Search PubMed⌕ Search

Biomedical subjects

L Castellani

Publications and source records attributed to L Castellani.

At least 37 records · Page 2Linked to original sources
PubMed1997

Complex genetic control of HDL levels in mice in response to an atherogenic diet. Coordinate regulation of HDL levels and bile acid metabolism.

Inbred strains of mice differ in susceptibility to atherogenesis when challenged with a high fat, high cholesterol diet containing 0.5% cholic acid. Studies of recombinant inbred (RI) strains derived from the susceptible strain C57BL/6J (B6) and the resistant strains C3H/HeJ (C3H) and BALB/cJ have revealed an association between fatty streak lesion size and a decrease in high density lipoprotein (HDL) levels on the diet. To better understand the genetic factors contributing to HDL metabolism and atherogenesis in response to the diet, we studied mice derived from an intercross between B6 and C3H using a complete linkage map approach. A total of 185 female progeny were typed for 134 genetic markers spanning the mouse genome, resulting in an average interval of about 10 cM between markers. A locus on distal chromosome 1 containing the apolipoprotein AII gene was linked to HDL-cholesterol levels on both the chow and the atherogenic diets, but this locus did not contribute to the decrease in HDL-cholesterol in response to the diet. At least three distinct genetic loci, on chromosomes 3, 5, and 11, exhibited evidence of linkage to a decrease in HDL-cholesterol after a dietary challenge. Since a bile acid (cholic acid) is required for the diet induced changes in HDL levels and for atherogenesis in these strains, we examined cholesterol-7-alpha hydroxylase (C7AH) expression. Whereas B6 mice exhibited a large decrease in C7AH mRNA levels in response to the diet, C3H showed an increase. Among the intercross mice, multiple loci contributed to the regulation of C7AH mRNA levels in response to the diet, the most notable of which coincided with the loci on chromosomes 3, 5, and 11 controlling HDL levels in response to the diet. None of these loci were linked to the C7AH structural gene which we mapped to proximal chromosome 4. These studies reveal coordinate regulation of C7AH expression and HDL levels, and they indicate that the genetic factors controlling HDL levels are more complex than previously suggested by studies of RI strains. Furthermore, we observed that two of the loci for C7AH expression contributed to differences in gallstone formation between these strains.

Animals↗
PubMed1997

Ruptured abdominal aortic aneurysm. A ten year experience.

METHODS: During the last ten years, 84 patients treated for ruptured infrarenal aortic aneurysm have been reviewed to evaluate complications and mortality rates, to determine which factors influenced these rates and to identify the means to improve these results. RESULTS: The intraoperative mortality and the overall mortality rates were respectively 21.4% and 57%. The factors which influenced hospital mortality were analyzed. The most important factors were the age, the depth of the initial shock, the volume of blood transfused and the location of rupture. CONCLUSIONS: These factors cannot be controlled by the surgeon and it should be noted that a significant reduction of the mortality rate may be very difficult or even impossible to achieve. These findings support the concept of aggressive elective resection of abdominal aortic aneurysms.

Aged↗
PubMed1997

Classification of the subclavian steal syndrome with transcranial Doppler.

Ultrasound has provided a highlight of the different types of subclavian steal. The authors report epidemiological and clinical data concerning 40,000 ultrasound examinations performed on epiaortic arteries and particularly the last 12,000 in which Doppler c.w., duplex scanner and transcranial Doppler were used. Various types of steal are described; five types of subclavian steal have been classified and patients stratified as being symptomatic and asymptomatic. The neurological symptoms are divided as follows: generalized cerebral ischemia, vertebro-basilar ischemia and hemispheric ischemia. Based on this clinical and haemodynamic outline, surgical therapy is indicated and type of surgery suggested.

Carotid Arteries↗
PubMed1996

Use of red blood cell transfusions in terminally ill cancer patients admitted to a palliative care unit.

Anemia is often associated with neoplastic disorders. Blood transfusions are used to alleviate the discomfort of anemic cancer patients. Of 246 terminally ill cancer patients admitted to our palliative care unit from October 1991 to December 1993 (128 women and 118 men), 31 patients (12.6%) (17 men and 14 women; age, 69.5 +/- 12 years) received on average 2.8 units of packed red blood cells (PRBCs) (range, 2-7 units/patient) in 35 separate admissions. PRBCs were transfused in the presence of low hemoglobin (Hb) levels ( < or = 8 g/dL) and/or severe fatigue or dyspnea. Pre-transfusion performance status, cognitive function, dyspnea, and fatigue at rest (evaluated by a four-point scale), complete blood count, serum albumin, and C-reactive protein were determined. The day after transfusion, subjective well-being was recorded as "yes/no" improvement in comparison with the pre-transfusion day. Improved subjective well-being after blood transfusion was reported in 51.4%, without significant relationship to pre-transfusion Hb levels or performance status. The influence of blood transfusion on subjective well-being was not related to the severity of dyspnea or fatigue. Twenty-one patients (60%), including seven with subjective improvement, died during the same hospitalization, a median of 49 days after transfusion. Pre-transfusion Hb level did not differ significantly in patients who benefited and did not benefit from transfusion, whereas time before death was significantly (P < 0.001) shorter in patients who did not benefit. In the discharged patients (40%), the median interval between transfusion and discharge was 13 days and the frequency of subjective improvement in well-being was 78.6%. Our data suggest that two main areas should be investigated, namely the relation between low Hb levels and symptoms and signs in terminally ill cancer patients, and the correct timing for effective blood transfusion. A combination of criteria is needed for effective transfusion; they must include not only Hb levels but also type and severity of anemic symptoms and signs. Furthermore, the identification of reliable prognostic indicators for survival would be useful.

Aged↗
PubMed1996

Remodeling of cytoskeleton and triads following activation of v-Src tyrosine kinase in quail myotubes.

To study the cellular signals underlying the regulatory mechanisms involved in maintenance of sarcomeric integrity, we have used quail skeletal muscle cells that reach a high degree of structural maturation in vitro, and also express a temperature-sensitive mutant of the v-Src tyrosine kinase that allows the control of differentiation in a reversible manner. By immunofluorescence and electron microscopy we show that v-Src activity in myotubes leads to an extensive cellular remodeling which affects components of the sarcomeres, the cytoskeleton network and the triad junctions. We have previously shown that activation of v-Src causes a selective dismantling of the I-Z-I segments coupled to the formation of aggregates of sarcomeric actin, alpha-actinin and vinculin, called actin bodies. We now show that intermediate filaments do not participate in the formation of actin bodies, while talin, a component of costameres, does. The I-Z-I segments are completely dismantled within 24 hours of v-Src activity, but the A-bands persist for a longer time, implying distinct pathways for the turnover of sarcomeric subdomains. Immunofluorescence labeling of markers of the triad junctions demonstrates that the localization of the alpha 1 subunit of the dihydropyridine receptor is disrupted earlier than that of the ryanodine receptor after tyrosine kinase activation. Furthermore, the location of junctional sarcoplasmic reticulum and transverse tubule membranes is maintained in myotubes in which the I-Z-I have been removed and the regular disposition of the intermediate filaments is disrupted, supporting a role for sarcoplasmic reticulum in the proper positioning of triad junctions. Altogether these results point to a tyrosine kinase signaling cascade as a mechanism for selectively destabilizing sarcomere subdomains and their tethering to the cytoskeleton and the sarcolemma.

Actins↗
PubMed1995

Maintenance of the differentiated state in skeletal muscle: activation of v-Src disrupts sarcomeres in quail myotubes.

We have used quail skeletal myotubes expressing a temperature-sensitive allele of the v-src oncogene to address the issue of the homeostasis of sarcomeric myofibrils in differentiated muscle cells. Reactivation of the v-Src tyrosine kinase by shifting the cultures to the permissive temperature leads within minutes to the formation of F-actin-containing bodies (ABs), that originate in the ventral region of the myotubes and increase in number concomitantly with the dismantling of the I-Z-I complex of the sarcomeres. This process is detailed by confocal and electron microscopy. Indirect immunofluorescence reveals that ABs contain muscle-specific protein isoforms associated with the I-Z-I complexes and vinculin, a component of the cytoskeletal network. Anti-phosphotyrosine antibodies label proteins in ABs and Z-discs. Evidence is presented indicating that this phenomenon specifically depends on the persistent activation of v-Src, rather than on a general increase in phosphotyrosine content such as that induced by vanadate. AB formation is prevented by activation of protein kinase C by phorbol ester or by treatment with the kinase inhibitor 2-aminopurine, without any detectable effect on tyrosine phosphorylation. Taken together these findings indicate that phosphorylation of specific target proteins by v-Src, although necessary, is not sufficient per se to induce AB formation. In addition, the signal transduction cascade that culminates in MAP kinase activation and its nuclear translocation is activated both by v-Src and phorbol ester, and is relatively unaffected by 2-aminopurine. These findings imply that both phorbol esters and 2-aminopurine operate, at least in part, at the level of alternative pathways that may diverge upstream of the MAP kinase and are presumably mediating the early effects of v-Src on the differentiated phenotype.

Actins↗
PubMed1994

Dystrophin is not essential for the integrity of the cytoskeleton.

Dystrophin is localized, in normal muscle fibers, on the cytoplasmic surface of the sarcolemma. The function of this protein is not known but, according to its structure and intracellular distribution, it seems likely that dystrophin interacts with other cytoskeletal proteins to form a complex linkage between myofibrils, sarcolemma and extracellular matrix. To evaluate the possibility that dystrophin deficiency induces, per se, a disarray in the cytoskeleton, we studied three components of this structure in muscle fibers of the dystrophic mdx mouse in a phase preceding the onset of necrosis. Vinculin, abundant in sarcolemmal structures called costameres, desmin, the principal component of intermediate filaments and nebulin, constituent of the so-called "third filament" within the sarcomere, were stained with the indirect immunofluorescence technique in cryostat sections. The same monoclonal antibodies were used in Western blots of proteins extracted from the same muscles. No difference was observed in the distribution or in the relative abundance of the three proteins, comparing muscles from 18 day-old mdx and control mice. Our results indicate that the lack of dystrophin does not induce, per se, alterations in the structures linking the sarcolemma to the contractile apparatus. It is likely that the structural damage in dystrophin-less muscle fibers is initially confined to limited portions of the plasma membrane. These focal lesions, impairing intracellular calcium homeostasis, can lead to muscle fiber necrosis.

Animals↗
PubMed1994

Glutamate-induced protein phosphorylation in cerebellar granule cells: role of protein kinase C.

Protein phosphorylation in response to toxic doses of glutamate has been investigated in cerebellar granule cells. 32P-labelled cells have been stimulated with 100 microM glutamate for up to 20 min and analysed by one and two dimensional gel electrophoresis. A progressive incorporation of label is observed in two molecular species of about 80 and 43 kDa (PP80 and PP43) and acidic isoelectric point. Glutamate-stimulated phosphorylation is greatly reduced by antagonists of NMDA and non-NMDA glutamate receptors. The effect of glutamate is mimicked by phorbol esters and is markedly reduced by inhibitors of protein kinase C (PKC) such as staurosporine and calphostin C. PP80 has been identified by Western blot analysis as the PKC substrate MARCKS (myristoylated alanine-rich C kinase substrate), while antibody to GAP-43 (growth associated protein-43), the nervous tissue-specific substrate of PKC, failed to recognize PP43. Our results suggest that PKC is responsible for the early phosphorylative events induced by toxic doses of glutamate in cerebellar granule cells.

Animals↗
PubMed1994

Rupture of pancreaticoduodenal artery aneurysm in duodenum. Report of a case.

We report the case of a 74 year-old woman presenting a rupture in the duodenum of pancreaticoduodenal artery aneurysm treated with success by an aorto-mesenteric by-pass and ligature of gastroduodenal artery. The pancreaticoduodenal artery is an uncommon aneurysmal localization; surgical treatment of which is often difficult on account of the proximity of the pancreatic parenchyma and arteriography is essential to guide the surgical procedure.

Aged↗
PubMed1994

[Pancreatic-duodenal artery aneurysm ruptured in the digestive tube. Report of a case].

We report the successful treatment of an aneurysm of the pancreatoduodenal artery which ruptured into the duodenum in a 78-year-old patient. The pancreatoduodenal arcades were excluded by aorto-mesenteric bypass and ligature of the gastroduodenal artery. Aneurysm are rarely located in pancreatoduodenal artery. Surgical repair is often difficult due to the close relations with the pancreatic parenchyma. Arteriography is essential to guide the operation.

Aged↗
PubMed1993

Mini-titins in striated and smooth molluscan muscles: structure, location and immunological crossreactivity.

Invertebrate mini-titins are members of a class of myosin-binding proteins belonging to the immunoglobulin superfamily that may have structural and/or regulatory properties. We have isolated mini-titins from three molluscan sources: the striated and smooth adductor muscles of the scallop, and the smooth catch muscles of the mussel. Electron microscopy reveals flexible rod-like molecules about 0.2 micron long and 30 A wide with a distinctive polarity. Antibodies to scallop mini-titin label the A-band and especially the A/I junction of scallop striated muscle myofibrils by indirect immunofluorescence and immuno-electron microscopy. This antibody crossreacts with mini-titins in scallop smooth and Mytilus catch muscles, as well as with proteins in striated muscles from Limulus, Lethocerus (asynchronous flight muscle), and crayfish. It labels the A/I junction (I-region in Lethocerus) in these striated muscles as well as in chicken skeletal muscle. Antibodies to the repetitive immunoglobulin-like regions and also to the kinase domain of nematode twitchin crossreact with scallop mini-titin and label the A-band of scallop myofibrils. Electron microscopy of single molecules shows that antibodies to twitchin kinase bind to scallop mini-titin near one end of the molecule, suggesting how the scallop structure might be aligned with the sequence of nematode twitchin.

Animals↗
PubMed1993

Concentration-dependent effects of eicosapentaenoic acid on very low density lipoprotein secretion by the isolated perfused rat liver.

The effects of increasing concentrations of eicosapentaenoic acid (20:5n-3; EPA) and oleic acid (18:1n-9; OA) on esterification to triacylglycerols (TG) and phospholipids (PL), and the relationship to formation and secretion of the very low density lipoproteins (VLDL) were compared in the isolated perfused rat liver. Mixtures of EPA and OA were also studied to determine whether substrate levels of one fatty acid might influence the metabolism of the other. The basal perfusion medium, which contained 30% (vol/vol) washed bovine erythrocytes, 6% (wt/vol) bovine serum albumin (BSA), and 100 mg glucose/dL in Krebs-Henseleit bicarbonate buffer (pH 7.4) was recycled through the liver for 2 h. EPA or OA, as a complex with 6% BSA, was infused at rates of 70, 105, 140 and 210 mumol/h. In other experiments, mixtures of EPA and oleic acid (70 mumol total), with molar percentages of 100, 75, 50, 25 and 0% of each fatty acid were infused per hour. BSA (6%) in the buffer was infused alone and served as the control. At an infusion rate of 70 mumol EPA per hour, hepatic VLDL lipid output was not different from that when fatty acid was not infused (approximately half that when 70 mumol OA/h was infused). However, when larger amounts of EPA and OA were infused individually, rates of VLDL secretion were stimulated to a similar extent with either fatty acid. The apparent inhibitory influence of EPA on TG synthesis and VLDL lipid output when 70 mumol EPA were infused per hour could also be overcome by the presence of as little as 25 mol% OA in a mixture.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Recanalization of occluded superficial femoral arteries using the rotational transluminal angioplasty catheter system (ROTACS).

A total of 85 occluded superficial femoral arteries were treated using the rotational transluminal angioplasty catheter system (ROTACS). The mean length of the occlusions was 7cm; 76% were uncalcified or only slightly calcified whereas 24% were calcified or highly calcified. The mean preoperative ankle:brachial index was 0.51. Primary success was achieved in 62 of 85 cases (73%). The mean length of reperfused occlusions was 6.2 cm: 26% of these lesions were calcified. The mean ankle:brachial index was 0.91. There were 23 primary failures (27%): reperfusion was impossible in 11 cases (including one complicated by perforation) and there were eight dissections, three cases where residual stenosis exceeded 50%, and one other unspecified failure. The mean length of these occlusions was 10.5 cm; 17% were calcified. Two patients developed a distal embolus and one died 10 days after reperfusion. The probability of primary patency of a reperfused artery was 44% at 1 year. Forty-two of the 62 patients who achieved primary success remained symptom free; the mean length of the original occlusion was 4.5 cm. Fifteen patients developed a new area of stenosis whereas five others exhibited new occlusion after a mean interval of 6 months. The mean length of these reperfused arteries was 9 cm. The probability of secondary patency at 1 year was 58%. Arterial calcification did not appear to influence the feasibility of reperfusion using the catheter. The main factor determining successful reperfusion was the length of the occlusal defect (P < 0.05). Reperfusion using the ROTACS did not improve the feasibility of reperfusion by conventional transluminal angioplasty.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

A calcineurin-like phosphatase is required for catch contraction.

The ability of certain molluscan smooth muscles to maintain a prolonged state of contraction, termed 'catch', has been correlated with the activity of a calcineurin-like Ca(2+)-regulated phosphatase. The release of this phosphatase through extensive treatment of fibers with detergent, as shown by Western blots and a calmodulin-binding overlay assay, results in the loss of catch tension maintenance. This effect is reversed by perfusion of the fiber with brain calcineurin. These findings suggest that the activity of the calcineurin-like phosphatase, switched on during the onset of active contraction, plays a critical role in the maintenance of catch.

Animals↗
PubMed1992

Dispositions of junctional feet in muscles of invertebrates.

The structure and disposition of the feet occupying the junctions between sarcoplasmic reticulum (SR) and surface membrane/transverse tubules were studied in muscles from a variety of invertebrates. Feet were imaged by rotary shadowing of isolated junctional SR vesicles and by filtering of micrographs from grazing views of the junction in thin sections. The overall size and shape of invertebrate feet is the same as that of feet in skeletal and cardiac muscle of vertebrates. However, the arrangement of feet in invertebrate muscles differs from that in vertebrates. These findings are discussed in terms of known variations in properties of excitation-contraction coupling of the two phyla.

Animals↗