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PubMed1998

Induction of B cell responses in the stomach of Helicobacter pylori- infected subjects after oral cholera vaccination.

We have evaluated the possibility of inducing antibody responses locally in the human stomach as a prerequisite for the development of a vaccine against Helicobacter pylori. Both H. pylori-infected and noninfected subjects were immunized with an oral B subunit whole cell (BS-WC) cholera vaccine, and total and vaccine-specific antibody-secreting cells (ASC) were determined by the enzyme-linked immunospot (ELISPOT) technique in cells isolated from the antrum and duodenum, respectively, before and after vaccination. Most of the subjects responded to the vaccination with high frequencies of vaccine-specific ASCs in the duodenum as well as high-serum antibody titers, and no significant differences were seen in the responses between H. pylori- infected and noninfected subjects. When studying the gastric mucosa, on the other hand, there were dramatic differences between the H. pylori-infected and the noninfected subjects. Thus, whereas none of the noninfected subjects responded to the immunization in antrum, most of the H. pylori-infected subjects had high frequencies of vaccine-specific ASCs in this location after vaccination. Furthermore, the H. pylori-infected subjects had strikingly higher (as a mean 80-fold) frequencies of total IgA-secreting cells in antrum than the noninfected subjects, whereas the frequencies of total IgA-secreting cells in the duodenum were comparable between the groups. In conclusion, these results demonstrate the possibility of inducing antibody responses locally in the gastric mucosa of H. pylori-infected individuals, a finding with obvious implications for the future development of a therapeutic vaccine against H. pylori.

Administration, Oral↗

PubMed2002

Brief report: prevalence of autism spectrum conditions in children aged 5-11 years in Cambridgeshire, UK.

The study aimed to establish prevalence of the broader autistic spectrum, including Asperger syndrome, in 5- to 11-year-olds in Cambridgeshire, UK. Cases of diagnosed autism spectrum condition (ASC) in children who were in Cambridgeshire schools and aged between 5 and 11 years on 31 December 1999 were sought using public records, screening instruments, educational psychology and special educational needs coordinator (SENCO) records. We report a prevalence of ASC in the age group 5-11 years of almost 0.6 percent (57 in 10,000). This is 11 times higher than the rate of classic autism but in line with other recent national and international rates for the broader spectrum. In the responding mainstream schools the prevalence was 0.33 percent. In the responding special school population it was 12.5 percent. The overall sex ratio of the children with ASC replicated findings for classical autism of 4:1 (M:F), but in those children being educated in mainstream schools the sex ratio was 8:1 (M:F).

Autistic Disorder↗

PubMed2003

Effect of long-term hormone replacement therapy on atherosclerosis progression in postmenopausal women relates to myeloperoxidase promoter polymorphism.

Myeloperoxidase (MPO) is an oxidative enzyme present in phagocytes and atherosclerotic lesions. The MPO gene has a promoter polymorphism -463G/A, which leads to high (GG) and low expression (AG, AA) genotypes. We investigated the effect of long-term hormone replacement therapy (HRT) on the progression of atherosclerosis in a 5-yr follow-up study of postmenopausal women with different MPO genotypes. Eighty-seven nonsmoking postmenopausal women, aged 45-71 yr, were divided into three groups based on the use of HRT. The HRT-EVP group (n = 25) used sequential estradiol valerate plus progestin, the HRT-EV group used estradiol valerate alone (n = 32), and the control group (n = 30) used no HRT. The atherosclerosis severity score (ASC) for abdominal aorta and carotid arteries was determined by ultrasonography, and the MPO genotype was analyzed. In subjects with the GG genotype, the progression of ASC was significantly faster in the control group than in the HRT group (genotype by time interaction, P = 0.042), whereas in A allele carriers there were no significant differences in ASC progression between control and HRT. The effects of HRT on atherosclerosis progression in subjects with the GG genotype seem to be especially beneficial compared with controls with the same genotype but without HRT. These results may help us understand in greater detail the benefit and possible risk of HRT in atherosclerotic diseases.

Aged↗

PubMed2003

Organizational factors affect comparisons of the clinical productivity of academic anesthesiology departments.

UNLABELLED: Productivity measurements based on "per operating room (OR) site" and "per case" are not influenced by staffing ratios and have permitted meaningful comparisons among small samples of both academic and private-practice anesthesiology groups. These comparisons have suggested that a larger sample would allow for clinical groups to be compared using a number of different variables (including type of hospital, number of OR sites, type of surgical staff, or other organizational characteristics), which may permit more focused benchmarking. In this study, we used such grouping variables to compare clinical productivity in a broad survey of academic anesthesiology programs. Descriptive, billing, and staffing data were collected for 1 fiscal or calendar year from 37 academic anesthesiology departments representing 58 hospitals. Descriptive data included types of surgical staff (e.g., academic versus private practice) and hospital centers (e.g., academic medical centers and ambulatory surgical centers [ASCs]). Billing and staffing data included total number of cases performed, total American Society of Anesthesiologists units (tASA) billed, total time units billed (15-min units), and daily number of anesthetizing sites staffed (OR sites). Measurements of total productivity (tASA/OR site), billed hours per OR site per day (h/OR/d), surgical duration (h/case), hourly billing productivity (tASA/h), and base units/case were compared. These comparisons were made according to type of hospital, number of OR sites, and type of surgical staff. The ASCs had significantly less tASA/OR site, fewer h/OR/d, and less h/case than non-ASC hospitals. Community hospitals had significantly less h/OR/d and h/case than academic medical centers and indigent hospitals and a larger percentage of private-practice or mixed surgical staff. Academic staffs had significantly less tASA/h and significantly more h/case. tASA/h correlated highly with h/case (r = -0.68). This study showed that the hospitals at which academic anesthesiology groups provide care are not all the same from a clinical productivity perspective. By grouping based on type of hospital, number of OR sites, and type of surgical staff, academic anesthesiology departments (and hospitals) can be better compared by using clinical productivity measurements based on "per OR site" and "per case" measurements (tASA/OR, billed h/OR/d, h/case, tASA/h, and base/case). IMPLICATIONS: Organizational factors, including type of hospital, number of operating rooms, and type of surgical staff, influence the clinical productivity of academic anesthesiology departments. Reporting quartile data by focused grouping variables allows anesthesiology groups to compare their clinical productivity with groups practicing in similar clinical settings.

Academic Medical Centers↗

PubMed1997

Genetic basis of the formation and identity of type I and type II neurons in Drosophila embryos.

The embryonic peripheral nervous system of Drosophila contains two main types of sensory neurons: type I neurons, which innervate external sense organs and chordotonal organs, and type II multidendritic neurons. Here, we analyse the origin of the difference between type I and type II in the case of the neurons that depend on the proneural genes of the achaete-scute complex (ASC). We show that, in Notch- embryos, the type I neurons are missing while type II neurons are produced in excess, indicating that the type I/type II choice relies on Notch-mediated cell communication. In contrast, both type I and type II neurons are absent in numb- embryos and after ubiquitous expression of tramtrack, indicating that the activity of numb and the absence of tramtrack are required to produce both external sense organ and multidendritic neural fates. The analysis of string- embryos reveals that when the precursors are unable to divide they differentiate mostly into type II neurons, indicating that the type II is the default neuronal fate. We also report a new mutant phenotype where the ASC-dependent neurons are converted into type II neurons, providing evidence for the existence of one or more genes required for maintaining the alternative (type I) fate. Our results suggest that the same mechanism of type I/type II specification may operate at a late step of the ASC-dependent lineages, when multidendritic neurons arise as siblings of the external sense organ neurons and, at an early step, when other multidendritic neurons precursors arise as siblings of external sense organ precursors.

Animals↗

PubMed1987

The effect of trans-4-guanidinomethylcyclohexanecarboxylic acid p-tert-butylphenyl ester hydrochloride (NCO-650) on Ascaris suum antigen-induced bronchoconstriction in dogs.

Antiallergic asthma effect of trans-4-guanidinomethylcyclohexane-carboxylic acid p-tert-butylphenyl ester hydrochloride (NCO-650), a new anti-allergic drug, was investigated in comparison with those of tranilast and disodium cromoglycate (DSCG) in anesthetized dogs. The asthmatic bronchoconstriction was induced by inhalation of Ascaris suum antigen (Asc-Ag) to naturally Ascaris-sensitive dogs. The airway resistance was determined using the modified Konzett-Rössler method. Both intravenous (1 and 5 mg/kg) and intraduodenal (10, 30 and 100 mg/kg) administrations of NCO-650 prior to the antigen challenge markedly inhibited the asthmatic bronchoconstriction induced by Asc-Ag inhalation. The antiasthmatic effect of NCO-650 was much stronger than that of DSCG (10 mg/kg, i.v.) and was about three-fold stronger than that of tranilast. On the other hand, when NCO-650 was administered after the antigen challenge, the agent had no inhibitory effect on the Asc-Ag induced bronchoconstriction. As for the effects on increased airway secretion at the time of asthmatic attack, NCO-650 inhibited the excessive secretions without any remarkable change in the viscosity of the secretions. NCO-650 had no effect on the bronchoconstriction induced by inhalation of acetylcholine, suggesting that NCO-650 appears to have no anti-cholinergic effect and thus no effect on the vagal reflex that occurred during the asthmatic responses. The above findings show that NCO-650 may be useful for the treatment of bronchial asthma as an orally active drug.

Acetylcholine↗

PubMed2005

Prevalence of positional sleep apnea in patients undergoing polysomnography.

STUDY OBJECTIVES: The primary aim of this study was to determine the prevalence of positional obstructive sleep apnea using a functional definition. Positional sleep apnea was defined as a total apnea-hypopnea index (AHI) > or = 5 with a > 50% reduction in the AHI between the supine and nonsupine postures, and an AHI that normalizes (AHI < 5) in the nonsupine posture. A secondary aim was to determine if positional sleep apnea can be diagnosed accurately during a split-night study. DESIGN: Retrospective chart review. SETTING: Two sleep centers in Buffalo, NY, one a Veterans Affairs Western New York Healthcare System Sleep Center (VAWNY) and the other a freestanding ambulatory center (Associated Sleep Center [ASC]). PATIENTS: Three hundred twenty-six patients from the VAWNY, including 57 patients who underwent a split-night study and 242 patients from the ASC who underwent polysomnography. INTERVENTIONS: None. MEASUREMENTS: Patient characteristics and sleep study results. RESULTS: Positional sleep apnea was seen in 49 of 99 patients (49.5%) with mild sleep apnea (AHI, 5 to 15/h), 14 of 72 patients (19.4%) with moderate sleep apnea (AHI, 15 to 30/h), and 5 of 77 patients (6.5%) with severe sleep apnea (AHI > 30/h). Sufficient sleep (> 15 min) in both postures was not seen in 104 of 269 patients (38.7%) and 80 of 242 overnight studies (33.1%) at the VAWNY and ASC, respectively, and was not seen in 47 of 57 split-night studies (82.5%). The percentage of studies with insufficient sleep in both postures was significantly greater for split-night studies (p < 0.0001). CONCLUSIONS: Positional sleep apnea is common particularly in patients with mild disease. Positional sleep apnea cannot usually be assessed during a split-night study.

Adult↗

PubMed2005

Immunophenotype of human adipose-derived cells: temporal changes in stromal-associated and stem cell-associated markers.

Adipose tissue represents an abundant and accessible source of multipotent adult stem cells and is used by many investigators for tissue engineering applications; however, not all laboratories use cells at equivalent stages of isolation and passage. We have compared the immunophenotype of freshly isolated human adipose tissue-derived stromal vascular fraction (SVF) cells relative to serial-passaged adipose-derived stem cells (ASCs). The initial SVF cells contained colony-forming unit fibroblasts at a frequency of 1:32. Colony-forming unit adipocytes and osteoblasts were present in the SVF cells at comparable frequencies (1:28 and 1:16, respectively). The immunophenotype of the adipose-derived cells based on flow cytometry changed progressively with adherence and passage. Stromal cell-associated markers (CD13, CD29, CD44, CD63, CD73, CD90, CD166) were initially low on SVF cells and increased significantly with successive passages. The stem cell-associated marker CD34 was at peak levels in the SVF cells and/or early-passage ASCs and remained present, although at reduced levels, throughout the culture period. Aldehyde dehydrogenase and the multidrug-resistance transport protein (ABCG2), both of which have been used to identify and characterize hematopoietic stem cells, are expressed by SVF cells and ASCs at detectable levels. Endothelial cell-associated markers (CD31, CD144 or VE-cadherin, vascular endothelial growth factor receptor 2, von Willebrand factor) were expressed on SVF cells and did not change significantly with serial passage. Thus, the adherence to plastic and subsequent expansion of human adipose-derived cells in fetal bovine serum-supplemented medium selects for a relatively homogeneous cell population, enriching for cells expressing a stromal immunophenotype, compared with the heterogeneity of the crude SVF.

Adipose Tissue↗

PubMed1992

Effects of copper, iron, and ascorbic acid on manganese availability to rats.

Four experiments were done to characterize the interactions of copper, iron, and ascorbic acid with manganese in rats. All experiments were factorially arranged Dietary Mn concentrations were less than 1 micrograms/g (Mn0) and 50 micrograms/g (Mn+). Dietary Cu was less than 1 mg/g (Cu0) and 5 micrograms/g (Cu+); dietary Fe was 10 micrograms/g (Fe10) and 140 micrograms/g (Fe140). Ascorbic acid (Asc) was not added to the diet or added at a concentration of 10 g/kg diet. Experiment 1 had two variables, Mn and Cu; in Experiment 2, the variables were Mn and Asc. In Experiment 3, the variables were Mn, Cu, and Asc; in Experiment 4, they were Mn, Cu, and Fe. Definite interactions between Mn and Cu were observed, but they tended to be less pronounced than interactions between Mn and Fe. Cu depressed absorption of 54Mn and accelerated its turnover. In addition, adequate Cu (Cu+), compared with Cu0, depressed liver, plasma, and whole blood Mn of rats. Absorption of 67Cu was higher in animals fed Mn0 diets than in those fed Mn+. Ascorbic acid depressed Mn superoxide dismutase activity and increased Cu superoxide dismutase activity in the heart. The addition of ascorbic acid to the diet did not affect Mn concentration in the liver or blood. Absorption of 54Mn was depressed in rats fed Fe140 compared with those fed Fe10. Interactions among Fe, Cu, and Mn resulted in a tendency for Mn superoxide dismutase activity to be lower in rats fed Fe140 than in rats fed Fe10. Within the physiologic range of dietary concentrations, Mn and Cu have opposite effects on many factors that tend to balance one another. The effects of ascorbic acid on Mn metabolism are much less pronounced than effects of dietary Cu, which in turn affects Mn metabolism less than does Fe.

Absorption↗

PubMed2005

Cytokine profile in Egyptian hepatitis C virus genotype-4 in relation to liver disease progression.

AIM: To observe the imbalance between T helper cell Th1 and Th2 cytokines in several chronic hepatitis disease at different stages of disease progression. METHODS: We measured the cytokine levels of Th1 (IL-2 and IL-2R), Th2 (IL-10) and the pro-inflammatory cytokines (IL-6 and IL-6R and TNF and TNF-RI and II) by the ELISA technique in the sera of 33 hepatocellular carcinoma (HCC) patients and 20 chronic liver disease (CLD) patients. In addition, 20 asymptomatic hepatitis C virus carriers and 20 healthy subjects negative for hepatitis C virus(HCV) markers served as controls. RESULTS: Anti-HCV antibodies were found to be positive in 94% of HCC cases and 75% of CLD cases. On the other hand, HCV viremia was detected using RT-PCR in 67% of HCC cases and 65% of CLD cases. HBsAg was positive in 9% of HCC cases and 30% of CLD cases. Also bilharzial-Ab was positive in 55% of HCC cases, 65% of CLD cases and in 70% of asymptomatic carriers (ASC). HCC patients had significantly higher values of IL-2R, TNF-RII (P<0.001), and TNF-RI (P>0.05), but lower TNFalpha (P<0.001) and IL-6 (P = 0.032) in comparison to ASC. But, in comparison to non-cancer controls, HCC patients had higher values of IL-2R, IL-6R, TNF-RI and TNF-RII, but lower TNF-alpha (P<0.001). CLD patients had higher IL-2R, TNF-RI, and TNF-RII (P<0.001) than ASC. But, in comparison to non-cancer controls, CLD patients had higher values of IL-2R, TNF-RI and TNF-RII, but lower TNF-alpha (P<0.001). IL-10 was higher (though not significantly) in HCC and CLD patients than in symptomatic carriers and non-cancer controls. CONCLUSION: Liver disease progression from CLD to HCC due to HCV genotype-4 infection is associated with an imbalance between Th1 and Th2 cytokines. IL-2R, TNF-RI, and TNF-RII could be used as potential markers.

Adult↗

PubMed2002

Correlation of tissue distribution, developmental phenotype, and intestinal homing receptor expression of antigen-specific B cells during the murine anti-rotavirus immune response.

The intestinal homing receptor, alpha(4)beta(7), helps target lymphocytes to Peyer's patches (PP) and intestinal lamina propria (ILP). We have previously shown that protective immunity to rotavirus (RV), an intestinal pathogen, resides in memory B cells expressing alpha(4)beta(7). In this study, using a novel FACS assay, we have directly studied the phenotype of B cells that express surface RV-specific Ig during the in vivo RV immune response. During primary infection, RV-specific B cells first appear as large IgD(-)B220(low)alpha(4)beta(7)(-)and alpha(4)beta(7)(+) cells (presumptive extrafollicular, Ab-secreting B cells), and then as large and small IgD(-)B220(high)alpha(4)beta(7)(-)cells (presumptive germinal center B cells). The appearance of B cells with the phenotype of large IgD(-)B220(low)alpha(4)beta(7)(+) cells in PP and most notably in mesenteric lymph nodes coincides with the emergence of RV-specific Ab-secreting cells (ASC) in the ILP. Thus, these B lymphocytes are good candidates for the migratory population giving rise to the RV-specific ASC in the ILP. RV-specific long-term memory B cells preferentially accumulate in PP and express alpha(4)beta(7). Nine months after infection most RV-specific IgA ASC are found in PP and ILP and at lower frequency in bone marrow and spleen. This study is the first to follow changes in tissue-specific homing receptor expression during Ag-specific B cell development in response to a natural host, tissue-specific pathogen. These results show that alpha(4)beta(7) is tightly regulated during the Ag-specific B cell response to RV and is expressed concurrently with the specific migration of memory and effector B cells to intestinal tissues.

Animals↗

PubMed2003

A common mucosal chemokine (mucosae-associated epithelial chemokine/CCL28) selectively attracts IgA plasmablasts.

IgA immunoblasts can seed both intestinal and nonintestinal mucosal sites following localized mucosal immunization, an observation that has led to the concept of a common mucosal immune system. In this study, we demonstrate that the mucosae-associated epithelial chemokine, MEC (CCL28), which is expressed by epithelia in diverse mucosal tissues, is selectively chemotactic for IgA Ab-secreting cells (ASC): MEC attracts IgA- but not IgG- or IgM-producing ASC from both intestinal and nonintestinal lymphoid and effector tissues, including the intestines, lungs, and lymph nodes draining the bronchopulmonary tree and oral cavity. In contrast, the small intestinal chemokine, TECK (CCL25), attracts an overlapping subpopulation of IgA ASC concentrated in the small intestines and its draining lymphoid tissues. Surprisingly, T cells from mucosal sites fail to respond to MEC. These findings suggest a broad and unifying role for MEC in the physiology of the mucosal IgA immune system.

Animals↗

PubMed1977

Suppressing effects of purified eosinophils derived from guinea pigs sensitized with Ascaris antigen on lymphocyte-blastformation.

Highly purified eosinophil (EOS) fractions were obtained from peritoneal exudate cells of guinea pigs immunized with with Ascaris lumbricoides suum antigen (Asc). These Eos suppressed the in vitro DNA synthesis of the lymph node cells (LNC) sensitized with Asc and then activated by this antigen or phytohemagglutinin (PHA). Although addition of Eos did not effect the viability of LNC in vitro, the blastformation of LNC was suppressed remarkably when 5-10 X 10(5) purified Eos were added to 10(6) LNC within 48 hr after the start of stimulation by Asc. The suppressive effects of Eos on the blastformation of LNC immunized with complete Freund's adjuvant with or without ovalbumin were observed when stimulated with purified protein derivates or ovalbumin. Such suppression were observed beyond the barrier of animal strain specificity; Eos from Hartley guinea pigs suppressed proliferation of LNC from either strain 13 or strain 2, and Eos from strain 13 suppressed that from strain 2. Such suppressing activity of Eos was reduced by heating them at 56 C for 1 hr or by sonication.

Animals↗

PubMed1993

Freestanding ambulatory surgery: cost-containment winner?

In many states, freestanding, ambulatory surgery centers (ASCs) are being permitted to provide overnight, postoperative recovery and observation services. As a result, ASCs are now able to perform surgical procedures that were once the exclusive province of hospital-based outpatient surgery departments. As an analysis of data gathered in Florida and North Carolina illustrates, freestanding ASCs usually have lower charges than their hospital-based counterparts. This finding suggests that hospitals will have to take steps to control their ambulatory surgery costs if they want to compete successfully in the race for ambulatory surgery dollars.

Ambulatory Surgical Procedures↗

PubMed1984

Medicare program; list of covered surgical procedures for ambulatory surgical centers--HCFA. Proposed notice and request for comment.

HCFA is seeking suggestions for possible additions or revisions to the current list of ambulatory surgical center (ASC) procedures covered under Medicare. Our current list of covered ASC procedures was published in the Federal Register on August 5, 1982 (47 FR 34099). In this notice we are also soliciting comments on additional ASC procedures that have been suggested by the public since publication of our current list.

Centers for Medicare and Medicaid Services, U.S.↗

PubMed1989

Miscellaneous Medicare and Medicaid amendments--HCFA. Final rule.

These regulations make the following changes in the Medicare and Medicaid rules: 1. Remove from the Medicare rules the lists of deductible and coinsurance amounts that are revised annually. 2. Establish the conditions for Medicare Part B to pay for an antigen that is administered by someone other than the physician who prepares the antigen. 3. Provide that specified equipment is required to be available in an ambulatory surgical center (ASC) only if the medical staff of the ASC considers it necessary. 4. Clarify the rules on agreements with Medicare intermediaries and carriers and on coordination of their activities with the activities of peer review organization (PROs). 5. Correct an involuntary omission by adding "skilled nursing facility services for individuals under 21" to the list of Medicaid services for which Federal financial participation may be continued for up to 30 days after termination of the provider agreement. 6. Revise the rules on denial of Medicare provider agreements to reflect Bankruptcy Code changes under which a provider agreement may not be denied solely because of bankruptcy. These amendments are necessary to simplify, clarify, or conform minor aspects of the Medicare rules on: Deductibles and coinsurance. Payment for antigens. Equipment required in ASCs. Agreements with intermediaries and carriers. Coordination of the activities of intermediaries and carriers and those of PROs. The amendments also correct an omission in the Medicaid rules on Federal financial participation. The first amendment is purely a matter of simplification. The other changes are intended to ensure that users of HCFA regulations have the clear understanding necessary for uniform application.

Centers for Medicare and Medicaid Services, U.S.↗

PubMedDate not supplied

Systematic screening of antioxidants for maximum protection against oxidation: an oxygen polarograph study.

The development of a simple method for rapid screening of antioxidants in the preformulation phase of drug development is reported. Using an easily oxidizable drug substance containing a tetrahydroisoquinoline nucleus, the relative antioxidant efficacies was determined by simultaneous measurement of dissolved oxygen depletion and drug disappearance rates in presence and absence of antioxidants by oxygen polarographic and high performance liquid chromatographic (HPLC) methods, respectively. Results showed an inverse correlation between oxygen depletion and drug disappearance rates (R2 > 0.85). In contrast, such a high correlation was not obtained when the standard redox potential of these antioxidants was used as a predictor of drug disappearance rates (R2 > 0.50). The rate at which sodium metabisulfite (BIS) and glutathione depleted dissolved oxygen was reduced in the presence of drug, indicating possible reaction between either of the two antioxidants and drug (OHM-11252). Hence, BIS and glutathione may not be suitable antioxidants for stabilizing OHM-11252 in solution. The oxygen depletion rate constants and percent of intact drug remaining were higher in presence of ascorbic acid (ASC) than BIS. Analysis of the reaction mixtures by HPLC diode array detection showed that the number and percent peak area of non-drug peaks formed from ASC-stabilized drug were lower than for BIS. Hence, ASC provides the drug better protection from oxidative degradation.

Antioxidants↗

PubMed1975

Regulation of antibody response in vitro. IX. Induction of secondary anti-hapten IgG antibody response by anti-immunoglobulin and enhancing soluble factor.

Attempts were made to induce antibody response of hapten-primed cells by stimulation with anti-immunoglobulin (Ig) antibody and cellfree supernatant (CFS) which contained nonspecific enhancing factor. Mesenteric lymph node cells were obtained from rabbits which were primed with dinitrophenylated ragweed antigen (DNP-Rag), and the primed cells were incubated in vitro with either anti-rabbit gamma-chain or anti-Fab antibody for 24 hr. After washing, the cells were cultured in CFS which was obtained from the culture of DNP-Ascaris (DNP-Asc)-primed lymph node cells with free carrier (Asc). The results showed that hapten-primed cells were triggered for IgG anti-DNP antibody response by the two reagents, i.e., anti-Ig antibody and CFS, both which did not share any antigenic specificity with the priming antigen (DNP-Rag). Neither anti-Ig alone nor CFS alone induced anti-hapten antibody response. Anti-Ig and CFS triggered not only hapten-primed B cells but also the other IgG-bearing (B) cells for IgG synthesis. Lymph node cells of umprimed animals were activated for IgG synthesis by the stimulation with anti-Ig followed by culture in CFS. Evidence was obtained that anti-Ig antibody has to be divalent for the activation of B cells. Stimulation of DNP-primed cells with the F(ab')2 fragment of the antibody and CFS-induced anti-hapten antibody response, whereas the Fag' fragment of the anti-Ig plus CFS failed to do so. The results suggested that bridging of cell-surface Ig receptors by multivalent ligand is the initial step of B cell activation. Another evidence for the activation of hapten-primed B cells by anti-Ig was obtained by supplemental immunization of DNP-Asc-primed animals with the Fc fragment of goat IgG. Stimulation of mesenteric lymph node cells from these animals with goat anti-rabbit-Ig alone (no CFS) resulted in the formation of anti-DNP IgG antibody. The results indicated that lymphocytes primed for goat IgG collaborated with DNP-primed IgG-B cells when the lymph node cells were stimulated with goat anti-Ig.

Animals↗