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Biomedical subjects

L Jacob

Publications and source records attributed to L Jacob.

At least 19 recordsLinked to original sources
PubMed1999

Clinical presentation and short-term outcome of endoscopic therapy of patients with symptomatic incomplete pancreas divisum.

BACKGROUND: The clinical significance of incomplete pancreas divisum (IPD) has not been fully described. In this study we report the clinical presentation and results of endoscopic treatment of the 32 (0.6%) patients with IPD seen at our center over a 10-year period. METHODS: The study population consisted of 24 women and 8 men (mean age 42 years, range 13 to 82 years). Ten (31%) patients presented with acute recurrent pancreatitis, 5 (16%) with chronic pancreatitis, and 3 (9%) with pancreatic type pain. Detailed history, laboratory tests, US, CT, and ERCP excluded other etiologies for their symptoms. The remaining 14 (44%) presented with biliary problems. The 18 symptomatic patients with IPD were treated as follows: 8 received dorsal duct stents, 3 underwent minor papilla endoscopic sphincterotomy and dorsal duct stent placement, 4 had minor papilla dilatation only, and 3 had ventral duct stents placed. RESULTS: Patients were then followed for recurrence of pancreatitis and pancreatic-type pain. Mean follow-up was 15.5 months (range 3 to 30 months). Six (60%) of the patients with acute recurrent pancreatitis and 4 (80%) with chronic pancreatitis benefitted from the endoscopic therapy. However, only 1 (33%) of the patients with pancreatic-type pain benefitted. CONCLUSION: The clinical presentation and response to endoscopic therapy of patients with ICP appeared to be similar to that of patients with complete pancreas divisum.

Abdominal Pain↗
PubMed1998

Bioavailability of morphine after administration of a new bioadhesive buccal tablet.

A new bioadhesive buccal morphine tablet was developed for controlled release delivery of drug and improved bioavailability compared with oral controlled release tablet. In order to characterize the pharmacokinetic properties of this bioadhesive buccal formulation, a bioavailability study was performed in 12 healthy volunteers who received: a 30 mg oral controlled release tablet (A); a 20 mg aqueous solution retained in the mouth for 10 min (B); and the 60 mg bioadhesive buccal tablet placed between the lower gum and lip for 6 h (C). The mean amount of morphine absorbed from the solution was very low, only 2 mg of the 20 mg dose. After administration of forms A and C, plasma levels exhibit typical sustained release concentration-time curves. The mean amount of drug recovered from the residual bioadhesive buccal tablet after 6 h indicated that approximately 50% of the dose was released from the bioadhesive buccal tablet. The relative bioavailability of the buccal tablet (corrected for residual unabsorbed dose) compared with the controlled-release tablet was 98% based on the morphine AUC values. Good correlations between the AUC and the Cmax of the bioadhesive tablet for the drug and metabolite plotted versus the amount of morphine absorbed were found.

Administration, Buccal↗
PubMed1998

Unexpected rhabdomyolysis with myoglobinuria in a patient in the supine position.

We report a case of post-operative rhabdomyolysis following transmandibular buccopharyngectomy without reconstruction in a patient remaining in the supine position throughout the procedure. Muscle compression induced by a cushion used during the procedure had probably contributed to the rhabdomyolysis. Outcome was favourable without acute renal failure. Prevention, early diagnosis and treatment are the keys to a successful recovery.

Aged↗
PubMed1997

Cytotoxic T-cell clone against rectal carcinoma induced by stimulation of a patient's peripheral blood mononuclear cells with autologous cultured tumor cells.

In an effort to establish cytolytic T lymphocytes (CTLs) against colorectal carcinoma (CRC) by stimulating patients' lymphocytes with autologous tumor cells, we used peripheral blood mononuclear cells (PBMC) from a patient with minimal residual rectal carcinoma following removal of the primary lesion and involved regional lymph nodes as a source to generate CTLs in culture. A CTL line and clone were established from the patient's PBMC following stimulation of PBMC with autologous, cultured tumor cells and interleukin-2. The CTL line and the clone consisted predominantly of CD4+ lymphocytes. The CTL clone expressed two T-cell receptor variable alpha chains (V alpha11 and V alpha22) and one beta chain (Vbeta14). The cytokine secretion pattern of the CTL line was of the Th1-type. Both the CTL line and the clone lysed the autologous rectal carcinoma cells, but not the allogeneic, partially human lymphocyte antigen (HLA)-matched or nonmatched CRC cells, autologous Epstein-Barr virus-transformed B cells, K562 (natural killer target) cells or Daudi (lymphokine-activated killer target) cells. Lysis of autologous tumor cells most likely was HLA class I-restricted. Our unique success in generating CTLs against this tumor type may rest in the inclusion of a patient with minimal residual, rather than advanced, disease.

Amino Acid Sequence↗
PubMed1997

Combinatorial antibodies against human malignant melanoma.

The general responsiveness of human melanoma to immunotherapy has been well established, but active immunotherapy of melanoma has been hampered by insufficient information on the immunogenicity of melanoma antigens in patients. We have attempted to identify melanoma-associated antigens recognized by patients' B cells using an antibody phage display approach. Antibody display on filamentous phages allows direct screening of cDNA libraries for expression of cell-surface-reactive antibodies, without the need for antibody production and purification using bacteria or eukaryotic cell systems. This approach was used to identify melanoma-associated cell-surface antigens recognized by patients' B cells. Antibodies produced by the B cells of a melanoma patient (in remission for > 7 years following periodic vaccination with allogeneic melanoma cell vaccine) were displayed as Fabs on the surfaces of filamentous phages. A library of 10(8) phages was absorbed to normal melanocytes, followed by phage binding to and elution from melanoma cells (human lymphocyte antigen nonmatched and vaccine melanoma cells). Phages were further selected for reactivities with tunicamycin-treated melanoma cells. These procedures resulted in a > 10(6)-fold enrichment of tumor-specific phages from the original phage library. One phage-Fab bound to melanoma cells, other tumor cells, and a few normal cells in cultured cell lines and in tissue sections.

Antibodies, Neoplasm↗
PubMed1996

ERCP guide wires.

Guide wires have become an essential part of therapeutic biliary and pancreatic endoscopy. The Teflon-painted stainless steel wire still remains the standard guide wire. However, special situations call for the use of some of the more specialized guide wires mentioned in this article. The endoscopist needs to be familiar with the type that is needed for any given situation. It may be prudent and cost-saving on the part of the endoscopist to anticipate early on in the procedure the type of wire or wires that would be needed, thereby enabling the endoscopist to choose one or two guide wires that would meet his or her needs rather than having to use several wires.

Cholangiopancreatography, Endoscopic Retrograde↗
PubMed1995

Induction of antigen-specific T and B cell immunity in colon carcinoma patients by anti-idiotypic antibody.

Polyclonal goat anti-idiotypic Abs directed against anti-human gastrointestinal carcinoma mAb GA733 were administered to 13 colon cancer patients who had their primary tumor and lymph node metastases removed before immunotherapy. Patients received four s.c. doses (0.5 to 8 mg each) of alum-precipitated anti-idiotypic Ab. Seven of the 13 patients produced anti-anti-Ids that bound specifically to the GA733 epitope on tumor cells and shared idiotopes with mAb GA733. In four of the seven responding patients, anti-Id therapy specifically modulated T cell responses. In two patients who did not demonstrate GA733 Ag/anti-Id-reactive T cells before therapy, anti-Id administration induced CD4+, MHC class II-dependent T cells that specifically proliferated in culture in response to stimulation with either anti-Id or GA733 Ag. In two other patients who did demonstrate Ag/anti-Id-reactive T cells before therapy, anti-Id administration transiently induced lymphocytes that suppressed the proliferative responses of cultured pretherapy lymphocytes to stimulation with anti-Id or GA733 Ag. Nine of the 13 treated patients showed no evidence of disease after 39 to 86 mo of observation. Five of these patients developed Ag-specific Ab3 and one had, in addition, a T cell response.

Adult↗
PubMed1995

Animal models of human-derived cancer vaccines.

Preclinical cancer vaccine studies must address vaccine safety, immunogenicity, and efficacy, as well as mechanism of vaccine action. Animal models of vaccines employing human tumor-associated antigen or epitopes (TAA, TAE) differ fundamentally from those employing tumor-specific antigens or epitopes (TSA, TSE). TSA and TSE vaccines will most likely demonstrate similar toxicity, immunogenicity, and efficacy in both tumor-bearing animals and patients. In contrast, TAA/TAE immunizations may have to overcome a host's immunological tolerance to TAA/TAE expressed not only on tumor, but also on normal tissues; immunity to TAA/TAE will potentially target normal tissues and thus may induce autoimmunity. Various experimental models for human-derived TAA/TAE vaccines have been developed. These models include transgenic mice, mice with severe combined immunodeficiency (SCID), and non-human primates. Recently, unique animal models of TAA/TAE cancer vaccines have been developed, taking advantage of the discovery of animal tissue antigens with significant sequence homologies to human TAA/TAE. These models mimic perhaps most closely the situation in cancer patients.

Animals↗
PubMed1995

Cloned antigens and antiidiotypes.

Both monoclonal and polyclonal antiidiotypic antibodies mimicking the human colorectal carcinoma (CRC) associated antigen CO17-1A/GA733 have induced antigen-specific humoral and cellular immunity in CRC patients. The immune responses may underlie the clinical responses observed in some of the treated patients. Recently, the CO17-1A/GA733 antigen has been molecularly cloned and expressed in baculo-, adeno-, and vaccinia viruses. In preclinical studies, these recombinant antigen preparations elicited specific humoral immunity (cytotoxic antibodies) and cellular immunity (DTH-reactive and proliferative T cells). Antibody titers elicited in animals by recombinant antigen were significantly higher than those elicited by antiidiotypes. The recombinant antigen has a potential as a vaccine for CRC patients.

Animals↗
PubMed1995

Tetanus toxoid-specific T cell responses in severe combined immunodeficiency (SCID) mice reconstituted with human peripheral blood lymphocytes.

SCID mice reconstituted with human peripheral blood lymphocytes (PBL) have repeatedly been shown to produce antigen-specific B cell responses. We have derived tetanus toxoid (TT)-specific human T cell lines from cells of the peritoneal cavity, spleen and lymph nodes of SCID mice reconstituted with human PBL and boosted with TT. Establishment of these cell lines was dependent on the time interval between reconstitution of the mice with human PBL and initiation of lymphocyte cultures in vitro. When lymphocytes were collected from the mice 8 weeks after reconstitution, human lymphocytes with TT-specific proliferative activity in vitro were isolated from the peritoneal cavity and spleen, but long-term cell lines could not be established after repeated lymphocyte stimulation with TT, IL-2 and autologous Epstein-Barr virus-transformed B cells. In contrast, three long-term (> 10 months) TT-specific human T cell lines were established from lymphocytes collected from two of the eight mice in the group 4 weeks after reconstitution. The T cell lines were either CD4+ (two lines derived from peritoneal cavity and lymph node, respectively) or CD8+ (one line derived from spleen) and all expressed CD3, T cell receptor alpha/beta, and human histocompatibility leucocyte class I antigen. The T cell lines, however, lacked cytotoxic, helper and suppressor activities. Thus, SCID mice can support human T cells that actively migrate to various organs and respond to antigenic stimuli both in vivo and in vitro, but these T cells lack characteristic functions.

Animals↗
PubMed1995

Limitations of the severe combined immunodeficiency (SCID) mouse model for study of human B-cell responses.

Mice lacking functional T and B lymphocytes offer an in vivo animal model for the study of human immune functions. We have attempted to optimize the reconstitution of severe combined immunodeficiency (SCID) mice with human peripheral blood lymphocytes (PBL) using radiation, anti-asialo GM1 antibody or cyclophosphamide (Cy) treatment of the mice and in vitro stimulation of human PBL with interleukin (IL)-2 prior to their transfer to the mice. Total human IgG and tetanus-toxoid (TT)-specific human IgG responses of the mice were used as parameters of successful reconstitution. Treatment of the mice with anti-asialo GM1 antibody significantly enhanced total human IgG levels, but not TT-specific antibody responses, whereas irradiation or Cy treatment of the mice had no effect on human antibody production. In vitro treatment of human PBL with IL-2 prior to engraftment significantly decreased total human IgG responses of human PBL-grafted SCID mice. The immune responses of individual mice within a group were highly variable, which constitutes a major disadvantage of this model.

Animals↗
PubMed1995

Hepatotoxicity from isoniazid and rifampin in inner-city AIDS patients.

OBJECTIVE: To determine the incidence of hepatotoxicity due to isoniazid and rifampin in inner-city patients with active tuberculosis. DESIGN: A hospital-based review of 70 consecutive in-patients in a 770-bed, inner-city hospital. The patient population is primarily African-American and Hispanic. METHODS: Fifty-eight men and 12 women were followed from 2-12 wk (median 4 wk). Patients had to be treated for at least 2 wk to be eligible for the study. Patients were excluded if they had been on any anti-tuberculous or any other hepatotoxic drug during the 2-month period before their hospitalization. Aminotransferases, alkaline phosphatase, bilirubin, and albumin were obtained at least every 2 wk. RESULTS: Hepatocellular toxicity, defined as AST and/or ALT greater than 200 IU/L, occurred in eight out of 70 (11.4%) patients. The mean age of these patients was 38.9 yr (22-58 yr). Patients with AIDS were significantly more likely to develop hepatotoxicity than those with any other risk factor (p < 0.01). CONCLUSIONS: Baseline aminotransferases followed by monitoring may be necessary in AIDS patients.

AIDS-Related Opportunistic Infections↗
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↗