Search PubMed⌕ Search

Biomedical subjects

R J Coffey

Publications and source records attributed to R J Coffey.

At least 163 records · Page 9Linked to original sources
PubMed1989

Overexpression of transforming growth factor alpha in psoriatic epidermis.

Transforming growth factor alpha (TGF-alpha) is produced by and required for the growth of epithelial cells and is angiogenic in vivo. Since epidermal hyperplasia and angiogenesis are hallmarks of psoriasis, TGF-alpha gene expression was analyzed in epidermal biopsies of normal and psoriatic skin. TGF-alpha messenger RNA and protein are much more abundant in lesional psoriatic epidermis than in normal-appearing skin of psoriatic patients or in normal epidermis. In contrast, messenger RNA levels of transforming growth factor beta 1 (TGF-beta 1), which inhibits epithelial cell growth, are not significantly different in normal, uninvolved, and lesional psoriatic epidermis. Thus, psoriatic epidermal hyperplasia may involve increased expression of a keratinocyte mitogen (TGF-alpha) rather than deficient expression of a growth inhibitor (TGF-beta 1).

Blotting, Northern↗
PubMed1989

Growth of normal human keratinocytes and fibroblasts in serum-free medium is stimulated by acidic and basic fibroblast growth factor.

Keratinocytes and fibroblasts isolated from human neonatal foreskin can be plated and grown through multiple rounds of division in vitro under defined serum-free conditions. We utilized these growth conditions to examine the mitogenic potential of acidic and basic fibroblast growth factor (aFGF and bFGF) on these cells. Our results demonstrate that both aFGF and bFGF can stimulate the proliferation of keratinocytes and fibroblasts. aFGF is a more potent mitogen than bFGF for keratinocytes. In contrast, bFGF appears to be more potent than aFGF in stimulating the growth of fibroblast cultures. Heparin sulfate (10 micrograms/ml) dramatically inhibited the ability of bFGF to stimulate the proliferation of keratinocytes. In comparison, heparin slightly inhibited the stimulatory effect of aFGF and had no effect on epidermal growth factor (EGF) stimulation in keratinocyte cultures. In fibroblast cultures the addition of heparin enhanced the mitogenic effect of aFGF, had a minimal stimulatory effect on the mitogenic activity of bFGF, and had no effect on EGF-stimulated growth. Our results demonstrate that the proliferation in vitro of two normal cell types found in the skin can be influenced by aFGF and bFGF and demonstrate cell-type specific differences in the responsiveness of fibroblasts and keratinocytes to these growth factors and heparin.

Cell Division↗
PubMed1989

Hypothalamic and basal forebrain germinoma presenting with amnesia and hyperphagia.

Patients harboring primary intracranial germinomas usually have had Parinaud's syndrome and hydrocephalus (with pineal tumors) or hypopituitarism, visual loss, and diabetes insipidus (with suprasellar tumors) at presentation. The few reported cases of verified intraparenchymal hypothalamic germinomas all have been in prepubertal males with progressive neurologic deficits, altered levels of consciousness, or clinically apparent panhypopituitarism. The subject of this report was an endocrinologically normal, primiparous 24-year-old woman who presented with hydrocephalus followed by worsening anterograde amnesia and hyperphagia despite having a functioning ventriculoatrial shunt. Computed tomography scanning and magnetic resonance imaging demonstrated an anterior hypothalamic, thalamic, and basal forebrain mass, which stereotactic biopsy proved to be a germinoma. Intraaxial germinomas restricted to the anterior hypothalamus or thalamus rarely have been reported. The clinical features of the current patient may be unique.

Adult↗
PubMed1989

Regulation of intestinal epithelial cell growth by transforming growth factor type beta.

A nontransformed rat jejunal crypt cell line (IEC-6) expresses transforming growth factor type beta 1 (TGF-beta 1) mRNA, secretes latent 125I-labeled TGF-beta 1 competing activity into culture medium, and binds 125I-labeled TGF-beta 1 to specific, high-affinity (Kd = 3.7 pM) cell surface receptors. IEC-6 cell growth is markedly inhibited by TGF-beta 1 and TGF-beta 2 with half-maximal inhibition occurring between 0.1 and 1.0 ng of TGF-beta 1 per ml. TGF-beta 1-mediated growth inhibition is not associated with the appearance of biochemical markers of enterocyte differentiation such as alkaline phosphatase expression and sucrase activity. TGF-beta 1 (10 ng/ml) increases steady-state levels of its own mRNA expression within 8 hr of treatment of rapidly growing IEC-6 cells. In freshly isolated rat jejunal enterocytes that are sequentially eluted from the crypt villus axis, TGF-beta 1 mRNA expression is most abundant in terminally differentiated villus tip cells and least abundant in the less differentiated, mitotically active crypt cells. We conclude that TGF-beta 1 is an autoregulated growth inhibitor in IEC-6 cells that potentially functions in an autocrine manner. In the rat jejunal epithelium, TGF-beta 1 expression is most prominently localized to the villus tip--i.e., the region of the crypt villus unit that is characterized by the terminally differentiated phenotype. These data suggest that TGF-beta 1 may function in coordination of the rapid cell turnover typical for the intestinal epithelium.

Animals↗
PubMed1989

Complex regulation of transforming growth factor beta 1, beta 2, and beta 3 mRNA expression in mouse fibroblasts and keratinocytes by transforming growth factors beta 1 and beta 2.

Regulation of transforming growth factor beta 1 (TGF beta 1), TGF beta 2, and TGF beta 3 mRNAs in murine fibroblasts and keratinocytes by TGF beta 1 and TGF beta 2 was studied. In quiescent AKR-2B fibroblasts, in which TGF beta induces delayed stimulation of DNA synthesis, TGF beta 1 autoregulation of TGF beta 1 expression was observed as early as 1 h, with maximal induction (25-fold) after 6 to 12 h. Increased expression of TGF beta 1 mRNA was accompanied by increased TGF beta protein production into conditioned medium of AKR-2B cells. Neither TGF beta 2 nor TGF beta 3 mRNA, however, was significantly induced, but both were apparently down regulated at later times by TGF beta 1. Protein synthesis was not required for autoinduction of TGF beta 1 mRNA in AKR-2B cells. Nuclear run-on analyses and dactinomycin experiments indicated that autoregulation of TGF beta 1 expression is complex, involving both increased transcription and message stabilization. In contrast to TGF beta 1, TGF beta 2 treatment of quiescent AKR-2B cells increased expression of TGF beta 1, TGF beta 2, and TGF beta 3 mRNAs, but with different kinetics. Autoinduction of TGF beta 2 mRNA occurred rapidly with maximal induction at 1 to 3 h, enhanced TGF beta 3 mRNA levels were observed after 3 h, and increased expression of TGF beta 1 occurred later, with maximal mRNA levels obtained after 12 to 24 h. Nuclear run-on analyses indicated that TGF beta 2 regulation of TGF beta 2 and TGF beta 3 mRNA levels is transcriptional, while TGF beta 2 induction of TGF beta 1 expression most likely involves both transcriptional and posttranscriptional controls. In BALB/MK mouse keratinocytes, minimal autoinduction of TGF beta 1 occurred at only the 12- and 24-h time points and protein synthesis was required for this autoinduction. The results of this study provide an example in which TGF beta 1 and TGF beta 2 elicit different responses and demonstrate that expression of TGF beta 1, and TGF beta 3 are regulated differently. The physiological relevance of TGF beta 1 autoinduction in the context of wound healing is discussed.

Animals↗
PubMed1989

Gamma knife radiosurgery for intracranial arteriovenous malformations in childhood and adolescence.

Eighteen children or adolescents with intracranial arteriovenous malformations (AVM) underwent stereotactic radiosurgery using the first North American gamma knife. This closed-skull, single-treatment therapy, utilizing 201 ionizing beams of gamma-irradiation, was used as an alternative to microsurgical removal in these selected patients (aged 34 months to 18 years, mean 12.3 years) beginning in August 1987. No significant perioperative morbidity occurred, and no patient rebled or died in the follow-up interval ranging between 7 and 19 months. Computed tomography (CT) and magnetic resonance imaging (MRI) were used to monitor the response to treatment and to determine when postoperative angiography was indicated. Of seven AVMs examined with cerebral angiography 1 year after treatment, three were completely obliterated; three others were significantly smaller, and their complete obliteration is anticipated by 2 years after treatment. Follow-up CT or MRI confirmed attenuation or signal changes suggestive of edema surrounding the treatment volume in 3 patients; 1 had transient worsening of a preexisting neurological deficit. Although a more long-term perspective is still required for this new technology now available in the United States, we believe that gamma knife stereotactic radiosurgery is a safe and effective method to obliterate AVM deemed too risky for microsurgical removal.

Adolescent↗
PubMed1989

Localization of transforming growth factor alpha and its receptor in gastric mucosal cells. Implications for a regulatory role in acid secretion and mucosal renewal.

Transforming growth factor alpha (TGF alpha) shares with epidermal growth factor (EGF) structural homology (35%), a common cell-surface membrane receptor (TGF alpha/EGF receptor), and a nearly identical spectrum of biological activity, including inhibition of gastric acid secretion. Herein, we report expression of TGF alpha mRNA in normal gastric mucosa of the adult guinea pig, rat, and dog. TGF alpha mRNA was also detected in matched surgically resected gastric mucosa and adjacent gastric carcinoma from 10 patients, and in gastric mucosa adjacent to a benign ulcer from an additional patient. TGF alpha protein was quantitated by radioimmunoassay and was present in tumor and adjacent mucosa. TGF alpha/EGF receptor mRNA was also detected in gastric mucosa from all species studied. Localization of TGF alpha and TGF alpha/EGF receptor mRNA expression was examined in samples of unfractionated guinea pig gastric mucosa and from chief cell-enriched and parietal cell-enriched fractions. All samples exhibited TGF alpha and TGF alpha/EGF receptor expression. The TGF alpha signal was greatest in the parietal cell fraction (5.8-fold increase), but was also enhanced in the chief cell fraction (1.9-fold increase) relative to the unfractionated gastric mucosa. Like TGF alpha expression, TGF alpha/EGF receptor mRNA expression was most intense in the parietal cell-enriched fraction (7.8-fold increase), but was also increased in the chief cell-enriched fraction (2.7-fold increase) relative to the unfractionated guinea pig gastric mucosa. We conclude that TGF alpha and TGF alpha/EGF receptor genes are expressed in normal adult mammalian gastric mucosa. These findings, when interpreted in light of described actions of TGF alpha and EGF, provide evidence that local production of TGF alpha could play an important role in the regulation of acid secretion and mucosal renewal in the stomach.

Adult↗
PubMed1989

Transforming growth factor-alpha gene expression and action in the seminiferous tubule: peritubular cell-Sertoli cell interactions.

The local production and action of an epidermal growth factor (EGF)-like substance within the seminiferous tubule was investigated as a potential mediator of cell-cell interactions. Peritubular (myoid) and Sertoli cells were isolated and cultured under serum-free conditions. Proteins secreted by Sertoli and peritubular cells were found to contain a component that bound to the EGF receptor in a RRA. Separation of secreted proteins by reverse phase chromatography fractionated a protein that contained EGF bioactivity in its activity to stimulate growth of an EGF-dependent cell line. Biochemical properties examined for both Sertoli and peritubular cell EGF activities were similar with each other, but distinct from murine EGF. Northern blot analysis with an EGF cDNA probe did not detect EGF gene expression in peritubular, Sertoli, or germ cells. The possible production of an EGF-like substance such as transforming growth factor-alpha (TGF alpha) was investigated with a molecular probe to human TGF alpha. Both peritubular and Sertoli cells contained a 4.5-kilobase mRNA species that hybridized in a Northern blot analysis with a human TGF alpha cRNA probe. An immunoblot with a TGF alpha antisera confirmed the production of TGF alpha by the detection of a protein in both Sertoli and peritubular cell secreted proteins. TGF alpha gene expression was not detected in freshly isolated germ cells. Scatchard analysis revealed the presence of high affinity EGF receptors on peritubular cells and the absence of such receptors on Sertoli or germ cells. TGF alpha was found to stimulate peritubular cell proliferation, but had no effect on Sertoli cell growth. The effects of hormones and TGF alpha on Sertoli cell function and differentiation were assayed through an examination of transferrin production by Sertoli cells. TGF alpha had no direct effect on transferrin production or the ability of hormones to influence Sertoli cells. However, the presence of peritubular cells in coculture with Sertoli cells allowed TGF alpha to stimulate transferrin production. TGF alpha was also found to have relatively rapid effects on peritubular cell migration and the promotion of colony formation in culture. Cocultures of peritubular and Sertoli cells also responded to TGF alpha by the formation of large clusters of cells. Observations demonstrate the local production of TGF alpha by Sertoli and peritubular cells, and action of TGF alpha on peritubular cells and, potentially, Sertoli cells. The local production and action of TGF alpha may have a critical role as a paracrine/autocrine factor involved in the maintenance of testicular function.

Animals↗
PubMed1989

Stereotactic drainage of Aspergillus brain abscess with long-term survival: case report and review.

Aspergillus species are second only to Cryptococcus neoformans as the most common cause of fungal infections of the central nervous system in immunocompromised patients. Survival following treatment of Aspergillus brain abscess has been reported only 4 times. In each case, craniotomy was performed for abscess drainage. We present a case of long-term survival following stereotactic drainage of a bilateral Aspergillus brain abscess. In all reported cases, including the present one, histological examination of the abscess contents established the correct diagnosis. Amphotericin B was used in combination with operation in 4 of the 5 cases of long-term survival.

Adult↗
PubMed1989

Intervertebral disc space infection and osteomyelitis due to Hemophilus species: report of two cases and review.

Vertebral osteomyelitis and intervertebral disk space infections in adults are most often caused by Staphylococcus aureus or Escherichia coli. Despite an increasing number of cases caused by other gram-negative bacteria, documented spinal infections with Hemophilus species remain exceedingly rare. All prior cases have involved the lumbar spine between the L2 and L4 levels. None has required surgical decompression or stabilization. We report two adult patients with intervertebral disk space infections and osteomyelitis outside the lumbar region. One patient, who had a Hemophilus influenzae infection of the T9-T10 disk space, was successfully treated with intravenous antibiotics and external bracing. Another patient, who had a Hemophilus aphrophilus infection that destroyed the C5-C6 disk space and adjacent vertebral bodies, required surgical debridement and stabilization in addition to antibiotic therapy and halovest immobilization. Neither patient had a significant underlying illness or extra-spinal source of infection. The clinical features and spinal levels affected in these two patients have expanded our knowledge of the spectrum of disease caused by Hemophilus species.

Adult↗
PubMed1988

A new type of transforming growth factor-beta, TGF-beta 3.

A new type of TGF-beta, TGF-beta 3, has been identified by cDNA characterization. The amino acid sequence of mature TGF-beta 3 and its precursor has been derived from porcine and human cDNA sequences. The human TGF-beta 3 gene is spread over seven exons as in the case of the TGF-beta 1 gene. Comparison with TGF-beta 1 and -beta 2 indicates a strong conservation of the mature sequences, but a relaxed homology in the precursor segments. TGF-beta 3 mRNA is mainly expressed in cell lines from mesenchymal origin, suggesting a biological role different from the other TGFs-beta.

Amino Acid Sequence↗
PubMed1988

Growth modulation of mouse keratinocytes by transforming growth factors.

The effects of exogenously added transforming growth factor (TGF alpha and TGF beta on the growth of BALB/MK cells were examined. TGF alpha supplanted the epidermal growth factor (EGF) requirement in these cells. In contrast, TGF beta reversibly inhibited the growth of BALB/MK cells by abrogating the stimulatory actions of EGF or TGF alpha. The inhibitory effects of TGF beta appeared to be mediated by events distal to EGF ligand-receptor interactions. Growth inhibition of BALB/MK cells by TGF beta did not result in the induction of differentiation. This finding is different from the growth inhibition of these cells induced by elevated calcium levels (1.5 mM) which was tightly coupled to terminal differentiation. The BALB/MK cells were found to express TGF alpha mRNA, as well as TGF beta mRNA and protein. In addition, TGF alpha, as well as EGF, enhanced TGF alpha gene expression. These studies suggest a role for endogenous TGFs in regulating BALB/MK proliferation. TGF alpha provides a positive growth signal, while TGF beta is a potent inhibitor of growth even in the presence of such positive modulators as TGF alpha and EGF.

Animals↗
PubMed1988

Supracallosal interhemispheric arachnoid cyst: resolution after intracystic hemorrhage and infection.

A case of a large, symptomatic, supracallosal interhemispheric arachnoid cyst is presented. Positive contrast-enhanced computed tomographic (CT) cystography after stereotactic puncture and aspiration demonstrated lack of communication between the cyst and the subarachnoid space or ventricular system. A cystoperitoneal shunt was successful in relieving the patient's symptoms for 5 years. A delayed shunt infection after gynecologic surgery necessitated removal of the shunt, and was complicated by asymptomatic intracystic hemorrhage. Thereafter, serial CT and magnetic resonance imaging scans showed eventual disappearance of the cyst.

Adult↗
PubMed1988

Type beta transforming growth factor reversibly inhibits the early proliferative response to partial hepatectomy in the rat.

Type beta transforming growth factor (TGF-beta), a factor produced by many cell types, is a potent inhibitor of hepatocyte DNA synthesis in vitro. To determine whether TGF-beta can influence hepatocyte proliferation in vivo, its effects were examined on the regenerative response of liver to partial hepatectomy (PH) in the rat. Porcine platelet-derived TGF-beta 1 (0.5 micrograms), administered intravenously at the time of PH and 11 hr later, reduced the fraction of hepatocytes engaged in DNA synthesis 22 hr after PH by 67% and inhibited the rate of hepatic [3H]thymidine incorporation by 50%. TGF-beta 2 produced a similar effect. A single dose of 0.5 micrograms of TGF-beta 1 given 11 hr after PH reduced liver [3H]thymidine incorporation by 32%; 4.5 micrograms of TGF-beta 1 or TGF-beta 2 inhibited DNA synthesis by 88% and the labeling index by 86%. Although sensitive to TGF-beta administered 11 hr after PH, late in the G1 phase of the cell cycle, a single dose of 0.5 micrograms given at the time of PH did not significantly influence DNA synthesis 22 hr after PH. The inhibitory effects of TGF-beta were transient; rats treated with two 0.5-microgram doses of TGF-beta at 0 and 11 hr had completely restored their original liver DNA mass 8 days after PH. Administration of 0.5 microgram of either TGF-beta 1 or TGF-beta 2 every 12 hr for 5 days failed to suppress the recovery of hepatic DNA mass. However, the nuclear labeling index of the TGF-beta-treated animals was significantly higher than that of the controls. There was no evidence of cytotoxicity from TGF-beta, as determined by liver histology and plasma concentrations of glucose, insulin-like growth factor I, and two hepatic enzymes. Thus, TGF-beta 1 and TGF-beta 2 reversibly inhibit the proliferative response of liver to PH and may be important in the modulation of normal liver growth and repair.

Alkaline Phosphatase↗
PubMed1988

Selective inhibition of growth-related gene expression in murine keratinocytes by transforming growth factor beta.

Transforming growth factor beta (TGF beta) is a potent inhibitor of epithelial cell proliferation. A nontumorigenic epidermal growth factor (EGF)-dependent epithelial cell line, BALB/MK, is reversibly growth arrested by TGF beta. TGF beta will also abrogate EGF-stimulated mitogenesis of quiescent BALB/MK cells. Increased levels of calcium (greater than 1.0 mM) will induce differentiation in BALB/MK cells; in contrast, TGF beta-mediated growth inhibition does not result in induction of terminal differentiation. In the present study, the effects of TGF beta and calcium on growth factor-inducible gene expression were examined. TGF beta markedly decreased c-myc and KC gene expression in rapidly growing BALB/MK cells and reduced the EGF induction of c-myc and KC in a quiescent population of cells. TGF beta exerted its control over c-myc expression at a posttranscriptional level, and this inhibitory effect was dependent on protein synthesis. TGF beta had no effect on c-fos gene expression, whereas 1.5 mM calcium attenuated EGF-induced c-fos expression in quiescent cells. Expression of beta-actin, however, was slightly increased in both rapidly growing and EGF-restimulated quiescent BALB/MK cells treated with TGF beta. Thus, in this system, TGF beta selectively reduced expression of certain genes associated with cell proliferation (c-myc and KC), and at least part of the TGF beta effect was at a posttranscriptional level.

Animals↗
PubMed1988

Regulation of ovarian cell growth through the local production of transforming growth factor-alpha by theca cells.

The rapid proliferation of a tissue often requires the local production of a specific growth factor. The ovarian follicle is a rapidly growing tissue which contains two primary somatic cell types, granulosa cells and theca cells. Theca cells and granulosa cells were isolated from bovine ovaries and cultured to assess the possible local production of a growth factor within the ovarian follicle. Serum-free conditioned medium from theca cells, but not from granulosa cells, was found to contain a component that specifically bound to the epidermal growth factor (EGF) receptor. Therefore, theca cells appear to produce an EGF-like substance as a potential regulator of follicle cell growth. This result provides physiological significance to the previous observation that granulosa cells contain EGF receptors and respond to EGF to increase cell proliferation. Transforming growth factor-alpha (TGF alpha) is a protein that is structurally and functionally related to EGF and binds to the EGF receptor. Using a molecular probe to TGF alpha, theca cells were found to express the TGF alpha gene, which is consistent with the presence of an EGF-like substance in conditioned medium, but granulosa cells had no detectable TGF alpha gene expression. Similar analysis with a molecular probe to EGF demonstrated the apparent lack of EGF gene expression in theca cells or granulosa cells. As previously demonstrated with granulosa cells, the data presented indicate that theca cells also contain high affinity EGF receptors. TGF alpha was found to stimulate the growth of both granulosa and theca cells. These observations imply that within the ovarian follicle TGF alpha is produced by theca cells, which can subsequently have both a paracrine and an autocrine role in regulating follicle cell proliferation. Results presented demonstrate production of TGF alpha by a normal adult mesenchymal tissue and provide an example of a growth factor-mediated mesenchymal-epithelial cell interaction between theca cells and granulosa cells.

Animals↗