Immunotherapy of murine bladder cancer with keyhole limpet hemocyanin (KLH)

Keyhole limpet hemocyanin (KLH) is a potent immunogen that is being evaluated as an immunotherapeutic alternative to BCG in the treatment of bladder cancer. In the mouse bladder tumor model (MBT2) intralesional KLH significantly reduced tumor incidence, growth rate, and mortality and exhibited antitumor activity similar to that achievable with BCG. Endotoxin contamination of KLH was not responsible for the antitumor activity, although endotoxin alone was shown to have anti-tumor activity in this animal model. Keyhole limpet hemocyanin is both safe and effective in the MBT2 model, and is an immunomodulator to consider for clinical trials.     

Esophageal stents may interfere with the swallowing reflex: an illustrative case history

For the first time, Kluver Bucy syndrome (KBS) is described in young children who had no environmental learning of sex. The syndrome has so far been noted only in adults after bilateral temporal lobe affection. A few of its components, especially the hypersexuality and hypermetamorphosis, are likely to manifest differently in very young children. Seven patients in the pre-pubertal age group, who developed KBS as a post-encephalitic sequelae, are described. The patients, 2.5-6 years old, suffered from acute herpes simplex encephalitis (HSE) at 10 months-5.5 years of age and developed KBS on regaining consciousness and ambulation. Altered emotional behaviour, changes in dietary habits, hyperorality and hypersexuality were present in all, while psychic blindness and hypermetamorphosis were noted in a few of the patients. All showed marked indifference and lack of emotional attachment towards their close relatives. Apathy and easy distractibility were rare. Bulimia and strong urge to put non-food items into the mouth were common. Hypersexuality manifested as frequent holding of genitals, intermittent pelvic thrusting movements and rubbing of genitals to the bed on lying prone. Due to lack of environmental learning of sex and also, due to emotional and physical dependence on parents, the manifestations in young children showed modification over those of adults.     

Local immunoglobulin G antibodies in the stomach may contribute to immunity against Helicobacter infection in mice

The central nervous system consumes 20% of the cardiac output for normal function. The neurons are very sensitive to the effects of ischemia. Cessation of cerebral blood flow results in severe damage to neurons and other brain structures. This is secondary to a combination of energy loss, excessive excitation promoting intracellular calcium (Ca2+) buildup, relative lack of inhibitory responses, generation of oxygen free radicals (especially during the reperfusion period) and several other destructive cascades. Medications that antagonize the effects of glutamate at post-synaptic receptors are either ineffective or have serious side-effects. Ca2+ entry blockers have shown disappointing results in clinical trials in patients with acute cerebral infarction. Data with protective effects of oxygen free radical scavengers in the post-ischemic period have shown conflicting results. There is recent interest with the use of agents that increase cerebral inhibitory responses after an ischemic insult. Such agents are effective when used before, during or up to 4 hours after the ischemic insult. Many such medications have few side-effects and are in clinical use for other indications. This review will summarize inhibitory mechanisms that may be important in cerebral ischemia, and provide experimental evidence for their potential efficacy.     

The kinetics of antibodies against hepatitis C virus may predict viral clearance in exposed hemophiliacs

Several studies have reported the spontaneous loss of hepatitis C virus (HCV) antibodies in HCV-exposed persons. However, the relationship between seroreversion and spontaneous virus clearance has yet to be precisely determined in a single homogeneous population of untreated immunocompetent patients. In this study, 32 human immunodeficiency virus-seronegative hemophiliacs who had been exposed to HCV were followed for a mean duration of 141 months; 22 remained chronic carriers (68.8%). All but 1 of the nonviremic patients (90.0%) showed partial (8 cases) or complete (2 cases) seroreversion. In contrast, all but 1 of the viremic patients (95.1%) had a stable serologic profile when analyzed by a recombinant immunoblot assay. The results indicate that any HCV antibody-positive immunocompetent patient with no detectable serum HCV RNA and normal alanine aminotransferase values and whose serial samples show a progressive decrease in the level of HCV antibodies present may be considered as having a resolved infection.     

Immunochemical mapping of human lutropin: II. Characterization of two monoclonal antipeptide antibodies reacting with the native beta-subunit

To investigate the epitopes present on the beta-subunit of the human lutropin (hLHbeta) and their topographical relationship at the surface of the molecule, we produced two monoclonal antipeptide antibodies, designated LHP03 and LHP04, capable of binding to the radiolabeled 125I-hLHbeta and directed to the 43-52 and 110-117 regions of the hLHbeta, respectively. Analysis of the accessibility of the epitopes on hLH and on the beta-subunit of human chorionic gonadotropin (hCGbeta), equine LH (eLHbeta) and ovine LH (oLHbeta) indicated that: (i) LHP03 binds to both the free hLHbeta subunit and dimeric hLH whereas LHP04 binds preferentially to the free hLHbeta, (ii) LHP03 recognizes weakly the hCGbeta and oLHbeta in comparison to hLHbeta and (iii) LHP04 binds oLHbeta as well as hLHbeta but does not bind to hCGbeta and eLHbeta. The topographical relationship of epitopes recognized by LHP03 and monoclonal antibodies recognizing dimer specific epitopes on hLH allowed us to localize discontinuous antigenic sites that overlaps or are located outside the hHLbeta(43-52) region. Together, our results demonstrated that the hHLbeta(43-52) portion is accessible on both the free hLHbeta subunit and hLH whereas the COOH-terminal portion, hHLbeta(110-117), is probably buried at the alpha/beta interface of the hormone.     

Clearance-inducing antibodies are responsible for protection against the acute phase of Trypanosoma cruzi infection in mice

Light chain deposition disease is a severe complication of certain immunoproliferative disorders, due to the secretion of a monoclonal light chain which precipitates close to basement membranes of several tissues. A kappa isotype restriction and an unusual frequency of a variable region subgroup (VkappaIV) suggest that precise structural features govern the propensity of pathogenic light chains to precipitate in extracellular spaces. We studied primary structures of light chains from six patients with light chain deposition disease in comparison with light chains from other pathological conditions. Sequence alignment revealed the presence of certain amino acids only in light chain deposition disease, in particular non-polar replacing hydrophilic residues. To determine the role of these residues, structures of the variable domain from four kappa chains belonging to VkappaI and VkappaIV subgroups responsible for deposition disease were modeled using known immunoglobulins as templates. The most evident structural features shared by all pathogenic light chains were hydrophobic residues exposed to the solvent in complementarity determining regions 1 or 3. In contrast to immunoglobulin light chain-related amyloidosis, where deposition of organized material might be due to electrostatic interactions between light chain dimers, hydrophobic interactions could enhance amorphous precipitation in non-amyloid light chain deposition disease.     

Isolation of high affinity antibodies to streptococcal group A polysaccharide reacting with thymus and cutaneous epithelial cells

Anti-streptococcal A polysaccharide (anti-A polysaccharide) antibodies were isolated from sera of rabbits immunized with group A streptococci by means of immunosorbents. The antibodies were studied by indirect immunofluorescence method on sections of skin and thymus tissues. Most preparations of high affinity antibodies reacting with A polysaccharide in the immunodiffusion test also react with skin and thymus epithelial cells. No preparations of low affinity anti-A polysaccharide antibodies reacted with thymus or skin epithelium. It was found that the reaction of antibodies to A-polysaccharide with epithelial cells does not depend on the availability of antibodies cross reacting with group L streptococcal polysaccharide. The reaction with thymus and skin epithelial cells is likely to be bound with high affinity antibodies to the specific determinant of A-polysaccharide.     

Relation of intensity of infection to disease in hamsters with acute schistosomiasis mansoni

Groups of young hamsters were exposed to 3, 20, 40, 80, or 160 cercariae. A highly significant correlation was observed between the number of cercariae, worm burdens, and liver and fecal egg counts. The most heavily infected animals were the first to lose weight and die. Hamsters exposed to 20 or more cercariae and harboring a mean of 4.2 or more worm pairs developed significant hepatosplenic disease by 10 weeks after infection as assessed by hepatomegaly, splenomegaly and the development of portal hypertension. Lightly infected animals with single worm pairs did not develop significant disease.     

Prevention of Jarisch-Herxheimer reactions by treatment with antibodies against tumor necrosis factor alpha

BACKGROUND: In patients with louse-borne relapsing fever (Borrelia recurrentis infection), antimicrobial treatment is often followed by sudden fever, rigors, and persistent hypotension (Jarisch-Herxheimer reactions) that are associated with increases in plasma concentrations of tumor necrosis factor alpha (TNF-alpha), interleukin-6, and interleukin-8. We attempted to determine whether sheep polyclonal Fab antibody fragments against TNF-alpha (anti-TNF-alpha Fab) could suppress the Jarisch-Herxheimer reaction. METHODS: We conducted a randomized, double-blind, placebo-controlled trial in 49 patients with proven louse-borne relapsing fever. Immediately before the intramuscular injection of penicillin, the patients received an intravenous infusion of either anti-TNF-alpha Fab or a control solution. RESULTS: Ten of the 20 patients given anti-TNF-alpha Fab had Jarisch-Herxheimer reactions with rigors, as compared with 26 of the 29 control patients (P = 0.006). The controls had significantly greater mean maximal increases in temperature (1.5 vs. 0.8 degrees C, P < 0.001), pulse rate (31 vs. 13 per minute, P < 0.001), and systolic blood pressure (25 vs. 15 mm Hg, P < 0.003), as well as higher mean peak plasma concentrations of interleukin-6 (50 vs. 17 micrograms per liter) and interleukin-8 (2000 vs 205 ng per liter) (P < 0.001 for both comparisons). Levels of TNF-alpha were undetectable after treatment with anti-TNF-alpha Fab. CONCLUSIONS: Pretreatment with sheep anti-TNF-alpha Fab suppresses Jarisch-Herxheimer reactions that occur after penicillin treatment for louse-borne relapsing fever, reduces the associated increases in plasma concentrations of interleukin-6 and interleukin-8, and may be useful in other forms of sepsis.     

Characterization of two monoclonal antibodies against the RON tyrosine kinase receptor

An anthropometric assessment was conducted at 238 !Kung San hunter-gatherers aged between 18 and 65 years (mean = 30.8 years), 156 Kavango horticultural pastoralists aged between 18 and 61 years (mean = 29.2 years) and for 87 urbanized Kavango people aged between 18 and 61 years (mean = 29.3 years) living as wage earning employees in northern Namibia. Weight status was estimated by using body mass index categories according to the recommendations of the WHO. As is typical for human populations, men were taller and heavier than women within the same ethnic groups. An interethnic comparison showed that both !Kung San women and men were lighter than Kavango women and men. The mean BMI of !Kung San women was 19.1 and of !Kung San men 19.4 kg/m2. Kavango people exhibited higher average BMI values, 19.4 for women, 20.3 kg/m2 for men. With the exception of the male urban Kavango people a high percentage (more than 30%) of the subjects were thin and underweight, as shown by a BMI of < 18.5 kg/m2. This was especially true of the !Kung San of both sexes and the rural Kavango men. Nearly 25% of !Kung San women met the criterion of weight depletion (BMI < 17.0). The cultural transition from nomadic hunter gatherer subsistence to a more sedentary life style over the last 20 years can be interpreted as an environmental stress which affected male as well as female nutritional status. The hard economic situation of the rural Kavango people may also be a stress factor which negatively influenced their nutritional status, especially of the men. The significantly better nutritional status of the urban Kavango men may be the result of the opportunities for work as wage earners or as soldiers.     

Monoclonal antibodies in the treatment of steroid-resistant acute graft-versus-host disease

Acute graft-versus-host disease (GVHD) remains the major obstacle for successful allogeneic bone marrow transplantation (BMT). The frequency of grade II or higher acute GVHD ranges from 30-50% in human leukocyte antigen (HLA)-matched sibling transplants and 50-80% in HLA-matched unrelated transplants. The mortality and morbidity associated with this complication are substantial. Corticosteroid and polyclonal antibodies such as antithymocyte globulin (ATG) have had little success in treating the disease; however, advances have been made in hybridoma technology and understanding its immunopathophysiology. Based on these new insights, monoclonal antibodies, either murine or "humanized," were tested as rescue treatment for acute GVHD in human trials. Complete response rates ranged from 20-40%, with relapse occurring often. Side effects consisted of constitutional symptoms such as fever, chills, hypotension, thrombocytopenia, and leukopenia. Limitations of monoclonal antibody treatment included low response rate and patient survival, high relapse rate, risk of infectious complication, and leukemic relapse. Future study should focus not only on improved side effects and efficacy of monoclonal antibodies but also on better patient survival.     

Do intestinal parasites interfere with the seroepidemiologic surveillance of Schistosoma mansoni infection?

In view of the known cross-reactivity of sera from patients with intestinal parasites to some Schistosoma mansoni antigens, field work was conducted in an area of Venezuela non-endemic for schistosomiasis using the routine immunoenzymatic assay (ELISA) with soluble egg antigen (SEA). False positive reactions represented 15.3% of the total population as determined by SEA-ELISA. SEA-immunoblotting of the false positive sera indicated that protein fractions of 91 and 80 kDa appear to be responsible for cross-reactivity. Sera from hookworm infected individuals produced a higher frequency and intensity of cross-reaction than other sera. SEA-fractions of 105, 54, 46, 42, 32, 25 and 15 kDa were the most specific.     

Characterization of monoclonal antibodies directed against the alpha-subunit of the human IgE high-affinity receptor

Effective ex vivo purging techniques can decrease the likelihood of infusing bone marrow contaminated with leukemic cells during autologous transplantation. In preliminary studies, OL(1)p53, a 20-mer phosphorothioate oligonucleotide directed against p53 mRNA, decreased the number of acute myelogenous leukemia (AML) cells in vitro, suggesting a possible role for OL(1)p53 in purging bone marrow harvests of leukemia cells. To demonstrate that OL(1)p53 was nontoxic to hematopoietic progenitor cells, normal bone marrow cells were incubated with 10 microM OL(1)p53 for 36 h, and hematopoietic progenitor cell survival was determined by in vitro colony assays. OL(1)p53 had no toxic effect on the growth of either myeloid (CFU-GM) or erythroid (BFU-E) progenitor cells. OL(1)p53 was then used to ex vivo purge bone marrow harvests from nine patients with either AML or myelodysplastic syndrome (MDS). Bone marrow cells were incubated with 10 microM OL(1)p53 for 36 h before transplantation. The median times posttransplantation for the patient to recover an absolute neutrophil count greater than 0.5 x 10(9)/L and a platelet transfusion independence were 30 days and 56 days, respectively. Incubation of bone marrow cells with OL(1)p53 had no detrimental effect on the growth of hematopoietic progenitor cells, and transplantation of autologous bone marrow cells treated with the phosphorothioate oligonucleotide, OL(1)p53, resulted in successful recovery of circulating neutrophils following high-dose therapy in patients with AML or MDS. The data show that OL(1)p53 can be used safely to purge autologous bone marrow harvests from patients with leukemia.     

Serological comparison of tospoviruses with polyclonal antibodies produced against the main structural proteins of tomato spotted wilt virus

The perfect bladder substitute has not been devised yet. The ileal orthotopic bladder substitute, however, provides adequate capacity, convenient voiding patterns, optimal continence rate, preservation of renal function, acid-base balance, and calcium metabolism. The authors describe important surgical details based on experience with more than 200 patients. To achieve a good functional result, patient selection, postoperative voiding reeducation, and meticulous follow-up are important.     

Rapid verification of the identity of questionable specimens using immunohistochemistry with monoclonal antibodies directed against HLA-class I antigens

PURPOSE: To evaluate the effect of substituting topical cyclosporin A 0.5% for topical corticosteroids in patients with postkeratoplasty glaucoma. METHODS: Topical cyclosporin A 0.5% was prospectively substituted for topical corticosteroids to treat 25 patients with postkeratoplasty glaucoma. RESULTS: Twenty-one (84%) of 25 patients showed a reduction in intraocular pressure (IOP) (range, 1-22 mm Hg; mean, 8.7 mm Hg). Follow-up ranged from 3 to 12 months (mean, 5.8). Graft clarity was maintained in all patients, with one allograft rejection episode. Thirteen patients were able to discontinue one or more glaucoma medication(s). CONCLUSION: Topical cyclosporin A 0.5% may be substituted for topical corticosteroids to aid in the management of postkeratoplasty patients with glaucoma. However, the resultant decrease in IOP may be associated with an increased risk for immune rejections.     

Methodology of the study of pre- and post-vaccination antibodies against serogroup C Meningococcus

Based on the recently resolved crystal structure of complex (-)-huperzine A-AChE, we simulated the interaction between (-)-huperzine A analogues and AChE using molecular dynamics method. It was revealed that the methyl group at the three carbon bridge of (-)-huperzine A can form a weak hydrogen bond with the phenol hydroxyl oxygen of Tyr121 and the main-chain oxygen of Gly118 of AChE, respectively.     

Detection of IgA antibodies as important markers of acute primary infection with Toxoplasma gondii

The diagnosis of Toxoplasma gondii infection is currently based on immunological tests, but tests for IgM and IgG antibodies alone are often insufficient to estimate the risk of active disease, especially during pregnancy and in immunodeficient patients. Classically the study of anti-toxoplasma immunity involves titration of IgG antibodies, which reflect immunity to the parasite, and IgM antibodies which of present, reveal acute infection. However, technical advances have shown the limitations of these tests as tests for IgM can be positive because of residual specific IgM or even in subjects free of acute infection due to the existence of natural interfering IgM. In addition, IgM can be absent in children with congenital toxoplasmosis or subjects with secondary reactivation. The purpose of our study was to evaluated of IgA antibodies to T. gondii in serum samples which were positive in screening test. Our results confirm the diagnostic value of testing for anti-toxoplasma IgA antibodies. These antibodies are absent in uninfected subjects and are detected rapidly after primary infection. The determination of IgA complements IgM determination for the diagnosis of toxoplasmosis.