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Biomedical subjects

Z Zhong

Publications and source records attributed to Z Zhong.

At least 73 records · Page 4Linked to original sources
PubMed2000

[Effect of combined operation including splenorenal shunt as the main technique for portal hypertension in children].

OBJECTIVE: To assess the effect of combined operation including splenorenal shunt as the main technique for portal hypertension in children. METHODS: 22 patients were reviewed and followed up from 1980 to 1998 (13 male, 9 female). The average age was 9.45 years. Intrahepatic type was shown in 16 patients and prehepatic type in 6. All patients had hematemesis, hematochezia or severe esophageal varices. Liver function was classified Child A in 14 patients, B in 7, and C in 1. Combined operation was performed in all patients. RESULTS: There was no operative death in this group. 21 patients (95.5%) were followed up, with the longest time for 19 years (average 9.58 years). Six patients had hemorrhage from the esophageal varices after operation, and two died of hemorrhage. The survival rates of < 3, -5, -10, -15, > 15 years were 95.2%, 100%, 93.8%, 100%, 100% respectively. No hepatic encephalopathy was noted. CONCLUSION: In treating and preventing hemorrhage from the esophageal varices, combined operation including splenorenal shunt as the main technique is the first choice for the portal hypertension in children. Attention must be paid to the patients who had hemorrhage from the esophageal varices after operation.

Adolescent↗
PubMed2000

[Direct determination of rare earth elements in rare earth chloride and light rare earth oxide by ICP-AES].

ICP-AES was used for the direct determination of 15 rare earth elements in synthetic solutions and real sample. Spectral interferences between REEs in the mixtures of rare earth were investigated with a high-resolution echelle spectrometer and suitable analytical lines of 15 rare earth elements were selected. The Multicomponent Spectral Fitting(MSF) models were made. The method was used to remove spectral interferences and background. The factors influence the modes were discussed. The influences of acidity and ICP parameters were investigated. The compromise condition of simultaneous determination of 15 REEs was selected. Axially viewed ICP torch was used to determine 15 REEs, The detection limits are Y 0.21 microgram.L-1, La 9.1 micrograms.L-1, Ce 14.1 micrograms.L-1, Pr 1.9 micrograms.L-1, Nd 7.8 micrograms.L-1, Tm 0.37 microgram.L-1, Yb 0.12, Lu microgram.L-1, Ho 0.06 microgram.L-1, Er 0.06 microgram.L-1, Tb 0.53 microgram.L-1, Sm 1.14 micrograms.L-1, Eu 0.09 microgram.L-1, Dy 0.08 microgram.L-1, Gd 0.30 microgram.L-1. The recoveries of this procedure are between 98.4% and 101.7%. The RSD is within 2%. The method is rapid and accuracy.

English Abstract↗
PubMed1999

Glycine: a new anti-inflammatory immunonutrient.

The mechanism of the immunosuppressive effects of glycine and its pathophysiological applications are discussed in this review. Glycine has been well characterized in spinal cord as an inhibitory neurotransmitter which activates a glycine-gated chloride channel (GlyR) expressed in postsynaptic membranes. Activation of the channel allows the influx of chloride, preventing depolarization of the plasma membrane and the potentiation of excitatory signals along the axon. Glycine has recently been shown to have similar inhibitory effects on several white blood cells, including hepatic and alveolar macrophages, neutrophils, and lymphocytes. Pharmacological analysis using a GlyR antagonist strychnine, chloride-free buffer, and radiolabeled chloride has provided convincing evidence to support the hypothesis that many white blood cells contain a glycine-gated chloride channel with properties similar to the spinal cord GlyR. Molecular analysis using reverse transcription-polymerase chain reaction and Western blotting has identified the mRNA and protein for the beta subunit of the GlyR in total RNA and purified membrane protein from rat Kupffer cells. Dietary glycine is protective in rat models against endotoxemia, liver ischemia-reperfusion, and liver transplantation, most likely by inactivating the Kupffer cell via this newly identified glycine-gated chloride channel. Glycine also prevents the growth of B 16 melanomas cell in vivo. Moreover, dietary glycine is protective in the kidney against cyclosporin A toxicity and ischemia-reperfusion injury. Glycine may be useful clinically for the treatment of sepsis, adult respiratory distress syndrome, arthritis, and other diseases with an inflammatory component.

Alcohols↗
PubMed1999

Evaluation of prognostic criteria for determining hospice eligibility in patients with advanced lung, heart, or liver disease. SUPPORT Investigators. Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments.

CONTEXT: Many individuals involved with care of the dying advocate expanding access to hospice care for persons with advanced lung, heart, or liver disease. However, to be eligible, these patients generally must have a prognosis for survival of less than 6 months. OBJECTIVE: To test the ability of currently available criteria to identify a population with a survival prognosis of 6 months or less among seriously ill hospitalized patients with 1 of 3 commonly fatal chronic diseases. DESIGN: Validation study using data from the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments (SUPPORT) phase 1 (June 1989-June 1991) and phase 2 (January 1992-January 1994), with a 6-month follow-up. SETTING AND PATIENTS: Consecutive sample of 2607 seriously ill patients from 5 US medical centers who were hospitalized with chronic obstructive pulmonary disease, congestive heart failure, or end-stage liver disease, and who survived to hospital discharge. MAIN OUTCOME MEASURES: Descriptive and operating characteristics of 5 general and 2 disease-specific clinical criteria for identifying patients with a survival prognosis of 6 months or less, and 3 sets of combination criteria (broad, intermediate, and narrow inclusion) aimed at providing low, medium, and high thresholds for hospice eligibility based on National Hospice Organization guidelines. RESULTS: Seventy-five percent of the sample survived more than 6 months after hospital discharge; 44% expressed a preference for palliative care. Broad inclusion criteria identified 923 patients eligible for hospice care, of whom 70% survived longer than 6 months. Intermediate inclusion criteria identified 300 patients, of whom 65% survived longer than 6 months. Narrow inclusion criteria identified 19 patients, of whom 53% survived longer than 6 months. Sensitivities and specificities of the combination criteria were 41.7% and 66.7% (broad inclusion), 16.2% and 90.1 % (intermediate inclusion), and 1.4% and 99.5% (narrow inclusion), respectively. CONCLUSIONS: These data indicate that for seriously ill hospitalized patients with advanced chronic obstructive pulmonary disease, congestive heart failure, or end-stage liver disease, recommended clinical prediction criteria are not effective in identifying a population with a survival prognosis of 6 months or less.

Adult↗
PubMed1999

Glycine improves survival after hemorrhagic shock in the rat.

This study investigated the effect of glycine on hemorrhagic shock in the rat. Rats were bled to maintain mean arterial pressure at 30-35 mm Hg for 1 h and subsequently resuscitated with 60% shed blood and lactated Ringer's solution. Only 20% of rats receiving saline just prior to resuscitation survived 72 h after shock. Survival was increased by glycine (11.2-90.0 mg/kg, i.v.) in a dose-dependent manner (half-maximal effect = 25 mg/kg) and reached maximal values of 78% at 45 mg/kg. Eighteen hours after resuscitation, creatinine phosphokinase increased 23-fold, transaminases increased 33-fold, and creatinine was elevated 2.4-fold, indicating injury to the heart, liver, and kidney, respectively. Pulmonary edema, leukocyte infiltration, and hemorrhage were also observed. In the kidney, proximal tubular necrosis, leukocyte infiltration, and severe hemorrhage in the outer medullary area occurred in rats receiving saline. Glycine reduced these pathological alterations significantly. It has been reported that oxidative stress and tumor necrosis factor(TNF)-alpha-production are involved in the pathophysiology of multiple-organ injury after shock. In this study, free radical production was increased 4-fold during shock, an effect blocked largely by glycine. Increases in intracellular calcium and production of TNF-alpha by isolated Kupffer cells stimulated by endotoxin were elevated significantly by hemorrhagic shock, alterations which were totally prevented by glycine. Taken together, it is concluded that glycine reduces organ injury and mortality caused by hemorrhagic shock by preventing free radical production and TNF-alpha formation.

Animals↗
PubMed1999

Dietary glycine and renal denervation prevents cyclosporin A-induced hydroxyl radical production in rat kidney.

Cyclosporin A (CsA) nephrotoxicity is associated with renal hypoxia and increases in free radicals in the urine. This study was designed to elucidate the mechanism of radical production caused by CsA. Pretreatment of rats with CsA (25 mg/kg, i.g.) for 5 days decreased glomerular filtration rates by 65%, an effect largely prevented by both dietary glycine (5%) or renal denervation. CsA dissolved in olive oil produced a 6-line alpha-(4-pyridyl 1-oxide)-N-tert-butylnitrone (4-POBN)/free radical signal in the urine, which partitioned predominantly into the aqueous phase after chloroform extraction (i.e., it is water soluble). Dimethyl sulfoxide (DMSO) is attacked by the hydroxyl radical to produce a methyl radical; administration of CsA with [(12)C]DMSO produced two radical species in urine, one with hyperfine coupling constants similar to the 4-POBN/methyl radical adduct found in aqueous solution. CsA given with [(13)C]DMSO produced a 12-line spectrum, confirming the formation of hydroxyl radicals. The methyl radical produced by the hydroxyl radical represented 62% of radicals detected in urine but only 15% in bile. Therefore, hydroxyl radicals are produced largely in the kidney. Free radicals in urine were increased about 5-fold by CsA, an effect completely blocked by the inhibitory neurotransmitter, glycine, or by renal denervation. CsA infusion for 30 min increased efferent renal nerve activity 2-fold, and dietary glycine (5%) totally blocked this phenomenon. Taken together, these data are consistent with the hypothesis that CsA increases hydroxyl radical formation by increasing renal nerve activity resulting in vasoconstriction and hypoxia-reoxygenation. Glycine blunts the effect of CsA on the renal nerve, which explains, in part, prevention of nephrotoxicity.

Animals↗
PubMed1999

Molecular and functional characteristics of a protective human monoclonal antibody to serotype 8 Streptococcus pneumoniae capsular polysaccharide.

The structural characteristics and biological activity of human antibodies that are reactive with the capsular polysaccharides of most serotypes of Streptococcus pneumoniae, including serotype 8, are unknown. This paper describes the generation, molecular structure, and protective efficacy of a human monoclonal antibody (MAb) reactive with the capsular polysaccharide of serotype 8 Streptococcus pneumoniae. We generated the immunoglobulin M(kappa) [IgM(kappa)] MAb D11 by Epstein-Barr virus transformation of peripheral lymphocytes from a Pneumovax recipient. Nucleic acid sequence analysis revealed that MAb D11 uses V3-15/V(H)3 and A20/V(kappa) gene segments with evidence of somatic mutation. In vitro studies revealed MAb D11-dependent complement deposition on the capsule of serotype 8 organisms via either the classical or the alternative complement pathway. In vivo, MAb D11 prolonged the survival of both normal and C4-deficient mice with lethal serotype 8 S. pneumoniae infection. Our findings demonstrate that a serotype-specific human IgM with certain structural and functional characteristics was protective in mice lacking a functional classical complement pathway and show that alternative complement pathway activation is an important determinant of pneumococcal protection.

Amino Acid Sequence↗
PubMed1999

Binge drinking disturbs hepatic microcirculation after transplantation: prevention with free radical scavengers.

Disturbances in hepatic microcirculation increase graft injury and failure; therefore, this study evaluates the effects of ethanol on microcirculation after liver transplantation. Donor rats were given one dose of ethanol (5 g/kg) by gavage 20 h before explantation, and grafts were stored in University of Wisconsin solution for 24 h before implantation. Acute ethanol treatment decreased 7-day survival of grafts from about 90 to 30%, increased transaminase release nearly 4-fold, and decreased bile production by 60%. Moreover, portal pressure increased significantly and liver surface oxygen tension decreased about 50%, indicating that ethanol disturbs hepatic microcirculation. Pimonidazole, a 2-nitroimidazole hypoxia marker, was given i.v. to recipients 30 min after implantation, and grafts were harvested 1 h later. Ethanol increased hepatic pimonidazole binding about 3-fold, indicating that ethanol led to hypoxia in fatty grafts. Ethanol also significantly increased free radicals in bile. Catechin (30 mg/kg i.v. upon reperfusion), a free radical scavenger, and Carolina Rinse solution, which contains several agents that inhibit free radical formation, minimized disturbances in microcirculation and prevented pimonidazole adduct formation significantly. These treatments also blunted increases in transaminase release and improved survival of fatty grafts. Destruction of Kupffer cells with GdCl(3) (20 mg/kg i.v. 24 h before explantation) or inhibition of formation of leukotrienes with MK-886 (50 microM in University of Wisconsin or rinse solution) also minimized hypoxia and improved survival after transplantation. Taken together, these results demonstrate that ethanol disturbs hepatic microcirculation, leading to graft hypoxia after transplantation, most likely by activating Kupffer cells and increasing free radical production.

Animals↗
PubMed1999

[The epidemiological study on limb deformities among children in Guangdong Province].

OBJECTIVE: To study the incidence of limb deformities of children in Guangdong province. METHODS: Physical examination on lined-up students and looked over one by one. Detailed examinations of orthopaedics or related subjects were performed on those with susceptive deformity. RESULTS: Results showed that there were 655 cases of limb deformities (0.64%) in 102,313 pupils of 7 to 14 years old, in which 550 cases (83.97%) needed surgical intervention. The incidence of deformity in economically poor areas was 2.88 times higher than those in advanced areas. CONCLUSION: Prevention and cure of limb deformities of children, especially those in rural area, should be addressed and emphasized.

Adolescent↗
PubMed1999

[Determination of impurities in osmium powder by ICP-AES using matrix separation].

An inductively coupled plasma-atomic emission spectrometry method has been developed for the determination of impurities in osmium powder. The sample was dissolved in nitric acid at 150-200 degrees C. Osmium was oxided and its oxide vapour was absorbed by NaOH. The residual solution was then analyzed by ICP-AES. The determination limit of the method is 0.005-0.134 microg x mL(-1). The recovery range of the method is 91%-112%. The precision of the method is less than 3%. This method can be used to determine 18 elements simultaneously. It is simple, rapid and precise.

English Abstract↗
PubMed1998

Ethanol, not fat accumulation per se, increases free radical production in a low-flow, reflow liver perfusion model.

BACKGROUND: Ethanol increases primary graft failure after liver transplantation, yet whether it acts via mechanisms involving fat accumulation remains unclear. METHODS: Rats were pair-fed a modified Lieber-DeCarli liquid diet containing 35% (high-fat) or 12% (low-fat) of calories as fat combined with 36% of calories as ethanol or isocaloric maltose-dextrin for 4-5 weeks. Reperfusion injury to the liver was studied using a low-flow, reflow perfusion model and a liver transplantation model, and free radicals were detected using electron spin resonance and the spin trapping technique. RESULTS: As expected, basal hepatic triglycerides were similar in livers from rats fed low- and high-fat control diets. Ethanol did not alter triglyceride levels significantly in rats fed a low-fat diet, but increased values about 2.4-fold in rats fed a high-fat diet. Ethanol increased lactate dehydrogenase release during reperfusion from 10 to 26 IU/g/h in rats fed a low-fat diet and from 17 to 34 IU/g/h in rats fed a high-fat diet, respectively. Portal pressure increased from about 3 to 10.5 cm H2O upon reperfusion in livers from high-fat, ethanol-fed rats, but only reached values of 9.1 in the low-fat, ethanol-fed group. A free radical adduct signal was detected in the bile of livers from ethanol-treated rats, and the magnitude of this signal was similar in livers of ethanol-treated rats fed high- or low-fat diets. However, radical adducts could not be detected in either group in the absence of dietary ethanol. Moreover, 67-77% rats given low-fat or high-fat control diets survived after liver transplantation, but only 11% survived if treated with ethanol. CONCLUSIONS: It is concluded that ethanol plays a major role in hepatic reperfusion injury, most likely via mechanisms involving free radicals. Increased hepatic fat content alone plays only a minor role, probably by causing slight disturbances in the hepatic microcirculation.

Animals↗
PubMed1998

Dietary juniper berry oil minimizes hepatic reperfusion injury in the rat.

Juniper berry oil is rich in 5,11,14-eicosatrienoic acid, a polyunsaturated fatty acid similar to one found in fish oil, yet less prone to peroxidation. Dietary fish oil treatment has been shown to effectively reduce reperfusion injury; therefore, the effects of a diet containing juniper berry oil on hepatic reperfusion injury in a low-flow, reflow reperfusion model were investigated in the rat. Rats were fed semisynthetic diets containing either juniper berry oil, fish oil, or corn oil for 14 to 16 days. Daily food consumption averaged around 20 g/d in both the control and treatment groups; average daily weight gain was around 4 g per 100 g rat weight in all three groups studied, and there were no significant differences in these parameters. Livers were initially perfused at low-flow rates to induce pericentral hypoxia followed by a 40-minute reperfusion period. Peak lactate dehydrogenase (LDH) release during reflow averaged 44 U/g/h in the corn oil group and 32 U/g/h in the fish oil group, but was only 21 U/g/h as a result of juniper berry oil treatment. Malondialdehyde (MDA), an end-product of lipid peroxidation, reached a maximum value of 62 nmol/g/h in the corn oil group, but only reached 43 nmol/g/h and 34 nmol/g/h in the fish oil and juniper berry oil groups, respectively. Both juniper berry oil and fish oil treatment improved rates of bile flow from 25 microL/g/h (corn oil) to 36 and 38 microL/g/h, respectively. Importantly, juniper berry oil reduced cell death in pericentral regions of the liver lobule by 75%. Trypan blue distribution time, an indicator of the hepatic microcirculation, was reduced by approximately 25% with fish oil and over 50% by juniper berry oil diets compared with corn oil controls. The rates of entry of fluorescein-dextran, a dye confined to the vascular space, were increased 1.8- and 2.6-fold, and rates of outflow were increased 4.4- and 4.3-fold by fish oil and juniper berry oil, respectively, also reflecting improved microcirculation. Juniper berry oil also blunted increases in intracellular calcium and release of prostaglandin E2 (PGE2) by cultured Kupffer cells stimulated by endotoxin. These results are consistent with the hypothesis that feeding a diet containing juniper berry oil reduces reperfusion injury by inhibiting activation of Kupffer cells, thus reducing vasoactive eicosanoid release and improving the hepatic microcirculation in livers undergoing oxidant stress.

Animal Feed↗
PubMed1998

Generation of lipid free radicals by adherent leukocytes from transplanted rat liver.

The production of free radicals in blood correlates with primary nonfunction of transplanted livers, but the source of the free radicals is unknown. The purpose of this study was to determine if adherent leukocytes in the transplanted liver are responsible for the radicals detected in blood. First, a new method to harvest adherent leukocytes from the liver without enzymatic digestion was developed and characterized by transplanting livers from ethanol-treated rats, which increases primary nonfunction, and from saline-treated controls. Free radicals were then detected in isolated leukocytes using the spin-trapping technique and electron spin resonance (ESR) spin spectroscopy. Livers were perfused with a balanced salt solution (200 ml), followed by a Ca(2+)-free solution containing EGTA and heparin (400 ml). Perfusion with Ca(2+)-free buffer removed greater than 90% of all adherent leukocytes from saline-treated livers and nearly 80% of all leukocytes from fatty livers without removing Kupffer cells. Transplanted fatty livers from rats given ethanol contained significantly more adherent leukocytes (5.0 x 10(7) cells/liver) than grafts from control donors (3.2 x 10(7) cells/liver) and almost double the number of adherent neutrophils and monocytes. Moreover, adherent white blood cells from transplanted livers produced the same three free radical species that have been detected previously in blood; however, cells from ethanol-treated livers produced about five times more radical adducts. These data show that adherent white blood cells produce free radicals that are important in the mechanism of primary graft nonfunction.

Animals↗
PubMed1998

A human IgM monoclonal antibody prolongs survival of mice with lethal cryptococcosis.

Antifungal therapy cannot eradicate Cryptococcus neoformans infections in immunosuppressed patient groups. Therefore, adjunctive antibody-based therapy is being considered to enhance host immune responses to C. neoformans. To characterize potentially protective reagents, the idiotypic repertoire of human antibodies to cryptococcal glucuronoxylomannan (GXM) elicited by the investigational conjugate vaccine GXM-tetanus toxoid was examined. The variable genes used by human antibodies to GXM were analyzed with an antigen-based ELISA and mouse monoclonal antibodies (MAbs) that recognize determinants of human VH1, VH3, and VH4 gene segments. Antibodies to GXM were shown to use VH3 gene segments, and antibodies with the greatest binding to GXM also bound to protein A. A VH3-positive human monoclonal IgM prolonged survival of C. neoformans-infected mice. This is the first report that a human antibody is protective against C. neoformans. These results suggest that human MAbs may have promise as therapeutic reagents against cryptococcosis.

Animals↗
PubMed1998

Physician experience caring for dying patients and its relationship to patient outcomes.

BACKGROUND: The quality of end-of-life care has become important to care systems and the public. No research has assessed how physician factors affect patient and family experience. OBJECTIVE: The objective of this study was to examine whether physicians' experience with dying is associated with differences in their patients' experiences while dying. METHODS: This was a prospective cohort study. Data were obtained from five geographically diverse teaching hospitals. The survey population was composed of 765 attending physicians who had at least one patient enrolled in a study of those with a high risk of dying. The patients were 8203 hospitalized adults who were at least 80 years of age or had one of nine serious illnesses. The physician survey provided information about physician characteristics. Physician experience with death was stratified into five groups according to self-reported rate of dying patients in the physician's practice. Patient outcomes included pain, anxiety, depression, satisfaction with pain relief, presence and timing of do-not-resuscitate orders, concordance with their physicians about cardiopulmonary resuscitation, and hospital resource use. RESULTS: Oncologists and pulmonologists or critical care physicians had more frequent contact with death. Physician characteristics other than specialty were not associated with death experience. Compared with the physician group having no experience with death, the adjusted odds ratios for accord on resuscitation preferences were 1.38 (95% confidence interval [CI], 0.96 to 1.98), 1.47 (95% CI, 1.03 to 2.11), 1.58 (95% CI, 1.10 to 2.26), and 1.64 (95% CI, 1.09 to 2.46) for the other four physician groups with progressively increasing experience. Other outcomes for patients were not associated with increasing physician experience. CONCLUSION: Most physicians have little experience with dying, and physicians' experience with death has little effect on patient outcomes. The concentration of experience in a small segment of physicians offers opportunities for targeting improvements in the care of dying patients, including physician education.

Journal Article↗
PubMed1998

Characterization of a murine monoclonal antibody to Cryptococcus neoformans polysaccharide that is a candidate for human therapeutic studies.

The murine monoclonal antibody (MAb) 18B7 [immunoglobulin G1(kappa)] is in preclinical development for treatment of Cryptococcus neoformans infections. In anticipation of its use in humans, we defined the serological and biological properties of MAb 18B7 in detail. Structural comparison to the related protective MAb 2H1 revealed conservation of the antigen binding site despite several amino acid differences. MAb 18B7 was shown by immunofluorescence and agglutination studies to bind to all four serotypes of C. neoformans, opsonize C. neoformans serotypes A and D, enhance human and mouse effector cell antifungal activity, and activate the complement pathway leading to deposition of complement component 3 (C3) on the cryptococcal capsule. Administration of MAb 18B7 to mice led to rapid clearance of serum cryptococcal antigen and deposition in the liver and spleen. Immunohistochemical studies revealed that MAb 18B7 bound to capsular glucuronoxylomannan in infected mouse tissues. No reactivity of MAb 18B7 with normal human, rat, or mouse tissues was detected. The results show that both the variable and constant regions of MAb 18B7 are biologically functional and support the use of this MAb in human therapeutic trials.

Amino Acid Sequence↗
PubMed1998

Antifungal activity of a human antiglucuronoxylomannan antibody.

The human immunoglobulin M (IgM) monoclonal antibody (MAb) 2E9 binds the glucuronoxylomannan (GXM) of Cryptococcus neoformans serotypes A, B, and D. This study was undertaken to determine the opsonic efficacy of 2E9 and its ability to promote the antifungal activity of human polymorphonuclear neutrophils (PMNs) against C. neoformans. We incubated purified PMNs with fluorescein isothiocyanate-labeled C. neoformans cells that were treated with the GXM IgM 2E9, IgM antibodies that do not bind GXM, and rabbit and human factor-B-deficient serum as complement sources. PMN-associated C. neoformans cells fluoresced and were detected with a fluorescence-activated cell sorter. The amount of phagocytosis was defined as the percent fluorescing PMNs, which was 37% for yeast cells opsonized with 2E9 plus rabbit serum and 57% for yeast cells opsonized with 2E9 plus factor-B-deficient serum. Phagocytosis was significantly greater for yeast cells that were treated with 2E9 plus a complement source than for yeast cells treated with the complement sources alone or treated with the control IgMs alone or with the complement sources. Fluorescence quenching and light and electron microscopy of the phagocytosis mixtures revealed that 2E9-opsonized yeast cells were internalized by PMNs. Maximal inhibition of C. neoformans growth occurred when PMNs were cocultured with yeast cells that were opsonized with 2E9 plus a complement source. Our data demonstrate that the human GXM IgM 2E9 can mediate PMN phagocytosis and C. neoformans growth inhibition in vitro. These findings strongly suggest that antibody-mediated deposition of complement components on the cryptococcal capsule can augment PMN complement receptor-mediated antifungal activity. Antibody activation of complement-mediated effector cell antifungal mechanisms may play a role in host defense against cryptococcosis and represents a goal for the use of MAbs to treat or prevent human C. neoformans infections.

Antibodies, Fungal↗