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Biomedical subjects

L Jacob

Publications and source records attributed to L Jacob.

At least 37 records · Page 2Linked to original sources
PubMed1995

Distribution of adenomatous polyps in African-Americans.

OBJECTIVES: Previous research has suggested that polyps and colon cancer occur more commonly in the right colon in African-Americans compared with the general population. The purpose of this study is to determine the pattern of distribution of colonic polyps in African-Americans. METHODS: We retrospectively evaluated 141 colonoscopies in which 179 polypectomies were done. The polyps were described on the basis of anatomical distribution, gross description, size, and histology. Sixty-nine males and 72 females had colonoscopic polypectomies. The mean age was 67 yr (range, 43-91 yr). RESULTS: Seventy-seven (43%) were classified as left sided, and 102 (57%) were right sided. Left-sided polyps were more likely to be pedunculated than right-sided polyps (p < 0.01). Larger polyps were more common on the left side than the right side (p < 0.01), but villous histology was almost as high on the right side as on the left side. Polyps that had the highest malignant potential were found almost as commonly on the right side as on the left side. CONCLUSIONS: This study supports previous work that suggests that there is a significant shift to the right in the anatomical distribution of polyps in African-Americans. It also shows that the malignant potential is as high for right-sided polyps as it is for those on the left. Current screening recommendations may not be effective enough for preventing colon cancer in this population.

Adult↗
PubMed1994

Potential therapeutic applications of magainins and other antimicrobial agents of animal origin.

Magainins are a family of linear, amphipathic, cationic antimicrobial peptides, 21 to 27 residues in length, found in the skin of Xenopus laevis. They kill microbial targets through disruption of membrane permeability. They exhibit selectivity, on the basis of their affinity for membranes which contain accessible acidic phospholipids, a property characterizing the cytoplasmic membranes of many species of bacteria. Magainins are broad-spectrum antimicrobial agents exhibiting cidal activity against Gram-negative and Gram-positive bacteria, fungi and protozoa. In addition these peptides lyse many types of murine and human cancer cells at concentrations 5-10-fold lower than normal human cells. Because of their selectivity, broad spectrum, low degree of bacterial resistance and ease of chemical synthesis, magainins are being developed as human therapeutic agents. The most advanced candidate is MSI-78, a 22-residue magainin analogue. This peptide is currently in human Phase IIb/III clinical trials in studies intended to evaluate its efficacy as a topical agent for the treatment of impetigo. Preclinical studies have demonstrated that analogues of magainin exhibit activity in vivo against malignant melanoma and ovarian cancer cells in mouse models. Intravenous administration of several magainin analogues has been shown to treat effectively systemic Escherichia coli infections in the mouse.

Amino Acid Sequence↗
PubMed1994

Nucleosome-restricted antibodies are detected before anti-dsDNA and/or antihistone antibodies in serum of MRL-Mp lpr/lpr and +/+ mice, and are present in kidney eluates of lupus mice with proteinuria.

OBJECTIVE: To compare the humoral response to nucleosomes with the response to their individual components (double-stranded DNA [dsDNA] and histones) and to assess the involvement of antinucleosome antibodies in immune deposits in the kidney of MRL mice. METHODS: We used enzyme-linked immunosorbent assays of sera and kidney eluates for antibody activity against purified nucleosomes, dsDNA, and histones. RESULTS: Antinucleosome antibodies emerged before anti-dsDNA and antihistone antibodies. A fraction of antinucleosome antibodies reacted exclusively with nucleosomes and not with their components, dsDNA and histones. These nucleosome-restricted antibodies were detected in the proteinuric MRL mouse kidney eluate. CONCLUSION: Our findings support the notion that nucleosomes play a major role in the emergence of antinuclear autoantibodies and that antinucleosome antibodies might be involved in the nephritogenic process in murine lupus.

Animals↗
PubMed1994

Anti-idiotype and recombinant antigen in immunotherapy of colorectal cancer.

The CO17-1A/GA733 antigen (Ag), bound by monoclonal antibodies (MAb) CO17-1A and GA733 that define two different epitopes on the Ag, has proven a useful target in passive and active immunotherapy of colorectal carcinoma (CRC). Previous studies suggest that the antitumor effects demonstrated in MAb-treated patients may be mediated by idiotypic cascades. In approaches to active immunotherapy against the Ag, polyclonal goat and monoclonal rat anti-idiotypic antibodies (Ab2) directed against MAb CO17-1A or GA733 (Ab1) were administered as alum precipitates to 54 patients with CRC (stage Dukes' B, C, and D). The majority of the patients treated with the various Ab2 preparations developed anti-anti-idiotypic antibodies (Ab3) that specifically bound to the CO17-1A or GA733 epitope and shared idiotopes with the corresponding Ab1. Approximately 30% of the patients tested developed specific cellular immunity, i.e., Ag-specific T-cells mediating delayed-type hypersensitivity (DTH) reaction in vivo or proliferating on stimulation with the Ag in vitro. The humoral and cellular immune responses may underlie the clinical responses observed in some of the treated patients. Recently, the CO17-1A/GA733 Ag has been molecularly cloned and expressed in baculo-, adeno-, and vaccinia viruses. In preclinical studies, these recombinant Ag preparations elicited specific humoral immunity (cytotoxic antibodies) and cellular immunity (DTH-reactive and proliferative T-cells), similar to the native Ag. Antibody titers elicited in experimental animals by recombinant Ag were significantly higher than those elicited by Ab2, presumably because Ag expresses numerous epitopes, whereas Ab2 mimics a single epitope. Recombinant CO17-1A/GA733 Ag has potential as a vaccine for CRC patients.

Animals↗
PubMed1994

Immunomodulatory activity of monoclonal anti-idiotypic antibody to anti-colorectal carcinoma antibody CO17-1A in animals and patients.

Monoclonal anti-idiotypic antibody (Ab2) VF2 was derived from rats immunized with anti-colorectal carcinoma (anti-CRC) monoclonal antibody (Ab1) CO17-1A. In rabbits the Ab2 induced anti anti-idiotypic antibodies (Ab3) that shared idiotopes with the Ab1, bound to the same epitope on CRC cells as Ab1, and bound to the isolated CO17-1A antigen. Monoclonal Ab2 VF2 was superior to the previously described polyclonal goat Ab2 against Ab1 CO17-1A in its capacity to elicit humoral immunity in animals. Ab2 VF2 also induced a specific delayed-type hypersensitivity (DTH) response to challenge with irradiated CO17-1A antigen-positive human CRC cells in mice. Of nine CRC patients immunized with aluminum hydroxide-precipitated Ab2 VF2, six developed antibodies that bound to Ab2, but only three patients developed Ab3 that bound to idiotypic determinants on Ab2. However, the Ab3 did not bind to CO17-1A antigen-positive CRC cells. In contrast, in a previously described trial with polyclonal goat Ab2 to Ab1 CO17-1A, most of the patients developed anti-CRC antibodies. Four of the nine patients immunized with Ab2 VF2 developed DTH responses to intradermal challenge with the Ab2, and in one patient DTH was both Ab2- and antigen-specific. Peripheral blood mononu-clear cells of the four DTH-reactive patients did not proliferate in response to in vitro stimulation with either Ab2 or antigen. These studies demonstrate that the immunomodulatory activity of monoclonal Ab2 VF2 in animals is only in part predictive of its activity in patients.

Animals↗
PubMed1994

Decreased mesenteric blood flow supplying retrosternal esophageal ileocoloplastic grafts during positive-pressure breathing.

Esophageal replacement after esophagogastric injury caused by ingestion of lye may require the interposition of a retrosternal ileocolic graft. In this new anatomic situation, the mesenteric circulation supplying the graft is subjected to the intrathoracic pressure surrounding the graft. Thus, mesenteric blood flow supplying the graft may be impaired when intrathoracic pressure is increased during mechanical ventilation. This study was designed to evaluate the effect of increasing intrathoracic pressure by application of a positive end-expiratory pressure on mesenteric blood flow supplying esophageal ileocolic grafts. Eight cases were studied in the immediate postoperative period. Miniaturized implantable Doppler microprobes were sutured to the single artery supplying the graft and connected to an 8 MHz pulsed Doppler flowmeter. Two sets of measurements were successively performed with zero end-expiratory pressure ventilation and after application of a 15 cm water positive end-expiratory pressure. Positive end-expiratory pressure induces mean arterial pressure (-12%); p < 0.05) and cardiac output (-17%; p < 0.05) decrease. Mesenteric blood flow also decreases (-38%; p < 0.05) as did the mesenteric blood flow/cardiac output ratio, suggesting a potential mesenteric vasoconstriction assessed by mesenteric vascular resistance increase and mesenteric diastolic blood flow velocity decrease. These results suggest that, in the particular anatomic situation of the graft, increased intrathoracic pressure induces mesenteric blood flow decrease in relation to systemic hemodynamic alterations associated with perivisceral pressure increase. This change may be deleterious to graft perfusion.

Adult↗
PubMed1993

Hepatic amyloidosis in intravenous drug abusers and AIDS patients.

The clinical and pathological features of four liver biopsies and 12 autopsies from 1981-1990 with hepatic amyloidosis were reviewed. All of the patients had a history of both intravenous and subcutaneous cocaine and heroin use with chronic suppurative skin ulcers. Five patients were proven to have the acquired immunodeficiency syndrome at autopsy. Systemic amyloidosis was diagnosed in only five out of the 16 patients prior to death. Hepatomegaly was present in 12 patients. The amyloid protein was AA in 14 and AL in one case. Definitive characterization of the amyloid substance was not possible in one case. There was no evidence of multiple myeloma or a plasma cell dyscrasia in the one patient with AL amyloid. The amyloid distribution in the liver was both parenchymal and vascular in 12 cases. Cholestasis, which appeared to occur preterminally, was the only histological finding that correlated with the patient's clinical condition. The histological pattern of amyloid in the liver could not predict the type of amyloid protein that was identified. Amyloidosis should be considered in the differential diagnosis of unexplained hepatomegaly in the acquired immunodeficiency syndrome with chronic suppurative infections.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Anti-histone reactivity in systemic lupus erythematosus sera: a disease activity index linked to the presence of DNA:anti-DNA immune complexes.

This study shows that purified murine monoclonal anti-DNA antibodies and human polyclonal anti-DNA antibodies (from systemic lupus erythematosus--SLE--patients), preincubated with DNA, acquire anti-histone reactivity. Conversely, DNAse I treatment of SLE patients' antibodies with anti-histone activity abolishes such activity. It has previously been demonstrated that anti-DNA antibodies bind to the cell membrane and recognize cell-surface polypeptides that have been identified with histones by partial sequencing. In a series of 33 sera from patients with clinically active disease and 29 sera from patients in clinical remission, positivity of an immunoblot analysis detecting antibodies against these polypeptides was associated with clinical activity of SLE (sensitivity, 0.88; specificity, 0.90). Anti-histone reactivity detected by ELISA appeared to be also a good marker of SLE activity (sensitivity, 0.64; specificity, 0.54). As expected, anti-native DNA antibody positivity and lowered complement dosage were also associated with clinical activity (sensitivity, 0.79 and 0.63, respectively; specificity, 0.48 and 0.93, respectively). Since anti-histone reactivity reflects, at least partly, the presence of anti-DNA antibodies complexed to DNA, which could bind to cell-membrane determinants, and is associated with disease clinical activity, it is suggested that this mechanism can contribute to explain the pathogenicity of anti-DNA antibodies.

Adult↗
PubMed1992

Anti-DNA antibodies and their relationships with anti-histone and anti-nucleosome specificities.

Systemic lupus erythematosus (SLE) is the archetypic non-organ specific autoimmune disease in which polyclonal B-cell activation is reflected by the wide range of auto-antibody specificities. Among these, anti-ds DNA antibodies bear special significance since they are disease specific, tend to occur at high titers in an active clinical state and are considered to be pathogenic through immune complex formation. However, data accumulated in the last few years have led to a somewhat more complex view of anti-DNA autoantibodies and SLE pathogenesis. For instance, the definition of pathogenic subpopulations of anti-DNA antibodies is an important question which has been addressed in terms of isotypes, idiotypes and DNA sequences of antibodies. Also, some of the cross reactivities described with monoclonal anti-DNA antibodies appear to be due to the formation of immune complexes with DNA, histones or nucleosomes. In addition, anti-DNA-nucleosome immune complexes can react with the cell membrane. These findings indicate that not only DNA but also the nucleosome as a multimolecular complex or its non-DNA component, i.e. histone, may be viewed as relevant target autoantigens in SLE. This review will focus on experimental data supporting this new representation of this set of autoantibodies directed against DNA, histone and the nucleosome, and their possible intervention in SLE pathogenesis.

Animals↗
PubMed1992

Usefulness of perioperative pulsed Doppler flowmetry in predicting postoperative local ischemic complications after ileocolic esophagoplasty.

Regional ischemia may induce cervical anastomosis leakage or stenosis or graft necrosis after esophageal reconstruction by retrosternal interposition of an ileocolic graft. These complications may be related to systemic or local hemodynamic alterations. This study was designed to evaluate the relationship between immediate postoperative arterial blood supply to the graft, arterial patency monitored by angiography, and clinical outcome. Eight patients (mean age 30 +/- 4 years; standard deviation) were studied. Miniaturized Doppler implantable microprobes were sutured to the single artery supplying the graft and connected to an 8 MHz pulsed Doppler flowmeter. Systemic hemodynamic parameters and mesenteric hemodynamic data were collected 3 hours after the end of the surgical procedure. These data were compared with the angiogram of the right superior colic artery supplying the graft, systematically performed on the fifteenth postoperative day, and with the clinical course of follow-up for 3 months. Five patients (group 1) had excellent clinical and angiographic results. Mean mesenteric blood flow in these patients was 51 +/- 49 ml.min-1 (+/- standard deviation, ranging from 9 to 122). Three patients (group 2) had a poor clinical outcome. One had early complete graft necrosis and the two others had leakage of the cervical anastomosis with poor distal arterial vascularization of the graft on the angiogram. Mean mesenteric blood flow was nul in the first patient and, respectively, 24 and 28 ml.min-1 in the two others. Cardiac output and mean arterial pressure were in the same range for all patients. Phasic velocity shape analysis revealed that the three group 2 patients had an end-systolic or end-diastolic reverse flow pattern that was not observed in the five group 1 patients, which suggested a submaximal increase in downstream vascular resistance. This reverse flow pattern seems to be a good predictor of ischemia-related complications. We conclude that perioperative pulsed Doppler blood flow monitoring in an ileocolic graft may be useful for the diagnosis and prevention of ischemic complications.

Adult↗
PubMed1992

Tracheobronchial necrosis after caustic ingestion.

Between 1968 and 1988, 679 patients were hospitalized for ingestion of caustic substances, and 87 had severe caustic burns of the entire esophagus, together with panparietal necrosis. Twenty-one of them had tracheobronchial necrosis with perforation. Fifteen have not been operated on; six have had operations, with success in four. We describe an original technique for repairing these tracheobronchial perforations with a pulmonary patch.

Adult↗
PubMed1992

Longitudinal radiologic evaluation of osteoarthritis of the knee.

Radiologic assessment appears to be an objective standard for longterm evaluation of osteoarthritis (OA) and it is inexpensive, quick, simple and noninvasive. We conducted a one year followup study of patients with OA of the knee to evaluate the reproducibility and validity of this evaluation. The intra and interobserver reproducibility of the radiologic variables were evaluated on 275 and 539 patients, respectively, and found to be satisfactory (intraclass coefficient of correlation above 0.70 for the evaluation of the space narrowing of the joint). During the one year followup study, there was a slight but statistically significant deterioration of the joint space narrowing, evaluated on a 6 grade scale on 360 patients (p less than 0.001). The changes in the joint space narrowing were more closely correlated with treatments received by the patients for OA (nonsteroidal antiinflammatory drug (NSAID) intake, synovial fluid aspiration) than with changes in the recorded clinical variables (pain on a visual analog scale, Lequesne algofunctional index). Moreover, some factors such as obesity, generalized OA and flares of OA appeared to be correlated with the deterioration of joint space narrowing. Further studies are necessary to confirm and/or explain the relationship between the deterioration of the joint space narrowing and such factors (i.e., NSAID intake, obesity, flares of OA, generalized OA), which were detected in this study.

Aged↗
PubMed1991

Purification and crystallization of yeast hexokinase isoenzymes. Characterization of different forms by chromatofocusing.

The yeast hexokinase isoenzymes PI and PII have been purified in large amounts (20 mg) from overproducing yeast strains. The purification procedures of hexokinase PI and PII include anion-exchange chromatography on DEAE-Sephacel and chromatofocusing on PBE 94, hydrophobic interaction chromatography on phenyl-Sepharose (necessary for the isolation of the isoenzyme PI); in the final step either a Mono Q HR 5/5 or a Fractogel EMD TMAE 650(S) column was used. Hexokinase preparations were characterized before crystallization by chromatofocusing on a Mono P HR 5/20 FPLC column, where different forms of hexokinase can be rapidly distinguished by their elution behaviour. From both purified hexokinase PI and PII, large crystals were grown that diffract X-rays to high resolution.

Chromatography, Ion Exchange↗