Quality evaluation of highly purified human menopausal gonadotropin preparations by means of gel electrophoresis and mass spectrometry.

Human gonadotropins are glycoprotein hormones with a highly complex structure, which demands the application of sophisticated analytical methodologies to assess their quality. The principal objective of this study was a comparative evaluation of gel electrophoretic techniques and mass spectrometry-based methods for the quality study of the two urinary-derived, highly purified, human menopausal gonadotropin preparations, Menopur 75/75 I. U. and Meriofert 75 I. U. Molecular mass (Mr), isoelectric point (pI), and isoform pattern of studied compounds were estimated via SDS-PAGE and 2D gel electrophoresis, whereas matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was used for the downstream characterization of peptides obtained after in-gel tryptic digestion of selected protein spots. Additionally, for the estimation of the glycosylation pattern of these biologics, the enzymatic release of oligosaccharides was performed, and the isoform pattern was studied. Gel electrophoresis showed a typical electrophoretic behaviour for protein biotherapeutics medicines consisting of extremely complex spot patterns migrating at different masses and pIs. MS analysis proved to be a powerful tool for the identification and detailed characterization of the gonadotropins and the relevant peptides were identified with high sequence coverages. The results of this study are not only useful for the quality assessment of this class of complex biopharmaceuticals but may also serve as a supporting platform for further development of biopharmaceuticals based on modulation of the glycosylation pattern to enhance efficacy or reduce side effects.

Supportive care in the acute phase of Stevens-Johnson syndrome and toxic epidermal necrolysis: an international, multidisciplinary Delphi-based consensus.

BACKGROUND: Supportive care is the cornerstone of management of adult and paediatric Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). However, consensus on the modalities of supportive care is lacking. OBJECTIVES: Our aim in this international multicentric Delphi exercise was to establish a multidisciplinary expert consensus to standardize recommendations regarding supportive care in the acute phase of SJS/TEN. METHODS: Participants were sent a survey via the online tool SurveyMonkey, consisting of 103 statements organized into 11 topics: multidisciplinary team composition, suspect drug management, infection prevention, fluid resuscitation and prevention of hypothermia, nutritional support, pain and psychological distress management, management of acute respiratory failure, local skincare, ophthalmological management, management of other mucosa, and additional measures. Participants evaluated the level of appropriateness of each statement on a scale of 1 (extremely inappropriate) to 9 (extremely appropriate). The results were analysed according to the RAND/UCLA Appropriateness Method. RESULTS: Forty-five participants from 13 countries (on three continents) participated. After the first round, a consensus was obtained for 82.5% of the 103 initially proposed statements. After the second round, a final consensus was obtained for 102 statements. CONCLUSIONS: We have reached an international Delphi-based consensus on best supportive care practice for SJS/TEN. Our expert consensus should help guide physicians in treating patients with SJS/TEN and thereby improve short-term prognosis and the risk of sequelae.

Labor Market Segmentation and Immigrant Competition: A Quantal Response Statistical Equilibrium Analysis.

Competition between and within groups of workers takes place in labor markets that are segmented along various, often unobservable dimensions. This paper proposes a measure of the intensity of competition in labor markets on the basis of limited data. The maximum entropy principle is used to make inferences about the unobserved mobility decisions of workers in US household data. The quantal response statistical equilibrium class of models can be seen to give robust microfoundations to the persistent patterns of wage inequality. An application to labor market competition between native and foreign-born workers in the United States shows that this class of models captures a substantial proportion of the informational content of observed wage distributions.

Increased prevalence of HCV and hepatic decompensation in adults with psoriasis: a population-based study in the United Kingdom.

BACKGROUND: The hepatitis C virus (HCV) is a major cause of global morbidity and mortality, with conflicting evidence regarding a possible association with psoriasis. OBJECTIVE: To determine the prevalence of HCV in psoriasis patients, compared to controls, and to determine the incidence of hepatic decompensation in HCV+ psoriasis patients compared to HCV+ controls. METHODS: Cross-sectional and cohort studies were conducted in The Health Improvement Network (THIN). RESULTS: In fully adjusted models, a statistically significant increase in prevalence was seen in the adults with psoriasis (OR: 1.24, 95% CI 1.10-1.40). A "dose-response" of HCV prevalence with increasing psoriasis severity was not observed. HCV+ patients with psoriasis had a non-statistically significant increased incidence of hepatic decompensation compared to HCV+ individuals without psoriasis (aHR: 1.58, 95% CI: 0.90-2.77). The risk was highest and statistically significant, in those with moderate-to-severe psoriasis (aHR: 21.51, 95% CI: 7.58-61.03). CONCLUSIONS: These results demonstrate a higher prevalence of HCV in adults with psoriasis and a higher rate of hepatic decompensation in HCV+ individuals with moderate-severe psoriasis.

Rosettes and other white shiny structures in polarized dermoscopy: histological correlate and optical explanation.

BACKGROUND: Rosettes are a specific form of a white shiny structure seen with polarized dermoscopy. The precise morphological correlate and optical explication are not known. OBJECTIVE: To estimate the frequency of rosettes in ex vivo dermoscopy and to find explication and morphologic correlate of this dermoscopic feature. METHODS: A series of 6108 consecutive skin biopsies were examined with ex vivo dermoscopy and when rosettes were present serial transverse sections with polarization were examined. RESULTS: In this series of 6108 consecutive skin biopsies, rosettes were found on ex vivo dermoscopy in 63 cases. When multiple we observed that they are always oriented at the same angle. Transverse sections with polarization of these lesions proved that smaller rosettes are mainly caused by polarizing horny material in adnexal openings, and larger rosettes by concentric perifollicular fibrosis. CONCLUSIONS: Rosettes are an optical effect of crossed polarization by concentric fibrosis or horny material and hence are not lesion-specific.

Post-acute phase and sequelae management of epidermal necrolysis: an international, multidisciplinary DELPHI-based consensus.

BACKGROUND: Long-term sequelae are frequent and often disabling after epidermal necrolysis (Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)). However, consensus on the modalities of management of these sequelae is lacking. OBJECTIVES: We conducted an international multicentric DELPHI exercise to establish a multidisciplinary expert consensus to standardize recommendations regarding management of SJS/TEN sequelae. METHODS: Participants were sent a survey via the online tool "Survey Monkey" consisting of 54 statements organized into 8 topics: general recommendations, professionals involved, skin, oral mucosa and teeth, eyes, genital area, mental health, and allergy workup. Participants evaluated the level of appropriateness of each statement on a scale of 1 (extremely inappropriate) to 9 (extremely appropriate). Results were analyzed according to the RAND/UCLA Appropriateness Method. RESULTS: Fifty-two healthcare professionals participated. After the first round, a consensus was obtained for 100% of 54 initially proposed statements (disagreement index < 1). Among them, 50 statements were agreed upon as 'appropriate'; four statements were considered 'uncertain', and ultimately finally discarded. CONCLUSIONS: Our DELPHI-based expert consensus should help guide physicians in conducting a prolonged multidisciplinary follow-up of sequelae in SJS-TEN.

Effect of Social Rank upon Estrus Induction and Some Reproductive Outcomes in Anestrus Goats Treated With Progesterone + eCG.

We evaluated the possible role of the social rank [R] (i.e., low-LSR, middle-MSR, or high-HSR) in anestrus goats exposed to a P4 + eCG [D] (i.e., 100 or 350 IU) estrus induction protocol (EIP). Adult, multiparous (two to three lactations), multiracial, dairy-type goats (Alpine-Saanen-Nubian x Criollo goats (n = 70; 25°51' North) managed under stall-fed conditions were all ultrasound evaluated to confirm anestrus status while the R was determined 30 d prior to the EIP. The variables of estrus induction (EI, %), estrus latency (LAT, h), estrus duration (DUR, h), ovulation (OVU, %), ovulation rate (OR, n), corpus luteum size (CLS, cm), pregnancy (PREG, %), kidding (KIDD, %), and litter size (LS, n) as affected by R, D, and the R × D interaction, were evaluated. While OVU and CLS favored (p < 0.05) HSR (96% and + 1.04 ± 0.07 cm), an increased (p < 0.05) LS occurred in D350 vs. D100 (2.06 ± 0.2 vs. 1.36 ± 0.2); neither R nor D affected (p > 0.05; 38.5%) KIDD. However, EI, LAT, DUR, OR, and PREG were affected by the R × D interaction. The HSR group had the largest (p < 0.05) EI % and DUR h, irrespective of D. The shortest (p < 0.05) LAT occurred in D350, irrespective of R. While the largest (p < 0.05) OR occurred in HSR and MSR within D350, the HSR + D350 group had the largest PREG (p < 0.05). These research outcomes are central to defining out-of-season reproductive strategies designed to attenuate seasonal reproduction in goats.

Does Size Matters? Relationships among Social Dominance and Some Morphometric Traits upon Out-of-Season Reproductive Outcomes in Anestrus Dairy Goats Treated with P4 + eCG.

The possible role of the social rank (R) (i.e., low-LSR, middle-MSR, or high-HSR) in anestrus goats exposed to a P4 + eCG (D) (i.e., 100 or 350 IU) estrus induction protocol (EIP) was evaluated. Goats (Alpine-Saanen-Nubian × Criollo; n = 70; 25° North) managed under stall-fed conditions were all ultrasound evaluated to confirm anestrous status, while the social rank was determined 30 d prior to the EIP. The response variables included estrus induction (EI, %), duration of estrus (DUR, h), ovulation rate (OR, n), live weight (LW, kg), thoracic perimeter (TP, cm), thoracic diameter (TD, cm), body length (BL, cm), height at withers (HW, cm), beard length (BEA, cm), compactness index (COM, cm), and anamorphosis index (ANA, cm), as affected by R, D, and the R × D interaction were evaluated, while the correlation coefficients among reproductive and morphometric variables were quantified. An R × D interaction (p < 0.05) affected the response variables EI, DUR, and OR. While the largest (p < 0.05) EI% occurred in the HSR goats, irrespective of eCG (i.e., 100 or 350 IU), both the shortest estrus duration (DUR, h) and the lowest ovulation rate (OR, n) occurred in the LSR + D100 combination, with no differences among HSR and MSR either with D100 or D350. Regarding the LW and morphometric response variables, (i.e., LW, TP, TD, BL, HW, BEA, COM, and ANA) all of them favored either the HSR and MSR groups, with the lowest phenotypic values occurring in the LSR-goats. The EI% was observed to be positively correlated (p < 0.05) with DUR (0.71), LW (0.28), TP (0.31), TD (0.34), BL (0.33), HW (0.35), COM (0.23), and ANA (0.23). While DUR was correlated (p < 0.05) with TP (0.26) and ANA (0.24), OR demonstrated no-correlation (p > 0.05) with any response variable, either reproductive or morphometric. As expected, LW had high correlation coefficients (p < 0.01) with TP (0.86), TD (0.88), BL (0.82), HW (0.75), BEA (0.51), COM (0.97), and ANA (0.75). In general, the morphometric variables as a whole demonstrated important correlation coefficients among them (p < 0.01), ranging from 0.38 up to 0.84. To estimate the importance of the morphometric differences between social rank upon estrus induction, a principal component (PC) analysis was performed based on the correlation matrix derived from the corporal measurements. The PC1 and PC2 explained 70.3% and 17.6% of the morphometric variation, respectively. The PC1 was a measure of the goat size (i.e., small, medium, large) and its association with estrus occurrence was evaluated using a logistic regression model; the bigger the goat, the increased probability of being in estrus, by up to five times compared to small goats. Our results confirm that the higher social ranked, larger goats amalgamated some fundamental factors to be successful: aggressiveness, primacy to food access, augmented live weight, and corporal size; all of these were able to modulate out-of-season reproductive success in crossbred dairy goats subjected to an estrus induction protocol and managed under stall-fed conditions in Northern Mexico.

Precision Betacarotene Supplementation Enhanced Ovarian Function and the LH Release Pattern in Yearling Crossbred Anestrous Goats.

The possible out-of-season effect of beta-carotene supplementation on ovulation rate (OR), antral follicles (AFN), and total ovarian activity (TOA = OR + AFN) as related to the LH release pattern in yearling anestrous goats was evaluated. In late April, Alpine-Saanen-Nubian x Criollo goats (n = 22, 26 N) were randomly allotted to: (1) Beta-carotene (BETA; n = 10, orally supplemented with 50 mg/goat/d; 36.4 ± 1.07 kg live weight (LW), 3.5 ± 0.20 units, body condition score (BCS) or (2) Non-supplemented (CONT; n = 12, 35.2 ± 1.07 kg LW, 3.4 ± 0.2 units BCS). Upon estrus synchronization, an intensive blood sampling (6 h × 15 min) was accomplished in May for LH quantifications; response variables included (pulsatility-PULSE, time to first pulse-TTFP, amplitude-AMPL, nadir-NAD and area under the curve-AUC). Thereafter, an ultrasonography scanning was completed to assess OR and AFN. The Munro algorithm was used to quantify LH pulsatility; if significant effects of time, treatment or interaction were identified, data were compared across time. Neither LW nor BCS (p > 0.05) or even the LH (p > 0.05); PULSE (4.1 ± 0.9 pulses/6 h), NAD (0.47 ± 0.13 ng) and AUC (51.7 ± 18.6 units) differed between treatments. Nonetheless, OR (1.57 vs. 0.87 ± 0.18 units) and TOA (3.44 vs. 1.87 ± 0.45 units) escorted by a reduced TTFP (33 vs. 126 ± 31.9 min) and an increased AMPL (0.55 vs. 0.24 ± 0.9 ng), favored to the BETA supplemented group (p < 0.05), possibly through a GnRH-LH enhanced pathway and(or) a direct effect at ovarian level. Results are relevant to speed-up the out-of-season reproductive outcomes in goats while may embrace translational applications.

Regional distribution, developmental changes, and cellular localization of CNTF-mRNA and protein in the rat brain.

Ciliary neurotrophic factor (CNTF) is a potent survival molecule for a variety of embryonic neurons in culture. The developmental expression of CNTF occurs clearly after the time period of the physiological cell death of CNTF-responsive neurons. This, together with the sites of expression, excludes CNTF as a target-derived neuronal survival factor, at least in rodents. However, CNTF also participates in the induction of type 2 astrocyte differentiation in vitro. Here we demonstrate that the time course of the expression of CNTF-mRNA and protein in the rat optic nerve (as evaluated by quantitative Northern blot analysis and biological activity, respectively) is compatible with such a glial differentiation function of CNTF in vivo. We also show that the type 2 astrocyte-inducing activity previously demonstrated in optic nerve extract can be precipitated by an antiserum against CNTF. Immunohistochemical analysis of astrocytes in vitro and in vivo demonstrates that the expression of CNTF is confined to a subpopulation of type 1 astrocytes. The olfactory bulb of adult rats has comparably high levels of CNTF to the optic nerve, and here again, CNTF-immunoreactivity is localized in a subpopulation of astrocytes. However, the postnatal expression of CNTF in the olfactory bulb occurs later than in the optic nerve. In other brain regions both CNTF-mRNA and protein levels are much lower.

Third Trimester Vitamin D Status Is Associated With Birth Outcomes and Linear Growth of HIV-Exposed Uninfected Infants in the United States.

BACKGROUND: Vitamin D status in pregnancy may influence the risk of prematurity, birth size, and child postnatal growth, but few studies have examined the relationship among pregnant women living with HIV. METHODS: We conducted a prospective cohort study of 257 HIV-infected mothers and their HIV-exposed uninfected infants who were enrolled in the 2009-2011 nutrition substudy of the Surveillance Monitoring for ART Toxicities (SMARTT) study. HIV-infected pregnant women had serum 25-hydroxyvitamin D (25(OH)D) assessed in the third trimester of pregnancy, and their infants' growth and neurodevelopment were evaluated at birth and approximately 1 year of age. RESULTS: The mean third trimester serum 25(OH)D concentration was 35.4 ± 14.2 ng/mL with 15% of women classified as vitamin D deficient (<20 ng/mL) and 21% as insufficient (20-30 ng/mL). In multivariable models, third trimester vitamin D deficiency and insufficiency were associated with -273 g [95% confidence interval (CI): -450 to -97] and -203 g (95% CI: -370 to -35) lower birth weights compared with vitamin D sufficient women, respectively. Maternal vitamin D deficiency was also associated with shorter gestation (mean difference -0.65 weeks; 95% CI: -1.22 to -0.08) and lower infant length-for-age z-scores at 1 year of age (mean difference: -0.65; 95% CI: -1.18 to -0.13). We found no association of vitamin D status with infant neurodevelopment at 1 year of age. CONCLUSION: Third trimester maternal vitamin D deficiency was associated with lower birth weight, shorter length of gestation, and reduced infant linear growth. Studies and trials of vitamin D supplementation in pregnancy for women living with HIV are warranted.

The human REC2/RAD51B gene acts as a DNA damage sensor by inducing G1 delay and hypersensitivity to ultraviolet irradiation.

HsRec2/Rad51B is a 350-amino acid protein with a molecular mass of 38,300 Da that appears to be involved in cell cycle regulation and UV-induced apoptosis. The mouse and human genes were isolated based on their homology to a recombinational repair gene from Ustilago maydis and contain functional domains to hRAD51 and hLIM 15 (M. C. Rice et al., Proc. Natl. Acad. Sci. USA, 94: 7417-7422, 1997). Here, we report the results of studies on the behavior of CHO cells containing a plasmid encoding a wild-type hsRec2/Rad51B, a full-length protein with a single mutation at residue 163, which lies in the putative src site, and a truncated version of hsRec2/Rad51B, containing only the first 100 amino acids at the NH2 terminus. Using fluorescence-activated cell sorting analysis to follow the progression of cells through the cell cycle, we find that stable transfectants constitutively overexpressing the wild-type human Rec2/Rad51B protein exhibit a G1 delay. In addition, when irradiated with UV at a dose of 15 J/m2, CHO cells transfected with the various hREC2/RAD51B vectors exhibited different responses. Cells expressing the wild-type human Rec2/Rad51B underwent apoptosis, with the greatest cell death occurring 24 h after irradiation. The control cells, which contained an empty vector, and the cells expressing truncated hsRec2/Rad51B or the full-length Rec2 with a mutation at residue 163 did not. In summary, these findings of cell cycle slowing and UV-induced apoptosis in CHO cells constitutively expressing the human Rec2/Rad51B protein suggest that hsRec2/Rad51B plays a role in a DNA damage surveillance pathway.

(5Z)-carbacyclin discriminates between prostacyclin-receptors coupled to adenylate cyclase in vascular smooth muscle and platelets.

(5E)- and (5Z)-carbacyclin are prostacyclin (PGI2) analogues endowed with antiaggregating and vasodilator properties, which stimulate adenylate cyclase activity in membranes from human platelets and cultured myocytes from rabbit mesenteric artery. In platelets they display the same efficacy as prostaglandin E1 (PGE1), and hence PGI2 both as activators of adenylate cyclase and as inhibitors of aggregation. In contrast, in vascular smooth muscle cells (5Z)-carbacyclin fails to produce the same degree of stimulation of the enzyme as PGI2, (5E)-carbacyclin and PGE1, nor does it induce the maximal relaxation of the mesenteric artery as do the other prostaglandins. (5Z)-carbacyclin is also able to antagonize the activation of adenylate cyclase and the relaxation elicited by PGE1 or PGI2 in the mesenteric artery, and therefore it displays partial agonist properties in these cells. We conclude that the receptors for PGI2 coupled to adenylate cyclase in platelets and vascular smooth muscle cells are different from each other, because (5Z)-carbacyclin can discriminate between them, being a partial agonist at myocyte but not at platelet level.

In vivo sequence variation of the human immunodeficiency virus type 1 env gene: evidence for recombination among variants found in a single individual.

To assess in vivo sequence heterogeneity of the human immunodeficiency virus type 1 (HIV-1) env gene, we used the polymerase chain reaction to amplify proviral sequences present in peripheral blood mononuclear cell DNA of a patient with acquired immunodeficiency syndrome (AIDS). The amplified env gene fragment (575 bp) contains the first hypervariable region and part of the first conserved region. Eleven and twelve clones were sequenced, respectively, from specimens collected two months apart. Notable heterogeneity was observed among sequences recovered from both specimens. Also, the proviral population recovered from the first specimen varied significantly from that found in the second specimen. Both specimens contained forms with and without an 18 bp duplication. The presence or absence of this duplication, in addition to several point mutations, appear to define two molecular groups evolving in parallel within this patient. Several genotypes which had sequences characteristic of both groups occurred primarily in the second specimen; these can best be explained by multiple recombinational events between representatives of the two groups during reverse transcription. This study demonstrates that recombination may contribute significantly to the generation of diversity among HIV variants within a single individual.

Financial expenditures for the care of cerebrovascular disease patients in an urban setting.

A study was undertaken to determine the magnitude of the charges and costs and the sources of reimbursements for the care of cerebrovascular disease (CVD) patients in an urban setting, Orleans Parish (County), Louisiana, in 1971. The study helps to put national data on the cost-burden of cerebrovascular disease into perspective at the community level. It is thought that such data may prove useful in planning and evaluation of intervention programs and more coordinated approaches to care. All hospitals, nursing homes, extended care facilities, and noninstitutional sources of care (home health and rehabilitation agencies) that were identified as providing services to CVD patients were invited to participate in the study, and a sample of such cases was selected from each participating facility. The billing records for these cases were then reviewed and analyzed to determine charges by category of service and sources of reimbursement. At government institutions, per diem rates were used to determine costs. Total charges for care of the CVD patients amounted to $6,070,000. Hospital care generated the major charge, amounting to $5,159,000 (85 percent of the total charges) during the study year. Nursing home care charges totaled $391,000 (6.5 percent), extended care services $373,000 (6.1 percent), and home health care and noninstitutional rehabilitation services $147,000 (2.4 percent). Analysis of the data according to type of service revealed that only a small percentage of the care dollar was spent for rehabilitation services. The greatest amounts were spent for room and board in institutional facilities and for drugs, diagnostic services, and miscellaneous other services in hospitals. Average expenditures per CVD case for rehabilitation services in institutions were highest in extended care facilities, being much lower in hospitals and negligible in nursing homes. Average expenditures for care by noninstitutional health service agencies were highest for home aide services, followed by nursing and rehabilitation services.

A consortium, graduate medical education, and Buffalo: defining a common ground.

Regional graduate medical education (GME) consortia are a strategy to align public support for GME with societal goals. One such consortium was established in Buffalo, NY, to pool financial resources, facilitate processing of Accreditation Council for Graduate Medical Education requirements, guarantee quality education, and more appropriately use community resources. Cooperation has attracted external funding from state and federal governments and private foundations, fostering community-wide undergraduate medical education, as well as GME. The American Association of Medical Colleges has identified 36 GME consortia in the United States. New York may lead the nation on a strategy to use consortia for the distribution of all state-appropriated GME support. The relationships fostered by consortial interactions have benefitted family medicine and provided opportunities for leading regional medical education into a primary care-specialty balanced future.

Magnesium deficit in a sample of the Belgian population presenting with chronic fatigue.

97 patients (25 per cent males, ages ranging from 14 to 73 years, median 38 years) with complaints of chronic fatigue (chronic fatigue syndrome, fibromyalgia or/and spasmophilia) have been enrolled in a prospective study to evaluate the Mg status and the dietary intake of Mg. An IV loading test (performed following the Ryzen protocol) showed a Mg deficit in 44 patients. After Mg supplementation in 24 patients, the loading test showed a significant decrease (p = 0.0018) in Mg retention. Mean values of serum Mg, red blood cell Mg and magnesuria showed no significant difference between patients with or without Mg deficiency. No association was found between Mg deficiency, CFS or FM. However serum Mg level was significantly lower in the patients with spasmophilia than in the other patients.

The Bailey-Boushay House: an AIDS facility.

Currently, the cost of caring for an AIDS patient in a nursing facility is about half as much as for the same services provided in a hospital. With the current emphasis on reducing the cost of healthcare, the Bailey-Boushay House serves as a model for others interested in providing specialized care for AIDS patients in a similar setting. If similar facilities are planned there will be opportunities for health information managers to participate in planning for a new, or remodeling an existing, facility. Only an individual's imagination will limit the possibilities.

Modular integrated fluidized bed bioreactor technology.

We describe the design and demonstrate the application of a modular integrated fluidized bed bioreactor system. Basically the system is a reactor vessel equipped with an extending cylinder and a liquid distributor plate. Instead of an external recirculation loop, as used in existing fluidized bed systems, a low shear stress impeller is used as the recirculation pump. The system has several unique features, such as modular exchangeable elements, efficient oxygenation and the option of operating as a stirred tank-, a packed bed- or a fluidized bed reactor. An example of a fluidized bed run using CHO-K1 cells is shown. Under standard culture conditions a 100-fold increase in cell density (up to 1.2 x 10(8) cells/ml) was achieved.