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B Kendrick

Publications and source records attributed to B Kendrick.

10 recordsLinked to original sources
PubMed2001

A specific molar ratio of stabilizer to protein is required for storage stability of a lyophilized monoclonal antibody.

The selection of the appropriate excipient and the amount of excipient required to achieve a 2-year shelf-life is often done by using iso-osmotic concentrations of excipients such as sugars (e.g., 275 mM sucrose or trehalose) and salts. Excipients used for freeze-dried protein formulations are selected for their ability to prevent protein denaturation during the freeze-drying process as well as during storage. Using a model recombinant humanized monoclonal antibody (rhuMAb HER2), we assessed the impact of lyoprotectants, sucrose, and trehalose, alone or in combination with mannitol, on the storage stability at 40 degrees C. Molar ratios of sugar to protein were used, and the stability of the resulting lyophilized formulations was determined by measuring aggregation, deamidation, and oxidation of the reconstituted protein and by infrared (IR) spectroscopy (secondary structure) of the dried protein. A 360:1 molar ratio of lyoprotectant to protein was required for storage stability of the protein, and the sugar concentration was 3-4-fold below the iso-osmotic concentration typically used in formulations. Formulations with combinations of sucrose (20 mM) or trehalose (20 mM) and mannitol (40 mM) had comparable stability to those with sucrose or trehalose alone at 60 mM concentration. A formulation with 60 mM mannitol alone provided slightly less protection during storage than 60 mM sucrose or trehalose. The disaccharide/mannitol formulations also inhibited deamidation during storage to a greater extent than the lyoprotectant formulations alone. The reduction in aggregation and deamidation during storage correlated directly with inhibition of unfolding during lyophilization, as assessed by IR spectroscopy. Thus, it appears that the protein must be retained in its native-like state during freeze-drying to assure storage stability in the dried solid. Long-term studies (23-54 months) performed at 40 degrees C revealed that the appropriate molar ratio of sugar to protein stabilized against aggregation and deamidation for up to 33 months. Therefore, long-term storage at room temperature or above may be achieved by proper selection of the molar ratio and sugar mixture. Overall, a specific sugar/protein molar ratio was sufficient to provide storage stability of rhuMAb HER2.

Antibodies, Monoclonal↗
PubMed1997

Spectroscopic study of secondary structure and thermal denaturation of recombinant human factor XIII in aqueous solution.

The secondary structure and thermal denaturation (in H2O vs D2O) of recombinant human factor XIII in aqueous solutions were investigated using infrared and circular dichroism (CD) spectroscopies. The infrared amide I spectrum of the protein in H2O solution at 25 degrees C exhibited an absorbance maximum near 1642 cm-1, indicating the presence of a predominantly beta-sheet structure. Quantitative analysis revealed that the native protein contains 13-16% alpha-helix, 41-49% beta-sheet, 29% beta-turn, and 10-14% extended strand structures. The presence of a strong low-wavenumber beta-sheet band at 1641 cm-1 and a weak high-wavenumber beta-sheet band at 1689 cm-1 indicated that the beta-sheet structure of the protein is predominantly antiparallel. Quantitative analysis of the CD spectrum using the SELCON method indicated a secondary structural content of 10% alpha-helix, 40-50% beta-sheet, 20-35% beta-turns, and 20-35% unordered elements, which matches that determined by X-ray crystallography. The apparent discrepancy with the contents of unordered element determined by infrared spectroscopy is reconciled by considering that CD spectroscopy and X-ray crystallography assign extended loops and strands to unordered elements, whereas infrared spectroscopy recognizes these as distinct structured elements. During heating above 60 degrees C, a pair of new infrared bands appeared at 1626 and 1693 cm-1 for the protein in H2O and 1619 and 1683 cm-1 in D2O, indicating a formation of intermolecular beta-sheet aggregates. The intensities of the new bands increased as a function of temperature, concomitant with an intensity decrease in bands for the native protein structural elements. As expected, there was an increase in thermal stability in D2O relative to that in H2O, which was manifested as an increase of about 5 degrees C in the temperature for initial loss of infrared bands assigned to native structural elements and for appearance of bands due to intermolecular beta-sheet. In addition, the midpoint of the thermally induced transitions in infrared spectra were about 2.5 degrees C higher in D2O than in H2O. Based on the infrared analysis, the thermally denatured state of the protein in both H2O and D2O contains predominantly intermolecular beta-sheet. The broad, poorly resolved absorbance that spans the region between the intermolecular beta-sheet bands was assigned to an ensemble of heterogeneous structural elements (including unordered), none of which is populated to a high enough degree to result in a distinct infrared band. Results from CD spectroscopy support these conclusions about the structure of the denatured, aggregated protein.

Circular Dichroism↗
PubMed1995

Indoor aeromycota in relation to residential characteristics and allergic symptoms.

The indoor aeromycota in several rooms of each of 15 residences in Kitchener-Waterloo, Ontario, Canada was studied from December 1991 to September 1993. There were significant differences in airborne spore concentrations among the types of rooms investigated. Numbers of airborne propagules were highest in the living rooms, followed by family rooms, kitchens, bathrooms and bedrooms. The highest fungal diversity was found in kitchens. Generally, presence of dampness and of carpets led to increased numbers of airborne spores. Forced air heating systems, humidifiers, air filters and air conditioners reduced concentrations of airborne fungi. Patients with respiratory allergies and known sensitivity to moulds reported allergic symptoms significantly less severe than average in residences with air conditioners, air filters, humidifers and forced air heating systems. In damp residences, their symptoms were significantly more severe than the average.

Air Conditioning↗
PubMed1995

A year-round study on functional relationships of airborne fungi with meteorological factors.

Air sampling was conducted in Waterloo, Canada throughout 1992. Functional relationships between aeromycota and meteorological factors were analysed. The meteorological factors were, in descending order of importance: mean temperature, minimum temperature, maximum temperature, mean wind speed, relative humidity (RH), rain, maximum wind speed and snow. The most important airborne fungal propagules in descending order were total fungal spores, unidentified Ascomycetes, Cladosporium, Coprinus, unidentified Basidiomycetes, Alternaria and unidentified fungi. Most airborne fungal taxa and highly significant relationship with temperature, but Aspergillus/Penicillium, hyphal fragments were positively associated with wind speed. In comparison with other airborne fungal taxa, Leptosphaeria and unidentified Ascomycetes were more closely correlated with rain and RH during the growing season.

Air Microbiology↗
PubMed1992

How much monitoring is needed for basilar skull fractures?

Basilar skull fractures account for approximately 19% of all skull fractures. There have been little data published concerning the need for intensive care monitoring in this injury. We retrospectively studied 259 patients admitted to our trauma center over an 8-year period with a diagnosis of basilar skull fracture. All patients were evaluated with cranial computed tomographic (CT) scans. These patients were admitted to the trauma service, and neurosurgical consultation was obtained in all cases. The diagnosis was made by clinical signs in 207 patients (80%), by CT scan in 47 (18%), and by plain films in 5 (2%). Ninety-two patients (group I) had intracranial pathology in addition to basilar skull fracture. Twenty-one patients in this group underwent craniotomy. In this group, the morbidity and mortality rates were 11% and 7%, respectively. Forty-four patients (group II) had no intracranial pathology and a Glasgow Coma Score (GCS) of less than 13. The morbidity was 2%, and the mortality was 2%. One hundred twenty-three patients (group III) had no intracranial pathology on CT scan and a GCS of 13 or greater. The complication rate in this group was 1%, and there was no neurologically related mortality. Patients who are admitted with a diagnosis of basilar skull fracture and who have a GCS of 13 or greater with no intracranial pathology on CT can be managed without intensive care monitoring.

Adolescent↗
PubMed1991

Efficient lipid staining in plant material with sudan red 7B or fluorol [correction of fluoral] yellow 088 in polyethylene glycol-glycerol.

Polyethylene glycol (400) with 90% glycerol (aqueous) is introduced as an efficient solvent system for lipid stains. Various lipid-soluble dyes were dissolved in this solvent system and tested for their intensity, contrast, and specificity of staining of suberin lamellae in plant tissue. The stability (i.e., lack of precipitation) of the various staining solutions in the presence of fresh tissue was also tested. When dissolved in polyethylene glycol-glycerol, Sudan red 7B (fat red) was the best nonfluorescent stain and fluorol yellow 088 (solvent green 4) was an excellent fluorochrome. These two dyes formed stable staining solutions which efficiently stained lipids in fresh sections without forming precipitates. Estimations of the solubilities of these dyes in the solvent compared with their solubilities in lipids of various chemical types indicated that they should both be effective stains for lipids in general.

Azo Compounds↗
PubMed1989

Laryngeal paralysis as the presenting sign of aortic trauma.

Disruption of the thoracic aorta is usually fatal without prompt surgical attention. Left recurrent laryngeal nerve paralysis has been reported in approximately 10% of patients who survive long enough to develop a pseudoaneurysm, but the time of onset has rarely been specified. In this study, 50 cases of thoracic aortic trauma were reviewed to determine the incidence and timing of laryngeal paralysis, compared with 50 cases of atherosclerotic aneurysms matched for location. Four patients in the traumatic group were hoarse, and the onset was immediate in 3. Six in the atherosclerotic group became hoarse. Results indicate that laryngeal paralysis following severe trauma can be a very early sign of aortic injury and requires prompt and thorough investigation.

Adolescent↗