Mutation analysis of the lamin A/C gene (LMNA) among patients with different cardiomuscular phenotypes.
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Adolescent↗
Biomedical subjects
M Gallina
Publications and source records attributed to M Gallina.
Cost-effectiveness of implantable cardioverter-defibrillators.
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Adult↗
Identification of the etiology of primary aldosteronism with adrenal vein sampling in patients with equivocal computed tomography and magnetic resonance findings: results in 104 consecutive cases.
The objectives of this study were to investigate the usefulness of adrenal vein sampling in identifying the etiology of primary aldosteronism (PA) in patients with equivocal CT and MR findings. Between 1990 and 1999, 104 referred hypertensive patients (45 women and 59 men, aged 49.6 +/- 11.6 yr) were diagnosed to have PA with inconclusive computed tomography scan and magnetic resonance results, based on established criteria. Adrenal vein sampling (AVS) for measurement of plasma aldosterone (A) and cortisol (C) levels was performed in all. Selectivity of AVS was assessed by the ratio between C levels in each adrenal vein and in the infrarenal inferior vena cava plasma (C(side)/C(IVC)). A receiver operator characteristics analysis was carried out to establish 1) the best AVS-derived index, 2) the degree of selectivity that could provide an accurate diagnosis, and 3) whether a correct diagnosis could be made from a unilaterally selective AVS. An aldosterone-producing adenoma (average diameter, 12.2 +/- 0.08 mm) was eventually diagnosed in 41 patients (39.4%) and was excluded in the rest. Adrenal vein rupture leading to partial adrenal loss occurred in 1 patient (0.9% complication rate). By assuming a cut-off value of C(side)/C(IVC) > or = 1.1, AVS was selective in 85.7% and 94.1% of cases on the right and left sides, respectively, and bilaterally in 80.6% of cases. Of all AVS-derived indexes, the A/C of one over the A/C contralateral side [(A/C)(side)/(A/C)(contralateral side)] furnished the best diagnostic accuracy. With a bilaterally selective AVS, a value of (A/C)(side)/(A/C)(contralateral side) > or = 2 provided a conclusive etiological diagnosis of PA in 79.7% of cases. At variance, no accurate diagnosis could be made from unilaterally selective AVS. AVS was feasible and safe in most PA patients with inconclusive computed tomography and magnetic resonance scans. When bilaterally selective (i.e. C(side)/C(IVC) > or = 1.1) a ratio of (A/C)(side)/(A/C)(control) > or = 2 provided the best compromise of sensitivity and false positive rate for lateralization of the etiology of PA.
Adenoma↗
Predicting culture results for Mycobacterium tuberculosis complex. Amplified mycobacterium tuberculosis direct test and acid-fast bacilli microscopy.
STUDY OBJECTIVE: To evaluate the usefulness of the Gen-Probe Amplified Mycobacterium Tuberculosis Direct Test (AMTDT; Gen-Probe; San Diego, CA) in predicting the results of cultures in routine laboratory analysis of a patient population with a high incidence of tuberculosis (TB). PATIENTS: Three hundred ten patients suspected of pulmonary mycobacterial infection or receiving antituberculous chemotherapy, accrued between 1996 and 1997. SETTING: Tertiary-care facility located in Northern Italy. DESIGN: We retrospectively compared the AMTDT results with the results of cultures. AMTDT results were also compared with those of acid-fast bacilli (AFB) staining of the same specimens. The study included 360 respiratory specimens from 310 patients collected between 1996 and 1997. In 1996, we used the initial version of AMTDT (50 microL of sediment); in 1997, we used the new version of AMTDT (450 microL of sediment). RESULTS: Compared with cultures, AMTDT and AFB staining had sensitivities of 87.2% and 68.4%, and specificities of 70.0% and 89.7%, respectively. When AMTDT and AFB staining were both positive, the sensitivity and specificity were 89.3% and 96.9%, respectively. When AMTDT and AFB staining were in disagreement, the sensitivity and specificity of AMTDT were 81.8% and 18.1%, respectively. CONCLUSION: We conclude that when AMTDT is used to predict culture outcome, the results should be evaluated in conjunction with AFB staining results before making decisions about TB management.
Bacteriological Techniques↗
Plasma levels of E-selectin in normolipemic and hyperlipemic arteriopathic patients after vasoactive and lipid-lowering treatment.
BACKGROUND: The authors studied the plasma levels of E-selectin in a group of arteriopathic patients, before and after vasoactive and lipid-lowering treatment. METHODS: The series consisted of 73 subjects (53 males, 20 females, aged 54 +/- 9 suffering from occlusive peripheral arteriopathy; 21 subjects with total cholesterol (TC) below 200 mg/dl were considered as normolipemics (group A); 24 subjects with TC between 200 and 240 mg/dl, mild hypercholesterolemics (group B); 18 with TC above 240 mg/dl, severe hypercholesterolemic (group C); 10 subjects who had high triglyceride values (above 200 mg/dl), (group D); 12 normal controls were also considered. All patients underwent a vasoactive treatment for 15 days; group B also underwent a standard hypolipidic diet (phase I NCEP, lipid 30% die) groups C and D underwent the same diet associated respectively with simvastatin (200 mg/die) and bezafibrate (400 mg/die). For each sample of plasma before and after treatment the determination of levels of E-selectin was carried out by an immunoenzymatic method (kit ELISA Amersham). RESULTS: In groups A-B-C-D a reduction of the plasma levels of E-selectin was found, which was significant (p < 0.05), for group C and D, compared to controls. In groups A-B-D significant changes of E-selectin were not found after treatment; in group C the difference between the values after treatment and at baseline was significant (p < 0.05). CONCLUSIONS: The reduction of the E-selectin plasma levels was proportional to the values of total cholesterol and triglycerides; the chronicity and the dyslipidemia may be responsible for the basal diminished biosynthetic endothelial function; in the severe hypercholesterolemics the lipid-lowering treatment caused a significant decrease of E-selectin, due to a probable reduced endothelial irritation dependent on the hyperlipemic stress.
Arterial Occlusive Diseases↗
Nitrite, endothelin and E-selectin plasma levels after arginine infusion in normal, obese and type 2 diabetic subjects.
BACKGROUND: The authors studied the behaviour of nitrites (specific end-products of nitric oxide), endothelin and E-selectin after arginine infusion (biosynthetic precursor of nitric oxide). METHODS: The series consisted of 28 female subjects (mean age 59 +/- 8) of whom: 12 normal controls; 12 suffering from essential obesity (BMI 31.4 +/- 0.7); 14 suffering from uncomplicated type 2 diabetes mellitus. Each subject received intravenous arginine (20 g in two hours); before the infusion and after 1 hour and 2 hours venous blood withdrawal was performed. For each plasma sample the levels of nitrites (colorimetric reaction), endothelin (ELISA method) and E-selectin (ELISA method) were determined. RESULTS: In the controls plasma nitrites decreased significantly (p < 0.05), more evidently at the second hour. In the obese subjects a sharp significant (p < 0.05) fall of nitrites was observed, more evidently at the second hour. In the diabetics nitrite values were reduced (p < 0.05) compared to the baseline. Endothelin levels after arginine were almost unchanged in normal and obese subjects, while in diabetics a significant (p < 0.05) reduction was observed. In the three groups of subjects E-selectin values were not modified by arginine. CONCLUSIONS: This study demonstrates that arginine infusion increase NO biosynthesis in normal, obese and diabetic subjects, inducing a significant reduction of nitrites for an early process of organic reconversion; endothelin showed a reductive trend, mainly in diabetics, probably due to an antagonistic balanced response towards an overproduction of nitric oxide. E-selectin did not change, without correlation with the nitrite and endothelin values, because of an independence from the production of the two "hemodynamic markers".
Analysis of Variance↗
Nitrite plasma levels in chronic lung disease patients.
BACKGROUND: The authors carried out a study in a group of lung disease patients, about the behaviour of the plasmatic levels of nitrites (stable, specific and irreversible end-products of nitric oxide). METHODS: The series consisted of 13 male patients (mean age 65 +/- 7 years) with chronic obstructive pulmonary disease with type 1 respiratory failure; 33 male subjects (mean age 58 +/- 5 years) without internistic disease were considered as controls. For each subject the determination of nitrite plasma levels by the Gutman and Hollywood method based on the Griess colorimetric reaction was performed. RESULTS: The mean value of the plasmatic nitrites was significantly reduced (p < 0.05) as compared to the controls (11 +/- 0.48 mumol/l vs 21 +/- 0.92 mumol/l). CONCLUSIONS: The authors hypothesized that in chronic lung disease patients there would be a condition of initial pulmonary hypertension; in this condition long-term endothelium-dependent nitric oxide production, aimed at the vasodilating effects with secondary excessive exhaled amount of NO, might cause a reduction in nitrite plasma levels. These levels may represent an early marker of pulmonary hypertension and suggest interesting therapeutic treatments through inhalation of exogenous NO.
Aged↗
Plasma levels of E-selectin in normolipemic and hyperlipemic arteriopathic patients.
BACKGROUND: The authors studied the plasmatic levels of E-selectin in a group of normolipemic and hyperlipemic arteriopathic patients. METHODS: The series consisted of 73 subjects (53 male, 20 female, age 54 +/- 9) suffering from occlusive peripheral arteriopathy; 21 subjects with total cholesterol (TC) below 200 mg/dl were considered as normolipemics (group A), 24 subjects with TC between 200 and 240 mg/dl, mild hypercholesterolemics (group B), 18 with TC above 240 mg/dl, severe hypercholesterolemics (group C); 10 subjects had high triglyceride values (above 200 mg/dl), (group D); 12 normal controls were also considered. For each subject the determination of the E-selectin E-plasma levels was performed with an immunoenzymatic method (kit ELISA Amersham). RESULTS: In group A a value of E-s (4.03 +/- 0.37 ng/ml) statistically lower (p < 0.05) compared to normal controls (5.71 +/- 0.61 ng/ml) was found; in group B the E-s value (3.81 +/- 0.31 ng/ml) was slightly lower than that of group A; in group C the value of E-s was 3.53 +/- 0.23 ng/ml, statistically lower compared normal controls (p < 0.01) and to group A (p < 0.05); in group D the E-s value (3.24 +/- 0.23 ng/ml) was sharply reduced compared to controls (p < 0.01) and to groups A-B-C (p < 0.05). CONCLUSIONS: The reduction or E-selectin, was proportional to the magnitude of total cholesterol and triglycerides; the chronicity of the vasculopathy and the dyslipidemia may be responsible for an impaired biosynthetic endothelial function.
Arterial Occlusive Diseases↗
Nitrite plasma levels after an oral fat meal in normolipemic subjects.
BACKGROUND: The authors, investigating the effects of an oral triglyceride-rich fatty load upon the endothelial function as regards the production of nitric oxide, performed the determination of plasma nitrites, which are stable, specific and irreversible end-products of nitric oxide. METHODS: The series consists of 13 metabolically normal female subjects (mean age 55 +/- 7 years); after an overnight fasting each subject undertook an oral fat load (butter 1 g/kg); a venous blood withdrawal was carried out before oral fat meal and after two and four hours. For each plasma sample total cholesterol, HDL-cholesterol and triglyceride plasma levels were determined by enzymatic methods; LDL-cholesterol was calculated by Friedwald's formula; the nitrite plasma levels were obtained by the Gutman and Hollywood colorimetric method. RESULTS: Total cholesterol, HDL-cholesterol, LDL-cholesterol did not show significant changes after the oral fat load; triglycerides rose significantly (p < 0.05) after 4 hours as compared to the basal value (226 +/- 12 vs 175 +/- 12 mg/dl, +30%). The nitrite plasma levels were almost unchanged before oral fat load and after 2 and 4 hours. CONCLUSIONS: The results suggest that the acute biochemical stress consisting of increased triglyceride-rich very low density lipoproteins was not able to stimulate the endothelial production of nitric oxide.
Butter↗
Nitrite plasma levels in normolipemic and hypercholesterolemic arteriopathics after vasoactive and lipid-lowering treatment.
BACKGROUND: The authors studied the plasmatic levels of nitrites, stable end-products of nitric oxide in arteriopathic patients before and after vasoactive and lipid-lowering treatment. METHODS: The series consisted of 63 subjects (mean age 64 +/- 9) suffering from peripheral arterial occlusive disease; 21 subjects with total cholesterol (TC) lower than 200 mg/dl were considered as normolipemic (group A); 24 subjects with TC ranging between 200 and 240 mg/dl were considered as mild hypercholesterolemic (group B); 18 subjects with TC higher than 240 mg/dl were consider as severe hypercholesterolemic (group C). All the patients were examined before and after 15 and 30 days of a vasoactive treatment (calciparine, aspirin, buflomedil and pentoxiphylline); group B after vasoactive and diet (NCEP phase 1) treatment and group C after vasoactive, diet and drug (simvastatin) treatment. Nitrite plasma levels were determined by the Gutman and Hollywood colorimetric method. RESULTS: In group A the basal value of nitrites was sharply (p < 0.05) lower than controls; after vasoactive treatment a significant increase (p < 0.05), was observed after 15 and 30 days; in group B the basal value was higher than controls; after 15 days a significant increase (p < 0.5) was noted, but a regression was found after 30 days. Also in group C the basal value of nitrites was higher (p < 0.05) than controls; after treatment significant changes were not found. CONCLUSIONS: The increase of nitrites in group A may be due to an improved endothelial function; this phenomenon, less appreciable in group B and no longer evident in group C may depend on the lipid-lowering treatment.
Aged↗
Nitrite plasma levels in normolipemic and hypercholesterolemic patients with peripheral occlusive arteriopathy.
BACKGROUND: The authors studied the nitrite plasma levels in a group of patients with peripheral obstructive arteriopathy. METHODS: The series consisted of 63 subjects (43 males, 20 females, mean age 64 +/- 9 years) suffering from peripheral arterial occlusive disease of the lower limbs, at II (55 cases) and III (8 cases) Fontaine stage; 21 subjects with total cholesterol (TC) lower than 200 mg/dl were considered as normolipemics, 24 subjects with TC values between 200 and 240 as mild hypercholesterolemics, 18 subjects with TC above 240 mg/dl as severe hypercholesterolemics. For each subject the determination of nitrite plasma levels was carried out, by the Gutman and Hollywood colorimetric method. RESULTS: In the normolipemic arteriopathics the basal value of nitrites was sharply reduced (p < 0.05) compared to the controls; in the mild hypercholesterolemics the mean basal value of nitrites was markedly higher compared to the controls; in the severe hypercholesterolemics the mean basal value of nitrites was statistically (p < 0.05) higher than that of the controls. In the arteriopathic patients, globally considered, the mean basal value of nitrites was superimposable on that of the normal control subjects. CONCLUSIONS: This study, carried out on the nitrite plasma levels in a group of arteriopathic patients allowed us to show the enhanced levels of nitric oxide due to the increase of LDL; this effect, previously observed in hypercholesterolemic diabetic and coronaropathic patients, leads us to the hypothesis of a stimulating effect of LDL upon NO endothelial synthesis; this would be a compensatory response to the damaging and vasoconstricting action of LDL.
Aged↗
The oxidation of dopamine and epinine by the two forms of monoamine oxidase from rat liver.
Information on the "in vitro" oxidation of epinine by monoamine oxidase (MAO) compared to dopamine is very poor. The aim of this work was to study the oxidative deamination of epinine and dopamine by rat liver MAO-A and MAO-B. The contributions of MAO-A and B to the metabolism of dopamine (55% and 45%, respectively) and epinine (70% and 30%, respectively) were similar. The results of this study show that epinine is a substrate for both forms of MAO in rat liver, although the contribution of MAO A to the deamination of this secondary amine appears to be slightly more important than that of MAO B.
Animals↗
Nitrite, endothelin and E-selectin plasma levels after arginine infusion in normal and vasculopathic subjects.
BACKGROUND: The authors carried out a study on the simultaneous modifications of nitrite, endothelin and E-selectin plasma levels after infusion of arginine (a precursor of nitric oxide endothelial synthesis) in normal and vasculopathic subjects. METHODS: The series consisted of 24 female subjects (mean age 58 +/- 7) of which: 12 normal controls; 12 suffering from chronic cerebral vascular disease and coronary heart diseases. Each subject, after a venous blood withdrawal, received arginine (20 g over 2 hours); withdrawals were repeated after 60 and 120 minutes. The levels of total nitrites (NO2-, colorimetric method), endothelin (ET-1, ELISA method) and E-selectin (E-s, ELISA method) were determined on each plasma sample. RESULTS: The levels of NO2-, specific end-products of nitric oxide, did not show significant changes after arginine infusion in the vasculopathic subjects (group B), whereas in the normal subjects (group A) a significant reduction was recorded. The ET-1 levels after arginine did not show significant differences between the two groups. The values of E-selectin presented no significant variations after arginine in the two groups. The basal values of nitrites, endothelin and E-selectin was significantly (p < 0.05) lower in group B than in group A. CONCLUSIONS: In conclusion, this study has demonstrated that arginine infusion did not alter the nitrite, endothelin and E-selectin plasma levels within two hours in vasculopathic subjects, suggesting a probable wide abiotrophic damage of the endothelial structures. The reduction of nitrites after arginine in the normal subjects may depend of an inverse organification process due to an enhanced bio-synthesis of nitric oxide.
Arginine↗
Nitric oxide plasma levels in patients with chronic and acute cerebrovascular disorders.
BACKGROUND: The authors carried out a study on plasma level of nitrites, stable end-products of nitric oxide, aimed at investigating some features of the cerebral microvascular function in chronic and acute cerebrovascular disorders, METHODS: The series consists of 16 patients with chronic cerebral vascular disease, 11 patients with TIA, 28 patients with thrombotic stroke and 27 normal controls; the diagnosis was done on the basis of clinical, ultrasonographic and tomodensitometric findings. For each subject the determination of nitrate plasma levels by a method based on the colorimetric reaction (developed by nitrites dissolved in an acid solution containing sulfanilamide) was performed; this reaction yields quantitative results exactly corresponding to the amount of nitric oxide. RESULTS: In chronic cerebrovascular patients NO2-values tendentially higher (16.4 +/- 0.52 mumol/l) but not statistically different from those of controls (13.2 +/- 0.52) were obtained; also the values found in the group with TIA, even if slightly reduced (8.0 +/- 1.4 mumol/l), did not differ from controls; in the stroke group a significant (p < 0.05) reduction (6.4 +/- 0.52 mumol/l), as compared to controls, was found. CONCLUSIONS: On the basis of these results and of the literature data on the physiopathological profile of NO, the authors suggest a compensatory increase of the basal tone of NO in chronic cerebrovascular diseases, while an impaired endothelial synthesis of the marker could play a critical role in TIA patients and more evidently in stroke patients, presenting a wide microvascular area completely and irreversibly excluded.
Acute Disease↗
Nitrite plasma levels in type 1 and 2 diabetics with and without complications.
BACKGROUND: The authors thought it interesting to examine the interrelationship between nitric oxide and diabetes mellitus by the determination of the nitrite plasma levels, stable end-products of nitric oxide, in various clinical patterns of diabetes mellitus. METHODS: Our series consisted of 161 female subjects (mean age 54 +/- 7 years, disease duration 5 +/- 3 months) subdivided into: a) 13 patients suffering from insulin-dependent diabetes (IDDM) without clinical and instrumental signs of micro- and macro-angiopathy; b) 148 suffering from non insulin-dependent diabetes mellitus (NIDDM) of whom: 1) 52 without vascular complications (28 normal weight, BMI < 25, and 24 obese, BMI > 30); 2) 40 with clinical and instrumental signs of non hypertensive coronary heart disease (CHD); 3) 25 with CHD and hypertension (arterial blood pressure over 160/95 mmHg); 4) 31 with hypercholesterolemia (values over 250 mg/dl). All patients were examined in good glycometabolic conditions reached by oral hypoglycemiant (12 cases) or insulin (149 cases) treatment. As normal control 37 female subjects (mean age 48 +/- 7) without internistic diseases were considered. For each sample we determined the plasma levels of nitrites by the Gutman and Hollywood method. RESULTS: Almost similar nitrite plasma levels in IDDM (17 +/- 0.5 mumol/L) and normal controls (17 +/- 0.2 mumol/L) were found; in non complicated non obese NIDDM a not significantly elevated value (21 +/- 0.8 mumol/L) as compared with the IDDM and control group was found; the obese NIDDM patients showed a value (18 +/- 0.4 mumol/L) not significantly different in comparison with the non obese NIDDM group. In the NIDDM group with non hypertensive CHD) the nitrite values was almost similar (20 +/- 0.5 mumol/L) to the corresponding group without vascular complications. In the patients with CHD and hypertension the nitrite level was superimposable (20 +/- 0.7 mumol/L) on the one recorded in NIDDM patients without vascular complications and in those with CHD without hypertension. In NIDDM patients with hypercholesterolemia the mean nitrite value was sharply elevated (24 +/- 0.8 mumol/L); the difference between this group and those of non hypercholesterolemic, non obese, obese and CHD (with or without hypertension) patients was significant (p < 0.05). CONCLUSIONS: It is conceivable that diabetes mellitus per se causes a tendential not significant increase of NO production in comparison with normal controls; some factors such as blood pressure, overweight, disease duration, therapeutic treatment and coronary complications appear not to influence NO production. In hypercholesterolemic diabetic patients the nitrite enhanced level in plasma might mean a compensatory response to a continuous inactivation of NO involved in a protective competition towards damaging factors and chiefly against oxidised LDL.
Adult↗
Preliminary pharmacokinetic study of ibuprofen enantiomers after administration of a new oral formulation (ibuprofen arginine) to healthy male volunteers.
The pharmacokinetics of ibuprofen enantiomers were investigated in a crossover study in which seven healthy male volunteers received single oral doses of 800 mg racemic ibuprofen as a soluble granular formulation (sachet) containing L-arginine (designated trade name: Spedifen), 400 mg (-)R-ibuprofen arginine or 400 mg (+)S-ibuprofen arginine. Plasma levels of both enantiomers were monitored up to 480 minutes after drug intake using an enantioselective analytical method (HPLC with ultraviolet detection) with a quantitation limit of 0.25 mg/l. Substantial inter-subject variability in the evaluated pharmacokinetic parameters was observed in the present study. After (+)S-ibuprofen arginine, the following mean pharmacokinetic parameters +/-SD were calculated for (+)S-ibuprofen: tmax 28.6 +/- 28.4 min; Cmax 36.2 +/- 7.7 mg/l; AUC 86.4 +/- 14.9 mg.h/l; t1/2 105.2 +/- 20.4 min. After (-)R-ibuprofen arginine, the following mean pharmacokinetic parameters were calculated for (+)S-ibuprofen and (-)R-ibuprofen, respectively: tmax 90.0 +/- 17.3 and 50.5 +/- 20.5 min; Cmax 9.7 +/- 3.0 and 35.3 +/- 5.0 mg/l; AUC 47.0 +/- 17.2 and 104.7 +/- 27.7 mg.h/l; t1/2 148.1 +/- 63.6 and 97.7 +/- 23.3 min. After racemic ibuprofen arginine, the following mean pharmacokinetic parameters were calculated for (+)S- and (-)R-ibuprofen, respectively: tmax 30.7 +/- 29.1 and 22.9 +/- 29.8 min; Cmax 29.9 +/- 5.6 and 25.6 +/- 4.4 mg/l; AUC 105.1 +/- 23.0 and 65.3 +/- 15.0 mg.h/l; t1/2 136.6 +/- 20.7 and 128.6 +/- 45.0 min. Tmax values of S(+)- and (-)R-ibuprofen after a single dose of 400 mg of each enantiomer did not differ significantly from the corresponding parameters obtained after a single dose of 800 mg of racemic ibuprofen arginine, indicating that the absorption rate of (-)R- and (+)S-ibuprofen is not different when the two enantiomers are administered alone or as a racemic compound. An average of 49.3 +/- 9.0% of a dose of the (-)R-ibuprofen arginine was bioinverted into its antipode during the study period (480 minutes post-dosing). The percent bioinversion during the first 30 minutes after (-)R-ibuprofen arginine intake averaged 8.1 +/- 3.9%. The mean AUC of (+)S-ibuprofen calculated after 800 mg racemic ibuprofen arginine (105.1 +/- 23.0 mg.h/l) was lower than the mean AUC value obtained by summing the AUCs of (+)S-ibuprofen after administration of 400 mg (+)S-ibuprofen arginine and 400 mg (-)R-ibuprofen arginine (133.4 +/- 26.6 mg.h/l). In conclusion, the administration of Spedifen resulted in very rapid absorption of the (+)S-isomer (eutomer) with tmax values much lower than those observed for this isomer when conventional oral solid formulations such as capsules or tablets of racemic ibuprofen are administered. This characteristic is particularly favourable in those conditions in which a very rapid analgesic effect is required.
Adult↗
Increased G-CSF responsiveness of bone marrow cells from hematopoietic cell phosphatase deficient viable motheaten mice.
The mouse mutation viable motheaten (me(v)) results in defects in the expression and catalytic activity of the cytoplasmic protein tyrosine phosphatase known as hematopoietic cell phosphatase (HCP). This reduction in HCP activity leads to the aberrant regulation of several myeloid and lymphoid cell lineages, including substantial increases in numbers of granulocytes. The differentiation, proliferation, and survival of cells in this lineage are normally supported by granulocyte-colony stimulating factor (G-CSF). In this study we have determined the consequences of the loss of HCP activity in me(v)/me(v) mice on the response of bone marrow cells to G-CSF. Bone marrow from these mice exhibited substantial increases in clonogenic and proliferative responses to G-CSF. These enhanced activities of G-CSF correlated with an increase in the level of immature granulocytic, G-CSF receptor positive cells in the bone marrow. These results suggested the possibility that HCP may regulate the G-CSF receptor by a direct interaction. However, under conditions where the previously described interaction between the erythropoietin receptor and HCP was readily observed, HCP did not detectably associate with the G-CSF receptor.
Animals↗
[A rare case of juvenile diabetes mellitus associated with APECED (autoimmune poly-endocrinopathy, candidiasis and ectodermal dystrophy) with strong X-linked familial inheritance].
The polyglandular autoimmune syndromes (PGA) are well known and are distinguished into type I, type II and type III. PGAI, also called APECED (autoimmune polyendocrinopathy, candidiasis and ectodermal dystrophy), is an autosomal recessive disorder, appearing in childhood and typically characterized by hypoparathyroidism (unusual in PGAII and PGAIII) and adrenal insufficiency. In APECED, autoimmune destruction of the pancreatic beta cells with development of insulin-dependent type 1 diabetes is possible, but less frequent than in the other PGAs, especially PGAII. The pathogenesis of this unique autoimmune disease is unknown. No HLA association seems to exist and genetic studies have assigned the autosomal APECED locus to chromosome 21. The case of a 28-years-old female suggesting the diagnosis of APECED, is presented, characterized by psycho-somatic abnormal development, teeth alterations, post-puberal gonadal failure with dystrophic hypoplasia of external genitalia, previous vaginal candidiasis, a slowly developing juvenile brittle diabetes. Intestinal malabsorption induced by Giardia lamblia occurred (probably resulting, like candidiasis, from immunological anergy). A strong familiarity linked to female sex was noticed (the mother, a sister, the little nice and some maternal female cousins being affected) while the father and a brother were healthy. Diabetes seems to be characterized by early onset and severe complications. In this patient no organo-specific antibodies were detected and the only immunologic disorder was a small decrease of CD3 and CD4/CD8 ratio, both CD4 and CD8 being at the lower normal range. This patient (and her female maternal relatives) needs a long-term follow-up in order to evaluate the function of endocrine glands and to initiate early treatment for hormonal deficits, as well as to detect the non-endocrine components of disease.
Adult↗