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P Macchi

Publications and source records attributed to P Macchi.

At least 19 recordsLinked to original sources
PubMed2001

An evaluation of the brachial plexus block at the humeral canal using a neurostimulator (1417 patients): the efficacy, safety, and predictive criteria of failure.

UNLABELLED: To evaluate the efficacy and safety of the multiple peripheral nerve block technique at the humeral canal (humeral block) with the use of a neurostimulator, we prospectively studied 1417 patients undergoing upper limb surgery with a brachial plexus block at the humeral canal (1468 blocks). The success rate (defined as sensory block [in all nerve distributions] and/or the absence of another anesthetic technique required to allow surgery) was 95%. The threshold of minimal stimulation used to locate each nerve before injecting the anesthetic solution was the unique predictive factor for identified failure. For the median nerve, the threshold was 0.8 mA with a relative risk of failure (RRf: relative risk evaluated by series of Taylor with a 95% confidence interval) = 1.49 (P = 0.04), for the radial nerve the threshold was 0.6 mA (RRf 1.3, P = 0.02), and 0.7 mA for the ulnar nerve (RRf 1.36, P = 0.04). For any equal or higher stimulation level, the risk of failure of the humeral block increased. For the musculocutaneous nerve, we did not observe a significant stimulation threshold for the risk of failure; although beyond 0.7 mA, the RRf was always more than 1.3. Adverse events occurred in 7% of all cases and were usually minor (nausea/vomiting, anxiety, local pain). Our study provides supplementary information on the efficacy and safety of this technique. Stimulation thresholds are clinically identified for the first time as the main factor linked to the failure of a technique using a neurostimulator. We conclude that the humeral block is a reliable peripheral block allowing good success rates results with minor complications, which can be used as an alternative to the axillary block. IMPLICATIONS: We prospectively evaluated the feasibility and the factors causing failure of a peripheral nerve block technique (humeral block) using neurostimulation in a large number of patients. The importance of the level of stimulation for the success of the block was evaluated for the first time.

Adolescent↗
PubMed2000

Interanionic O-H small middle dot small middle dot small middle dotO Interactions: The Charge Density Point of View The Oak Ridge National Laboratory is managed by Lockheed Martin Energy Research Corporation for the US Department of Energy (DE-AC05-96OR22464). Prof. M. Moret and Dr. L. Carlucci are thanked for help in crystallizing large samples suitable for the neutron study. P.M. gratefully acknowledges DANSYNC center under the Danish Natural Science Research Council for a post-doctoral grant.

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Journal Article↗
PubMed1999

[Pt]

The intermediacy of CO/NO substitution in the condensation of [Pt(19)(CO)(22)](4-) into [Pt(38)(CO)(44)](2-) (structure shown) has been demonstrated. Two high-nuclearity carbonyl metal clusters, including one with an unprecedented nitrosyl ligand, have been synthesized and structurally characterized.

Journal Article↗
PubMed1998

Partial respecification of nasotemporal polarity in double-temporal chick and chimeric chick-quail eyes.

In chick embryos, naso-temporal polarity of the retina becomes established before Hamburger-Hamilton stage 10. To examine the plasticity of the early eye anlage, double-temporal eyes were made using stage 10-11 (E1.5) chick embryos and stage 8-9 quail embryos. In vivo and in vitro experiments revealed that these double-temporal compound eyes were not completely temporal but nasal in a large peripheral part of the graft. Four hours after transplantation, the nasal-specific fork head transcription factor CBF1 was not expressed in double-temporal eyes but was clearly detectable 24 h later. This suggests that in the peripheral part of the graft, temporal positional values were changed into nasal positional values by a respecification process.

Animals↗
PubMed1997

Structural and functional basis for JAK3-deficient severe combined immunodeficiency.

Mutations of the Janus family kinase JAK3 have been found to be responsible for autosomal recessive severe combined immunodeficiency (SCID) in humans. We report here the analysis of four new unrelated patients affected by JAK3-deficient SCID. The genetic defects were heterogeneous and included a large intragenic deletion as well as different point mutations, leading to missense substitutions, early stop codons, or splicing defects. We performed a series of studies of the biochemical events induced by cytokines on lymphoblastoid B-cell lines obtained from these patients. Abnormalities in tyrosine phosphorylation of JAK3 in response to interleukin-2 (IL-2) and IL-4 were present in all patients. Accordingly, IL-2-mediated phosphorylation of STAT5 was also absent or barely detectable. On the contrary, in all cases, we could show reduced but clear phosphorylation of STAT6 upon IL-4 stimulation. In one patient carrying a single amino acid change (Glu481Gly) in the JH3 domain of JAK3, we observed partially conserved IL-2 responses resulting in reduced but detectable levels of JAK3 and STAT5 phosphorylation. Interestingly, the patient bearing this mutation developed a substantial number of circulating CD4(+)/CD45RO+ activated T lymphocytes that were functionally impaired. In two cases, patients' cells expressed JAK3 proteins with mutations in the JH2 pseudo-kinase domain. A single cysteine to arginine substitution (Cys759Arg) in this region resulted in high basal levels of constitutive JAK3 tyrosine phosphorylation unresponsive to either downregulation by serum starvation or cytokine-mediated upregulation. The characterization of the genetic defects and biochemical abnormalities in these JAK3-deficient patients will help define the role of JAK3 in the ontogeny of a competent immune system and may lead to a better understanding of the JAK3 functional domains.

B-Lymphocytes↗
PubMed1996

Monocyte function in a severe combined immunodeficient patient with a donor splice site mutation in the Jak3 gene.

Janus kinase-3 (Jak3) is a nonreceptor tyrosine kinase functionally coupled to cytokine receptors which share a "common" gamma chain (gamma c). Mutations in gamma c and Jak3 genes have been identified in X-linked and autosomal severe combined immuno deficiency (SCID), respectively. Jak3 is expressed and activated in myelomonocytic cells. The present study was designed to define the structural alteration responsible for lack of Jak3 in a patient with autosomal SCID and to characterize monocyte function in the absence of this signal transduction element, as well as to establish the whole exon-intron structure. Polymerase chain reaction analysis, performed with primers designed on exon sequences, identified 20 exons spanning approximately 15 kb. These primers, or others designed on the flanking sequences provided in the present report, can be used to amplify the whole gene, allowing the definition of the molecular defects in all cases, including prenatal diagnosis, in which transcript analysis is not possible. On this basis, the deletion transcript found at the homozygous state in patient CM, with both his consanguineous parents being heterozygous for the deletion, was associated with mutation (T to C) of a splice donor site of intron 16 that was also detected in his mother's DNA. Monocytes from Jak3-SCID showed normal cytokine production in response to interleukin-4 (IL-4) (release of IL-1 receptor antagonist) and IL-2 (release of tumor necrosis factor-alpha and IL-8). Lipopolysaccharide-induced cytokine production was also normal and was blocked by IL-4 in Jak3- SCID monocytes. Interferon-gamma induced augmented expression of major histocompatibility class II in Jak3-SCID monocytes. These data indicate that Jak3, expressed and activated in myelomonocytic cells, is dispensable for monocyte differentiation and responsiveness to cytokines that interact with gamma c receptors as well as to other regulatory signals.

Base Sequence↗
PubMed1996

The ZNF75 zinc finger gene subfamily: isolation and mapping of the four members in humans and great apes.

We have previously reported (Villa et al. (1993), Genomics 18: 223) the characterization of the human ZNF75 gene located on Xq26, which has only limited homology (less than 65%) to other ZF genes in the databases. Here, we describe three human zinc finger genes with 86 to 95% homology to ZNF75 at the nucleotide level, which represent all the members of the human ZNF75 subfamily. One of these, ZNF75B, is a pseudogene mapped to chromosome 12q13. The other two, ZNF75A and ZNF75C, maintain an ORF in the sequenced region, and at least the latter is expressed in the U937 cell line. They were mapped to chromosomes 16 and 11, respectively. All these genes are conserved in chimpanzees, gorillas, and orangutans. The ZNF75B homologue is a pseudogene in all three great apes, and in chimpanzee it is located on chromosome 10 (phylogenetic XII), at p13 (corresponding to the human 12q13). The chimpanzee homologue of ZNF75 is also located on the Xq26 chromosome, in the same region, as detected by in situ hybridization. As expected, nucleotide changes were clearly more abundant between human and orangutan than between human and chimpanzee or gorilla homologues. Members of the same class were more similar to each other than to the other homologues within the same species. This suggests that the duplication and/or retrotranscription events occurred in a common ancestor long before great ape speciation. This, together with the existence of at least two genes in cows and horses, suggests a relatively high conservation of this gene family.

Amino Acid Sequence↗
PubMed1996

Partial regression, yet incomplete eradication of mammary tumors in transgenic mice by retrovirally mediated HSVtk transfer 'in vivo'.

Mice transgenic for the activated rat neu oncogene under the control of the mouse mammary tumor virus long terminal repeat (MMTV-LTR) (neu+ mice), develop breast tumors in 100% of cases. We have previously reported that double transgenic mice obtained from crossing neu+ mice with mice transgenic for the herpes simplex virus thymidine kinase (HSVtk) gene can be used as a suitable model to test the 'suicide gene' strategy for mammary tumor gene therapy in vivo. In the present study, we evaluated the efficacy of the HSVtk/ganciclovir (GCV) system in the neu+ mice by inoculating cells producing a retroviral vector bearing the HSVtk gene in the mammary tumors on one side of the animals, and comparing their weight with that of the contralateral tumors, after systemic GCV administration. A statistically significant effect of this therapy was clearly seen (P < 0.001) but complete eradication of the tumors could not be achieved. This was not due to the inefficient delivery of GCV, as no HSVtk expression was detected in the residual tumors, but could be related to the low transduction efficiency (< 10%) and to inability of the 'bystander effect' (probably due to the absence of functional gap-junctions among mammary tumor cells) to kill nontransduced neoplastic cells. These data suggest that results obtained by in vivo models using transplanted tumor cell lines as targets for gene therapy might not be immediately transferable to spontaneously arising tumors in animals or humans.

Adenocarcinoma↗
PubMed1995

Mutations of Jak-3 gene in patients with autosomal severe combined immune deficiency (SCID).

Severe combined immune deficiency (SCID) represents a heterogenous group of hereditary diseases. Mutations in the common gamma-chain (gamma c), which is part of several cytokine receptors including those for interleukin (IL)-2, IL-4, IL-7, IL-9 and IL-15, are responsible for X-linked SCID, which is usually associated with a lack of circulating T cells and the presence of B lymphocytes (T- B+ SCID). The gene(s) responsible for autosomal recessive T- B+ SCID is still unknown. The Jak-3 protein kinase has been found to associate with the gamma c-chain-containing cytokine receptors. Therefore Jak-3 or other STAT proteins with which it interacts are candidate genes for autosomal recessive T- B+ SCID. Here we investigate two unrelated T- B+ SCID patients (both from consanguineous parents) who have homozygous mutations in the gene for Jak-3. One patient carries a mutation (Tyr100-->Cys) in a conserved tyrosine residue in the JH7 domain of Jak-3 which is absent in more than 150 investigated chromosomes. The other patient carries a homozygous 151-base-pair deletion in the kinase-like domain, leading to a frameshift and premature termination. Both mutations resulted in markedly reduced levels of Jak-3. These findings show that abnormalities in the Jak/STAT signalling pathway can account for SCID in humans.

B-Lymphocytes↗
PubMed1995

The genomic organization of the human transcription factor 3 (TFE3) gene.

We have determined the exon-intron structure of the human TFE3 gene located on Xp11.22-23. By designing PCR primers, we were able to amplify various segments of the TFE3 genomic region, thus establishing that this gene is composed of seven exons, the first six of which are small (from 56 to 159 nt). The 5' UT region is contained entirely in the first exon, while the 3' UT region is contained in the seventh exon. The comparison of the genomic and the published cDNA versions revealed that the deduced amino acid sequence of TFE3 in the C-terminus region is 125 amino acids shorter than previously reported. This eliminates most of the putative proline- and arginine-rich domain and makes the human sequence more similar to its mouse homolog. The activation domain at the N-terminus is contained in exon 2, as has been described for the mouse. The basic helix-loop-helix (BHLH) motif is spread over exons 4 to 6, while the leucine zipper (LZ) is almost all contained in the last portion of exon 6. This split BHLH is different from other BHLH-LZ genes whose genomic structures have been determined up to now.

Animals↗
PubMed1995

X-linked thrombocytopenia and Wiskott-Aldrich syndrome are allelic diseases with mutations in the WASP gene.

X-linked thrombocytopenia (XLT) is a rare recessive hereditary disorder characterized by isolated thrombocytopenia with small-sized platelets. The XLT locus has been located to chromosome Xp11 by linkage analysis, which is also where the recently cloned Wiskott-Aldrich syndrome (WAS) gene, maps. The relationship between XLT and WAS has long been debated; they might be due to different mutations of the same gene or to mutations in different genes. We now show that mutations in the WAS gene, different from those found in WAS patients, are present in three unrelated male patients with isolated thrombocytopenia and small-sized platelets. Our results demonstrate that XLT and WAS are allelic forms of the same disease, but the causes of the differences need to be further investigated.

Alleles↗
PubMed1995

Local regression of breast tumors following intramammary ganciclovir administration in double transgenic mice expressing neu oncogene and herpes simplex virus thymidine kinase.

Females from a mouse lineage transgenic for the activated rat neu oncogene under the control of the mouse mammary tumor virus (MMTV) long terminal repeat (LTR) all develop breast tumors with high reproducibility within the first 2-3 months of life. These animals were crossed with mice from a lineage transgenic for the herpes simplex virus thymidine kinase gene (HSVtk) under the control of its own promoter and polyoma enhancer. Double transgenic mice (for both neu and tk) developed breast neoplasias with the same kinetics as the neu-only mice. Tumor-bearing double transgenic mice, treated intratumorally with the antiviral agent ganciclovir (GCV), showed an inhibiting effect on tumor growth. However, this effect was not seen either on GCV-treated neu-only transgenic mice or on saline-injected controls. This suggests that tk-engineered breast tumors are susceptible to GCV administered locally, and implies that neu-mice could be a useful model for testing the effectiveness of HSVtk-bearing vectors followed by systemic GCV on breast cancer cells.

Animals↗
PubMed1995

Characterization of nine novel mutations in the CD40 ligand gene in patients with X-linked hyper IgM syndrome of various ancestry.

X-linked immunodeficiency with hyper-IgM (HIGMX-1) is a rare disorder caused by defective expression of the CD40 ligand (CD40L) by activated T lymphocytes, resulting in inefficient T-B cell cooperation and failure of B cells to undergo immunoglobulin isotype switch. In the present work, we describe nine patients of various ancestry who bear different mutations in the X chromosome-specific CD40L gene. Two of the mutations were nonsense mutations, one each resulting in premature stop codons at amino acid residues 39 and 140. Three patients had single point missense mutations, one each at codons 126, 140, and 144. Another patient had a 4-bp genomic deletion in exon 2, resulting in a frameshift and premature termination. Three patients showed insertions, one each of 1, 2, and 4 nt, probably because of polymerase slippage, resulting in frameshift mutation and premature termination. Overall, these observations confirm the heterogeneity of mutations in HIGMX-1. However, the identification of two patients whose mutation involves codon 140 (previously shown to be altered in two other unrelated subjects) suggests that this may be a hotspot of mutation in HIGMX-1. In two additional patients with clinical and immunological features indistinguishable from canonical HIGMX-1, no mutation was detected in the coding sequence, in the 5' flanking region, or in the 3' UTR.

Base Sequence↗
PubMed1983

[Adsorption of insulin directly added to infusion bottles].

A study of insulin adsorption to infusion system was undertaken in the situation of direct addition of insulin alone in the infusion bottles, with use of 125I-labelled insulin and non labelled insulin. The infusion solutions tested were glucose solutions (5, 10, 15 and 30%). There is an important adsorption of insulin (75%) to the infusion system when the insulin concentration in the solution is low. The effluent insulin is not degraded. The glucose content of the solution does not influence the phenomenon. Adsorption of insulin decreases when the insulin concentration in the solution is increased and a plateau is reached starting from an insulin concentration in the solution of about 400 ng/ml; at higher concentrations, 80 to 90% of insulin that has been initially put in the bottle is recovered. Since the insulin concentrations in the solutions used in clinical practice are higher than 400 ng/ml, this adsorption phenomenon can be neglected and therefore can explain the efficiency of this mode of insulin-therapy. Kinetics of effluent insulin is a plateau, stable all along the infusion. Thus, direct addition of insulin alone into infusion bottles is an efficient and controlled mode of insulin-therapy if a minimal insulin concentration in the infused solution has been reached.

Adsorption↗
PubMed1983

[Adsorption of insulin introduced directly into perfusion bottles].

A study of insulin adsorption to infusion system was undertaken in the situation of direct addition of insulin alone in the infusion bottles, with use of 125I-labelled insulin and non labelled insulin. The infusion solutions tested were glucose solutions (5, 10, 15 and 30%). There is an important adsorption of insulin (75%) to the infusion system when the insulin concentration in the solution is low. The effluent insulin is not degraded. The glucose content of the solution does not influence the phenomenon. Adsorption of insulin decreases when the insulin concentration in the solution is increased and a plateau is reached starting from an insulin concentration in the solution of about 400 ng/ml; at higher concentrations, 80 to 90% of insulin that has been initially put in the bottle is recovered. Since the insulin concentrations in the solutions used in clinical practice are higher than 400 ng/ml, this adsorption phenomenon can be neglected and therefore can explain the efficiency of this mode of insulin-therapy. Kinetics of effluent insulin is a plateau, stable all along the infusion. Thus, direct addition of insulin alone into infusion bottles is an efficient and controlled mode of insulin-therapy if a minimal insulin concentration in the infused solution has been reached.

Adsorption↗