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Biomedical subjects

J Thomson

Publications and source records attributed to J Thomson.

At least 109 records · Page 6Linked to original sources
PubMed1991

Effect of production method on the systemic clearance rate of a human monoclonal antibody in the rat.

Pharmacologic studies of human immunoglobulins (IgM) in non-primate animal models, whether directed toward efficacy or toxicity, rely on pharmacokinetic parameters to achieve optimal doses and schedules. In rodents, human IgMs have an effective circulatory half-life of 11 h and a plasma clearance rate of 0.044 ml/min/kg. Studies of a new group of human monoclonal antibodies (hMAb) specific for Gram-negative bacteria and endotoxin revealed an IgM molecule, hMAb-10058, which, when purified from tissue culture medium, exhibited a suprisingly short circulatory lifetime in rodents. Investigations into possible explanations for this short circulatory half-life resulted in the development of a simple and efficient method for producing hMAbs in the immunodeficient NIH-3 mouse (bg x nu x XID). This method of production of hMAb-10058 had dramatic effects on its half-life. Whereas hMAb-10058 produced in serum-free, defined medium had a clearance rate of 14.4 ml/min/kg and an effective half-life of 0.12 h, the same hMAb-10058 raised in mouse ascites had a decreased clearance rate of 0.092 ml/min/kg and an increased effective half-life of 12 h. This 100-fold enhancement of the hMAb's half-life was not affected by the purification process. Some potential molecular structures involved in the circulatory half-life of this hMAb are discussed.

Animals↗
PubMed1990

Phenotypic analysis of ovine bone marrow cells using monoclonal antibodies and lectins.

Three major subpopulations of ovine bone marrow cells were identified by flow cytometry on the basis of differences in forward (FSC) versus right angle (SSC) light scattering properties and binding of monoclonal antibodies. Region 1 (low FSC, low SSC) contained erythroid series cells and some small lymphocytes. Region 2 (high FSC, low SSC) contained monocytes, myeloid blast cells, medium-large lymphocytes and virtually all of the progenitor/stem cells capable of forming colonies in soft agar cultures. Region 3 (high SSC) contained granulocytes at various stages of development, predominantly (greater than 90%) neutrophils and eosinophils. Using this technique it was possible to identify several cell-surface antigens on bone marrow cells of different lineages using specific monoclonal antibodies and lectins. Amongst the haemopoietic stem/progenitor cell population, immature colony-forming cells were leucocyte common antigen (LCA) negative while more mature colony-forming cells expressed LCA. A proportion of progenitor cells were MHC class I positive. This analysis is an important first step in characterising ovine haemopoietic cells for future studies on: the development of inflammatory cells, the migration of stem/progenitor cells in vivo and the tropism of pathogens.

Analysis of Variance↗
PubMed1990

High-resolution structure of a mutagenic lesion in DNA.

The self-complementary dodecanucleotide d[CGC(m6G)AATTTGCG]2 (where m6G is O6-methylguanine), which contains two m6G.T base pairs, has been analyzed by x-ray diffraction methods and the structure has been refined to a residual error of R = 0.185 at 2.0-A resolution. The m6G.T mispair closely resembles a Watson-Crick base pair and there are very few structural differences between the m6G.T duplex and the native analogue. The similarity between the m6G.T base pair and a normal G.C base pair explains the failure of mismatch repair enzymes to recognize and remove this mutagenic lesion. A series of ultraviolet melting studies over a wide pH range on a related dodecamer indicate that the m6G.C mispair can exist in two conformations; one is a wobble pair and the other is a protonated Watson-Crick pair. The former, which predominates at physiological pH, will be removed by normal proofreading and repair enzymes, whereas the latter is likely to escape detection. Hence, the occasional occurrence of the protonated m6G.C base pair may explain why the presence of m6G in genomic DNA does not always give rise to a mutation.

Base Composition↗
PubMed1989

Dermatoses in five related female carriers of X-linked chronic granulomatous disease.

Eight female members of a family with X-linked chronic granulomatous disease were identified. Five were shown to be carriers of the disease gene. Each of these female carriers of the gene had a history of skin eruptions. The identification of the carrier state is important as genetic counselling should be offered and the prenatal diagnosis of this disorder is possible.

Adult↗
PubMed1989

Novel variants of human papillomavirus type 2 in warts from immunocompromised individuals.

Twenty cutaneous warts from I8 renal transplant recipients (RTR) and a single wart sample from a patient suffering from Hodgkin's disease were screened for the presence of human papillomavirus (HPV) sequences by Southern blot analysis. Thirteen samples were shown to contain HPV DNA sequences, one was identified as HPV-3, two as HPV-4, six as HPV-2 and four were unidentifiable by restriction digest analysis. HPV-3 was identified in the wart sample from the patient suffering from Hodgkin's disease. In the six samples in which HPV-2 was found, the viral genome showed polymorphism for the PvuII and PstI sites. Two PvuII patterns and one PstI pattern are novel.

Blotting, Southern↗
PubMed1989

Capillary and size interrelationships in developing rat diaphragm, EDL, and soleus muscle fiber types.

The effects of maturation on the interrelationship between skeletal muscle fiber area and capillarization was investigated in specific fiber types (I, IIa, IIb, IIc) of male Wistar rats at seven developmental periods ranging from 8 to 85 days postnatal. Fiber type specific developmental properties were compared in three different muscles, the diaphragm (DIA), extensor digitorum longus (EDL), and soleus (SOL), which are known to differ widely in function. All fiber types in each of the three muscles examined exhibited large increases in area (FA), the magnitude and time course of the increase being related to both the type of fiber and the muscle in which the fiber was located. For type I fibers, areas increased from 3- to 18-fold (SOL greater than EDL greater than DIA), whereas in type IIa fibers, area increased ranged between 5- to 11-fold (SOL greater than EDL greater than DIA). Growth rates in IIb fibers were more homogeneous between muscles ranging from 11- to 14-fold. Capillarization, as indicated by the capillary contacts per fiber (CC), increased in all fiber types regardless of muscle origin. These increases ranged between 1.7- and 2.2-fold for type I fibers, between 2.4- and 2.5-fold for type IIa fibers, and between 2.0- and 3.0-fold for type IIb fibers. In general, capillary density expressed as the ratio of the number of capillary contacts divided by the fiber area (CC/FA) progressively declined in all fiber types with age. The rate of the decline in CC/FA was mediated in large part by the changes in fiber area.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1989

Occult intrasacral meningocele: clinical and radiographic diagnosis.

We evaluated four patients who had occult intrasacral meningocele with multimodality radiographic imaging techniques. The clinical features, radiological findings, gross appearances of the lesion at surgery, surgical technique, histopathological features of the cyst wall, and surgical outcome are described. The role of magnetic resonance imaging in the preoperative evaluation compared with standard radiographic techniques is discussed. Theories regarding the pathogenesis of this lesion are reviewed.

Female↗
PubMed1989

Isoelectric focusing of recombinant interferon-beta.

Recombinant human interferon-beta (IFN-beta), a highly basic and hydrophobic protein, has been isoelectric focused using the nonionic detergent polyoxyethylene 12 lauryl ether (laureth 12). Laureth 12 preserved the solubility of IFN-beta during isoelectric focusing (IEF) under conditions where other nonionic reagents were ineffective. This detergent may perhaps be useful with other hydrophobic or membrane proteins. A highly automated electrophoresis system with short run times was adapted for rapid method development with a protein requiring non-standard conditions by hand-casting specialized gels for the system.

Autoanalysis↗
PubMed1988

Oxidative potential in developing rat diaphragm, EDL, and soleus muscle fibers.

To examine the effect of postnatal development on changes in oxidative potential of fibers of specific types (I, IIa, IIb, and IIc) in the rat diaphragm, determinations of succinate dehydrogenase (SDH) activity were made using microphotometric measures of optical density. Samples of the costal region of the diaphragm were extracted from 56 male Wistar rats ranging in age from 8 to 85 days and subgrouped into seven developmental periods (1, 2, 3, 4, 6, 9, and 12 wk). For type I fibers, increases of 17% (P less than 0.05) in SDH activity occurred during 2nd wk, remained elevated through 4th wk, and increased further (P less than 0.05) to 137% of 1-wk values by the end of 6th wk. No further increases were noted between 6 and 12 wk. A similar maturational trend was evident for type IIa fibers, although SDH activities remained higher throughout development when compared with type I fibers. In contrast, SDH in type IIb fibers, although increasing by 14% during the first two measurement weeks (P less than 0.05), declined from 6 to 9 wk before ultimately reaching a value similar to 3 wk. SDH activity was also assessed in a typical slow- (soleus) and fast-twitch (extensor digitorum longus, EDL) muscle of the hindlimb to contrast their development with that of the diaphragm. Generally, SDH in type I and IIa fibers was approximately 40 and 20% higher, respectively, in the diaphragm than in matched fiber types in the other muscles throughout development (diaphragm greater than EDL greater than soleus).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphatases↗
PubMed1987

Structure and stability of gamma-crystallins. Denaturation and proteolysis behavior.

The denaturation behavior of bovine lens gamma-crystallin fractions II, III, and IV and their susceptibility to proteolysis in vitro was compared to determine whether differences in their stability could play a role in cataract formation. Tertiary and secondary structure changes induced by increasing concentrations of urea, guanidine hydrochloride, and sodium dodecyl sulfate and by increasingly alkaline pH were followed by near-UV and far-UV circular dichroism, Trp fluorescence emission, and exposure of sulfhydryl groups. Major differences were found in the denaturation and proteolysis behavior of the three gamma-crystallin fractions. In general, the unfolding of gamma-II and gamma-III crystallins is rather gradual, suggesting the presence of intermediate unfolding states; in contrast, the order-disorder transition of gamma-IV crystallin is abrupt. The gamma-IV crystallin fraction is the most stable in urea and guanidine hydrochloride, but is most susceptible to nonspecific proteolysis and alkaline pH denaturation. Differences in denaturation and proteolysis behavior are attributed to the inherent differences in the tertiary structures of these crystallins.

Animals↗