Biomedical subjects

M Kam

Publications and source records attributed to M Kam.

11 recordsLinked to original sources

PubMed2001

Signature authentication by forensic document examiners.

We report on the first controlled study comparing the abilities of forensic document examiners (FDEs) and laypersons in the area of signature examination. Laypersons and professional FDEs were given the same signature-authentication/simulation-detection task. They compared six known signatures generated by the same person with six unknown signatures. No a priori knowledge of the distribution of genuine and nongenuine signatures in the unknown signature set was available to test-takers. Three different monetary incentive schemes were implemented to motivate the laypersons. We provide two major findings: (i) the data provided by FDEs and by laypersons in our tests were significantly different (namely, the hypothesis that there is no difference between the assessments provided by FDEs and laypersons about genuineness and nongenuineness of signatures was rejected); and (ii) the error rates exhibited by the FDEs were much smaller than those of the laypersons. In addition, we found no statistically significant differences between the data sets obtained from laypersons who received different monetary incentives. The most pronounced differences in error rates appeared when nongenuine signatures were declared authentic (Type I error) and when authentic signatures were declared nongenuine (Type II error). Type I error was made by FDEs in 0.49% of the cases, but laypersons made it in 6.47% of the cases. Type II error was made by FDEs in 7.05% of the cases, but laypersons made it in 26.1% of the cases.

Expert Testimony↗

PubMed1998

Modulation of circulatory residence of recombinant acetylcholinesterase through biochemical or genetic manipulation of sialylation levels.

Sialylation of N-glycans associated with recombinant human acetylcholinesterase (rHuAChE) has a central role in determining its circulatory clearance rate. Human embryonal kidney 293 (HEK-293) cells, which are widely used for the expression of recombinant proteins, seem to be limited in their ability to sialylate overexpressed rHuAChE. High-resolution N-glycan structural analysis, by gel permeation, HPLC anion-exchange chromatography and high-pH anion-exchange chromatography (HPAEC), revealed that the N-glycans associated with rHuAChE produced in HEK-293 cells belong mainly to the complex-biantennary class and are only partly sialylated, with approx. 60% of the glycans being monosialylated. This partial sialylation characterizes rHuAChE produced by cells selected for high-level expression of the recombinant protein. In low-level producer lines, the enzyme exhibits a higher sialic acid content, suggesting that undersialylation of rHuAChE in high-level producer lines stems from a limited endogenous glycosyltransferase activity. To improve sialylation in HEK-293 cells, rat liver beta-galactoside alpha-2,6-sialyltransferase cDNA was stably transfected into cells expressing high levels of rHuAChE. rHuAChE produced by the modified cells displayed a significantly higher proportion of fully sialylated glycans as shown by sialic acid incorporation assays, direct measurement of sialic acid, and HPAEC glycan profiling. Genetically modified sialylated rHuAChE exhibited increased circulatory retention (the slow-phase half-life, t12beta, was 130 min, compared with 80 min for the undersialylated enzyme). Interestingly, the same increase in circulatory residence was observed when rHuAChE was subjected to extensive sialylation in vitro. The engineered HEK-293 cells in which the glycosylation machinery was modified might represent a valuable tool for the high level of expression of recombinant glycoproteins whose sialic acid content is important for their function or for pharmacokinetic behaviour.

Acetylcholinesterase↗

PubMed1997

Energy budget in free-living animals: a novel approach based on the doubly labeled water method.

We provide a theoretical and practical model for the calculation of energy balance of free-living animals using the doubly labeled water method. Energy expenditure, metabolizable energy intake, and body energy balance (energy retention, negative or positive) of animals are estimated using CO2 production, water influx, and dietary habits. This model accounts for CO2 produced from the 1) oxidation of dietary substrates, 2) catabolism of body tissue, and 3) deposition of body energy. We examined the model using data from studies on five homeotherms reported in the literature. The ratios between daily energy expenditure using our model and that presented in the reports ranged between 0.76 and 1.18. Metabolizable energy intakes were as low as 43% of energy expenditure in negative energy-balanced hummingbirds and as high as 245% of energy expenditure in positive energy-balanced koala bears. This model is the first that allows theoretical calculation of all energy budget components, including energy retention, in free-living animals using the doubly labeled water method.

Animals↗

PubMed1994

Specificity in the recognition of crystals by antibodies.

We show that IgG molecules isolated from the serum of rabbits injected with crystals of monosodium urate monohydrate, magnesium urate octahydrate and allopurinol, can each catalyze the nucleation of the same type of crystal to which they were exposed. These results generalize previous findings related to monosodium urate monohydrate and assess the idea that the invasion of a foreign crystal into an organism may amplify a population of antibodies which bear in their binding sites an imprint of the crystal surface structure. Such antibodies can further act as nucleating templates which accelerate crystal formation in vitro. Antibodies isolated from rabbits injected with sodium urate crystals do not cross-react or cross-react only to a low extent with antibodies isolated from rabbits injected with crystals of either magnesium urate or allopurinol. These results indicate a high specificity of the elicited antibodies, as these can distinguish between nuclei of crystals having similar molecular and structural characteristics.

Allopurinol↗

PubMed1994

Seasonal plasma levels of luteinizing and steroid hormones in male and female domestic ostriches (Struthio camelus).

Ostriches are low-latitude birds and can be considered to be seasonal breeders. However, they are also opportunistic in that they can breed all year round. Monthly hormonal plasma concentrations were measured in six female and six male domestic ostriches kept at a latitude of 31 degrees 20'N. Measurements were made over a year, during which time each female laid an average of 28.7 eggs. Egg laying occurred between March and September, with peak numbers in May-June. Concentrations of plasma luteinizing hormone (LH) increased in February in both sexes and started declining before termination of egg laying. Plasma testosterone concentrations in males increased in April, about 2 months after the increase in LH. In females, plasma estradiol concentrations peaked in May but were elevated from March to August, basically all of the egg-laying period. Plasma hormonal changes in the ostriches were gradual and not abrupt, as seen in many wild seasonal breeders of higher latitude.

Animals↗

PubMed1992

Antibodies against crystals.

We suggest that crystals, when introduced into an organism, may behave as conventional antigens, mediating the production of specific antibodies. These antibodies would bear an imprint of the crystal surface and may consequently behave as a nucleating matrix in a new crystallization event. Thus, they would behave as catalytic antibodies. We show that IgG antibodies isolated from patients suffering from gout, a joint disease caused by crystals of monosodium urate monohydrate (MSUM), accelerate the appearance of new crystals of MSUM from a supersaturated solution of the salt in vitro. The same effect is not observed for IgG antibodies isolated from the joint fluids of patients with other joint diseases, such as pseudogout, rheumatoid arthritis, or osteoarthritis. Furthermore, IgG antibodies obtained from rabbits injected subcutaneously with crystals of MSUM, were also nucleating towards MSUM crystals.

Allopurinol↗

PubMed1990

NMR studies of the interaction of chromomycin A3 with small DNA duplexes. Binding to GC-containing sequences.

The interaction of chromomycin A3 with the oligodeoxyribonucleotides 1, d(ATGCAT), 2, d(ATCGAT), 3, d(TATGCATA), and 4, d(ATAGCTAT), has been investigated by 1H and 31P NMR. In the presence of Mg2+, chromomycin binds strongly to the three GC-containing oligomers 1, 3, and 4 but not to the CG-containing oligomer 2. The proton chemical shift changes for 1 and 3 are similar, and these DNA duplexes appear to bind with a stoichiometry of 2 drugs:1 Mg2+:1 duplex. The same stoichiometry of 2 drugs:1 duplex is confirmed with 4; however, proton chemical shift changes differ. An overall C2 symmetry is exhibited by the drug complex with 1, 3, and 4. At a molar ratio of 2.0 (drugs:duplex), no free DNA proton NMR signals remain. Two-dimensional nuclear Overhauser exchange spectroscopy (NOESY) of the saturated chromomycin complex with 1 and 3 positions both chromomycinone hydroxyls and the E carbohydrates in the minor groove and provides evidence suggesting that the B carbohydrates lie on the major-groove side. This is supported by several dipolar coupling cross-peaks between the drug and the DNA duplex. Drug-induced conformational changes in duplex 1 are evaluated over a range of NOESY mixing times and found to possess some characteristics of both B-DNA and A-DNA, where the minor groove is wider and shallower. A widening of the minor groove is essential for the DNA duplex to accommodate two drug molecules. This current minor-groove model is a substantial revision of our earlier major-groove model [Keniry, M.A., Brown, S.C., Berman, E., & Shafer, R.H. (1987) Biochemistry 26, 1058-1067] and is in agreement with the model recently proposed by Gao and Patel [Gao, X., & Patel, D. J. (1989a) Biochemistry 28, 751-762].

Base Composition↗

PubMed1989

The solution conformation of the antibiotic anticancer chromomycin A3 by two-dimensional NMR spectroscopy.

The solution conformations of chromomycin A3 (CRA) and dechromose-A chromomycin A3 (CRA-B) in dichloromethane and methanol were studied by two-dimensional (2D) NMR techniques. In dichloromethane, the drugs are found in a compact wedged-like conformation, with the phenolic hydroxyls at the tip and the side chains folded back to one side of the aglycon plane, oriented parallel to each other. The overall structure is stabilised by intramolecular hydrogen bonds and by the formation of a hydrophobic pocket, enclosed by the three side chains. In methanol, the drugs have the expected open conformation with extended side chains. Like its parent drug, CRA-B binds to d(ATGCAT)2 duplex with a major groove orientation, a 2:1 drug/duplex ratio and a two-fold symmetry of the resultant complex. The drug molecule is suggested to reside diagonally across the two strands of the duplex and to span 3 base pairs, while all three side chains of the drug are folded away from the major groove of the DNA. The observed nonequivalent positions of CRA and CRA-B within the major groove of the duplex results from the different conformation adopted by the sugar side-chains in the two complexes.

Chromomycin A3↗

PubMed1988

Solution conformation of the antitumor antibiotic chromomycin A3 determined by two-dimensional NMR spectroscopy.

A conformational analysis and a complete assignment of the nonexchangeable proton resonances of chromomycin A3, dechromose-A chromomycin A3, and deacetylchromose-B chromomycin A3 were carried out in organic solvents. The resulting conformation in methanol has the three side chains of chromomycin A3 fully extended, away from one another and from the aglycon. In dichloromethane on the other hand, the drug was shown to adopt a highly compact conformation in which most of the 26 oxygen atoms in the molecule point out toward the solvent. The two carbohydrate side chains extend parallel to each other on the same side of the aglycon. Two intramolecular nuclear Overhauser enhancement contacts have been observed between different sugar units on these side chains, indicating close proximity for these moieties. In addition, the aliphatic side chain is folded toward the aglycon, parallel to the two oligosaccharide side chains. The overall conformation has a wedge-like shape with the two phenoxy groups exposed at the pointed edge. The presence of some exchange cross-peaks in the NOESY spectra suggests the presence of intramolecular hydrogen bonds that probably help to maintain the compact conformation. The derivatives of chromomycin A3 have qualitatively similar conformations, though their respective conformations are not as compact as the parent drug. The significance of these results is discussed in terms of a model of chromomycin A3 binding to DNA in the major groove.

Chromomycin A3↗

PubMedDate not supplied

Level of energy intake affects the estrous cycle in Sundevall's jird (Meriones crassus).

Effects of energy intake on the estrous cycle of the desert gerbillid, Sundevall's jird (Meriones crassus; 80 g; n=22) were studied. Females were offered either maintenance or below maintenance levels of millet seeds and ad lib. Atriplex halimus leaves and stems; drinking water was not available. Vaginal smears were used to determine sexual stage. We hypothesized that the estrous cycle ceases at low levels of energy intake and commences when sufficient energy is available. Females lost body mass linearly with a decrease in metabolizable energy intake. Estrous cycle averaged 4.46 d at maintenance energy intake but increased to an average of 7.81 d at 70% of maintenance energy intake. A cessation of the cycle occurred at an energy intake below 70% of maintenance requirements, which resulted in a body mass loss of more than 1% per day. More variability in the length of the different stages of the cycle was found with lower levels of energy intake. When offered ad lib. millet seeds and A. halimus (n=14), recovery to the normal cycle was attained within 10 d by 43% of the females and within 16 d by the rest of the females. Recovery time was longest in females that previously had the lowest energy intake. We concluded that the estrous cycle of M. crassus is sensitive to energy intake. With restricted energy intake, the estrous cycle and reproductive activities cease but can be restored with provision of adequate energy. This strategy ensures that reproduction occurs when conditions of food availability and body condition of the females are favorable.

Animals↗

PubMedDate not supplied

Fiber digestion and energy utilization of fat sand rats (Psammomys obesus) consuming the chenopod Anabasis articulata.

Most herbivorous rodents consume a variety of plants and, when available, select ones low in fiber content. In contrast, the fat sand rat (Psammomys obesus), a diurnal gerbillid rodent that is wholly herbivorous, is able to survive while consuming only the halophytic chenopod Anabasis articulata. We hypothesized that these gerbils are able to digest chenopods efficiently and that fiber digestion contributes substantially to their energy budget. Digestibility of total fibers (NDF), hemicellulose, and cellulose was 51.6%, 66.4%, and 44.0%, respectively. Energy derived from fiber digestion was 211.7 kJ kg(-0.75) d(-1) and resulted mostly from hemicellulose digestion. Average daily metabolic rate was 658.4 kJ kg(-0.75) d(-1), and basal metabolic rate (BMR) was determined to be close to 192.6 kJ kg(-0.75) d(-1). Therefore, fiber digestion provided 32% of maintenance requirements and 110% of BMR requirements, one of the highest values reported thus far for placental mammals. The efficiency of utilization of the chenopod was 0.29, a low value compared to other dietary items. We concluded that A. articulata fulfills all the energy and nutrient requirements of fat sand rats, even though energy yields and efficiency of utilization of its energy is low.

Adaptation, Physiological↗