Hereditary angioedema in Czechoslovakia. Clinical, immunological, genetic and therapeutic studies of 16 families

The analysis of the findings in 16 families with hereditary angioedema detected in Czechoslovakia over the years 1975-1986 is being presented. In 14 families C1-inhibitor deficiency and in two families afunction of C1-inhibitor was established. Of the total number of 175 examined family members C1-inhibitor defect was registered in 66 subjects (60 with deficiency and 6 with afunction), and of these 48 suffered from clinical symptoms of edematous attacks affecting the skin, larynx, intestine and urinary tract, whereas 18 subjects were asymptomatic. Genealogical studies confirmed that the defect is inherited as an autosomal dominant trait. In 16 patients long-term prophylactic treatment with Danol was introduced. The effective minimum dosage was tested individually for each patient.     

The recollection of affect

A group of psychiatric in-patients significantly over-estimated the intensity of their depression when asked to recollect how depressed they had been one week earlier. The initial level of depression affected the accuracy of recall. Unexpectedly, patients who were more depressed initially had more accurate recall, particularly for biological and symptomatically negative items of the Zung Self-Rating Depression Scale.     

Delivery of matrix metalloproteinase-1 attenuates established liver fibrosis in the rat

BACKGROUND & AIMS: During hepatic fibrogenesis, the hepatic extracellular matrix changes to fibrillar collagens types I and III, and cirrhosis is believed to produce an irreversible scar. In this study, we investigated whether gene delivery of human matrix metalloproteinase-1, which degrades collagens types I and type III, would attenuate established hepatic fibrosis in the rat, induced by either thioacetamide or bile duct ligation. METHODS: Hepatic fibrosis induced by thioacetamide for 7 weeks was persistent for at least 2 months, even after discontinuation of the treatment. The rats were infected once with a recombinant adenovirus, Ad5MMP-1, into which human pro-human matrix metalloproteinase-1 complementary DNA was packaged, or with a control adenovirus, Ad5LacZ. RESULTS: In Ad5MMP-1-infected, but not in Ad5LacZ-infected, rats, the fibrosis was dramatically attenuated at 2 weeks after the infection. It is interesting to note that the number of activated hepatic stellate cells was also decreased in Ad5MMP-1-infected rats. Moreover, disorganization of the hepatic trabecula, heterogeneity in the size of hepatocytes, and increased dried liver weight were observed only in Ad5MMP-1-treated rats, suggesting that human matrix metalloproteinase-1 stimulated hepatocyte proliferation, which was confirmed by bromodeoxyuridine staining. After 4 weeks, the proliferative effect of human matrix metalloproteinase-1 almost disappeared, but the hepatic fibrosis remained attenuated, whereas the fibrosis in Ad5LacZ-treated rats persisted. Furthermore, the administration of Ad5MMP-1, but not Ad5LacZ, decreased type I collagen and generated a small collagen fragment in hepatic fibrosis induced by bile duct ligation. CONCLUSIONS: Our findings show that transient human matrix metalloproteinase-1 overexpression in the liver effectively attenuates established fibrosis and induces hepatocyte proliferation.     

PC-1 (ENPP1) K121Q polymorphism in overweight and obese type 2 diabetic coronary heart disease patients

AIM: The aim of the present study was to investigate the prevalence of the PC-1 121Q allele and to test its association to cardiovascular risk factors in type 2 diabetes mellitus (DM) patients. METHODS: A total of 103 unrelated Caucasians from Serbia, including 71 DM patients without CHD (aged 59.4 +/- 8.9 years, with a mean body mass index (BMI) of 33.3 +/- 4.8 kg/m2) and 32 DM patients who suffered from coronary heart disease (DM+CHD) (aged 59.3 +/- 8.0 years, with a mean BMI of 30.37 +/- 3.71 kg/m2), were genotyped for PC-1 K121Q using a mutagenic separated PCR assay. RESULTS: The prevalence of the PC-1 121Q allele was significantly higher in DM+CHD, compared to DM (P < 0.001) and control (P < 0.001) groups, since it was found in 10 (14%) DM patients, 13 (41%) DM+CHD patients and 10 (17%) control subjects.When the association of PC-1 121Q allele and the risk of suffering from CHD were assessed within the DM group in a binary logistic regression model adjusting for age and sex, PC-1 121Q allele carriers had a 76% lower risk (OR 0.24; 95% CI: 0.08-0.67, P = 0.006) for developing CHD compared to subjects who exhibited PC-1 wild-type. CONCLUSION: The prevalence of the PC-1 121Q allele was significantly higher in type 2 diabetic patients who suffered from CHD, compared to type 2 diabetic patients without CHD. However, after a binary logistic regression model analysis, adjusting for age and sex., PC-1 121Q allele carriers had a 76% lower risk (OR 0.24; 95% CI: 0.08-0.67, P = 0.006) for developing CHD compared to subjects who exhibited PC-1 wild-type. Since these data were cross-sectional, the potential patient selection and survival bias, as well as community underdiagnosis of DM and CHD, could most likely substantially underestimate the genetic influence.     

Efficient sampling of early signal arrival for estimation of perfusion and transit time in whole-brain arterial spin labeling

Arterial spin labeling can be used to measure both cerebral perfusion and arterial transit time. However, accurate estimation of these parameters requires adequate temporal sampling of the arterial spin labeling difference signal. In whole-brain multislice acquisitions, two factors reduce the accuracy of the parameter estimates: saturation of labeled blood in transit and inadequate sampling of early difference signal in superior slices. Label saturation arises when slices are acquired inferior-to-superior such that slice selection in proximal slices spoils the label for a distal slice. Inadequate sampling arises when the time spent acquiring inferior slices is too long to allow early sampling of the difference signal in superior slices. A novel approach to multislice imaging is proposed to address these two issues. In round-robin arterial spin labeling, slices are acquired in a different order after every pair of control-label acquisitions. Round-robin arterial spin labeling enables the acquisitions of all slices across the same range of postlabel delays in a descending superior-to-inferior order. This eliminates the temporal sampling problem and greatly reduces label saturation. Arterial transit time estimates obtained for the whole brain with round-robin arterial spin labeling show better agreement with a single-slice acquisition than do conventional multislice acquisitions.     

Interferon-gamma release assays are a better tuberculosis screening test for hemodialysis patients: A study and review of the literature

Diagnosing latent tuberculosis (TB) infection (LTBI) in dialysis patients is complicated by poor response to tuberculin skin testing (TST), but the role of interferon-gamma release assays (IGRAs) in the dialysis population remains uncertain. Seventy-nine patients were recruited to compare conventional diagnosis (CD) with the results of two IGRA tests in a dialysis unit. Combining TST, chest x-ray and screening questionnaire results (ie, CD) identified 24 patients as possible LTBI. IGRA testing identified 22 (QuantiFERON Gold IT, Cellestis, USA) and 23 (T-spot.TB, Oxford Immunotec, United Kingdom) LTBI patients. IGRA and CD correlated moderately (κ=0.59). IGRA results correlated with history of TB, TB contact and birth in an endemic country. TST was not helpful in identifying LTBI patients in this population. The tendency for IGRAs to correlate with risk factors for TB, active TB infection and history of TB argues for their superiority over TST in dialysis patients. There was no superiority of one IGRA test over another.     

AT1 receptor expression in glomeruli from NO-deficient rats

Chronic inhibition of nitric oxide synthase promotes renin-dependent hypertension and renal injury. The present study examines how renal angiotensin II receptors are expressed in this model. N(G)-nitro-L-arginine methyl ester (L-NAME) was given orally to rats for 1 month and was associated or not with captopril during the 4 last days of the administration. 125I-[Sar1, Ile8]-Ang II binding, AT1)mRNA and cytosolic calcium were studied in isolated glomeruli from L-NAME and control rats and in cultured mesangial cells from normal rats. Renal injury was marked in rats receiving L-NAME. Type I angiotensin II (AT1) receptor number and mRNA expression were decreased (p < 0.05) in glomeruli isolated from L-NAME-treated rats compared with controls, unless they received captopril in combination. The low level of AT1 receptor expression was associated with an attenuated rise of cytosolic calcium in response to angiotensin II. Angiotensin-converting enzyme activity in glomeruli and angiotensin II concentration in renal cortex were increased (p < 0.05) in rats receiving L-NAME alone, whereas aminopeptidase A activity was not modified. To better discriminate between the direct and indirect effects of nitric oxide deficiency, rat mesangial cells were exposed or not for 24 h to S-nitroso-N-acetyl penicillamine, a nitric oxide donor. Angiotensin II binding, AT1 mRNA expression and calcium response to angiotensin II were decreased in presence of the nitric oxide donor (p < 0.01). These results suggest that the decrease of AT1 receptor expression after 1 month of L-NAME treatment does not depend on a direct effect of nitric oxide deficiency but results from the high local angiotensin II concentration due to the stimulated angiotensin-converting enzyme activity. They also show that the renin-angiotensin dependence of this model of hypertension does not result from the overexpression of AT1 receptors.     

Bone marrow microenvironment in cancer patients: immunological aspects and clinical implications

The bone marrow (BM) of cancer patients is considered an essential secondary lymphoid organ with substantial impact on tumor cell dissemination and tumor–immune responses. Recent advances in the understanding of BM/primary tumor crosstalk, homing processes, premetastatic niche formation, tumor cell dormancy, and ultimately, identification of the BM micromilieu cytokines, chemokines, and growth factors may provide the basis for the development of targeted therapeutic strategies potentially rendering primary cancers and cancer bone metastases more susceptible to chemotherapy. The present review aims to dissect the individual components of the BM microenvironment in cancer patients, compare it to the healthy BM, and discuss its impact on interactions between the tumor and the immune system.