.10 (0.04-0.46), P < 0.001., Conclusion: SCH predicted lower EPC count, which improved with T(4) treatment, independent of other CV risk factors, providing additional evidence that T(4) replacement may improve CV risk in SCH.

Background: Asymmetric dimethylarginine (ADMA) is a competitive inhibitor of endothelial nitric oxide synthase (eNOS) that is associated with endothelial dysfunction, and is a risk marker for cardiovascular disease, a significant problem in Type 1 diabetes. The aim of the present study was to measure circulating ADMA, and define its association with endothelial dysfunction and endothelial markers in people with Type 1 diabetes with low likelihood of macrovascular disease., Methods: Sixty-one young people with Type 1 diabetes without macrovascular disease or nephropathy and 62 healthy volunteers underwent brachial artery flow-mediated dilatation (FMD) and assay of plasma ADMA and adhesion molecules., Results: Age, gender, BMI, lipid profile and renal function were similar in the two groups. People with Type 1 diabetes had impaired FMD compared to healthy controls (5.0 +/- 0.4 vs 8.9 +/- 0.4%; p < 0.001). Plasma ADMA levels were significantly lower in the people with diabetes compared to healthy controls (0.52 +/- 0.12 vs 0.66 +/- 0.20 micromol/l, p < 0.001). Plasma ICAM-1, E-selectin and PAI-1 levels were significantly higher in people with diabetes compared to healthy controls (median 201 (IQR 172-226) vs 180 (156-216) microg/l, p = 0.027; 44.2 (32.6-60.9) vs. 33.1 (22.4-51.0) microg/l; p = 0.003 and 70.8 (33.3-85.5) vs 46.3 (23.9-76.8) microg/l, p = 0.035). Plasma ADMA and VCAM-1 levels were positively correlated (r = 0.37, p = 0.003) in people with diabetes. There was no correlation between the plasma ADMA and FMD., Conclusion: ADMA levels are not associated with endothelial dysfunction in young adults with Type 1 diabetes without microalbuminuria or known macrovascular disease. This suggests that the impaired endothelial function in these individuals is not a result of eNOS inhibition by ADMA.

The aim of the article was to use prospectively collected data on people with type 1 diabetes to assess which routinely collected clinical measures predict the development of macrovascular disease in people with type 1 diabetes. Data have been collected in a structured format at an annual review since 1985. For this study, all people with type 1 diabetes in the database in both 1992 and 2001 were ascertained. Data were extracted for a diagnosis of coronary artery disease, stroke, and peripheral vascular disease (macrovascular complications). Presence of other microvascular complications was also ascertained. Forty-one of 404 (10.1%) people had macrovascular disease at the index visit in 1992 and 61 others developed macrovascular complications during follow-up. People who developed macrovascular complications were older (48 +/- 12 versus 36 +/- 11 [SD] years; P = 0.000), had longer duration of diabetes (28 +/- 12 versus 18 +/- 11 years; P = 0.000), higher BMI (26.7 +/- 4.6 versus 25.4 +/- 3.6 kg/m2; P = 0.041), higher base line serum cholesterol (5.9 +/- 1.7 versus 5.2 +/- 1.1 mmol/L, P = 0.007), higher median base line triglyceride levels (1.5 [IQ range 0.9-2.6] versus 1.1 [0.8-1.7] mmol/L; P = 0.002), higher systolic BP (145 +/- 21 versus 129 +/- 20 mmHg; P = 0.000), and higher serum creatinine (102 +/- 57 versus 86 +/- 17 micromol/L; P = 0.038) than those who did not. We found no significant difference in the base line glycated hemoglobin in the two groups. The multivariate model showed that age, duration of diabetes, systolic BP, and serum cholesterol and creatinine levels predicted the development of macrovascular complications, which were also associated with the later development of microalbuminuria. Macrovascular complications developed in 16.8% of people with type 1 diabetes over a 9-year follow-up, and were predicted by potentially modifiable factors including higher BP, BMI, and serum triglyceride and cholesterol levels.

Objective: To review clinical presentation, management and outcomes following different therapies in patients with pituitary apoplexy., Methods: Retrospective analysis of case-records of patients with classical pituitary apoplexy treated in our hospitals between 1983-2004., Results: Forty-five patients (28 men; mean age 49 years, range 16-72 years) were identified. Only 8 (18%) were known to have pituitary adenomas at presentation. Thirty-four (81%) patients had hypopituitarism at presentation. CT and MRI identified pituitary apoplexy in 28% and 91% cases, respectively. Twenty-seven (60%) patients underwent surgical decompression, whilst 18 (40%) were managed conservatively. Median time from presentation to surgery was 6 days (range 1-121 days). Patients with visual field defects were more likely than those without these signs to be managed surgically (p = 0.01). Complete or near-complete resolution occurred in 93% (13/14), 94% (15/16) and 93% (13/14) of the surgically treated patients with reduced visual acuity, visual field deficit and ocular palsy, respectively. All patients with reduced visual acuity (4/4), visual field deficit (4/4) and ocular palsy (8/8) in the conservative group had complete or near-complete recovery. Only 5 (19%) patients in the surgical group and 2 (11%) in the conservative group had normal pituitary function at follow up. One (4%) patient in the surgical group and 4 (22%) in the conservative group had a recurrence of pituitary adenoma., Conclusions: This large series suggests that the patients with classical pituitary apoplexy, who are without neuro-ophthalmic signs or exhibit mild and non-progressive signs, can be managed conservatively in the acute stage.

Hyperprolactinaemia frequently causes secondary hypogonadism through central suppression of gonadotropin secretion. Macroprolactinomas (> 1 cm diameter) are more common in males and may additionally cause more generalised hypopituitarism. Recovery of the thyrotropic and/or corticotropic axes is well described following selective adenomectomy, but remains poorly defined in relation to medical (dopamine-agonist) therapy of macroprolactinomas. We therefore performed a retrospective examination of case records of male patients who had received medical therapy alone for macroprolactinoma between 1980-2001 (n = 35) and in whom tumor shrinkage was documented by interval pituitary imaging (reported throughout by a single neuroradiologist). Mean prolactin level at baseline was 59,932 mU/L (median 31,400; range 3,215-332,000); mean period of follow up was 4.2 years (median 2.6; range: 1.0-15). Defects of the following axes were evident at diagnosis: LH/FSH-testosterone (n = 27; 77%), TSH-T4 (n = 14; 41%-not including one case with pre-existing 1 degress hypothyroidism), ACTH-cortisol (n = 8; 23%). Overall, 14 men (40%) were deficient in 1 axis, seven (20%) in 2 axes and seven (20%) in 3 axes. Growth hormone secretory status was not systematically evaluated. In all but 6 patients, prolactin levels fell to normal or near-normal levels (mean 764 mU/L; median 260; range: < 10-4,833). Of the patients in whom adequate reassessment had been performed, thyrotroph function recovered in 4/9, corticotroph function in 4/6 and gonadotroph function in 16/26 cases. In four cases (11%) previously described, development of visual impairment as a result of the chiasmal traction syndrome necessitated a dose reduction in medical therapy to allow a degree of controlled tumor re-expansion. The prevalence at diagnosis of TSH and ACTH deficiency in men with macroprolactinomas was 41% and 23%, respectively. Among eight patients with insufficiency of TSH and/or ACTH secretion who underwent complete interval reassessment over several years of treatment, recovery of at least one axis occurred in six cases (75%). This study highlights the importance of screening ACTH- and/or TSH-deficient men during dopamine agonist therapy in order to identify cases where hypopituitarism has resolved.

Objective: There is an association of sleep apnea among patients with untreated hypothyroidism. Thyroxine therapy is considered to reduce AHI (apnea-hypopnea index) significantly. A study of 20 successive hypothyroid patients was undertaken to investigate the occurrence of sleep apneas, and response to thyroxine therapy after achieving euthyroid state., Methods: Sleep studies were conducted in 20 consecutive hypothyroid patients at our sleep centre while they were hypothyroid. All were restudied during euthyroid state subsequent to three months of thyroxine therapy., Results: Nine (45%) of untreated 20 patients had obstructive sleep apnea syndrome (OSAS). Restudy of them during euthyroid state showed complete recovery in six, partial improvement in two and no change in one. Besides them, three other patients developed sleep apnea syndrome of central origin after euthyroid state was achieved. Central respiratory drive improved in 17 patients, while it was reduced among three of nine patients with OSAS who did not show recovery., Conclusion: Our experience suggests that there is high incidence of sleep apnea among hypothyroid patients. Thyroxine treatment could achieve disappearance of these apneas in majority of them. Few hypothyroids may develop sleep apnea despite the achievement of euthyroid state. Central respiratory drive probably plays an insignificant role in the pathogenesis of sleep apnea among hypothyroids.

This review describes oncogenic C-type virus and virus-associated antigens as phenotypic expressions of virus activities in malignant cells and cell surface antigens acquired by malignant transformation. The range of host-immune responses to these antigens in experimental systems is discussed in relation to the immunotherapy and immunoprophylaxis of human cancer patients.

Sibal, Louis R. (University of Illinois College of Medicine, Chicago), Arthur V. Kroeger, Dan Kumarich, and Esther Meyer. Serological specificity of acid-soluble antigens of Bacterionema matruchottii. J. Bacteriol. 83:811-818. 1962.-The serological specificity of acid-soluble antigens extracted from the oral, filamentous organism, Bacterionema matruchottii, was demonstrated by the microprecipitin reaction. There was no evidence of cross-reaction with antisera prepared against Leptotrichia buccalis, Actinomyces, or Lactobacillus species, and these results were confirmed by quantitative complement-fixation tests with selected antisera. Since all of the B. matruchottii isolates studied possess antigens in common, it was concluded that the microprecipitin reaction offers a useful aid in the differentiation of this genus from other filamentous organisms. The results do not provide definitive evidence regarding the taxonomic relationship of B. matruchottii to any genus tested, and tend to support the recent proposal for establishment of a new genus, Bacterionema. Preliminary data obtained with the indirect fluorescent antibody technique appear to indicate that the antigens of the intact bacterial cell are as specific as the acid-soluble extracts.