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Efficiency of transgenic T cell generation from gene-marked cultured human CD34+ cord blood cells is determined by their maturity and the cytokines present in the culture medium.

Success of gene therapy for diseases affecting the T cell lineage depends on the thymic repopulation by genetically engineered hematopoietic progenitor cells (HPC). Although it has been shown that retrovirally transduced HPC can repopulate the thymus, little information is available on the effect of the culture protocol. Moreover, for expansion of the number of HPC, cytokine supplemented culture is needed. Here, we transduced purified human umbilical cord blood (CB) CD34+ cells in cultures supplemented with various combinations of the cytokines thrombopoietin (TPO), stem cell factor (SCF), flt3/flk-2 ligand (FL), interleukin-3 (IL-3) and IL-6, and investigated thymus-repopulating ability of gene-marked HPC in vitro. Irrespective of the cytokine cocktail used, transduced CD34+CD38- CB cells, expressing the marker green fluorescent protein (GFP) encoded by the MFG-GFP retrovirus, have both superior proliferative and thymus-repopulating potential compared with transduced CD34+CD38+ CB cells. Effectively transduced GFP+CD34+CD38- HPC, cultured for 3 or 17 days, more readily generated T cells than GFP- HPC from the same culture. The reverse was true in the case of CD34+CD38+ HPC cultures. Finally, our results indicate that the number of GFP+ T cell progenitors actually increased during culture of CD34+CD38- HPC, in a magnitude that is determined by the cytokine cocktail used during culture.

Animals↗

Fate of bone marrow-derived cultured mast cells after intracutaneous, intraperitoneal, and intravenous transfer into genetically mast cell-deficient W/Wv mice. Evidence that cultured mast cells can give rise to both connective tissue type and mucosal mast cells.

Both connective tissue mast cells and mast cells grown in vitro are derived from multipotential hematopoietic stem cells, but these two mast cell populations exhibit many differences in morphology, biochemistry, and function. We investigated whether the phenotype of cultured mast cells or their progeny was altered when the cells were transferred into different locations in vivo. Cultured mast cells were immature by ultrastructure, and stained with alcian blue but with neither safranin or berberine sulfate, a fluorescent dye that binds to the heparin of connective tissue mast cell granules. By contrast, mast cells recovered from the peritoneal cavity of congenitally mast cell-deficient (WB X C57BL/6)F1-W/Wv (WBB6F1-W/Wv) mice 10 wk after intraperitoneal injection of cultured WBB6F1-+/+ or C57BL/6-bgJ/bgJ mast cells stained with both safranin and berberine sulfate. Staining with berberine sulfate was prevented by treatment of the cells with heparinase but not chondroitinase ABC, suggesting that the adoptively transferred mast cell population had acquired the ability to synthesize and store heparin. Furthermore, the recovered mast cells were indistinguishable by ultrastructure from the normal mature peritoneal mast cells of WBB6F1-+/+ mice, and contained substantially more histamine than mast cells studied directly from culture. Intravenous injection of cultured mast cells resulted in the development of safranin-and berberine sulfate-positive mast cells in the peritoneal cavity, spleen, skin, and glandular stomach muscularis propria. Mast cells also developed on the glandular stomach mucosa, but these cells stained with alcian blue rather than safranin, and did not stain with berberine sulfate. This result suggests that cultured mast cells can give rise to mast cells of either the connective tissue type or mucosal phenotype, depending on anatomical location. Furthermore, transplantation of cultured mast cells into WBB6F1-W/Wv mice had no measurable effect on the anemia of the recipient mice, suggesting a possible strategy for repairing the mast cell deficiency of WBB6F1-W/Wv mice without affecting other bone marrow-derived populations such as erythrocytes. Intravenous injection of representative connective tissue type mast cells (30-50% pure peritoneal mast cells derived from WBB6F1-+/+ mice) gave results similar to those obtained with cultured mast cells: mast cells developing in the peritoneal cavity, skin, spleen, and glandular stomach muscularis propria of WBB6F1-W/Wv recipients stained with safranin and berberine sulfate, whereas mast cells developing in the mucosa of the glandular stomach stained only with alcian blue.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Analysis of 281,797 consecutive blood cultures performed over an eight-year period: trends in microorganisms isolated and the value of anaerobic culture of blood.

The results for 281,797 blood culture sets of specimens collected from adult patients at the Mayo Clinic over an approximately 8-year period (1 November 1984 through 30 November 1992) were analyzed in order to determine whether there were differences in the types of microorganisms isolated over this time and to assess the usefulness of anaerobic culturing of blood. Each blood culture set consisted of two aerobic blood cultures (Septi-Chek [Becton Dickinson, Sparks, MD] and Isolator [Wampole Laboratories, Cranbury, NJ]) and one anaerobic culture (nonvented tryptic or trypticase soy broth [NVTSB; Difco Laboratories, Detroit, or Becton Dickinson]). The relative frequency of isolation of aerobic and facultatively anaerobic gram-positive bacteria and obligately anaerobic bacteria increased over the second half of the 1984-1992 surveillance period. The value of the NVTSB anaerobic blood culture was demonstrated for diagnosing bloodstream infections caused by certain facultatively anaerobic bacteria in addition to obligately anaerobic bacteria and supported the inclusion of the NVTSB anaerobic blood culture as a standard part of the three-component blood culture set used at this institution.

Adult↗

Altered nitrogen metabolism associated with de-differentiated suspension cultures derived from root cultures of Datura stramonium studied by heteronuclear multiple bond coherence (HMBC) NMR spectroscopy.

De-differentiation of transformed root cultures of Datura stramonium has previously been shown to cause a loss of tropane alkaloid synthetic capacity. This indicates a marked shift in physiological status, notably in the flux of primary metabolites into tropane alkaloids. Nitrogen metabolism in transformed root cultures of D. stramonium (an alkaloid-producing system) and de-differentiated suspension cultures derived therefrom (a non-producing system) has been compared using Nuclear Magnetic Resonance (NMR) spectroscopy. (15)N-Labelled precursors [((15)NH(4))(2)SO(4) and K(15)NO(3)] were fed and their incorporation into nitrogenous metabolites studied using Heteronuclear Multiple Bond Coherence (HMBC) NMR spectroscopy. In both cultures, the same amino acids were resolved in the HMBC spectra. However, marked differences were found in the intensity of labelling of a range of nitrogenous compounds. In differentiated root cultures, cross-peaks corresponding to secondary metabolites, such as tropine, were observed, whereas these were absent in the de-differentiated cultures. By contrast, N- acetylputrescine and gamma-aminobutyric acid (GABA) accumulated in the de-differentiated cultures to a much larger extent than in the root cultures. It can therefore be suggested that the loss of alkaloid biosynthesis was compensated by the diversion of putrescine metabolism away from the tropane pathway and toward the synthesis of GABA via N-acetylputrescine.

Alkaloids↗

Inhibition of Salmonella typhimurium adhesion to Caco-2 cell cultures by Lactobacillus strain GG spent culture supernate: only a pH effect?

The effect of Lactobacillus GG and its spent culture supernate on the adhesion of Salmonella typhimurium to Caco-2 cells was investigated. Lactobacillus GG cells which had adhered to Caco-2 monolayers prior to the addition of S. typhimurium did not inhibit the adhesion. Adhesion of S. typhimurium was reduced in the presence of spent culture supernate from MRS broth cultures (spent culture supernate I). Similar inhibition was observed with acidified fresh MRS. The viability experiments with Caco-2 cells indicated that the inhibition was presumably due to the death of cells under acidic conditions. Adhesion of S. typhimurium was reduced by pre-treating the bacteria with spent culture supernate I or with acidified MRS and whey broth prior to adhesion to Caco-2 monolayers. Pre-treatment with spent culture supernate II (from whey broth cultures) did not influence the adhesion. No inhibition was detected at neutral pH values. Therefore, the observed inhibition of S. typhimurium adhesion to Caco-2 monolayers with spent culture supernate I was most likely a pH effect.

Bacterial Adhesion↗

Application for regenerative medicine of epithelial cell culture-vistas of cultured epithelium.

This review describes culture techniques for the epithelial system as well as trends in the clinical application of cultured keratinocytes in our department and the possibility of applying the techniques to other organs. Cultured epithelium and cultured dermis in particular have considerably preceded regeneration of other organs in the field of regenerative medicine. Since 1988 we have grafted cultured keratinocytes by the Rheinwald-Green modified method in at least 500 patients with large skin defects. As a result of the establishment of a culture technique for individual patients, it is now possible to prepare enough regenerated epithelium to cover the body surface area of as many as 10 adult patients in approximately three weeks after collecting 1 cm(2) of skin, and then remaining cultured keratinocytes can be cryo-preserved for two-stage dermatoplasty at another site. This procedure makes it possible to avoid frequent skin collection from the same patient and thereby improves patients' quality of life and activities of daily living. On the other hand, to solve the problem of regenerated epithelium shrinking and problems with graft efficiency on dermis defect lesion, we have developed a proteinase-resistant regenerated dermis by mixing a certain protein with a fibrin scaffold. Recently we also took the initiative in grafting hybrid-type regenerated trachea in an animal experiment by using the epithelial and dermal cell culture technique, and some results of the graft were obtained.

Animals↗

Comparison of the BacT/Alert pediatric blood culture system, Pedi-BacT, with conventional culture using the 20-milliliter Becton-Dickinson supplemented peptone broth tube.

The performance of the Pedi-BacT system, the BacT/Alert (Organon Teknika Corp., Durham, N.C.) pediatric blood culture bottle, was compared with that of a conventional 20-ml supplemented peptone broth tube (Becton-Dickinson Corp., Cockeysville, Md.) (BD system) in matched aerobic cultures. The tubes of the BD system were visually examined daily for 7 days and were subcultured during the first 24 h of incubation. Pedi-BacT cultures were mechanically agitated and continuously monitored for growth by the instrument. Of the 6,628 compliant pairs, 331 (5.0%) were positive in both systems, 220 (3.3%) were positive in the Pedi-BacT system only, and 170 (2.6%) were positive in the BD system only. One (0.02%) false-negative culture and 15 (0.2%) false-positive cultures occurred with the Pedi-BacT system while 20 (0.3%) false-negative cultures and 35 (0.5%) false-positive cultures occurred with the BD system. Of 288 clinically significant organisms detected in matched pairs from which a single isolate was recovered, 176 (61%) were recovered from both systems, 83 (29%) were recovered from the Pedi-BacT system only (P < 0.0001), and 29 (10%) were recovered from the BD system only. Members of the family Enterobacteriaceae (P < 0.01), miscellaneous nonfermenters (P < 0.05), and Candida spp. (P < 0.01) were isolated more frequently in the Pedi-BacT system than in the BD system. No significant difference in recovery of other organisms was found between the systems. The average time to detection for the Pedi-BacT system ranged from 11.5 h for streptococci to 29.7 h for enterococci, while that for the BD system ranged from 20.3 h for streptococci to 66.4 h for some nonfermenters. The BacT/Alert system is a reliable, labor-saving alternative to conventional blood culture methods.

Bacteremia↗

Three days of incubation may be sufficient for routine blood cultures with BacT/Alert FAN blood culture bottles.

BacT/Alert FAN blood culture bottles have been shown to enhance the recovery of bacteria and yeast from blood compared with standard BacT/Alert bottles. It is well established that standard BacT/Alert blood culture bottles require no more than 5 days of incubation for the detection of routine bacteria and yeast. It is less clear, however, whether FAN bottles also routinely require 5 days of incubation. To address this question, we recently reviewed the results of 17,887 blood culture sets collected in FAN blood culture bottles at Geisinger Medical Center. Of these cultures, 1,780 were positive for bacteria or yeast, yielding a total of 1,242 clinically significant isolates. The numbers of isolates recovered on days 1, 2, 3, 4, and 5 were as follows: (values in parentheses are percentages of total significant isolates): 877 (71%), 269 (22%), 65 (5%), 18 (1%) and, 13 (1%), respectively. In total, 97.5% of all clinically significant isolates were detected in the first 3 days of incubation. Of the 31 significant isolates detected on day 4 or 5 of incubation, 17 were detected in concurrent blood cultures within the first 3 days of incubation. Chart reviews were conducted for the 13 patients with the remaining 14 isolates detected on day 4 or 5 to determine whether therapy was changed due to this blood culture result. Therapy was changed for only 1 patient. These results suggest that it may not be necessary to routinely incubate FAN blood culture bottles for more than 3 days.

Aerobiosis↗

Comparison of the BacT/Alert PF pediatric FAN blood culture bottle with the standard pediatric blood culture bottle, the Pedi-BacT.

The performance of the BacT/Alert PF (Organon-Teknika Corp., Durham, N.C.), a new nonvented pediatric FAN blood culture bottle, was compared to that of the original pediatric bottle, the Pedi-BacT, with matched aerobic cultures obtained from two separate facilities. A total of 244 clinically significant isolates were recovered from 4,015 compliant pairs. Among the positive cultures, 170 (70%) isolates were detected in both the BacT/Alert PF and the Pedi-BacT bottles, while 47 (19%) isolates were recovered in the BacT/Alert PF bottle only and 27 (11%) isolates were recovered in the Pedi-BacT bottle only. Although isolation of specific microorganisms was comparable for the two bottles, the total number of organisms recovered by the BacT/Alert PF was greater than that by the Pedi-BacT (P = 0.0272). In addition, more organisms were recovered by the BacT/Alert PF bottle from the blood of patients receiving antimicrobial therapy (P = 0.0180). Overall time to detection was similar for the two bottles; however, a significantly decreased mean time to detection was recorded for yeast from the BacT/Alert PF bottle (22.9 h; P = 0.0001) and staphylococci from the Pedi-BacT bottle (22.5 h; P = 0.0056). One false-negative culture and five false-positive cultures occurred with the Pedi-BacT bottle, compared to one false-positive culture with the BacT/Alert PF bottle. The BacT/Alert PF bottle is a reliable blood culture bottle for pediatric blood culture specimens and may offer improved recovery of microbes from patients on antimicrobial therapy. The use of the nonvented bottle will both facilitate bottle processing and decrease expenditures for materials due to the elimination of the venting needles required for the original vented bottles.

Adolescent↗

Cultural care of older Greek Canadian widows within Leininger's theory of culture care.

Cultural care themes were abstracted from a large scale study of older Greek Canadian widows conceptualized within Leininger's theory of Cultural Care Diversity and Universality. Ethnonursing, ethnographic, and life health-care history methods were used. Data were collected using observation-participation and interviews in three Greek Canadian communities with 12 widowed key informants and 30 general informants. Enabling tools used were interview inquiry guides, Leininger's Life History Health Care Protocol, Leininger's Acculturation Rating and Profile Scale of Traditional and Non-Traditional Lifeways, and field journal recordings. Data were analyzed using Leininger's phases of analysis for qualitative data. The two major cultural care themes which were abstracted from the raw data and patterns were: (1) Cultural care for Greek Canadian widows meant responsibility for, reciprocation, concern, love, companionship, family protection, hospitality, and helping, primarily derived from their kinship, religious, and cultural beliefs, and values, and (2) Cultural care continuity diminished the spousal care void and contributed to the health of Greek Canadian widows. These findings will stimulate future nursing research related to cultural care of diverse populations and guide nursing practice to provide culturally congruent care which will assist widows to reduce their spousal care void. The author thanks Dr. Madeleine Leininger, Dr. Judith Floyd, Dr. Marjorie Isenberg, and Dr. Bernice Kaplan for their guidance in completing the large scale study on which this article is based.

Canada↗

Orthogonal cultural identification theory: the cultural identification of minority adolescents.

A theory of cultural identification is presented indicating that identification with different cultures is orthogonal. Instead of cultures being placed at opposite ends of a continuum, cultural identification dimensions are independent of each other, and increasing identification with one culture does not require decreasing identification with another. Studies of Native-American and Mexican-American youth show that: (1) identification with Anglo (White American) culture is related to having Anglo friends and to family acceptance of an Anglo marriage, (2) identification with either the minority or the majority culture is a source of personal and social strength, and (3) this greater strength, however, does not translate automatically into less drug use, because drug use is related to how much the culture that the person identifies with approves or disapproves of drugs.

Acculturation↗

Validation of D value by different SCD culture medium manufacturer and/or different SCD culture medium constituent.

Variation in decimal reduction (D) time/value for attaining sterility assurance was reported in terms of difference between lot to lot and/or manufacturer to manufacturer of soybean casein digest (SCD) culture medium. The D value variation phenomenon itself due to SCD culture medium was reported by Graham et al; however, it was not sufficiently clarified what constituent(s) of SCD culture medium would mainly contribute to the variation of D value. If it is not well clarified, the reproducible sterility assurance cannot be successfully attained. The authors studied individually the constituent of SCD broth (SCDB), SCD agar (SCDA) and SCD broth plus 1.5% agar (SCDB/A). As a result, the culture medium constituent causing D value variation among SCD culture medium was determined as the difference of calcium (Ca) amount as well as the presence and the absence of K2HPO4 in SCD culture medium. Additionally, it was clarified D value differed significantly between SCDB and SCDA. D value using the former was around 1 min lower than that using the latter. This phenomenon can be explained from the formation of insoluble CaHPO4 in SCDB culture medium, resulting in insufficiency of usable Ca to B. stearothermophilus in SCDB culture medium.

Caseins↗

Community dynamics of a mixed-bacterial culture growing on petroleum hydrocarbons in batch culture.

The effects of various hydrocarbon substrates, and a chemical surfactant capable of enhancing crude-oil biodegradation, on the community structure of a mixed-bacterial inoculum were examined in batch culture. Of 1000 TSA-culturable isolates, 68.6% were identified at the genus level or better by phospholipid fatty acid analysis over 7-day time course experiments. Cultures were exposed to 20 g/L Bow River crude oil with and without 0.625 g/L Igepal CO-630 (a nonylphenol ethoxylate surfactant), 5 g/L saturates, 5 g/L aromatics, or 125 g/L refinery sludge. A group of six genera dominated the cultures: Acinetobacter, Alcaligenes, Ochrobactrum, Pseudomonas/Flavimonas, Stenotrophomonas, and Yersinia. Species from four of the genera were shown to be capable of hydrocarbon degradation, and counts of hydrocarbon degrading and total heterotrophic bacteria over time were nearly identical. Pseudomonas/Flavimonas and Stenotrophomonas normally dominated during the early portions of cultures, although the lag phase of Stenotrophomonas appears to have been increased by surfactant addition. Acinetobacter calcoaceticus was the most frequently isolated microorganism during exposure to the saturate fraction of crude oil. Regardless of substrate, the culture medium supported a greater variety of organisms during the latter portions of cultures. Understanding the community structure and dynamics of mixed bacterial cultures involved in treatment of heterogeneous waste substrates may assist in process development and optimization studies.

Biodegradation, Environmental↗

The influence of Mannheimia haemolytica A1 seed culture inoculum cell density on the production of leukotoxin in submerged culture supernatant.

Mannheimia haemolytica leukotoxin is produced during the logarithmic growth phase in submerged culture in RPMI 1640 medium with and without the addition of foetal calf serum or albumin. In order to establish a pattern of optimal leukotoxin production in small volumes in submerged cultures and to define some parameters involved, two high leukotoxin producing Mannheimia haemolytica strains were grown in RPMI 1640 medium containing either FCS or BSA. The cell growth and leukotoxin production abilities of each strain were determined concomitantly every hour in RPMI 1640 medium containing each of the additives over a time period of 6 h. The growth performance of three dilutions of a standardized seed culture inoculum prepared with each of the cultures and additives were simultaneously compared with each other using the above parameters. The different seed culture inoculum dilutions had a definite effect on the time and quantity of leukotoxin production. Both strains demonstrated peak leukotoxin production after 4 h of active growth. The addition of albumin to both isolates gave slightly increased leukotoxin levels, and both showed that the peak leukotoxin was not associated with peak cell concentration. Obvious quantitative differences in the ability of different M. haemolytica strains to produce leukotoxin were noted. Strain 12296 produced optimal leukotoxin concentration from the medium (1/25) dilution of the seed culture inoculum after 4 h, whereas strain 1/10 produced the same concentration with the low (1/5) dilution seed culture inoculum, possibly reflecting the superior production ability of the first strain. However, each strain of M. haemolytica appeared to have its own specific logarithmic cell growth and leukotoxin production pattern. The peak cell density of M. haemolytica grown in submerged RPMI 1640 culture medium cannot be used as an indication of optimal leukotoxin levels.

Albumins↗

[Isolation and culture of mouse marrow mesenchymal stem cells (MSCs) and biological characteristics of MSCs cultured in conditions for spermatogonia in vitro].

OBJECTIVE: To isolate, culture and purify mouse bone marrow mesenchymal stem cells (MSCs) and observe the main biological characteristics of MSCs cultured in conditions for spermatogonia in vitro. METHODS: The tibias and femurs were dissected from 5 - 6-week old mice and the marrow in the tibias and femurs was flushed out with medium. MSCs were isolated, cultured, purified in vitro by Percoll density gradient centrifugation combined with adherent method and identified by dynamic observation of stem cell characteristics by transmission electron microscope, HE staining, and immunohistochemical detection of cell markers. The quantities of such cytokines as IL-6, IL-8, G-CSF and SCF in culture liquid with MSCs were measured by ELISA, and compared with those of the control group. MSCs of the third generation were divided into two groups to be induced and cultured. MSCs of the control group were cultured with basal medium, while those of the experimental group with conditional medium. The results were analysed by microscopic observation, HE staining and immunohistochemical methods. RESULTS: Pure MSCs were obtained. The cultured cells, with stem cell characteristics, shuttle-shaped at HE staining, immature under the transmission electron microscope and CD44 and CD90 positive by immunohistochemical detection, could be identified as MSCs. Compared with the control group, the quantities of IL-6, IL-8, G-CSF and SCF in the experimental group increased significantly (P < 0.05). The shapes of MSCs changed and immunohistochemical staining for CD27, CD119 and Oct-4 was positive in the experimental group, but both were just the opposite in the control group. CONCLUSION: Pure MSCs can be obtained by Percoll density gradient centrifugation combined with adherent method and identified by dynamically observing stem cell characteristics, HE staining, observation under the transmission electron microscope and immunohistochemical detection of cell markers. MSCs can secrete cytokines such as IL-6, IL-8, G-CSF, SCF, and so on. MSCs cultured in conditions for spermatogonia may show some biological characteristics of spermatogonia.

Animals↗

Monocyte long-term cultivation on microvascular endothelial cell monolayers: morphologic and phenotypic characterization and comparison with monocytes cultured on tissue culture plastic.

Human monocytes were cultured on monolayers of a newly established microvascular endothelial cell strain. As compared to monocytes cultured on plastic, these endothelium-"derived" monocytes (EDM) showed distinct morphology, higher motility, and different antigen-expression pattern for several surface markers, as detected by cytofluorimetry. The MO-1- and the Leu-M1-marker were maintained on EDMs while they were lost on plastic-cultured cells. The MAX 1-26-termed markers failed to increase on EDMs, in contrast to plastic-cultured monocytes. For seven additional markers, expression after two weeks in vitro was higher on EDMs than on plastic-cultured monocytes. Functionally EDMs showed typical monocyte/macrophage behavior and were easily removable from the culture system for further experimentation. Our data suggest that monocytes cultured on microvascular endothelial cells are maintained for several weeks in a more physiologic state than monocytes cultured on plastic.

Animals↗

Effect of donor and culture age on the function of neutrophils harvested from long-term bone marrow culture.

Neutrophils harvested from the supernatants of long-term bone marrow cultures that were initiated from young and old mice were tested for their functional activity. Superoxide generation was measured, as was the secretion of the enzymes lysozyme, myeloperoxidase, and glucuronidase, both basally and following stimulation by phorbol myristate acetate. The function of the neutrophils harvested from cultures that were initiated from young mice was identical to that of cells derived from young mouse peritoneal cavities at the time of death. A minimal decline in function in culture-derived cells was seen over the 15-18 weeks of study. For each of the above measurements examined, neutrophils obtained from cultures initiated from old mice gave values significantly lower than those in neutrophils recovered from cultures initiated from young mice. For some parameters (superoxide generation, myeloperoxidase), the rate of decline in function was more rapid for neutrophils from old rather than young mouse cultures. For other measurements the rates of decline were equal. The results indicated adequate neutrophil function in long-term bone marrow culture for extended periods of time. They also demonstrated that the age-related diminution in neutrophil function observed in vivo persisted in in vitro culture.

Aging↗

Culture-specific delusions. Sense and nonsense in cultural context.

It can be said that a definition of delusions requires the invocation of cultural understandings, standards of acceptability, as well as conceptions of reality and the forces that animate it. For these reasons, the determination of delusional or normative ideation can only be effected properly within particular cultural contexts. The cross-cultural record suggests that it is difficult to separate the delusional from the cultural; a belief that is patterened and culturally specific is, by definition a cultural, not a delusional belief. One must rely upon particular, relevant local cultural understandings to ascertain when the bounds of culture have been transgressed and meaning has given way to unshareable nonsense.

Cross-Cultural Comparison↗