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Biomedical subjects

L Wolpert

Publications and source records attributed to L Wolpert.

At least 91 records · Page 5Linked to original sources
PubMed1982

Cell shape and cartilage differentiation of early chick limb bud cells in culture.

The onset of chondrogenesis in te embryonic chick is preceded by a prechondrogenic condensation of the prospective cartilage cells. Similarly, in culture, the chondrogenic phenotype is only expressed by limb mesoderm cells plated at densities above confluence. This has led to the proposal that chondrogenic differentiation requires immediate histogenic interactions prior to overt chondrogenesis (Solursh et al., 1978, In Vitro 14, 51-61; and, 1980, Dev. Biol. 78, 141-150). It is noticeable that in both the in vitro situations cells secreting a cartilaginous matrix are rounded in shape. Recently, Glowacki, Trepman and Folkman (personal communication) have shown a dependence of phenotypic expression by mature chondrocytes on cell shape. Cells maintained in a rounded configuration by culturing on a semi-adhesive substratum (poly(HEMA)) synthesised more sulphur-containing extracellular matrix than cells allowed to flatten on normal tissue culture plastic. We have investigated whether there is a similar shape-dependent relationship in the differentiation of chick embryonic mesoblasts into actively secreting chondroblasts. Our results show that a rounded cell shape is conductive to the synthesis of a sulphated matrix.

Animals↗
PubMed1982

Alcohol consumption in persons on methadone maintenance therapy.

Alcohol use among methadone maintenance treatment program (MMTP) patients is substantial and a frequent impression is that addicts accelerate their consumption once in MMTP. This study reports an attempt to more clearly define alcohol consumption in opioid dependence as well as changes associated with methadone maintenance therapy. Two-day alcohol consumption (2-day EtOH) data were collected initially and quarterly on participants in a randomized controlled trial of intervention for alcoholism. Blood alcohol levels (BAL) were also determined. 17% of the participants were classified as active alcoholics (AA) and 8% as inactive alcoholics (IA). Two-day EtOH and BAL were significantly higher for AA than AI and nonalcoholics (NA, and AI higher than NA. Two-day EtOH decreased significantly over time for AA, AI, and NA. These findings indicate that AA among narcotic addicts and those on MMTP consume large quantities of EtOH but that consumption decreases with time on MMTP. The results, in confirmation of the work of others, suggest that entry and participation in MMTP has a broader effect than just on the use of narcotic drugs.

Alcohol Drinking↗
PubMed1981

Positional information and pattern formation.

Spatial patterns of cellular differentiation may arise from cells first being assigned a position, as in a coordinate system, and then interpreting the positional value that they have acquired. This interpretation will depend on their genetic constitution and developmental history. Different patterns may thus arise from similar positional fields. The specification of positional value may involve a positional signal, such as the concentration of a diffusible morphogen, but can also depend on how long the cells remain in a particular region, such as a progress zone. Positional values may also be acquired by direct transfer from one cell layer to another, as in directed embryonic induction. Positional value, unlike a positional signal, involves long-term memory, and can be regarded as a type of cell determination. Cells of the same differentiation class may have different positional values and may thus be non-equivalent. Evidence is presented for a signal providing positional information along the antero-posterior axis during chick limb development. This signal has properties similar to those of a diffusible morphogen.

Animals↗
PubMed1981

Effects of biochemical inhibitors on positional signalling in the chick limb bud.

In 3- to 4-day embryonic chick limb buds, a region at the posterior margin of the limb, the zone of polarizing activity, appears to be responsible for signalling positional information along the anteroposterior axis. Our experiments were designed to test which biosynthetic processes are required for polarizing activity. We have treated polarizing regions with biochemical inhibitors, and then assayed their abilities to induce limb reduplications when grafted into anterior sites on host limb buds and also measured their capacities for protein, RNA, and DNA synthesis. DNA synthesis, and possibly oxidative phosphorylation, do not seem to be required for polarizing activity. But, glycolysis and protein and RNA synthesis are necessary, although not sufficient, for polarizing region activity. Activity seems particularly sensitive to inhibitors (actinomycin D and alpha-amanitin) of RNA synthesis.

Animals↗
PubMed1981

Pattern formation along the anteroposterior axis of the chick wing: the increase in width following a polarizing region graft and the effect of X-irradiation.

A study is made of the widening of the chick limb bud that occurs after a graft of an additional polarizing region. Such buds are about 50% wider than controls, after 36 h. By contrast, growth along the proximodistal axis in unaffected. This widening is reduced by treating the host embryo with 10 Gy X-irradiation and the altered pattern of digits is consistent with a diffusible morphogen model for the specification of positional information along the anteroposterior axis.

Animals↗
PubMed1981

Positional signalling along the anteroposterior axis of the chick wing. The effect of multiple polarizing region grafts.

We have proposed that positional information along the anteroposterior axis is specified by a signal from the polarizing region and that position may be specified by the concentration of a diffusible morphogen. While this model can account for a variety of results it is now clear that a model based on intercalation by growth of positional values can do the same. The distinction between the two models lies in whether a grafted polarizing region can alter existing positional values and in the distance over which it exerts its influence. The two models make different predictions as to the effect of grafting two polarizing regions. The intercalation model predicts that this effect will be the sum of two single grafts, whereas the morphogen model predicts different results depending on how close together the two polarizing regions are placed. The pattern of digits following grafts of two polarizing regions show that it is sensitive to the distance between the grafts and consistent with a model based on long-range interaction, such as a diffusible morphogen.

Animals↗
PubMed1981

Muscle nerve branches do not develop in chick wings devoid of muscle.

If the somitic mesoderm of a 2-day chick embryo is destroyed by X-irradiation, the adjacent limb develops with a normal pattern of connective tissues, but is devoid of muscle. The innervation of muscleless wings produced in this way was examined in silver-stained whole mounts, fixed 3 to 8 days later. The main nerve trunks and their cutaneous branches developed normally; but the nerve branches which in a normal limb would lead to individual muscles were generally absent. In almost all those exceptional cases where muscle nerve branches were present, muscle was found to be present also, despite the X-irradiation. Where there was no muscle, the muscle nerve branches apparently did not even begin to form. As a control for side effects of the X-irradiation, wing buds were grafted from normal to irradiated embryos and vice-versa, and again analysed for their innervation. The results confirmed that the absence of muscle nerve branches was due to the absence of muscle cells in the limb. Thus (1) the routes taken through a limb by the main mixed nerve trunks and by their cutaneous branches are determined by the connective tissues, and not by any mechanisms requiring muscle cells; but (2) muscle cells are necessary to provoke the formation of the side branches leading to the sites of individual muscles.

Animals↗
PubMed1979

The effect of cell killing by x-irradiation on pattern formation in the chick limb.

It has been suggested that positional information along the proximo-distal axis of the limb-bud is specified by time spent in the progress zone. Mesenchyme cells have been killed by X-irradiation, reducing the rate cells leave the zone. The time spent there by some cells is thus increased. When limbs, stage 18/19, stage 21, or tips of stage 24, are treated with increasing doses of X-irradiation, from 1000 rads to 2500 rads proximal structures are progressively lost, whereas distal ones--the digits--are relatively unaffected. There was no evidence for intercalation of missing parts. These effects are due to killing or damage of mesenchyme cells: the ectoderm is not affected at these doses. The results are consistent with a quantitative analysis based on the progress zone model, in which viable cells repopulate the progress zone and gradually restore it to normal as non-dividing cells are diluted out. It is suggested that any treatment causing damage to the mesenchyme at early stages will give similar results. The mesenchyme cells appear to be surprisingly resistant to radiation damage. The form of the limb-bud is not altered by damaging the mesenchyme. Differences in the development of structures at similar proximo-distal levels, following irradiation, is considered in terms of the requirement of a threshold number of cells.

Abnormalities, Radiation-Induced↗
PubMed1979

Somite formation in the early chick embryo following grafts of Hensen's node.

Quail grafts of Hensen's node were examined for their potential to induce somites in chick blastoderms. The origin of the structures induced depended on the distance of the graft from the host's midline. Nodes placed at the margin of the area pellucida resulted in structures differentiated from the cells of the graft, whereas medially the graft organized host cells to form rows of somites. The results are discussed in terms of competence of graft and host mesenchyme and a positional signal from the node.

Animals↗
PubMed1978

Cell contacts and sorting out in vivo: the behaviour of some embryonic tissues implanted into the developing chick wing.

The interaction of cells from embryonic liver, neural retina and mesonephros with cells from limb-bud mesenchyme has been investigated in vivo by grafting these tissues into the developing chick wing-bud. The implanted cells were in all cases from quail tissue which can be recognized histologically. As embryonic liver and neural tube are tissues that sort externally to limb-bud mesenchyme in mixed aggregates, it would be expected, from a differential adhesiveness hypothesis, that heterotypic adhesions along the borders of graft and host would be favoured over cell-cell adhesions in the graft. No morphological signs of this were evident: rather the grafted cells maximized like-like contacts. The cells of the grafts, including those from control mesenchyme, did not invade into the wing. The results were the same irrespective of whether the graft was a fragment of tissue or a pellet of reaggregated cells. This supports the idea that cells within tissues are not actively moving around and also provides controls for assaying the invasiveness of other cell types, such as malignant cells into the wing.

Animals↗
PubMed1978

The development of the pattern of growth.

It is proposed that the varying patterns of growth in development can be viewed as an aspect of pattern formation, and that different growth programmes are specified at an early stage. This is illustrated largely with respect to the development and growth of the chick wing. The spatial pattern of cellular differentiation and programme for growth can be considered in terms of the concept of positional information. The lengths of the cartilaginous elements are determined by the initial length of the primordium and its later growth, involving cell multiplication enlagement and matrix secretion. It seems that tissues have a high degree of autonomy with respect to differentiation and growth after they have had their position specified. The cellular basis of programmed growth is discussed.

Animals↗