Effects of taurine and structurally related analogues on Ca2+ uptake and respiration rate in rat liver mitochondria.
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Animals↗
Biomedical subjects
L Bianchi
Publications and source records attributed to L Bianchi.
In vivo release of taurine from rat neostriatum and substantia nigra.
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Animals↗
Role of taurine in thermoregulation and motor control. Behavioural and cellular studies.
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Animals↗
Detection and typing of hepatitis C RNA in liver biopsies and its relation to histopathology.
This paper describes the correlation of hepatitis C genotypes detected in liver tissue with histological grading (inflammatory activity) and staging (degree of fibrosis/cirrhosis). The viral genotype was analysed by type-specific polymerase chain reaction (PCR) and correlated with histology and age of patients. In 69 patients with chronic hepatitis C (HCV) infection, genotypes 1a and 1b were detected in 13 (18.8%) and 31 (44.9%) liver biopsies, respectively. Genotypes 2a and 2b were each detected once (1.5%) and 12 (17.4%) tissue samples showed a mixed infection with two genotypes. In 11 (15.9%) biopsies, no genotype could be established. The liver specimens were grouped according to the presence or absence of genotype 1b: group A consisted of specimens infected with genotypes 1a, 2a, and 2b (n = 16), Group B contained biopsies infected with genotype 1b (n = 42), and group C were biopsies with no detectable genotype (n = 11). Activity (grade) of chronic hepatitis was not different in these three groups. However, advanced fibrosis/cirrhosis was observed in 16 (38.1%) biopsies in group B (containing genotype 1b), compared with none in group A (P = 0.01). The mean age of patients in group B was significantly higher than that in group A (P = 0.038), and the mean age of patients with advanced fibrosis was higher than that of patients with low fibrosis scores within these two groups (P = 0.004). Stepwise logistic regression revealed an independent association of age and genotype 1b (group B) with advanced fibrosis/cirrhosis. These data indicate that patients infected with genotype 1b have an higher risk of developing cirrhosis than do patients with other genotypes.
Adolescent↗
Assessment of myocardial area at risk by technetium-99m sestamibi during coronary artery occlusion: comparison between three tomographic methods of quantification.
The aim of this study was to directly compare three currently used quantitative methods of analysis of technetium-99m sestamibi images in patients with selective balloon-induced transmural ischaemia. The area at risk (AR) was assessed in 19 patients undergoing single-vessel percutaneous transluminal coronary angioplasty by injecting the 99mTc-sestamibi at the time of coronary artery occlusion during balloon inflation. After imaging, the patients were classified according to localization of the perfusion defect as having anteroseptal (group I, 11 patients) or posterolateral defects (group II, eight patients). The planimetric technique based on polar maps, proposed by Verani et al. (J Am Coll Cardiol, 1988) (method A), the method described by Tamaki et al. (Circulation, 1982) (method B) and the technique validated by O Connor et al. (Eur J Nucl Med, 1990) (method C) were tested. Three threshold values of 45%, 50% and 60% of the maximum left ventricular count were used to define the limits of the perfusion defect. The mean values of the AR calculated by the three techniques with the original cut-off level (method A=16.5%+/-12.9; method B=10.4%+/-7.6%; method C=29.6%+/-15.7%) were statistically different (one-way analysis of variance: P<0.001; paired t test: method A vs B, P=0.003; method B vs C and method A vs C, P<0.0001). There was no significant difference between the mean values of the AR estimated by the three methods using the same cut-off levels. The use of 60% of the maximum left ventricular count provided the best correlation between the techniques (method A vs B, r=0.95; method B vs C, r=0.92; method A vs C, r=0.95). Nevertheless, a difference >10% between the values of AR assessed by the three methods was found in four subjects. There was no significant difference between the three methods in the evaluation of AR in the subjects of group I and group II. Reproducibility was good for all methods. It is concluded that the three methods of analysis of the AR by 99mTc-sestamibi SPET imaging showed comparable performance and good reproducibility using the same cut-off level. The location of perfusion defect does not affect the comparability of the three techniques. We suggest the use of a cut-off level of 60% for all three methods in the assessment of the AR by 99mTc-sestamibi SPET imaging.
Angioplasty, Balloon, Coronary↗
Hyperinsulinemia, family history of hypertension, and essential hypertension.
The aim of this study was the evaluation of the relationships among hyperinsulinemia, a family history of hypertension, and essential hypertension. Insulin and C-peptide responses to an oral glucose load were studied in 175 lean normotensives (N) and untreated hypertensives (H) with (F+) and without (F-) a family history of hypertension: 30 NF-, 30 NF+, 45 HF-, and 70 HF+. The groups were comparable for age, sex, body mass index, and blood pressure. The following parameters were evaluated: plasma glucose (G), serum insulin (I), and C-peptide (Cp) before and 30, 60, 90, and 120 min after the glucose load, fasting glucose/insulin ratio (ISI), fasting insulin/C-peptide ratio (I/Cp), and 24-h ambulatory blood pressure monitoring. Plasma glucose was measured, fasting and during the test, and it and I/Cp were similar in the four groups. Serum insulin and Cp, both fasting and stimulated, were significantly higher and ISI lower in normotensives and hypertensives with hypertensive parents. Grouping the subjects first on the basis of blood pressure and then on the basis of family history, no differences were found between normotensives and hypertensives, whereas I and Cp, fasting and stimulated, were significantly higher and ISI lower in subjects with positive as compared to negative family history. The closest correlations between insulin and ambulatory blood pressure were found in normotensive with hypertensive parents; in hypertensives with hypertensive parents we only found a direct correlation between fasting Cp and nocturnal blood pressure fall; in hypertensives with normotensive parents insulin inversely correlated with nocturnal blood pressure fall. Insulin resistance seems to have a familial basis, independently of the presence of hypertension. Instead of showing a causal relationship between insulin resistance and hypertension, our results indicate that the two are partly independent components of a common familial pattern.
Adult↗
Oocyte donation program: pregnancy and implantation rates in women of different ages sharing oocytes from single donor.
OBJECTIVE: To investigate the importance of uterus age as regards of pregnancy, implantation, and abortion rates using the oocyte donation model. DESIGN: Retrospective data analysis of cases where recipients of different ages shared oocytes from single donor. SETTING: A tertiary infertility center. PATIENTS: One hundred fourteen women (21 to 49 years of age) undergoing a total of 114 cycles of oocyte donation were divided into two groups according to age (group A < = or 39 years: group B between 40 and 49 years). INTERVENTIONS: Hormonal replacement therapy was given using increasing doses of 17 beta-E2 (2, 4, and 6 or 8 mg) and either 100 mg of P in oil or 600 mg of micronized P through the vaginal route. MAIN OUTCOME MEASURES: Pregnancy, abortion, and implantation rates. RESULTS: Fifty-seven transfer cycles were performed per age group. Twenty-seven clinical pregnancies were achieved in Group A and 14 in group B, with pregnancy rates (PRs) of 47.3% and 24.5%, respectively. There were four abortions in group A and one in group B, resulting in abortion rates of 14.8% and 7%, respectively. Thirty-four of 137 transferred embryos in group A and 20 of 134 in group B implanted, resulting in implantation rates of 24.8% and 14.9%, respectively. CONCLUSION: This study seems to suggest that there are differences in pregnancy and implantation rates in recipients of different ages because of uterine receptivity. Fertility therefore does not depend merely on oocyte age and quality but also on uterine age.
Adult↗
Fixed versus titrated interferon-alpha 2B in chronic hepatitis C. A randomized controlled multicenter trial. The Swiss Association for the Study of the Liver.
BACKGROUND/AIM: Interferon has become the mainstay of treatment of chronic hepatitis C; however, duration of treatment and dose remain unresolved questions. The present study aimed to compare standard dose interferon with a titrated dose regimen carried out for 1 year. METHODS: This was a randomized, controlled multicenter trial. Patients with chronic hepatitis C were randomly allocated to a control group (n = 30), to a fixed dose group (n = 31) where interferon-alpha 2b 3 MU thrice weekly was given for 1 year or a titrated group (n = 34) where interferon was titrated starting at 5 MU thrice weekly to the lowest dose keeping the patient in remission as assessed by a normal ALT value. Liver biopsies were obtained before and at the end of treatment; in addition, galactose elimination capacity was measured as a measure of cytosolic function. RESULTS: In the control, fixed and titrated groups a complete response was achieved in 2/29, 10/28 and 15/31, respectively (p < 0.001 in favor of treatment, p = n.s. for the two treatments). The corresponding figure for sustained response was 1/29, 5/28 and 6/ 31 (p = n.s). In the titrated group, a complete (sustained) response was achieved with 5 MU in 2 (2), with 4 MU in 1 (0), with 3 MU in 4 (0), with 2 MU in 3 (0) and with 1 MU in 5 (4). Liver biopsy score and galactose elimination capacity improved significantly in responders but not in treatment failures. CONCLUSIONS: Both fixed and titrated dosing of interferon given for 1 year induced virus clearance in only a minority of treated patients. However, in a small number of patients, a complete and sustained response can be achieved with low doses of interferon. Dose titration could be an interesting approach to decreasing the cost and side effects in the treatment of chronic hepatitis C.
Adult↗
Endometrial Evaluation in Asymptomatic Postmenopausal Women by Transvaginal Sonography and Color Flow Doppler
We attempted to correlate transvaginal ultrasound endometrial assessment with histologic and hysteroscopic findings in 910 asymptomatic postmenopausal women. The women all had been postmenopausal for at least 1 year, and had no sonographically documented adnexal masses, no hormone therapy, and no history of uterine bleeding. Endometrial thickness of 5 mm and less was considered normal, and no further investigations were performed. All women with endometrial thickness 8 mm or greater were advised to undergo hysteroscopy and endometrial biopsy if necessary. When endometrial thickness was 6 to 7 mm, hysteroscopy was recommended if irregular endometrial echotexture was observed; otherwise another ultrasound examination within 3 to 6 months was suggested. We observed 83 (9.1%) asymptomatic women with endometrial thickness 8 mm or greater and 77 (8.5%) with a thickness of 6 to 7 mm, in whom a total of 89 hysteroscopies were performed. Three endometrial cancers, 8 hyperplasias, 27 endometrial polyps, and 5 submucosal myomas were detected in those with endometrial thickness of 8 mm or greater. Of the 21 women with endometrial thickness 6 to 7 mm who underwent hysteroscopy, 7 had endometrial polyps, 4 hyperplasia, and 3 submucosal myomas. Based on sensitivity and specificity analyses, an endometrial thickness of 8 or 10 mm in asymptomatic postmenopausal women seems to be an effective cut-off to select candidates for more invasive diagnostic procedures.
Journal Article↗
Effect of beta-carotene on cell cycle progression of human fibroblasts.
The uptake of beta-carotene (BC) and its effect on the cell cycle progression of normal human fibroblasts in primary culture were investigated by using two different delivery methods: exposure to BC solubilized in the organic solvent tetrahydrofuran (THF) or to BC incorporated into dipalmitoylphosphatidylcholine (DPPC) liposomes. Cell cycle progression was evaluated by immunofluorescence detection and flow cytometric analysis of the proliferating cell nuclear antigen (PCNA). In contrast to THF, which induced a marked reduction in the number of cells in S phase and in the extent of PCNA immunolabeling, DPPC liposomes proved to be an effective delivery system that does not interfere with cell proliferation. Cellular uptake of 0.23 nmol/10(6) cells was found after 24 h incubation in BC-containing DPPC liposomes. This value increased to 1.2 nmol/10(6) cells after 72 h. After the first day of incubation, the number of cells in S phase was reduced by approximately 50%, with a consequent accumulation of cells in G1 phase. This effect was maintained up to 3 days incubation, with no detectable effects on cell viability. This cell cycle delay was found to be reversible, returning the percentage of cells in S phase to the control value 24 h after removal of BC from the medium. In order to determine whether the activity of BC could be attributed to the molecule itself or to its conversion into retinoids, the production of BC metabolites was assessed. Analysis of cellular levels of retinoids failed to demonstrate the presence of retinal, retinol, retinoic acid or retinyl esters during an incubation period of 6 days. These results suggest that in normal human fibroblasts, BC induces a cell cycle delay in the G1 phase and that this effect is independent of conversion to known retinoids.
1,2-Dipalmitoylphosphatidylcholine↗
Oocyte donation programme: results obtained with intracytoplasmic sperm injection in cases of severe male factor infertility or previous failed fertilization.
Intracytoplasmic sperm injection was carried out in 15 oocyte donation cycles of 15 infertile couples where oocytes had failed to fertilize after in-vitro fertilization (IVF) procedures or where the male partner had severe male factor infertility. A total of 62 oocytes were donated, but only 46 of these, in metaphase II, were injected. Of the injected oocytes, 31 (67.3%) had two pronuclei the morning after the injection procedure. On the following day, 29 embryos were obtained (93% of the fertilized oocytes) and 25 were transferred. Two patients were not successful and consequently did not undergo embryo transfer. A total of five clinical pregnancies were obtained, giving pregnancy rates of 33.3 and 38.4% per started cycle and embryo transfer respectively.
Adult↗
Post-infantile giant cell hepatitis in patients with primary sclerosing cholangitis and autoimmune hepatitis.
In post-infancy, multinucleated giant cell hepatitis is rare. Various conditions and diseases associated with post-infantile giant cell hepatitis have been described, but the pathogenesis remains unknown. In this paper we review the case reports of four patients (3 male, 1 female; aged 22 to 32 years) with primary sclerosing cholangitis and autoimmune hepatitis. The follow-up ranges from five to seven years. All patients showed cholestasis and repeated elevation of hepatic transaminases. Patients with viral infections, metabolic disorders and toxic influences were excluded. Histopathology of liver tissue in all four patients revealed giant cell formation with up to 20 nuclei in 20-70% of all hepatocytes. Post-infantile giant cell hepatitis was defined histopathologically. The clinical course of all four patients markedly improved after immunosuppressive treatment. Further improvement was observed with the addition of ursodeoxycholic acid. Follow-up liver biopsies during treatment showed reduced inflammation and a decreased number of giant cells. One patient, who initially was admitted to the hospital with liver cirrhosis died five years later due to a sepsis. The clinical course of the other three patients remained stable during the observation period, and no progression of liver fibrosis was recorded as long as immunosuppressive treatment was continued. Cholestasis and autoimmunity seem to be two important mechanisms triggering hepatic giant cell formation in post-infancy. In the reported cases long-lasting cholestasis in primary sclerosing cholangitis together with features of autoimmune hepatitis seem to have triggered the formation of syncytial hepatic giant cells.
Adrenal Cortex Hormones↗
Bombesin enhances monocyte and macrophage activities: possible role in the modulation of local pulmonary defenses in chronic bronchitis.
Increased lung levels of bombesin-related peptides (BRPs) have been described in smokers and in patients with chronic obstructive pulmonary diseases (COPDs). Moreover, previous studies have shown that BRPs are endowed with immunoregulatory activities. The aim of the present study was to assess the in vitro influence of synthetic bombesin on the activity of mononuclear phagocytes obtained from healthy donors and from COPD patients. Bombesin significantly enhanced in vitro phagocytosis of monocytes and alveolar macrophages in both groups of subjects, restoring deficient phagocytosis in a group of COPD patients. Moreover, bombesin stimulated superoxide anion production and interleukin-8 release by peripheral monocytes.
Aged↗
Soluble or bound laminin elicit in human neuroblastoma cells short- or long-term potentiation of a K+ inwardly rectifying current: relevance to neuritogenesis.
Changes in the resting potential (VREST) and in the underlying ionic conductances were measured by the patch-clamp technique in SH-SY5Y human neuroblastoma cells exposed to substrate-bound or soluble Laminin (bLN; sLN), as compared to integrin-independent substrates (polylysine (PL); bovine serum albumin (BSA)). While PL and BSA were ineffective, both forms of LN caused an early (5-15 min) activation of a peculiar type of Inwardly Rectifying K+ current (IIR) characterised by a voltage-dependent inactivation in the range of membrane potentials around -50/0 mV. IIR was blocked by Cs+ ions and by the antiarrhythmic drug E-4031, a specific inhibitor of the HERG-codified channels. In cells adherent to bLN, IIR potentiation (85%) persisted for 90-120 min and was accompanied by a similar, but transient, increase in the leakage conductance (GL). Successively, the persistence of a high IIR conductance and the decrease of GL progressively bring VREST from -12 to approximately -30 mV in about 120 min. On the other hand, in cells adherent to PL, exposure to sLN produced a similar but not persistent activation of IIR, without any increase in GL: this caused a rapid, transient hyperpolarisation of VREST. The effects of bLN and sLN were mimicked by antibodies raised against the integrin beta 1 subunit, suggesting a specific integrin-mediated mechanism. In fact, when bound to the culture dishes, these antibodies simultaneously activated the IIR and GL, whereas in soluble form they only activated IIR. Cells adherent to bLN emitted neurites, a process impaired by the block of IIR by E-4031 and Cs+. On the whole data suggest that the integrin-mediated activation of IIR plays a crucial role in the commitment to neuritogenesis of neuroblastoma cells, independently on the effects of this activation on VREST.
Cell Adhesion↗
[Role of hepatotropic viruses in liver pathology in Southwestern Cameroon].
Between 1990 and 1992 (2 years), 102 patients with clinical liver pathology underwent standardized clinical, pathological, sonographic and serologic investigations (HAV, HBV, HCV, HDV autoantibodies and tumor markers). During the same period seroepidemiological studies with the same parameters as above were performed on the following control groups: healthy pregnant women (n = 383), blood donors (n = 85), HIV-positive individuals (n = 93), and hospitalized patients in all age groups with minor ailments unrelated to liver pathology (n = 108). The results are discussed in detail. Virtually all adults had HAV infection. HBV and HCV infection appears to play a major role in chronic liver pathology in southern Cameroon. The two infections frequently occur together (over 40% of liver cases) and correlate significantly with liver cirrhosis. The marked prevalence of HBV and HCV markers in healthy pregnant women is of epidemiological concern due to the potential for vertical transmission of the infection (immunization). Endemic infections such as falciparum malaria are probably responsible for unspecific stimulation of the immune system, which is reflected in a generally marked prevalence of autoimmune markers in liver patients and controls, since histologically there was no evidence of autoimmune liver disease.
Abdomen↗
A novel inward-rectifying K+ current with a cell-cycle dependence governs the resting potential of mammalian neuroblastoma cells.
1. Human and murine neuroblastoma cell lines were used to investigate, by the whole-cell patch-clamp technique, the properties of a novel inward-rectifying K+ current (IIR) in the adjustment of cell resting potential (Vrest), which was in the range -40 to -20 mV. 2. When elicited from a holding potential of 0 mV, IIR was completely inactivated with time constants ranging from 13 ms at -140 mV to 4.5 s at -50 mV. The steady-state inactivation curve (h(V)) was found to be independent of [Na+]o and [K+]o (2-80 mM) and could be fitted to a Boltzmann curve with a steep slope factor of 5-6, and a V1/2 around Vrest. Divalent ion-free extracellular solutions shifted h(V) to the left by about 28 mV. 3. Peak chord conductance, whose maximal value was approximately proportional to the square root of [K+]o, could be fitted to a Boltzmann curve independently of [K+]o, with a V1/2 value around -48 mV and a slope factor of 18. Extracellular Cs+ and Ba2+ blocked the IIR in a concentration- and voltage-dependent manner, but Ba2+ was less effective than it is on classical inward-rectifier channels. 4. Under control culture conditions the values of Vrest and V1/2 of h(V) varied widely among cells. The knowledge of V1/2 proved crucial or the theoretical prediction of Vrest. After cell synchronization in the G0-G1 phase of the cell cycle, or at the G1-S boundaries, the cells reduced their variability of h(V). The same occurred after cell synchronization in G1 by treatment with retinoic acid. 5. The experimental data could be fitted to a classical model of an inward rectifier, after removing the dependence of conductance activation on (V-EK), and incorporating an inactivation with an intrinsic voltage dependence. Moreover, the model predicts, for this novel inward rectifier and in contrast with the classical inward rectifier, the incapacity of maintaining, in physiological media, a Vrest more negative than -35 to -40 mV, which is an important feature of cancer cells.
Cells, Cultured↗
[Does serum HCV-RNA-positive hepatitis C differ from serum HCV-RNA-negative hepatitis C?].
Viral RNA is detectable in the serum of the majority but not all patients with chronic hepatitis C. Whether the viremic form differs from the non-viremic form of the disease is unknown. We therefore compared histology (modified Knodell score) and liver function (conventional liver function tests, galactose elimination capacity and aminopyrin breath test) of viremic (n = 45) and non-viremic (n = 37) patients with chronic hepatitis C. Neither the total histologic score, nor any of the individual histologic parameters assessed differed significantly in serum HCV RNA positive and negative patients. Compared to non-viremic subjects, patients with detectable HCV RNA in serum had slightly higher transaminases (p = ns), lower serum albumin (p < 0.05) and decreased galactose elimination capacity (p < 0.05). This trend towards more severe functional hepatic impairment in serum HCV RNA positive patients persisted when cirrhotics and non-cirrhotics were analyzed separately; it fell just short of reaching statistical significance, however, most probably due to the small number of subjects per patient group. The median age of serum HCV RNA positive cirrhotics was 17 years, and that of serum HCV RNA negative cirrhotics 22 years higher than that of the respective non-cirrhotics. Biochemical (transaminases) and histological (intralobular and piece-meal necrosis) markers of disease activity, as well as metabolic functional reserve (aminopyrin breath test, galactose elimination capacity) and histologic severity of fibrosis correlated only loosely (Rs = 0.24-0.56), albeit significantly (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
An inward rectifier K+ current modulates in neuroblastoma cells the tyrosine phosphorylation of the pp125FAK and associated proteins: role in neuritogenesis.
The relationships between the integrin-mediated activation of inward rectifyier K+ channels (KIR), the phosphorylation of pp125FAK and the rescue of neuritogenesis were studied in 41A3 mouse neuroblastoma cells. Neuritogenesis, elicited by adhesion to FN-enriched substrata, was reversibly impaired by pretreating these cells with the tyrosine kinase inhibitor Herbimycin A. This impairment mimicked that operated by Cs+ ions, which selectively inhibited the integrin-mediated activation of KIR channels. Various phosphotyrosine containing cellular proteins underwent a marked increase upon cell adhesion to FN-coated dishes. This increase was significantly reduced by Cs+ addition. Immunoprecipitation of pp125FAK revealed that the phosphorylation of this kinase and several associated proteins was significantly and reversibly inhibited by Cs+, indicating that integrin-mediated activation of KIR channels is a limiting step upstream to the phosphorylation of pp125FAK in the commitment to neuritogenesis.
Animals↗