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C Schreiner

Publications and source records attributed to C Schreiner.

At least 19 recordsLinked to original sources
PubMed2003

Properties of a new intravenous immunoglobulin (IGIV-C, 10%) produced by virus inactivation with caprylate and column chromatography.

BACKGROUND AND OBJECTIVES: Current manufacture of intravenous immunoglobulin (Gamimune N) uses four cold-ethanol precipitation steps and solvent-detergent treatment. Our objective was to design a new manufacturing process to maximize immunoglobulin G (IgG) purity, achieve robust viral safety, preserve all the biological activities of antibody and avoid unnecessary protein loss. MATERIALS AND METHODS: The new process combines multiple functions in single steps. Caprylate is added to precipitate non-IgG proteins and to inactivate enveloped viruses. Two successive anion-exchange columns are used to purify IgG and remove caprylate. The new product, IGIV-C (Gamunex, 10%) is formulated with glycine at 100 mg/ml IgG, pH 4.25. Vials are incubated for 21 days at 23-27 degrees C in a final virus-inactivation step. RESULTS: Compared with the process for production of Gamimune N, that for IGIV-C requires a shorter production time, achieves more robust virus inactivation, increases IGIV yield from plasma, improves physiological IgG subclass distribution (resulting in higher levels of IgG4), and improves purity, with lower levels of IgA (40 microg/ml), IgM (< 2 microg/ml) and albumin (< 20 microg/ml). Antibody binding, opsonization and protective activities are similar. CONCLUSIONS: Compared with the current commercial process, the new IGIV-C manufacturing process produces a more highly purified preparation that contains slightly higher levels of IgG4 and retains antibody activities required for clinical efficacy.

Animals↗
PubMed2000

Toxicity evaluation of petroleum blending streams: inhalation subchronic toxicity/neurotoxicity study of a light catalytic reformed naphtha distillate in rats.

A 13-wk whole-body inhalation study was conducted with Sprague-Dawley CD rats (16/sex/group) exposed to a light catalytic reformed naphtha distillate (LCRN-D, CAS number 64741-63-5) at target concentrations of 0, 750, 2500, and 7500 ppm for 6 h/d, 5 d/wk. Sixteen rats per sex in the control and high-dose groups were maintained after final exposure for a 4-wk recovery period. The highest exposure concentration was 75% of the lower explosive limit. Standard parameters of subchronic toxicity were measured throughout the study; at necropsy, organs were weighed and tissues processed for microscopic evaluation. Neurotoxicity evaluations consisted of motor activity (MA) and a functional operational battery (FOB) measured pretest, throughout exposure and after the recovery period. Neuropathology was evaluated at termination. No test-related mortality or effects on physical signs, body weight, food consumption, or clinical chemistry were observed. In males exposed to 7500-ppm LCRN-D, a statistically significant decrease in white blood cell counts and lymphocyte counts was observed at the termination of exposure that was not present in animals after the 4-wk recovery period. However, mean corpuscular volume was slightly decreased in high-dose males after the recovery period. Statistically significant increases in kidney weights relative to body weights in 7500-ppm male rats correlated with microscopically observed hyaline droplet formation and renal tubule dilation, indicative of light hydrocarbon nephropathy, a condition in male rats that is not toxicologically significant for humans. Statistically significant decrease in absolute and relative spleen weights in 7500-ppm male rats correlated with decreases in hematologic parameters but had no microscopic correlate and was not observed in animals after 4 wk of recovery. This mild, reversible effect in white blood cell populations may relate to the presence of aromatics in the distillate. The only effect of LCRN-D on neurobehavioral parameters was significantly higher motor activity counts among high-dose (7500 ppm) males after the 4-wk recovery period, suggesting a possible delayed effect of LCRN-D. However, there was no evidence of hyperactivity or abnormal behavior from the functional observational battery evaluations, and there were no microscopic changes in neural tissue to support this observation. The no-observed-adverse-effects level (NOAEL) for LCRN-D was 2500 ppm for both subchronic toxicity and neurotoxicity. The no-observed-effects level (NOEL) was 750 ppm.

Administration, Inhalation↗
PubMed2000

Toxicity evaluation of petroleum blending streams: reproductive and developmental effects of light catalytic reformed naphtha distillate in rats.

A distillate of light catalytic reformed naphtha (CAS number 64741-63-5, LCRN-D) administered by inhalation was tested for reproductive and developmental toxicity in Sprague-Dawley rats, following a modified OECD Guideline 421, Reproductive/Developmental Toxicity Screening protocol. LCRN-D was administered as a vapor, 6 h/d, 7 d/wk at target concentrations of 0, 750, 2500 or 7500 ppm to female rats for approximately 6 wk from 2 wk prior to mating, during mating through gestational d 19, and to males beginning 2 wk prior to mating for approximately 7 consecutive weeks. Dams and litters were sacrificed on postnatal d 4 and males were sacrificed within the week after the last litter was necropsied. Parental systemic effects observed at the 7500 ppm exposure level included slightly lower body weights for males throughout the study. Increased kidney to body weight and increased liver to body weight ratio in male rats exposed to 7500 ppm LCRN-D may be related to slightly lower final mean body weights. Body and organ weight data for female rats in all exposure groups were comparable to controls. No test-material-related microscopic changes were observed in the reproductive organs or nasal turbinate tissue of either sex. Reproductive performance was unaffected by exposure to LCRN-D. The mating and fertility indices were 100% in all groups. There were no significant exposure-related differences in implantation sites or live pups per litter, and no gross abnormalities were observed in pups from treated dams. Pups born from LCRN-D-exposed dams showed comparable body weights and weight gain to control pups. The viability index on postpartum d 4 was > or =97%. Under conditions of this study, the no-observed-adverse-effect level (NOAEL) for exposure to light catalytic reformed naphtha distillate for parental effects was 2500 ppm and the NOAEL for reproductive and developmental toxicity was 7500 ppm.

Alkanes↗
PubMed1999

Toxicity evaluation of petroleum blending streams: reproductive and developmental effects of light catalytic cracked naphtha distillate in rats.

A distillate of light catalytic cracked naphtha (CAS number 64741-55-5, LCCN-D), administered by inhalation, was tested for reproductive and developmental toxicity in Sprague-Dawley rats, following a modified OECD Guideline 421, Reproductive/Developmental Toxicity Screening Protocol. LCCN-D was administered as a vapor, 6 h/d, 7 d/wk at target concentrations of 0, 750, 2500 or 7500 ppm to female rats for approximately 7 wk from 2 wk prior to mating, during mating through gestational d 19, and to males beginning 2 wk prior to mating for 8 consecutive weeks. Dams and litters were sacrificed on postnatal d 4, and males were sacrificed within the following week. Parental systemic effects observed at the 7500 ppm exposure level were increased kidney weights and relative liver weights in males and increased spleen weights in high-dose females. Livers and spleens from rats in the high-dose group were normal in appearance at necropsy. IncreaSed kidney weights in high-dose males were indicative of male-rat-specific light hydrocarbon nephropathy. No test-related microscopic changes were observed in the reproductive organs or nasal turbinate tissues of either sex. Reproductive performance was unaffected by treatment with LCCN-D. Fertility index was > or =90% in all dose groups. There were no exposure-related differences in implantation sites and live pups per litter, and no gross abnormalities were observed. Pups born from treated dams showed comparable body weights and weight gains to controls. The viability index on postpartum d 4 was > or =97%; the high-dose group had more male than female pups at birth and at d 4 postpartum. Under the conditions of this study, the no-observable-adverse-effect level (NOAEL) for exposure to light catalytic cracked naphtha distillate for parental toxicity was 2500 ppm and the NOAEL for reproductive performance and developmental toxicity was 7500 ppm.

Alkanes↗
PubMed1998

Toxicity evaluation of petroleum blending streams: inhalation subchronic toxicity/neurotoxicity study of a light alkylate naphtha distillate in rats.

A 13-wk inhalation study was conducted with Sprague-Dawley CD rats (12/sex/group) were exposed by inhalation for 13 weeks to a light alkylate naphtha distillate (LAND-2, C4-C10; average molecular weight 89.2) at actual average concentrations of 0 (room air), 668, 2220, or 6646 ppm, 6 h/d, 5 d/wk; 12 additional rats/sex in the control and high dose groups were held after final exposure for a 4-wk recovery period. The highest exposure concentration was 75% of the lower explosive limit. Standard parameters of subchronic toxicity were measured throughout the study; at necropsy, organs were weighed and tissues processed for microscopic evaluation. Neurotoxicity evaluations consisted of motor activity (MA) and a functional operational battery (FOB) measured pretest, during 5, 9, and 14 wk of the study, and after the 4-wk recovery period. Whole-body perfusion and microscopic examination of selected organs and nervous tissue from the control and high dose rats were conducted at the end of exposure. No test-related mortality or effects on physical signs, body weight, or food consumption were observed. Statistically significant increases in absolute and relative kidney weights in high-exposure males correlated with microscopically observed hyaline droplet formation and renal nephropathy, effects in male rats that are not toxicologically significant for humans. Increased liver weights in both sexes at the highest dose had no microscopic correlate and appeared reversible after the 4-wk recovery period. Exposure to LAND-2 at any dose did not produce neurotoxicity measured by MA, FOB, or neuropathology. The no-observed-effects level (NOEL) for LAND-2 was 2220 ppm for subchronic toxicity and > or =26646 ppm for neurotoxicity.

Administration, Inhalation↗
PubMed1998

Solid-phase immunoassays for HCV antibodies in Gamimune N.

BACKGROUND AND OBJECTIVES: Occasional false-positive results for the presence of HCV antibodies occur when testing pH 4 Gamimune N immune globulin intravenous (human) (IGIV) using commercially available immunoassay kits. We investigated the causes. MATERIALS AND METHODS: EIA test results were compared with Nile red hydrophobic dye binding. RESULTS: There was a strict correlation of reactive EIA results with a larger relative proportion of molecules in a low pH-dependent hydrophobic conformation. Conversely, the greater the hydrophilic contribution to the population of IgG molecules (favored at neutral pH), the more nonreactive the EIA test results became for the same lots. An IGIV test preparation procedure consisting of pH neutralization followed by 48-hour incubation at 37 degrees C decreased positive test result outcomes in four different immunoassay formats by shifting the IgG population to a more hydrophilic conformation. CONCLUSIONS: The hydrophobic conformation of IgG favored at low pH appears to give rise to significant levels of nonspecific binding in solid phase immunoassays.

Coloring Agents↗
PubMed1997

Toxicity evaluation of petroleum blending streams: reproductive and developmental effects of hydrodesulfurized kerosine.

Hydrodesulfurized kerosine (HDS kerosine), applied dermally, was tested for reproductive and developmental toxicity in Sprague-Dawley rats, using a modified OECD Guideline 421, Reproductive/Developmental Toxicity Screening Protocol. A preliminary acute dermal irritancy test demonstrated that dilution of HDS kerosine in either a light (100 Saybolt universal seconds, SUS) or moderate viscosity (340 SUS) USP mineral oil reduced irritation of the neat material comparably. Similar dermal absorption was observed in vitro for neat HDS kerosine or diluted in either of the mineral oils. HDS kerosine diluted to 494 (60%), 330 (40%), or 165 (20%) mg/kg/day in Squibb mineral oil (340 SUS) was applied daily at 1 ml/kg to the shaved backs of rats for 7 wk (premating, mating to d 19 of gestation) to females and 8 wk to males. Dams and litters were sacrificed on postpartum d 4 and males were sacrificed within the following week. HDS kerosine produced slight to moderate skin irritation at the highest dose in both sexes but no apparent maternal, reproductive, or developmental toxicity. No clinical signs of toxicity and no effects on body weight, food consumption, or absolute organ weights were observed. Relative kidney weights were heavier in male rats at the high dose. Skin changes were observed microscopically in male rats in all groups and in females at the high dose. No microscopic changes were observed in reproductive organs of parental animals. There were no differences in mean number of corpora lutea, implantation sites, and live pups per litter, and no gross anomalies were observed. Pups born from treated dams showed comparable body weights and weight gains to controls. The viability index on postpartum d 4 was > or = 93%. In conclusion, the no observable adverse effect level (NOAEL) for HDS kerosine for reproductive and developmental toxicity in rats is 494 mg/kg/d.

Administration, Topical↗
PubMed1996

Temporal processing deficits of language-learning impaired children ameliorated by training.

Children with language-based learning impairments (LLIs) have major deficits in their recognition of some rapidly successive phonetic elements and nonspeech sound stimuli. In the current study, LLI children were engaged in adaptive training exercises mounted as computer "games" designed to drive improvements in their "temporal processing" skills. With 8 to 16 hours of training during a 20-day period, LLI children improved markedly in their abilities to recognize brief and fast sequences of nonspeech and speech stimuli.

Child↗
PubMed1996

Language comprehension in language-learning impaired children improved with acoustically modified speech.

A speech processing algorithm was developed to create more salient versions of the rapidly changing elements in the acoustic waveform of speech that have been shown to be deficiently processed by language-learning impaired (LLI) children. LLI children received extensive daily training, over a 4-week period, with listening exercises in which all speech was translated into this synthetic form. They also received daily training with computer "games" designed to adaptively drive improvements in temporal processing thresholds. Significant improvements in speech discrimination and language comprehension abilities were demonstrated in two independent groups of LLI children.

Algorithms↗
PubMed1995

A unique repeated DNA sequence in the cyclosporin-producing strain of Tolypocladium inflatum (ATCC 34921).

Recombinant lambda clones containing repeated DNA sequences were isolated from the cyclosporin A-producing fungus Tolypocladium inflatum (ATCC 34921) by differential hybridization with total fungal DNA and rDNA probes. From this survey 1% of the lambda clones appeared to contain repeated sequences. Subsequent analysis led to the identification of a dispersed repetitive DNA element. It was named CPA element (cyclosporin production associated) and appears to be strain specific, since it is absent from other related strains or fungi. Hybridization with chromosomal restriction fragments indicates an equal distribution of the CPA element in the genome. The copy number was estimated to be between 20 and 30 per haploid genome. Sequence analysis of a 0.9-kb XhoI fragment from three copies of the CPA element revealed strong conservation of this sequence among all copies. A 200-bp region exhibits similarities to a repeated sequence from Zea diploperennis. The use of this DNA sequence as a molecular marker for identification of this cyclosporin-producing strain ATCC 34921 is discussed as is the relevance of repeated DNA sequences for rearrangements of fungal karyotypes.

Base Sequence↗
PubMed1994

Significance of laser treatment in arthroscopic therapy of degenerative gonarthritis. A prospective, randomised clinical study and experimental research.

To ascertain the efficiency of different techniques of arthroscopic therapy for gonarthritis and establish the relevance of the extent of chondromalacia, clinical and experimental studies were performed. In principle, the process of chondromalacia determines the course of the disease. Treatment of additional meniscus lesions temporarily leads to better clinical results, but after only a few months the symptoms caused by the arthritic process reappear. Compared with the temporary relief of complaints after debridement and lavage, smoothing with a xenon chloride excimer laser in grade II chondromalacia leads to statistically significantly better clinical results. Scanning electron microscopic studies confirm the extremely good smoothing. These studies permit clear statements as to the various methods of treatment and their application in the different grades of chondromalacia, thus leading to differentiated arthroscopic treatment of degenerative gonarthritis.

Arthritis↗
PubMed1994

Gait outcome in ambulatory hemiparetic patients after a 4-week comprehensive rehabilitation program and prognostic factors.

BACKGROUND AND PURPOSE: Although gait training is prominent in the rehabilitation of hemiparetic stroke patients, little is known about its outcome and prognostic factors in mildly affected patients. We therefore intended to assess gait in ambulatory stroke patients before and after a 4-week inpatient rehabilitation program based on the neurodevelopmental technique. METHODS: We measured vertical ground reaction forces by force plates in 148 stroke patients. Variables were stance durations, peak vertical ground reaction forces at heel strike (Fz1) and toe-off (Fz2), loading and deloading rates, time to Fz1, and time to Fz2. The absolute changes for both legs and symmetry outcome were calculated. In addition, we assessed maximal walking speed, walking endurance, stair climbing ability, and the Motricity Index. RESULTS: Stance duration, weight acceptance, push-off of both legs, and the stance duration symmetry improved independent of changes of gait velocity. The symmetry of the ground reaction forces did not improve. Results were even worse for Fz1 and the loading rate at the end of treatment. Sex, age, side of hemiparesis, motor strength, stroke interval, and sensory impairment had no influence on the outcome of symmetry. Functional performance did not improve considerably. CONCLUSIONS: The absolute changes of the ground reaction forces indicated better weight acceptance and push-off of both legs and thus confirmed the efficacy of the neurodevelopmental technique. The symmetry outcome and the functional performance at the end of treatment, however, challenge the efficacy of intensive rehabilitation therapy for 4 weeks in its attempts to restore physiological gait in these mildly affected patients.

Adolescent↗
PubMed1993

Neural mechanisms of tinnitus.

The theoretical concepts underlying the neural origin of tinnitus are outlined. Several neurophysiological models are reviewed critically and the impact of the pathological ensemble spontaneous activity of the auditory system for the diagnosis and therapy of tinnitus is described in more detail.

Animals↗
PubMed1993

Functional role of the cytoplasmic domain of the integrin alpha 5 subunit.

The purpose of this study was to explore the functional role of the cytoplasmic domain of the alpha subunit of the alpha 5/beta 1 integrin, a fibronectin receptor. Mutant CHO cells that express very low levels of endogenous hamster alpha 5 subunit (CHO clone B2) were transfected with an expression vector containing full-length or truncated human alpha 5 cDNAs to form chimeric human alpha 5/hamster beta 1 integrins. Three transfectants were examined: B2a27 expresses a full-length human alpha 5 subunit with 27 amino acids in the cytoplasmic domain; B2a10 expresses an alpha 5 with a 17-amino acid cytoplasmic truncation; B2a1 expresses an alpha 5 with a 26-amino acid truncation. Levels of alpha 5/beta 1 surface expression in B2a27 and B2a10 cells were similar to that in wild type CHO cells. The expression of alpha 5/beta 1 in B2a1 cells was less, amounting to 15-20% of WT levels, despite message levels that were three to five times greater than those of B2a27. The transfectants were used to examine the role of the alpha 5 cytoplasmic domain in cell adhesion, cell motility, cytoskeletal organization, and integrin-mediated tyrosine phosphorylation. The adhesion characteristics of B2a27 and B2a10 cells on fibronectin substrata were similar to each other and to wild type CHO cells. B2a1 cells displayed slight reductions in the strength and rate of adhesion to fibronectin. Cell motility in the presence of fibronectin was similar for B2a27, B2a10, and wild type CHO cells, while the B2a1 cells were substantially less motile. Comparable degrees of cell spreading and extensive organization of actin filaments were observed for B2a27, B2a10, and wild type CHO cells on fibronectin substrata. The B2a1 cells spread to a lesser degree, and some organization of actin was observed; the untransfected B2 cells remained round on fibronectin substrata and showed no actin reorganization. Since the reduced motility and cell spreading observed in the B2a1 cells might be due either to reduced surface expression of alpha 5/beta 1 or to the truncation in the alpha 5 cytoplasmic domain, we used flow cytometric cell sorting to select populations of B2a1 and B2a27 cells expressing similar levels of cell surface alpha 5. The deficits in spreading and motility were present in B2a1 cells expressing high levels of alpha 5. Thus the region of the alpha 5 cytoplasmic domain adjacent to the membrane seems to play an important role in cytoskeletal organization and cell motility. We also examined whether alpha subunit truncation would affect integrin-mediated tyrosine phosphorylation.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMed1993

Nucleus pulposus regeneration after chemonucleolysis with chymopapain?

Chemonucleolysis was unsuccessful in 100 out of 519 patients with herniated lumbar discs treated within a period of 3 years. These patients were subsequently submitted to open surgery. Disc material from 88 of the 100 patients was examined by light microscopy (hematoxylin and eosin, van Gieson's, Nissl's and periodic acid-Schiff staining) to verify the effect of enzymatic activity compared to the histologic findings in a similar control group. In 84 of the 88 cases, signs of enzymatic activity were revealed by eosinophilia of the ground substance, altered Nissl staining and positive periodic acid-Schiff reaction within the chondrocyte halos. These alterations indicate that the enzyme was active and confirm the results of previous studies with smaller numbers of cases. Histologic alterations were quantified according to the intensity and extent of staining. The signs of enzymatic activity were significantly (P < 0.01) stronger after short time intervals between chemonucleolysis and surgery than after long intervals. These findings may be interpreted as indicating a regenerative potential of the nucleus pulposus.

Adult↗
PubMed1993

[Osteochondral fracture of the lateral tibial pilon].

In this paper we report a case of osteochondral fracture of the lateral tibial pilon. A young man fell while he was playing soccer. In the following months the ankle was swollen and painful. Later the reason for his ankle pain was clearly visible on the X-ray pictures, which revealed a severe osteochondral fracture of the lateral tibial pilon. We describe the arthroscopic and X-ray grading of osteochondral fractures of the ankle and their treatment.

Adult↗