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Biomedical subjects

H G Sachs

Publications and source records attributed to H G Sachs.

At least 19 recordsLinked to original sources
PubMed1985

Age-dependent alterations in rat ventricular myocardium: a quantitative analysis.

A quantitative electron microscopic examination of the ventricular myocardium of the male Fischer 344 rat was undertaken to determine the extent of age-dependent changes in ultrastructure. Rats of 6, 16 and 30 months of age were examined using a non-biased stereological test system. Volume fractions of mitochondria, myofibrillar mass and lipid remained unchanged during aging. Dense body volume fraction increased four-fold over the period studied, while the sarcoplasmic reticulum volume increased only from 6 months to 16 months and did not change thereafter. Biochemical analysis of the specific activities of the two lysosomal enzymes, acid phosphatase and beta-glucuronidase demonstrated a differential response to aging, with acid phosphatase remaining constant and beta-glucuronidase increasing slightly. Neither enzyme activity correlated with the pronounced change in dense body volume fraction. This study provides clear evidence that the previously observed changes in cardiac performance associated with aging are not readily explicable on the basis of a degradation of cardiac ultrastructure.

Acid Phosphatase↗
PubMed1985

Lymphocyte requirement for the functional development of follicle-associated epithelium.

Follicular development in the bursa of Fabricius was disrupted by testosterone treatment and chorioallantoic membrane grafting. Analysis by a quantitative histological technique demonstrated that testosterone treatment causes a dose dependent delay in development by inhibiting lymphoid proliferation. Inhibition of lymphoid development prevented the development of carbon transport ability by follicle associated epithelium. Reconstitution of follicular development by grafting treated bursae to the chorioallantoic membrane of untreated hosts results in the development of functional follicle associated epithelium. These results establish the lymphoid requirement for the development of transport ability by the follicle-associated epithelium.

Allantois↗
PubMed1983

The development of transport ability by embryonic follicle-associated epithelium.

The development of transport ability by follicle-associated epithelium was studied in embryonic chick bursae. Developing lymphoid follicles were divided into three morphological types to determine the relationship of epithelial function to lymphoid development. Transport ability was first observed on day 13, two days earlier than obvious morphological evidence of follicle-associated epithelial development. Functional differentiation of the epithelium was, however, closely associated with lymphoid development rather than a day-specific developmental event. It is probable that the lymphoid cells have an inductive influence on the development of the overlying epithelium. Evidence of early embryonic transport by relatively undifferentiated epithelium also suggests that lymphoid development in the bursa may be influenced by epithelial transport.

Animals↗
PubMed1982

The influence of embryonic testosterone treatment on bursal epithelial pinocytotic activity.

Developing White Leghorn chicks were treated with testosterone propionate in ovo to effect a partial chemical bursectomy. After hatching, birds were administered carbon particles or horseradish peroxidase via the cloaca, and the transport of these tracers by the bursal epithelium was examined. Uptake of both tracers was inhibited in the treated when compared to untreated birds. The degree of development of interaction between bursal epithelium and underlying lymphoid tissue appeared to play a major role in determining ability of the epithelium to transport these tracers. Epithelium associated with follicles possessing medullary and cortical divisions was able to transport, while intraepithelial follicles or regions of the epithelium overlying diffuse lymphoid tissue did not transport either carbon or horseradish peroxidase. Bursal function in regional defense of the gut may depend on a local interaction of bursal epithelium with lymphoid, and perhaps other cell types.

Animals↗
PubMed1978

Species-related difference in calcium accumulation by cardiac mitochondria.

1. Mitochondria isolated from the ventricles of Cavia porcellus, Mesocricetus auratus, Rattus rattus and Mus musculus accumulate calcium in an energy-linked process. 2. Measurements of the initial velocity of accumulation by dual-wavelength spectrophotometry show species-dependent variation, with Cavia demonstrating the fastest rate and Rattus the slowest rate of accumulation. 3. Total amount of calcium accumulated per unit protein varied in a manner similar to rate of accumulation, with Cavia accumulating the greatest amount of calcium and Rattus the least.

Animals↗
PubMed1978

Electrophysiological study of Syrian hamster hereditary cardiomyopathy.

This study was performed to determine if the intracellular electrical activity of adult cardiac papillary muscle from a strain of Syrian hamster (B10 14.6) with a genetically determined cardiomyopathy was different from that of a control strain (B10 RB). Muscles driven at rates from 1 Hz through the physiological range. Resting potentials of muscle from the two strains were not significantly different, except in increased [C2+]0, where the control was slightly hyperpolarised. Action potential overshoot was significantly greater in the myopathic at all frequencies, while the upstroke velocity was not significantly different, except at 8 Hz where the myopathic value was depressed. Action potential durations at 20, 50 and 95% repolarisation were significantly greater in the myopathic, at all rates and with increased [C2+]0. Response of the muscles to verapamil and D600 were complex, with a decrease seen in duration at 20% repolarisation and an increase in 50% duration at 1 Hz rate. No strain-related difference in sensitivity to the drugs was seen. The results supporty the hypothesis that a sarcolemmal defect is intimately related to the genesis of the cardiomyopathy.

Action Potentials↗
PubMed1977

Ultrastructure of the aging myocardium: a morphometric approach.

Left ventricular tissue from adult and aging Syrian hamster heart was compared at the ultrastructural level, using both qualitative and morphometric electron microscopy. The aging myocardium often showed indented nuclei, lipid droplets and aggregations of dense bodies. The volume fractions of muscle cells occupied by mitochondria, lipid and lysosomes (including both primary lysosomes and residual bodies) was significantly greater in the old animals, while there was no significant difference in nuclear volume fraction or myofibrillar mass. Sarcoplasmic reticular volume and membrane surface area fell during aging. The area of mitochondrial inner membrane plus cristae per mitochondrial volume also fell. When sarcoplasmic reticular and mitochondrial area were expressed per myofibrillar volume fraction, the sarcoplasmic reticular ratio fell, while the mitochondrial parameter remained constant. Discoordinate aging of cellular components in the mammalian myocardium is proposed.

Aging↗
PubMed1977

Antibody production in organ culture by bursae of mature chickens and the development of immunological compentence.

Antibody responsiveness of bursal lymphocytes was studied in vitro. Organ culture of bursal tissue in the presence of antigen, either sheep erythrocytes or bovine serum albumin, results in significant numbers of plaque-forming cells (PFC) compared to controls. The response in organ culture is age-dependent in that only bursae from chickens at least three weeks of age contained significantly increased numbers of secreting cells. Prolonged culture of normally unresponsive bursae from newly hatched birds results in a PFC response to antigen, suggesting that in vitro maturation occurs.

Age Factors↗
PubMed1975

The effect of potassium on the cell membrane potential and the passage of synchronized cells through the cell cycle.

The cell membrane potential of cultured Chinese hamster cells is known to increase at the start of the S phase. The putative role of the cell membrane potential as a regulator of cell proliferation was examined by following the cell cycle traverse of synchronized Chinese hamster cells in the presence or absence of high exogenous levels of potassium. An increase in external potassium levels results in a depressed membrane potential and a reduced rate of cell proliferation. A potassium concentration of 115 mM was used in experiments with synchronized cells since at that level cell proliferation is almost completely halted, recovery of growth is rapid and complete, and the membrane potential is reduced to a level well below that normally found in cells in the G1 phase. A mitotic population was divided into four aliquots and plated in either control medium or medium containing 115 mM K+. Cells placed directly into high K+ medium were retarded in their exit from mitosis and displayed a delayed and abnormal entry into the S phase. If control medium was added after two hours, cell cycle traverse was normal, but delayed by two hours compared to control cells. If the mitotic cells were plated directly into control medium and two hours later were shifted to high K+ medium, the cells entered the S phase in the absence of the normally observed increase in membrane potential and proceeded to the next mitosis normally. It was concluded that the increase in membrane potential observed at the start of the S phase in isolated synchronized cells is not a requirement for the initiation of DNA synthesis. In addition, sensitivity to the high potassium regimen was found at two different times during the cell cycle. In one case, cells were impeded in their transit through mitosis. Such cells displayed an altered chromosome structure which may account for the partial mitotic block. In the second case, synchronized cells displayed a sensitivity to the high potassium regimen in early G1 which appeared to be separate from the block in mitosis and independent of a change in the membrane potential.

Animals↗
PubMed1975

Electrical activity in embryonic heart cell aggregates. Developmental aspects.

Action potential parameters were measured in beating heart cell aggregates which were formed from trypsin-dissociated cells of embryonic chick heats aged 2 1/2, 4 or 7 days. 1. In aggregates composed of cells from the whole heart there was an increase in the maximum diastolic potential, overshoot, maximum rate of rise of the action potential (V max), and action potential duration between days 2 1/2 and 7. 2. Action potential parameters from 4- or 7-day aggregates composed exclusively of atrial or ventricular cells were similar to those in whole heart aggregates of the same age with the exception of the action potential duration in which atrial less than whole heart less than ventricular. Between days 4 and 7 the increases in duration were approximately 14% in atrial, 35% in whole heart, and 50% in ventricular aggregates. Differences in action potential duration, within or between ages, were not due solely to differences in the rate of beating. 3. Action potentials in whole heart aggregates aged 2 1/2 days were insensivitive to TTX (10-5 g/ml) but abolished by D600 (1 MUG/ML). Conversely, at 7 days activity was suppressed by TTX (2 X 10-8 G/ML) WHILE D600 (1 mug/ml) shortened the action potential duration and reduced the overshoot without influencing V max. 4. Adrenaline (1 mug/ml) restored the action potential overshoot and duration in 7-day aggregates treated with D600. 5. Action potential development in embryonic heart cells appears to be characterized by the functional appearance of fast inward channels. The slow channel mechanism, previously utilized in action potential generation, may gradually assume its adult role of carrying inward current during the plateau phase. 6. In contrast to monolayer cultures, embryonic heart cells cultured in aggregate form seem to have membrane properties similar to those of intact tissue.

Action Potentials↗
PubMed1975

Electrical activity in embryonic heart cell aggregates. Pacemaker oscillations.

Aggregates were formed from dissociated heart cells of 7-day chick embryos. When spontaneous action potentials were blocked with 10-8 to 10-7 g/ml tetrodotoxin (TTX) oscillatory pacemaker potentials were sometimes seen. The emergence of these pacemaker potentials was critically dependent on the external potassium concentration. In 1.3 mM potassium medium TTX suppression of action potential generation always led to a stable resting potential close to the threshold level (-55 to -50 mV). In 4.3 mM potassium TTX suppression was followed by a train of pacemaker potentials which usually gave way to a stable resting potential of about -70 mV. Raising the calcium concentration from 1.8 to 5 mM often induced long lasting (3 hrs) pacemaker oscillations of 20 to 30 mV peak to peak amplitude. These were abolished by raising the potassium concentration to 8.3 mM or upon the addition of 1.5 mM Mn2 plus. The responses of TTX-treated aggregates are discussed in terms of Noble and Tsien's pacemaker theory for Purkinje fibers. The results are well described by assuming the existence of an ik2-like potassium current in embryonic heart cells. The role of calcium is unclear but it may help provide the inward current against which the outward potassium current can function.

Action Potentials↗
PubMed1973

Tetrodotoxin desensitization in aggregates of embryonic chick heart cells.

Spontaneous beating of heart-cell aggregates from 4-day chick embryos was initially blocked by 10(-5) g/ml tetrodotoxin (TTX). With continued exposure to the drug, the fraction of blocked aggregates decreased from about 80% at 15 min to about 25% at 2-3 h, at which time, beating aggregates had become desensitized to the toxin, showing no response to a fresh dose. Aggregates from 5-day hearts were more sensitive to TTX, but fewer became desensitized in its presence. Desensitization to TTX was not seen in 6- and 7-day aggregates. Inhibition of protein synthesis by cycloheximide did not affect beating or initial sensitivity to TTX of 4-day aggregates, but desensitization failed to occur. Before TTX, the mean value of maximal upstroke velocity (V(max)) of the action potentials in 4-day aggregates was 33 V/s. After desensitization V(max) was 12 V/s. Activity of desensitized aggregates in the presence of TTX was augmented by elevated calcium levels, and suppressed by presumed inhibitors of slow inward current (manganese, D600). Desensitization was reversible; upon removal of TTX 10(-5) g/ml, aggregates regained their responsiveness to a fresh dose of the drug with a 2-3 h time-course similar to that of desensitization. This was prevented by continued exposure to TTX at concentrations as low as 10(-8) g/ml. These data suggest that (a) desensitization involves a change in the mode of action-potential generating from one involving Na-specific, TTX-sensitive channels to one utilizing slower Mn-sensitive channels; (b) the process of desensitization occurs over a period of 2-3 h and is dependent upon the products of protein synthesis; and (c) desensitization is reversible after removal of TTX over a 2-3 h time-course similar to its onset.

Action Potentials↗