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Biomedical subjects

M Shapiro

Publications and source records attributed to M Shapiro.

At least 91 records · Page 5Linked to original sources
PubMed1999

Preliminary evaluation of safety and activity of recombinant human interleukin 11 in patients with active Crohn's disease.

BACKGROUND & AIMS: Recombinant human interleukin 11 (rhIL-11) is a cytokine with thrombocytopoietic activity and anti-inflammatory and mucosal protective effects. The objectives of this study were to investigate the safety and tolerability of rhIL-11 in patients with Crohn's disease and to explore the effects of dose and schedule on platelet count and Crohn's disease activity. METHODS: A multicenter, double-masked, placebo-controlled, dose-escalation study of 76 patients with active Crohn's disease was performed. Patients were randomized to receive subcutaneous placebo or rhIL-11 at doses of 5, 16, or 40 microgram. kg-1. wk-1 given 2 or 5 times weekly for 3 weeks. Clinical and laboratory safety data were recorded, and disease activity was measured at each visit. RESULTS: Subcutaneous injection of rhIL-11 generally was well tolerated. Significantly greater increases in platelet counts were found among patients receiving rhIL-11 40 microgram. kg-1. wk-1 as 2 or 5 weekly doses and 16 microgram. kg-1. week-1 as 5 weekly doses compared with patients receiving placebo (P < 0.05). Patients receiving 16 microgram. kg-1. wk-1 had the highest clinical response rates, with a response seen in 42% of patients (5/12) receiving 5 weekly doses and 33% of patients (4/12) receiving 2 weekly doses, compared with 7% of patients (1/15) receiving placebo. CONCLUSIONS: Short-term treatment with rhIL-11 is well tolerated in patients with active Crohn's disease. The thrombocytopoietic effect of rhIL-11 seems to be both dose and schedule dependent and may be minimized with retained clinical benefit in Crohn's disease at 16 microgram. kg-1. wk-1 given in 2 equal doses.

Adult↗
PubMed1999

The distribution of gentamicin in the rabbit cornea following iontophoresis to the central cornea.

The purpose of this study was to evaluate the penetration of gentamicin into the central, midperipheral and peripheral cornea of rabbits following iontophoresis to the central 3 mm of the cornea. Four groups (groups 1-4) of five rabbits (one eye per rabbit) underwent corneal iontophoresis using gentamicin dissolved in agar. Low (1 mg/ml) and high (10 mg/ml) concentrations of gentamicin in agar were used for one or ten minutes. Two control groups (groups 5 and 6) of five eyes each underwent mock iontophoresis with low and high concentrations of agar-gentamicin mixture. Following sacrifice of the rabbits, the central, midperipheral and peripheral parts of each cornea were excised. Gentamicin concentration was determined in each part of every cornea. High concentrations of gentamicin (951.6 +/- 369.4 microg/ml to 26.6 +/- 41.34 microg/ml) were obtained in the central parts of all the iontophoresis-treated corneas. In each group, except group 6, central corneas had higher concentrations of gentamicin compared to midperipheral corneas (p = 0.038 to p = 0.021), and midperipheral corneas had higher levels than peripheral corneas (p = 0.038 to p = 0.021). Following iontophoresis, gentamicin is found in all portions of the corneas; however, the highest concentration of the drug remains in the central cornea.

Analysis of Variance↗
PubMed1999

Spiradenoma arising in a nevus sebaceus of Jadassohn: case report and literature review.

Nevus sebaceus (NS) of Jadassohn is usually a verrucous plaque on the scalp or face that arises secondary to disordered development of epithelial, pilar, sebaceous, and apocrine structures. The emergence of neoplasia is a late stage in the natural history of NS. Although most neoplastic proliferations are benign, several malignant tumors have arisen in this lesion. We describe the first case of a benign spiradenoma arising in an NS on the scalp in a 72-year-old Caucasian woman. Reexcision was recommended to prevent the development of a second neoplastic process and to avoid the rare occurrence of a malignant transformation of the existing neoplasia. The patient declined reexcision and remains under observation. The spectrum of tumors arising in NS are described and are categorized according to behavior. Syringocystadenoma papilliferum is the most commonly observed benign growth, whereas basal cell carcinoma is the most frequently seen malignant process. The signs of tumor development (benign or malignant) within an NS are reviewed, and treatment recommendations are provided. The clinical course of rare and unique aggressive neoplasms originating in NS is summarized.

Adenoma, Sweat Gland↗
PubMed1999

Hydrodynamics of resonance oscillations of columns of inelastic particles.

We study oscillations of a one-dimensional (1D) column of N slightly inelastic particles, produced by a piston vibrating at one end of a closed tube. It is found that for large enough vibrational amplitudes of the piston, the column oscillates periodically with the period equal to the vibrational period. The oscillation patterns are governed by the shock waves propagating across the column. The averaged kinetic energy per particle is shown to be proportional to the square of the vibrational frequency, omega. This energy also strongly depends on the vibrational amplitude. The maximal value of this kinetic energy achievable by these external vibrations is found to be of order omega(2)L(2), where L is the total volume (length) of the tube free of particles. The above results on the column resonance oscillations are also predicted by a 3D hydrodynamic model of an inelastic granular gas.

Journal Article↗
PubMed1999

Epidural steroids for treating "failed back surgery syndrome": is fluoroscopy really necessary?

UNLABELLED: Epidural steroids are commonly administered in the treatment of "failed back surgery syndrome." Because patient response is dependent on accurate steroid placement, fluoroscopic guidance has been advocated. However, because of ever-increasing medical expenditures, the cost-benefit of routine fluoroscopy should be critically evaluated. Therefore, 50 patients were enrolled into this institutional review board-approved, prospective, controlled, single-blinded study. At a predetermined intervertebral level, the epidural space was identified using an air loss of resistance technique. Thereafter, an epidural catheter was inserted 2 cm through the epidural needle. To determine the accuracy of the clinical placement, contrast medium was administered through the epidural catheter; antero-posterior and lateral lumbar spine radiographs were then obtained. The number of attempts required to successfully locate the epidural space, the reliability of the air loss of resistance technique in indicating successful epidural penetration in failed back surgery syndrome, the ability of the clinician to accurately predict the intervertebral space at which the epidural injection was performed, and the spread of contrast medium within the epidural space were recorded. A total of 48 epidurograms were performed. The number of attempts to successfully enter the epidural space was 2 +/- 1. In 44 cases, the radiological studies confirmed the clinical impression that the epidural space had been successfully identified. In three patients, the epidural catheter was in the paravertebral tissue. One myelogram was recorded. In 25 patients, the epidural catheter did not pass through the predetermined intervertebral space. In 35 cases, the contrast medium did not reach the level of pathology. IMPLICATIONS: The clinical sign of loss of resistance is a reliable indicator of epidural space penetration in most cases of "failed back surgery syndrome." However, surface anatomy is unreliable and may result in inaccurate steroid placement. Finally, despite accurate placement, the depot-steroid solution will spread to reach the level of pathology in only 26% of cases.

Adult↗
PubMed1998

Human class I supertypes and CTL repertoires extend to chimpanzees.

Using an in vitro peptide stimulation strategy, two chimpanzees that were acutely infected by the hepatitis B virus (HBV) produced peripheral blood CTL responses to several HBV-encoded epitopes that are known to be recognized by class I-restricted CTL in acutely infected humans. One animal responded to three HBV peptides that, in humans, are restricted by HLA-A2; the other animal responded to three peptides that are restricted by HLA-B35 and HLA-B51, members of the HLA-B7 supertype in man. The peptides recognized by each chimp corresponded with the ability of its class I molecules to bind peptides containing the HLA-A2 and HLA-B7 supermotifs. Similar, apparently class I-restricted CTL responses to some of these peptides were also detected in occasional HBV-uninfected chimps. These results demonstrate that the CTL repertoire overlaps in humans and chimps and that the HLA-A2 and HLA-B7 supertypes extend to the chimpanzee. Based on these results, the immunogenicity and efficacy of vaccines designed to induce CTL responses to human HLA-restricted viral epitopes may be testable in chimpanzees.

Amino Acid Sequence↗
PubMed1998

Cytotoxic lymphocyte gene expression in peripheral blood leukocytes correlates with rejecting renal allografts.

BACKGROUND: We have shown previously that heightened expression of the cytotoxic lymphocyte (CL) effector genes perforin (P), granzyme B (GB), and Fas ligand (FasL), is closely correlated with acute allograft rejection, particularly when two or more target genes are up-regulated. METHODS: We used quantitative reverse transcription-polymerase chain reaction to analyze CL gene expression from peripheral blood leukocytes (PBLs) and renal allograft biopsies in 31 paired samples of PBLs and renal tissue from 25 renal allograft recipients. Our aims were (1) to determine whether the expression of CL gene expression in PBLs correlates with expression of these genes in renal allograft biopsy tissue and (2) to determine whether CL gene expression in PBLs correlates with the histological diagnosis. RESULTS: Coordinate gene expression in PBLs and acutely rejecting allografts was found in 9/11 (82%) for P, 07/11 (64%) for GB, and 10/11 (91%) for FasL. Coordinate absence was found in 15/20 (75%) for P, 17/20 (85%) for GB, and 16/20 (80%) for FasL in nonrejecting allografts. Furthermore, up-regulation of any two genes in PBLs correlated with pathological diagnosis of rejection with excellent positive (100%) and negative (95%) predictive values. CONCLUSION: Coordinate CL gene expression in PBLs and the allograft is usually detected. CL gene expression in PBLs is closely associated with a pathologic diagnosis of rejection. CL gene expression in PBLs may serve as a noninvasive method of monitoring for renal allograft rejection.

Adult↗
PubMed1998

Sequences surrounding the Src-homology 3 domain of phospholipase Cgamma-1 increase the domain's association with Cbl.

SH3 domains are protein modules that interact with proline-rich polypeptide fragments. Cbl is an adapter-like protein known to interact with several SH3 domains, including the PLCgamma1 SH3 domain and the Grb2 amino terminal SH3 domain. Here we explore whether sequences surrounding the PLCgamma1 SH3 domain core sequence (aa.796-851) can affect the binding to Cbl, a target used as a prototypical ligand. Consistent with previous reports, our results demonstrated a weak binding of Cbl to GST fusion proteins that strictly encompass the structural core of the PLCgamma1 SH3 domain but a high-avidity binding to the Grb2 amino-terminal SH3 domain. Inclusion of amino acids immediately flanking the PLCgamma1 SH3 core domain, however, substantially increased binding of Cbl to a level comparable to that of the Grb2 amino-terminal SH3 domain. The interaction of this extended PLCgamma1 SH3 domain fusion protein with Cbl was shown to depend entirely upon the interaction of the domain with a proline-rich motif in Cbl, ruling out the possibility that amino acids adjacent to the core SH3 domain of PLCgamma1 provide independent Cbl binding. These data suggest that sequences surrounding the SH3 domain of PLCgamma1 may contribute to or stabilize the association of the domain with the target protein, thus increasing its binding efficiency.

Binding Sites↗
PubMed1998

Neutropenic enterocolitis as a complication of high dose chemotherapy with stem cell rescue in patients with solid tumors: a case series with a review of the literature.

BACKGROUND: This case series with an accompanying review of the literature describes neutropenic enterocolitis as a complication of high dose chemotherapy with stem cell rescue in patients with solid tumors. METHODS: Neutropenic enterocolitis is documented in two patients undergoing autologous stem cell transplantation. A review of MEDLINE from 1970 to the present was performed to delineate the prior related disease settings in which this condition has been described. The nature of the clinical syndrome and controversies regarding management are discussed. RESULTS: The authors report two patients who each received autologous stem cell transplantation for the treatment of a solid tumor. Both patients presented with progressive abdominal pain, signs of peritoneal irritation on examination, and pneumatosis intestinalis. In the first case, the syndrome developed rapidly over several hours, requiring emergent surgical intervention during the period of postchemotherapy nadir. In the second case, the patient developed a slowly progressive clinical picture that was managed successfully with medical therapy alone. A review of the literature suggests that neutropenic enterocolitis arises due to drug-induced bowel wall mucosal injury followed by superinfection with colonic and opportunistic organisms. Surgical intervention potentially is beneficial in patients who develop an acute syndrome that is unresponsive to antibiotic and supportive therapy. Those patients who can be stabilized with medical management often will recover once reengraftment occurs. CONCLUSIONS: Neutropenic enterocolitis is described in two patients undergoing autologous stem cell transplantation for solid tumors. The management of this life-threatening complication is controversial and governed by the nature of the clinical presentation.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Abolition of long-term stability of new hippocampal place cell maps by NMDA receptor blockade.

Hippocampal pyramidal cells are called place cells because each cell tends to fire only when the animal is in a particular part of the environment-the cell's firing field. Acute pharmacological blockade of N-methyl-D-aspartate (NMDA) glutamate receptors was used to investigate how NMDA-based synaptic plasticity participates in the formation and maintenance of the firing fields. The results suggest that the formation and short-term stability of firing fields in a new environment involve plasticity that is independent of NMDA receptor activation. By contrast, the long-term stabilization of newly established firing fields required normal NMDA receptor function and, therefore, may be related to other NMDA-dependent processes such as long-term potentiation and spatial learning.

Animals↗
PubMed1998

Increased CD40 ligand gene expression during human renal and murine islet allograft rejection.

BACKGROUND: The interaction between CD40 and its ligand CD40L is essential for the development and maintenance of vigorous immunity. We have sought to determine: (i) whether a heightened level of CD40L transcripts is evident during acute allograft rejection and (ii) the kinetics of CD40L gene expression during allograft rejection. METHODS: By using quantitative reverse transcriptase-assisted polymerase chain reaction techniques, we found that heightened CD40L gene expression is a correlate of acute human renal allograft rejection (P<0.01). RESULTS: In a murine model of MHC-mismatched islet allografts, our results showed that CD40L transcripts were rarely detected at day 2 after transplantation, but were remarkably heightened at day 5 after transplantation. The transcript levels then steadily increased and peaked at the time of rejection. CONCLUSION: These data suggest that therapy aimed at blocking the CD40 to CD40L interaction should be applied during the immediate posttransplant period.

Animals↗
PubMed1998

Transcripts of a chimeric cDNA clone of hepatitis C virus genotype 1b are infectious in vivo.

We constructed a chimeric cDNA clone of hepatitis C virus (HCV) that is infectious. The chimeric genome encodes the polyprotein of a genotype 1b strain (HC-J4) of HCV and replicates via 5' and 3' untranslated regions of a genotype 1a strain. The infectivity of three full-length cDNA clones was tested by direct injection of RNA transcripts into the liver of a chimpanzee. The chimpanzee became infected with HCV and the viral titer increased over time from 10(2) genome equivalents (GE)/ml at week 1 postinoculation (p.i.) to 10(4)-10(5) GE/ml during weeks 3-11 p.i. Antibodies to HCV were detected from week 18 p.i. However, the chimpanzee did not develop hepatitis. Sequence analysis of PCR products amplified from the serum of the chimpanzee demonstrated that only one of the three clones was infectious. Sequence comparisons with the cloning source, an acute-phase infectious plasma pool derived from an experimentally infected chimpanzee, showed that this infectious clone had three amino acids that differed from the consensus sequence of HC-J4, whereas the two noninfectious clones had seven and nine amino acid differences, respectively. Together, genotype 1b, represented by the infectious molecular clone described herein, and genotype 1a, represented by the two cDNA clones previously shown to be infectious for chimpanzees, account for the majority of HCV infections in the United States, Europe, and Japan.

Amino Acid Sequence↗
PubMed1998

The GDPAL region of the pre-S1 envelope protein is important for morphogenesis of woodchuck hepatitis virus.

The pre-S envelope protein of duck hepatitis B virus (DHBV) contains a region, Asp-Asp-Pro-Leu-Leu (DDPLL), that is specifically required for virus assembly and secretion (Lenhoff and Summers, J Virol 1994;68:4565-4571). We found that amino acids 201 to 205 of the pre-S envelope protein of woodchuck hepatitis virus (WHV) form a conserved amino acid cluster, Gly-Asp-Pro-Ala-Leu (GDPAL), which resembles the DDPLL sequence of DHBV. To determine whether the GDPAL region was functionally equivalent to the DDPLL region, we deleted this region from the pre-S protein of WHV or mutated individual amino acids within the region. The mutant DNA was transfected into human hepatoma cell line Huh7, and the medium was assayed for virion production by immunoprecipitation and Southern blot analysis. We found that an in-frame deletion of this small region inhibited virion formation, suggesting that the GDPAL region of the pre-S envelope protein was required for virus assembly and/or secretion of WHV. Individual replacement of alanine 204, leucine 205, or serine 206 with other amino acid residues did not affect virus production. However, substitution of either aspartic acid 202 with valine or proline 203 with leucine dramatically inhibited WHV production. Furthermore, the GDPAL mutants were individually tested for their abilities to complement a pre-S1 defective genome. The results showed that the GDPAL region functioned as part of the pre-S1 protein but was not required to function as part of the pre-S2 protein.

Amino Acid Sequence↗
PubMed1998

New cell lines from heliothis virescens: characterization and susceptibility to baculoviruses

New cell lines from embryos of Heliothis virescens were recently developed. Six primary cultures were initiated in June 1995. From these initial cultures, two produced sufficient cell growth to allow subcultivation and eventually led to the establishment of seven cell strains, three of which are maintained at low temperatures (17 degreesC). The strains were compared with a previously established cell line from H. virescens by isozyme analysis and shown to be from the same species. All the strains were inoculated with various baculoviruses, including Autographa californica nucleopolyhedrovirus (NPV), Anagrapha falcifera NPV, Anticarsa gemmatalis NPV, Rachoplusia ou NPV, Lymantria dispar NPV (LdMNPV), Orgyia pseudotsugata NPV (OpSNPV), O. leucostigma NPV (OlMNPV), and Helicoverpa zea NPV (HzSNPV). All seven strains were highly susceptible to the noctuid NPVs, and large numbers of occlusion bodies (OBs) were produced in most of the inoculated cells. The HzSNPV infection developed at a slower rate (requiring 1 week or more before a substantial number of cells contained OBs compared with 2-3 days for the other three noctuid NPVs). Three of the H. virescens strains were also susceptible to OpSNPV although only 10-20% of the cells produced OBs with this virus. We did not observe cytopathology (CPE) in any cells inoculated with OlMNPV or LdMNPV. Our results suggest that these new strains can be useful for the study and possibly the production of baculoviruses for which no effective cell systems are available and for comparative studies on multiple virus species.

Journal Article↗