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Biomedical subjects

I K Cohen

Publications and source records attributed to I K Cohen.

At least 19 recordsLinked to original sources
PubMed1992

Biology of fetal wound healing: collagen biosynthesis during dermal repair.

The rapid restoration of tissue integrity and breaking strength in healing fetal wounds is mainly a function of fetal wound collagen. In this study, the fetal and adult tissue responses to injury were characterized in terms of changes in collagen biosynthesis. Linear wounds and unwounded skin were incubated with radioactive proline, and collagen synthesis was measured as isotope incorporation into collagenase-sensitive protein. Likewise, noncollagen protein synthesis was represented by isotope incorporation into collagenase-resistant protein. Adult wounds demonstrated a preferential stimulation of collagen as compared with noncollagen protein synthesis after wounding. In contrast, both collagen and noncollagen protein synthesis were significantly elevated in the fetus during the first 5 days postwounding. Despite marked increases in fetal wound collagen synthesis above both unwounded fetal skin and adult wound levels, fetal wounds exhibited no evidence of excessive collagen deposition or scar formation after wounding. These findings suggest that the fetal response to tissue injury is a function of the distinctive qualities of fetal fibroblasts associated with the extracellular wound matrix and may involve rapid collagen turnover and degradation.

Animals↗
PubMed1992

In vivo degradation of fetal wound hyaluronic acid results in increased fibroplasia, collagen deposition, and neovascularization.

Fetal tissue repair occurs without acute inflammation, prominent fibroplasia, or marked neovascularization. The fetal wound extracellular matrix is rich in hyaluronic acid (HA), while collagen is deposited in an organized normal dermal pattern. In various biologic systems, including regeneration and development, the controlled accumulation and subsequent degradation of hyaluronic acid is associated with distinct cellular and matrix events. Therefore, it is hypothesized that the abundance of hyaluronic acid in fetal wounds may influence cellular and/or matrix events such that tissue repair is highly organized and adult-like scarring does not occur. To test this hypothesis, the hyaluronic acid content of fetal rabbit wounds was reduced by specific degradation with Streptomyces hyaluronidase. Control wounds were treated with either enzyme buffer (n = 12) or denatured enzyme solution (n = 8) and exhibited a normal fetal healing response with scattered peripheral fibroblasts, a matrix of hyaluronic acid, and no infiltrating collagen. In marked contrast, the hyaluronidase-treated wounds (n = 14) demonstrated increased fibroblast infiltration, collagen deposition, and capillary formation. A significant reduction in the hyaluronic acid content of the hyaluronidase-treated wounds was confirmed biochemically. Since the degradation of hyaluronic acid resulted in an altered healing response, this study demonstrates that hyaluronic acid affects the cellular and matrix events in fetal healing and may be partially responsible for the unique qualities of this regenerative repair process.

Animals↗
PubMed1992

Scarless wound healing in the mammalian fetus.

Fetal wound healing is a remarkable process that is fundamentally different than postnatal healing. Healing of primarily closed, linear wounds occurs rapidly and without scarring. In late gestational age fetal sheep, a transition to adult-like healing occurs as evidenced by minimal scar formation. Acute inflammation is not involved, fibroblast recruitment and proliferation is minimal, the matrix of the wounds is enriched with HA and collagen deposition is highly organized so that scarring is minimal or nonexistent. Open wounds in several species do not contract, an observation that may be because of an inhibitor of contraction in amniotic fluid. The underlying mechanisms that regulate fetal wound repair are currently not well understood. An altered supply or activity of growth factors may be instrumental. Fibroblasts may preferentially produce HA secondary to a factor present within the fetal system, and HA may influence cellular and matrix events within the wound. As greater knowledge of the biologic factors of scarless healing in the fetus is gained, applications to abnormal adult healing may be developed. As the age of fetal surgery is approaching, it is essential to understand the injury response in these new patients.

Adult↗
PubMed1991

Hyaluronic acid is a major component of the matrix of fetal rabbit skin and wounds: implications for healing by regeneration.

The extracellular matrix (ECM) of fetal rabbit wounds contains an abundance of the glycosaminoglycan hyaluronic acid (HA) but is devoid of excessive collagen. Thus, fetal wounds heal without scarring, such that tissue repair grossly resembles regeneration. To obtain further insight into the process of fetal wound healing, the ECM of normal fetal rabbit skin was analyzed, thus providing a comparative endpoint for the ECM of healing fetal wounds. Similarities between the matrices would support the theory of healing by regeneration. The glycosaminoglycan (GAG) component of fetal rabbit skin from 24- and 29-day gestational age fetuses was extracted and then quantitated using an alcian blue binding assay. The extracted GAG was characterized by cellulose acetate electrophoresis and HA was identified by its selective digestion by Streptomyces hyaluronidase. The mean GAG content, measured as ng GAG per mg dry weight skin, was 260 +/- 200 for the 24-day group (n = 28) and 280 +/- 220 for the 29-day group (n = 26). The only GAG identified at both times of gestation was HA. This study has demonstrated that HA is the predominant GAG present in fetal rabbit skin and its quantity is stable during the period studied late in gestation. A major component of the ECM of both wounded and normal fetal skin is HA, indicating a close compositional similarity. These observations provide biochemical support for the hypothesis that the reparative process of injured tissue in the fetal rabbit proceeds in an attempt to reconstitute normality, i.e. regeneration.

Animals↗
PubMed1991

Analysis of skin grafting techniques in the fetal rabbit.

The experimental model reported here was developed initially to examine the possibility of in utero coverage of congenital soft tissue defects using several types of reconstructive techniques. To pursue this, full-thickness skin grafts, pedicle flaps, and skin "islands" were fashioned on the backs of fetal rabbits; equivalent adult control wounds were also created. While all pedicle flaps and skin islands remained viable, none of the full-thickness grafts survived in the fetus. All adult control flaps, skin islands, and skin grafts were viable. Angiogenesis is crucial to full-thickness skin graft survival. These observations suggest that the death of full-thickness fetal skin grafts may be related to a failure of neovascularization in the graft bed. Further analysis using this model may help elucidate the factors involved in fetal angiogenesis. Additionally, this model may permit testing of putative angiogenic factors applied under a full-thickness skin graft; graft survival offers an easy, objective, and quantifiable means of data analysis.

Animals↗
PubMed1990

The role of mammography in detecting breast cancer in augmented breasts.

Recent reports suggest that mammographic findings may be compromised in patients who have undergone augmentation mammoplasty. Therefore, early detection of breast cancer by mammography may be obscured. We reviewed records for our patients with breast cancer after augmentation mammoplasty to define further the role and accuracy of mammography. Six patients aged 34 to 52 years (mean, 42 years) had a diagnosis of breast carcinoma 4 to 14 years (mean, 7.2 years) after augmentation mammoplasty. Five patients had preoperative mammographic examinations. Suspicious lesions were seen in 4 patients, and microcalcifications were identified in the fifth. The sixth patient had a normal xeromammogram. Pathological diagnosis was infiltrating ductal carcinoma in 5 patients and intraductal carcinoma in 1. Findings for lymph nodes were negative in 3 patients; 2 others had positive findings in one lymph node, and 1 had positive results in four lymph nodes. Five patients had a suspicious mass that was palpated on self-examination or by the patient's plastic surgeon, and the sixth patient had a routine screening mammogram. Two of 3 patients with positive lymph nodes received adjuvant chemotherapy. This report confirms the role of mammography as a screening tool in making the diagnosis of breast cancer in women who have undergone augmentation mammoplasty. The importance of self-examination and follow-up by the plastic surgeon is stressed. The data suggest that mammography remains an accurate method for detecting breast lesions.

Adult↗
PubMed1990

Models of wound healing.

The investigation of wound healing is dependent on the use of various models. This paper reviews several methods used to study wound healing, particularly in regard to connective tissue metabolism. The usefulness and potential pitfalls of cell culture are discussed. Several species of animals have been used as models for human healing, rodents being the most frequently employed. In an attempt to provide better wound tissue sampling from these animals, insertable devices have been developed that allow the ingrowth of healing tissue. Several of these devices are reviewed with reference to their advantages and disadvantages. Connective tissue deposition into wounds can be evaluated by wound strength measurement and hydroxyproline quantitation. Histologic methods are available to evaluate the cellular and matrix details within the wound. Additionally, methods developed in molecular biology are becoming applicable to healing studies and a safe means of investigating collagen metabolism in humans by the use of a stable oxygen isotope is being developed. The study of fetal wound healing provides an excellent example of the utility of many of these methods in achieving an understanding of the biology of this remarkable scarless process.

Animals↗
PubMed1990

Fetal skin organ culture.

The fetal response to cutaneous injury has been investigated in a variety of models; most have studied the differences between fetal and adult healing mechanisms in vivo and in cell culture. Further disclosure of the cellular and biochemical events requires a model that can be manipulated to study single factors influencing fetal tissue repair without the complex interactions that occur in vivo, but in a system that more closely approximates normal skin than cell culture models. This paper presents a method for the organ culture of fetal skin and its advantages as a model to help elucidate fetal healing mechanisms. Skin sections (1 x 1 cm) excised from the backs of fetuses of New Zealand white rabbits on day 27 gestation (term = 31 days) were placed eccentrically in 65-mm culture dishes and fed daily with 2.5 mL of DMEM containing 10% fetal calf serum, antibiotics, and 10 mM ascorbic acid. A separate group, treated similarly, received 4-mm punch wounds to assess the in vitro response to wounding. The specimens were incubated at 37 degrees C in humidified room air on a rocker platform to provide alternate exposure of the skin to air and medium. Gross observation at 3 weeks showed cells extending into the central wound, indicating that viable cells were proliferating and/or migrating from the tissue. Skin was examined histologically and was viable over the 3-week period studied. Organ culture, by maintaining tissue in the natural extracellular matrix, allows cell-to-cell contact and communication to be maintained while allowing controlled environmental manipulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Analysis of fibrogenic processes in denervated tissues of spinal cord injury patients.

To test the hypothesis that altered collagen metabolism is a contributing factor in the apparent delayed wound healing in denervated regions of spinal cord injury (SCI) patients, a tissue implant (PVA) was used to directly measure collagen deposition. Sterile PVA implants were placed subcutaneously in the inner aspect of the upper arm above the cord injury (innervated) and in the inner aspect of the upper leg below the cord injury (denervated) of 20 spinal cord injury patients and compared to eight healthy volunteers. On day 14, the implants were removed and analyzed histologically by trichrome stain and biochemically for hydroxyproline as a measure of collagen deposition. No remarkable histologic differences were observed in the sponge material removed from the upper regions compared to the lower denervated regions of the spinal cord injury patients. Sponges from both areas were infiltrated with fibroblasts containing well-developed rough endoplasmic reticulum and large quantities of trichrome-positive collagen. Likewise, upper and lower histology of controls was identical and nondistinguishable from the corresponding sections obtained from the spinal cord injury patients. Quantitation of the hydroxyproline in the arms of the spinal cord injury patients (n = 20) showed 4.3 +/- 0.7 nmol hydroxyproline per milligram of sponge compared to 4.1 +/- 0.4 nmol/mg in the denervated regions of the lower limb. The hydroxyproline content in the arms of control volunteers was 5.2 +/- 0.7 nmol/mg compared to 3.9 +/- 0.8 nmol/mg in the leg (n = 8). These observations suggest that fibrogenic processes in denervated regions are not reduced significantly compared to innervated regions.

Adult↗
PubMed1988

Transforming growth factor beta (TGF-beta) induces fibrosis in a fetal wound model.

The adult cellular response to tissue injury is characterized by acute inflammation followed eventually by fibroblast proliferation and collagen synthesis. Fetal tissue responses to injury differ markedly from those of the adult; an early acute inflammatory response is absent, few fibroblasts participate, and no collagen is deposited. The object of the present study was to analyze the effects of transforming growth factor beta (TGF-beta), an important regulatory molecule in adult healing events, on the fetal tissue response following wounding. Fetal cellular and extracellular matrix responses to injury were evaluated by placing subcutaneous wound implants containing TGF-beta (0.01 to 10 ng) in fetal rabbits at 24 days gestation (term = 31 days). Histologic responses one to seven days later were compared with fetal and adult control implants without TGF-beta. The histology of the adult implant was characterized by an early acute inflammatory response: by day 7 fibroblasts and collagen were predominant. In contrast, control implants removed from fetal rabbits had no histologic evidence of acute inflammation or fibroblast penetration and no collagen was deposited. When implants containing 1.0 ng TGF-beta were removed from fetal rabbits at seven days, a grossly fibrotic reaction was observed: histology confirmed marked fibroblast penetration with collagen deposition. Fetal implants containing 0.01 ng or 10 ng TGF-beta showed few fibroblasts but had increased numbers of inflammatory cells compared with controls. These observations demonstrate that the fetal response becomes adultlike with fibroblast proliferation and collagen accumulation when TGF-beta is added, thus documenting the responsiveness of the fetal system to adult repair signals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Effect of beta-aminopropionitrile and ascorbate on fibroblast migration.

Ascorbate and beta-aminopropionitrile (BAPN) have direct, but diverse affects on collagen matrix production. Ascorbate is necessary for the intracellular hydroxylation of prolyl and lysyl residues during collagen biosynthesis whereas BAPN inhibits the enzyme lysyl oxidase in the extracellular space thus preventing collagen crosslink formation. To study the influence of these two agents on fibroplasia, an in vitro model was used to analyze fibroblast migration, proliferation, and collagen synthesis. Biopsies of chicken tendon were covered with a fibrin clot to simulate an in vivo wound environment, and then they were exposed to either ascorbate or BAPN for up to 7 days. Fibroblast migration into the fibrin clot was measured using a Zeiss Mopp II planimeter, DNA synthesis by 125IUDR incorporation, and collagen synthesis by [3H]proline incorporation into collagenase-digestible protein. Tendon biopsies treated daily with fresh ascorbate (0.1 mM) had significantly greater fibroblast migration than controls without ascorbate (P less than 0.05). Cellular proliferation, collagen synthesis, and total protein synthesis were not significantly altered by ascorbate treatment. In contrast, BAPN inhibited fibroblast migration in a dose-dependent fashion without inhibiting proliferation (0.25 and 0.5 mM), collagen, and noncollagen protein synthesis. Therefore, the effect of BAPN on migration does not appear to be due to generalized cytotoxicity. These combined studies suggest that compounds such as ascorbate and BAPN which can modify collagen may also modify fibroblast migration.

Aminopropionitrile↗
PubMed1987

Induction of prolyl hydroxylase activity in a nonadherent population of human leukocytes.

A nonadherent population of human monocytes has been shown to express the collagen hydroxylating enzyme prolyl hydroxylase in vitro. Enzyme levels present in freshly isolated nonadherent cells were induced 300% during the first 72 hours of culturing, which could be suppressed by cycloheximide. Maximum induction required both a feeder layer of adherent leukocytes, and 10-15% autologous plasma. Biosynthesis of Clq, a protein which also is hydroxylated by prolyl hydroxylase, by the nonadherent cells was significantly less than the adherent monocytes. Therefore, this collagen biosynthetic marker enzyme was not associated with Clq synthesis, which suggests that the enzyme is present for collagen biosynthesis.

Cells, Cultured↗