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Biomedical subjects

M H Johnson

Publications and source records attributed to M H Johnson.

At least 307 records · Page 17Linked to original sources

Hemoglobin connecticut (beta 21 (B3) Asp leads to Gly): a hemoglobin variant with low oxygen affinity.

Electrophoretic analysis of a hemolysate from a young man undergoing a routine physical examination revealed an abnormal hemoglobin with a mobility similar to Hb S on cellulose acetate (pH, 8.4). This new variant, designated Hb Connecticut, was found in three generations of a family of Polish descent. Several individuals possessing the variant exhibited mild anemia. Structural analysis of the abnormal beta-chain indicated that the amino acid substitution was at position 21 (B3), and involved the replacement of aspartic acid with glycine. Oxygen dissociation studies revealed low oxygen affinity. The alkaline Bohr effect and the degree of cooperativity were unchanged. Analysis of the crystal structure of the variant suggested that the low oxygen affinity was due to the possible disruption of salt bridges between aspartic acid 21(B3) and lysines 61(ES) and 65(E9), changes that could lead to steric interference in oxygen binding.

Adolescent↗

The foundation of two distinct cell lineages within the mouse morula.

The division of single cells, isolated from an 8-cell mouse embryo, to give 2 x 1/16 cells has been studied by sampling cells for analysis at defined stages during and after the division. Cells were analyzed for evidence of polarity in their surface organization as assessed by fluorescent ligand binding and distribution of microvilli. Individual 1/8 cells are polarized. At division, most (82%) divide such that both the pole of ligand binding and the pole of microvilli are distributed to only one of the two daughter cells. A couplet is thereby formed with a large polar cell and a small apolar cell. Some 1/8 cells divide through the pole, generating a couplet of two polar cells, the poles being contiguous at the midbody. Elements of the surface polarity observed in the 1/8 cells can be found at all stages throughout division. Analysis of couplets of cells derived from newly formed 16-cell morulae also reveals that most consist of a polar:apolar pair and some consist of a polar:polar couplet in which the poles are contiguous at the midbody. The results indicate that two distinct cell populations are generated at division. These cells are known to occupy different positions within the morula, the polar cells being peripheral and the apolar cells being central. Since peripheral and central cells give rise to trophectoderm and inner cell mass in the blastocyst, we therefore suggest that the foundation of the trophectoderm and inner cell mass lineages may occur by a process of differential inheritance. This conclusion supports the recently proposed polarization hypothesis, which is discussed.

Animals↗

Induction of polarity in mouse 8-cell blastomeres: specificity, geometry, and stability.

We studied the cellular mechanisms underlying the induction of polarity in individual blastomeres of the 8-cell mouse embryo. The ability to induce polarity is lacking in the membranes of unfertilized and newly fertilized mouse eggs, then develops during the 2-cell stage, and is present in membranes of cells from 4-, 8-, and 16-cell stages. The axis of polarity takes 3-5 h to become established and thereafter appears to be stable. Multiple cell contacts affect the orientation of the axis of polarity, and no polarity develops in cells which are totally surrounded. Polarized cells show evidence of an limited capacity for slight adjustments in their position relative to other cells. The implications of these results for the mechanisms by which a blastocyst is generated are discussed briefly.

Animals↗

Skin conductance characteristics of depressed subjects before and after therapeutic intervention.

Three hypotheses were tested in a population of depressed patients: a) electrical skin conductance levels and responses are lower in depressed individuals; b) skin conductance levels and responses are lower in the right hand than the left hand of right-handed depressed individuals; and c) skin conductance levels and responses will increase in magnitude after successful therapeutic intervention. The data supported only the first hypothesis. Results may have implications for a trait vs. state differentiation of the depressive process.

Adult↗

Freeze-dried cadaveric dural grafts can stimulate a damaging immune response in the host.

Clinical experience with freeze-dried cadaveric dura mater has suggested that it is an acceptable dural substitute which does not seem to provoke a significant immune response in the host. A patient is described in whom a cadaveric dural graft provoked an immune reaction leading to meningitis, long after any bacterial contamination or 'chemical' reaction would have declared itself. Removal of the graft resulted in full recovery of the patient in parallel with abatement of the immune response as measured in the cerebrospinal fluid. We discuss the experimental basis for claims that this material is not immunogenic and point out that the mechanism for a damaging immune response does exist.

Adult↗

Endogenous amino acid pool sizes in mouse eggs and preimplantation embryos.

The endogenous pool sizes of 17 amino acids were measured directly in samples of mouse eggs, 8-cell embryos and blastocysts by estimation of the fluorescent product of the reaction of o-phthalaldehyde and primary amines. Taurine, glycine, alanine, glutamate and aspartate were detected at high levels. During the transition to the blastocyst, most amino acid pools increased 2-3-fold, but the taurine and glycine pools decreased to about 50 and 10%, respectively, of the egg value. The amino acid distribution in cumulus masses was similar to that of the egg and embryo samples but different from that of serum.

Amino Acids↗

Hemoglobin Cubujuqui (alpha 141 Arg-Ser): functional consequences of the alteration of the C-terminus of the alpha chain of hemoglobin.

Hemoglobin Cubujuqui (1) was detected in several members of a Mexican-American family. Structural analysis of this hemoglobin indicated that the carboxyl terminal arginine at position 141 in the alpha chain had been replaced by serine. This residue is critical not only in stabilizing the deoxy or T conformation by electrostatic interactions, but it is also involved in the Bohr effect through its linkage with Val 1 alpha of the opposite alpha chain in the tetramer. The variant exhibits high affinity for oxygen that is associated with destabilization of the deoxy conformation, and reduced cooperativity. The pH and the chloride sensitivity of the variant are also reduced, as compared to Hb A.

Amino Acid Sequence↗

Concentrating on the process of learning while teaching clearly defined communication skills.

The authors found that students using the composite are more motivated and enthusiastic about learning than before, and claim to have greater confidence in themselves and the skills they possess in relating to others. In addition, the "Level of Response Scale" gives them a concrete framework for choosing the most therapeutic response for a given situation; this has had implications for their performance clinically and theoretically in terms of testing. The experience of developing this composite of materials and clarifying the teaching-learning process has been growth producing for the authors as well as the students, since it required the authors to be very clear and specific in their expectations and it provided them with more time for counseling individual students. In conclusion, this experience further demonstrates that communicating effectively is is not strictly intuitive but a skill that can be taught and learned in an enjoyable and satisfying manner when a motivating learning environment is provided.

Communication↗

Molecular studies on cells of the trophectodermal lineage of the postimplantation mouse embryo.

Embryonic ectoderm (EmE), extraembryonic ectoderm (EE), ectoplacental cone diploid cells (EPC) and secondary giant cells (GC) were isolated from 7 1/2-day mouse embryos and their polypeptide synthetic profile assessed by fluorography of 2D polyacrylamide gels. Fifty polypeptides showed different distributions amongst the tissues, permitting characterization of each tissue by an array of polypeptide markers typical for the tissue at that developmental stage. The three tissues on the presumptive trophectoderm lineage did not show identical synthetic patterns. However, culture of EE cells in vitro resulted in conversion of their polypeptide synthetic profile to that of EPC after 2 days and of GC after 6 days, whilst culture of EPC cells converted their polypeptide synthetic profile to that of GC after only 4 days. These changes in polypeptide synthesis correlated well with the ploidy levels of the tissues at different times in culture.

Animals↗

Comparison of methods for estimating digoxin dosing regimens.

Five methods of predicting serum digoxin concentrations (SDCs), used in conjunction with three equations for estimating creatinine clearance, were compared. Radioimmunoassay was used to determine the nadir SDCs in 79 patients (38 men, 41 women) meeting predetermined study criteria. All patients, whose ages ranged from 33 to 94 years, had steady-state digoxin levels, were on oral digoxin, and were free from thyroid dysfunction, malabsorption syndromes, dehydration, and renal failure. Three equations, involving combinations of age, lean body weight, and serum creatinine, were used to estimate creatinine clearance (Clcr). These Clcr values were then used in each of five equations to estimate SDCs. The estimated SDCs were compared to actual SDCs in the 79 patients, and the effects of changing the fraction of dose absorbed and the method of determining Clcr were analyzed. No substantial difference in predictive reliability was evident among the methods studied. Poor correlations existed between observed and calculated SDCs (r less than 0.70), and these correlations were not significantly affected by gender, fraction of dose absorbed, or method of Clcr estimation. Higher correlations were found for the oldest and youngest age groups. Severe limitations are associated with the use of the formulas studied.

Adult↗

Hemoglobin Tampa:beta 79 (EF3) aspartic acid replaced by tyrosine.

Hemoglobin Tampa was detected in a 6-year-old male caucasian who is homozygous for this variant hemoglobin. The variant hemoglobin has an electrophoretic mobility between Hb F and Hb S on cellulose acetate (pH 8.5) and a mobility between Hb S and Hb C on citrate agar (pH 6.0). In acid buffer globin chain analysis revealed an abnormal beta chain with a mobility between the beta A and beta S chains, and in alkaline buffer the mobility of the chain was at the beta S position. Structural characterization of the variant beta chain indicates that aspartic acid is replaced with tyrosine at position 79, the site of a previously reported mutation, Asp replaced by Gly (Hb Hsi-Tsou). The clinical histories of the available family members including the homozygous propositus appear to be unremarkable.

Amino Acids↗

Cell surface interaction induces polarization of mouse 8-cell blastomeres at compaction.

The development of the polarized surface binding of the fluoresceinated ligand concanavalin A (FITC-Con A) was studied in blastomeres of the early mouse embryo. Single 8-cell blastomeres, natural 8-cell couplets derived from the in vitro division of individual 4-cell blastomeres, and reagregated couplets made from dissociated 8-cells were cultured for varying periods of time and on a variety of substrata. The development of surface polarity was found to be highly dependent upon cell contact. Over 50% of the cells in couplets were polarized after 4-5 hr in culture, with the smaller cell in the couplet usually more advanced in its polarization than the larger cell. The orientation of the poles of FITC-Con A binding was opposite the point of contact between cells in the couplets regardless of their previous orientation within the embryo or the plane of cleavage.

Animals↗