Correlation of immune complexes in disseminated neuroblastoma with serum antibody to bovine serum albumin.

To evaluate the relationship between tumor burden and circulating immune complexes (IC) in children with neuroblastoma (NBL), we studied sera collected at intervals from patients with disseminated (Stage III or IV) NBL. Sera from 10 of 12 patients contained IC by the Raji cell assay at some time during the first 9 to 11 months of the study. Higher IC levels were observed in sera of female patients. Fluid-phase C1q binding tests detected IC in only 16% of sera. IC measurements by either assay did not correlate with tumor burden. However, serum IC levels, as measured by the Raji cell assay, correlated significantly with serum antibody to bovine serum albumin (BSA) (rs = 0.54; p less than 0.001, rs = r as determined by Spearman rank correlation test). Measurement of anti-BSA antibodies in sera from the 12 patients, tested serially for circulating IC, and from five additional patients revealed that these had significantly higher anti-BSA activity than was found in sera from 13 age-matched controls. Sera from females also had relatively high levels of anti-BSA. Levels of antibody to bovine gamma-globulin and casein were not abnormal. Three sera with high IC levels (greater than 800 micrograms equivalents of heat-aggregated IgG) and relatively low anti-BSA activity appeared to contain "hidden" antibodies to BSA. These were demonstrated by measuring the increase in the ability of sera to bind 125I-BSA after they had been briefly acidified and then neutralized in the presence of the labeled BSA. The possible relevance of these results to the pathophysiology of NBL is discussed in light of earlier work that reported that serum IC levels correlate with the stage of the disease in NBL.

Synthesis of antigens, cross-reactive with bovine serum albumin, by cultured neuroblastoma cells.

Antisera to bovine serum albumin (BSA) react with biosynthetic products of the LAN-1 neuroblastoma cell line. This immunological reaction was shown by analysis of immunoprecipitates prepared with anti-BSA and products of this cell line intrinsically labeled by the incorporation of 3H- or 35S-labeled amino acids. Moreover, antibodies in sera from two patients with neuroblastoma precipitate intrinsically labeled macromolecules produced by these tumor cells. Release of antigens cross-reactive with BSA by neuroblastomas may explain, in part, the high levels of antibody to BSA and circulating immune complexes containing hidden or "blocked" antibodies to BSA found in some patients with this tumor.

Tumor cytotoxicity of peritoneal macrophages and peripheral blood monocytes from patients with ovarian, endometrial, and cervical cancer.

The purpose of this study was to compare the cytotoxic capacity of peritoneal macrophages (PM) and peripheral blood monocytes (PBM) from patients with ovarian, endometrial, and cervical cancers after in vitro activation with gamma interferon (IFN-gamma) and lipopolysaccharide (LPS). Peritoneal macrophages were obtained from ascites or peritoneal washings and peripheral blood monocytes via peripheral venipuncture from 58 patients: 17 with ovarian, 19 with endometrial, and 10 with cervical cancers. PBM and PM from 12 patients with nonmalignant gynecologic conditions served as controls. Cytotoxicity was assessed by the ability of PBM and PM to lyze Cr51-labeled Chang hepatoma cells. Activated peripheral blood monocytes of ovarian and endometrial cancer patients and peritoneal macrophages from ovarian cancer patients were significantly more cytotoxic than those from nonactivated controls. Activated PBM and PM from cervical cancer and PM from endometrial cancer did not demonstrate increased cytotoxicity compared to nonactivated controls. There was no significant correlation of the cytotoxicity with grade, stage, differentiation or age of the cancers. These in vitro data would suggest that ovarian cancer and possibly endometrial cancer should receive further evaluation and consideration of cytokine-based and/or adoptive cellular immunotherapy.

Dementia associated with hyperphosphatemic tumoral calcinosis.

Hyperphosphatemic tumoral calcinosis (HTC) is a rare inherited metabolic disorder manifested by pararticular calcification and hyperphosphatemia, caused by an elevated renal phosphate reabsorption threshold and elevated serum 1,25-dihydroxyvitamin D levels. The disorder usually affects African-American subjects, but has also been described in Caucasians and Hispanics. Vascular calcifications and angioid streaks have been reported to be associated with the disorder; however, dementia has not been previously reported. Our medical center has followed two African-American siblings, with HTC for over 30 years, who have developed dementia at 56 years and 67 years of age. Neither man has been hypertensive, however, magnetic resonance imaging (MRI) scans in both cases revealed multiple periventricular infarcts, suggestive of infarcts caused by vascular calcification in the central nervous system. These two brothers with HTC suggest that periventricular infarcts with dementia may be a long term complication of this disorder.

Depression.

Depression occurs in up to 45% of medically hospitalized older patients. The diagnosis of depression in this population is particularly difficult. Assessing for depression is made easier by the use of scales for screening and is best accomplished using the inclusive approach. These depressions can be divided into two groups: "reactive" depression and major depression. Depression is treatable using a variety of modalities that include psychotherapy, pharmacotherapy, and electroconvulsive therapy.

Regulon controlled by the GppX hybrid two component system in Porphyromonas gingivalis.

The periodontal pathogen Porphyromonas gingivalis experiences a number of environmental conditions in the oral cavity, and must monitor and respond to a variety of environmental cues. However, the organism possesses only five full two-component systems, one of which is the hybrid system GppX. To investigate the regulon controlled by GppX we performed RNA-Seq on a ΔGppX mutant. Fifty-three genes were upregulated and 37 genes were downregulated in the ΔGppX mutant. Pathway analyses revealed no systemic function for GppX under nutrient-replete conditions; however, over 40% of the differentially abundant genes were annotated as encoding hypothetical proteins indicating a novel role for GppX. Abundance of small RNA was, in general, not affected by the absence of GppX. To further define the role of GppX with respect to regulation of a hypothetical protein observed with the greatest significant relative abundance change relative to a wild-type control, PGN_0151, we constructed a series of strains in which the ΔgppX mutation was complemented with a GppX protein containing specific domain and phosphotransfer mutations. The transmembrane domains, the DNA-binding domain and the phosphotransfer residues were all required for regulation of PGN_0151. In addition, binding of GppX to the PGN_0151 promoter regions was confirmed by an electrophoretic mobility shift assay. Both the ΔGppX mutant and a ΔPGN_0151 mutant were deficient in monospecies biofilm formation, suggesting a role for the GppX-PGN_0151 regulon in colonization and survival of the organism.

Highly efficient methane biocatalysis revealed in a methanotrophic bacterium.

Methane is an essential component of the global carbon cycle and one of the most powerful greenhouse gases, yet it is also a promising alternative source of carbon for the biological production of value-added chemicals. Aerobic methane-consuming bacteria (methanotrophs) represent a potential biological platform for methane-based biocatalysis. Here we use a multi-pronged systems-level approach to reassess the metabolic functions for methane utilization in a promising bacterial biocatalyst. We demonstrate that methane assimilation is coupled with a highly efficient pyrophosphate-mediated glycolytic pathway, which under oxygen limitation participates in a novel form of fermentation-based methanotrophy. This surprising discovery suggests a novel mode of methane utilization in oxygen-limited environments, and opens new opportunities for a modular approach towards producing a variety of excreted chemical products using methane as a feedstock.

Clozapine-associated neutropenic enterocolitis.

Clozapine's use has been restricted to the treatment of schizophrenic patients unresponsive to conventional antipsychotics, secondary to its propensity to cause agranulocytosis. Because of this restriction, side effects associated with clozapine's use have probably not been fully elucidated. The authors describe a case of a male schizophrenic who developed clozapine-induced agranulocytosis and subsequently a neutropenic enterocolitis. Neutropenic enterocolitis related to clozapine-induced neutropenia or agranulocytosis has not previously been reported in the literature. The history of clozapine, its side effects, and the phenomenon of neutropenic enterocolitis are briefly reviewed.

Minor depression: a review of the literature.

OBJECTIVE: The clinical experience of the authors has suggested there is a significant group of elderly and individuals with medical illness and depressive symptoms who do not meet DSM-IV criteria for major depression. We were interested in all available data regarding minor depression in both the medically ill and community individuals. METHODS: MEDLINE was searched from 1965 to 1995, using the terms "depressive disorders" and "medical illness," as well as "atypical depression" and "elderly." Relevant references from these primary articles were also utilized. RESULTS: In medical patients, depressive symptoms were associated with decreased likelihood of discharge to home. Although diagnostic criteria vary, some suggest anhedonia as the central feature. From 3 to 16 percent of medical outpatients suffer from minor depression. Up to 64 percent of medical inpatients will complain of depressed mood. Studies in community samples found that minor depression was responsible for 9 to 16 percent of total disability days, and was associated with absenteeism from work, as well as separation and divorce. Little is known about the natural history and prognosis of minor depression. CONCLUSIONS: Minor depression is both common and has a significant impact on the health care system, and therefore deserves further study.

Shear bond strength of composite resin porcelain repair materials bonded to metal and porcelain.

Two composite resins, bonding agents, surface treatment agents, dental porcelains, and nickel-chromium porcelain bonding dental casting alloys were used to test shear bond strengths of composite resins bonded to metal and porcelain. Bond strengths to porcelain were greater than to metal and to oxidized metal were greater than to machined metal. Significant differences were found between types of porcelains and casting alloys.

In vivo formation of hybrid aspartate transcarbamoylases from native subunits of divergent members of the family Enterobacteriaceae.

The genes encoding the catalytic (pyrB) and regulatory (pyrI) polypeptides of aspartate transcarbamoylase (ATCase, EC 2.1.3.2) from several members of the family Enterobacteriaceae appear to be organized as bicistronic operons. The pyrBI gene regions from several enteric sources were cloned into selected plasmid vectors and expressed in Escherichia coli. Subsequently, the catalytic cistrons were subcloned and expressed independently from the regulatory cistrons from several of these sources. The regulatory cistron of E. coli was cloned separately and expressed from lac promoter-operator vectors. By utilizing plasmids from different incompatibility groups, it was possible to express catalytic and regulatory cistrons from different bacterial sources in the same cell. In all cases examined, the regulatory and catalytic polypeptides spontaneously assembled to form stable functional hybrid holoenzymes. This hybrid enzyme formation indicates that the r:c domains of interaction, as well as the dodecameric architecture, are conserved within the Enterobacteriaceae. The catalytic subunits of the hybrid ATCases originated from native enzymes possessing varied responses to allosteric effectors (CTP inhibition, CTP activation, or very slight responses; and ATP activation or no ATP response). However, each of the hybrid ATCases formed with regulatory subunits from E. coli demonstrated ATP activation and CTP inhibition, which suggests that the allosteric control characteristics are determined by the regulatory subunits.

Prospective clinical evaluation of mandibular implant overdentures: Part I--Retention, stability, and tissue response.

Seventeen subjects with preexisting conventional complete dentures were evaluated in this prospective clinical study. Two implants were placed bilaterally in the anterior mandible. In a crossover experimental design, the conventional dentures were modified, and the retention, stability, and tissue response for conventional dentures were compared with implant overdentures that had O-ring and magnet overdenture attachments for all subjects. The study indicated statistical superiority of the implant overdenture to the conventional denture. The O-ring attachment proved significantly better than the magnet attachment for retention and stability. The soft tissue response showed a slight but significant improvement with implant overdenture therapy.