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Biomedical subjects

B Berman

Publications and source records attributed to B Berman.

At least 91 records · Page 5Linked to original sources
PubMed1991

Stimulation of collagen and glycosaminoglycan production in cultured human adult dermal fibroblasts by recombinant human interleukin 6.

Interleukin (IL) 6 is a pleiotropic cytokine synthesized by fibroblasts in response to many stimuli, including IL-1 beta. To evaluate the possibility that previously observed stimulation of fibroblast biosynthetic functions by IL-1 beta may be mediated by autocrine IL-6, we investigated the effect of recombinant human (rh) IL-6 on the connective tissue-related biosynthetic functions of three lines of cultured human adult dermal fibroblasts. We found that rhIL-6 mimicked some of the activities of IL-1 beta, as 24-96-h treatment of confluent fibroblast cultures with rhIL-6 caused concentration (10 to 1000 ng/ml)-dependent increases in the production of collagen and the glycosaminoglycans (GAG), hyaluronic acid and chondroitin-4/6-sulfates, but had little effect on fibronectin or total protein production. Although the effective stimulating concentrations of IL-6 were within the range (approximately 100 ng/ml) we found produced by rhIL-1 beta-treated fibroblast cultures, rhIL-1 beta at 0.2-1.0 ng/ml induced significantly greater amounts of collagen and GAG than the maximum effective concentrations of IL-6. Moreover, an anti-rhIL-6 antibody, which effectively neutralized the fibroblast-stimulating activities of rhIL-6, only fractionally blocked the fibroblast-stimulating actions of rhIL-1 beta, suggesting autocrine IL-6 only partially mediates the effects of IL-1 beta on fibroblasts. Conversely, the fibroblast-stimulating effects of rhIL-6 are unlikely due to autocrine IL-1 beta, as an anti-rhIL-1 beta antibody had only minimal inhibitory action on rhIL-6-treated fibroblast cultures. Overall these results suggest that IL-6 could function as a paracrine/autocrine regulator of dermal fibrotic repair.

Adult↗
PubMed1991

Regulation of the proliferation and biosynthetic activities of cultured human Peyronie's disease fibroblasts by interferons-alpha, -beta and -gamma.

To determine the therapeutic potential of interferon (IFN) treatment for Peyronie's disease, we investigated the effect of human recombinant (hu-r) IFNs on cultured fibroblasts derived from a Peyronie's disease penile plaque. Treatment of cultured fibroblasts with hu-r-IFN-alpha2b, hu-r-IFN-beta-ser17 and hu-r-IFN gamma caused a concentration dependent inhibition of both fibroblast proliferation and collagen production, as well as an increase in collagenase production. Hu-r-IFN-alpha and beta had no effect on fibroblast glycosaminoglycan (GAG) or fibronectin production, while hu-r-IFN-gamma markedly increased both GAG and fibronectin production. These results demonstrate that IFNs, especially IFNs-alpha and beta, exhibit antifibrotic activity on Peyronie's disease fibroblasts and suggest a rationale for using IFNs to treat Peyronie's disease.

Cell Division↗
PubMed1991

Cerebral palsy and rhizotomy. A 3-year follow-up evaluation with gait analysis.

A recent increase in the popularity of selective rhizotomy for reduction of spasticity in cerebral palsy has led to a demand for more objective studies of outcome and long-term follow-up results. The authors present the results of gait analysis on 14 children with spastic cerebral palsy, who underwent selective posterior rhizotomy in 1985. Sagittal plane gait patterns were studied before surgery and at 1 and 3 years after surgery using a digital camera system. The parameters measured included the range of motion at the knee and thigh, stride length, speed of walking, and cadence. The range of motion at the knee was significantly increased at 1 year after surgery and further improved to a nearly normal range at 3 years after surgery. In contrast, postoperative measurements of thigh range exceeded normal values at 1 year, but decreased toward normal range at 3 years. While improvements in range of motion continued between Years 1 and 3, the children developed a more extended thigh and knee position, which indicated a more upright walking posture. Stride length and speed of walking also improved, while cadence remained essentially unchanged. This 3-year follow-up study, the first to examine rhizotomy using an objective approach, has provided some encouraging results regarding early functional outcome.

Adolescent↗
PubMed1990

Urinary cytokines following photodynamic therapy for bladder cancer. A preliminary report.

This preliminary study was undertaken to test for the presence of urinary cytokines whose detection would provide evidence in support of the theory that photodynamic therapy (PDT) produces an immunologic response in patients treated for bladder cancer. Gamma interferon, interleukin 1-beta, interleukin 2, and tumor necrosis factor-alpha were assayed for in the urine of 4 patients treated with photodynamic therapy for bladder cancer, in 7 control patients undergoing transurethral surgical procedures, and in 5 healthy control subjects. Quantifiable concentrations of all cytokines, except gamma interferon, were measured in urine samples from the PDT patients with the highest light energies, while no urinary cytokines were found in the PDT patient who received the lowest light energy nor in any of the control subjects. These findings suggest that a local immunologic response may occur following PDT for bladder cancer.

Adult↗
PubMed1990

Eruptive seborrheic keratoses in a young woman with acromegaly.

The sign of Leser-Trélat, or eruptive seborrheic keratoses, is purported to be a cutaneous marker for many underlying malignancies. Elevation in levels of growth factors has been postulated to be the stimulus for the sudden eruption of multiple new seborrheic keratoses. In support of this hypothesis we present a case of eruptive seborrheic keratoses in a young woman with acromegaly and elevated levels of growth hormone.

Acromegaly↗
PubMed1990

Diagnosis of cerebrovascular disease in sickle cell anemia by magnetic resonance angiography.

The study of blood flow by means of magnetic resonance techniques has led to a noninvasive magnetic resonance angiography (MRA) technique for imaging large cerebral vessels. Ten children with sickle cell hemoglobinopathy and a history of acute neurologic syndromes were studied with combined parenchymal magnetic resonance imaging (MRI) and MRA. Six had abnormal MRI findings and MRA-defined luminal lesions in the vascular distribution of these parenchymal infarctions. The three children with previous intraarterial angiography had MRA abnormalities that corresponded with vascular lesions on conventional angiograms. Four had normal MRI and MRA findings. We conclude that a combination of MRI and MRA provides a noninvasive screening test for large-vessel disease in this population.

Anemia, Sickle Cell↗
PubMed1990

Pentoxifylline inhibits the proliferation of human fibroblasts derived from keloid, scleroderma and morphoea skin and their production of collagen, glycosaminoglycans and fibronectin.

Pentoxifylline, an analogue of the methylxanthine theobromine, inhibits the proliferation and certain biosynthetic activities of fibroblasts derived from normal human skin. Fibroblasts from the skin of patients with keloids, scleroderma and morphoea were cultured in vitro in the presence and absence of pentoxifylline (100-1000 micrograms/ml) to determine whether it inhibits fibroblast proliferation and the production of collagen, glycosaminoglycans (GAG), fibronectin and collagenase activity. The exposure of subconfluent fibroblast cultures to pentoxifylline resulted in non-lethal, dose-dependent reductions in serum-driven fibroblast proliferation, with 1000 micrograms/ml pentoxifylline virtually negating the proliferative effect of serum on the cells. The fibroblasts assayed as confluent cultures produced reduced amounts, by up to 95%, of collagen and GAG, dependent on the concentration of pentoxifylline, both in the presence and absence of serum. Pentoxifylline similarly inhibited the fibronectin production by keloid and scleroderma fibroblasts, but had no effect on collagenase activity.

Cell Division↗
PubMed1990

The effect of rhizotomy on movement in patients with cerebral palsy.

Selective posterior lumbar rhizotomy has recently become an alternative method for relieving spasticity in patients with spastic cerebral palsy. This procedure involves the selective sectioning of the lumbosacral posterior nerve rootlets. Because the whole nerve root is not cut, tactile and proprioceptive sensation remain intact. The present study measured the changes that occurred in 29 patients with spastic cerebral palsy 2 days before surgery and from 4 to 14 months after surgery. Each patient was used as his or her own control. In addition to the clinical evaluation of function, gait was analyzed on appropriate patients with a simple digital camera and microcomputer. The results indicated positive gains after rhizotomy. These gains were, however, dependent on the patients' abilities before surgery. The most significant improvement occurred in thigh and knee ranges of movement. This somewhat controversial new method of treating spasticity shows promise in improving the quality of life of patients with spastic cerebral palsy and in facilitating their treatment.

Adolescent↗
PubMed1989

Assessing dermatitis in epidemiologic studies: occupational skin disease among California grape and tomato harvesters.

We conducted a cross-sectional investigation to determine whether table grape harvesters, who have significant cutaneous contact with crop-associated materials that may cause skin disease, are more likely to develop dermatitis than are a control group of tomato workers performing mechanical harvesting with minimal cutaneous contact with crop-associated substances. A secondary aim was to develop methods for studying skin disease in farm workers, including a standard questionnaire and physical examination. California table grape workers (n = 183) and tomato workers (n = 43) completed an interviewer-administered questionnaire and waist-up physical examination at their work site during harvest operations. On physical examination, pustular eruptions such as acne and folliculitis were present in 30% of subjects, and eczematous rashes were noted in 10% of subjects. Irritant or allergic contact dermatitis was diagnosed in 2% of subjects. No significant differences in prevalence for these skin conditions were observed between the two groups of workers. In contrast to the physical examination results, grape workers were more likely than tomato workers to report a rash occurring in the previous 3 months (52% vs. 19%, p less than 0.001). Explanations for this discrepancy are discussed. The sensitivity of the questionnaire for current skin conditions was 31%, and the specificity was 94%. Improved sensitivity was seen for eczematous skin conditions (55%). We conclude that questionnaires provide an efficient means of assessing subject characteristics, but may have limited sensitivity for some dermatologic outcomes.

Agricultural Workers' Diseases↗
PubMed1989

Differential regulation of glycosaminoglycan, fibronectin, and collagenase production in cultured human dermal fibroblasts by interferon-alpha, -beta, and -gamma.

In order to determine whether interferons (IFNs) play a universal role in terminating the fibrotic response by inhibiting other fibroblast functions in addition to growth and collagen production, we investigated the effect of human recombinant (hu-r) IFN-alpha, -beta, and -gamma on the glycosaminoglycan, fibronectin, and collagenase production of cultured human dermal fibroblasts. Our results show that short-term (48 h) treatment of confluent fibroblast cultures with hu-r-IFN-alpha 2 and hu-r-IFN-beta-ser17 causes a concentration (1 to 1 x 10(5) U/ml)-dependent inhibition of glycosaminoglycan production, has no effect on fibronectin production, and markedly increases collagenase production. In contrast, hu-r-IFN-gamma not only causes a concentration-dependent increase in collagenase production but also increases both glycosaminoglycan and fibronectin production. These results demonstrate that IFNs differently regulate fibroblast functions rather than universally inhibit all functions, and show that IFN-alpha and -beta exhibit a broader antifibrotic spectrum that IFN-gamma.

Cells, Cultured↗
PubMed1989

Trypsin inhibitors inhibit induction by interferon-gamma of HLA-DR antigen expression on human skin cells.

Serine protease inhibitors with a specificity for trypsin inhibit interferon-gamma (INF-gamma)-induced HLA-DR expression on a hybrid human epidermal cell line (H12), dermal fibroblasts, and primary keratinocytes. Protease inhibitors with a specificity for chymotrypsin or papain fail to inhibit IFN-gamma. The inhibitory effect of the trypsin inhibitors is similar to that of glucocorticoids in that it is a transient event, fading with length of exposure to IFN-gamma, and is reversed by the addition of dibutyryl cyclic AMP (dbcAMP) and phospholipase C(PLC) from Clostridium perfringens. In H12 cells, dbcAMP and PLC enhance the IFN-gamma induction of HLA-DR, but do not induce in the absence of INF-gamma. Evidence suggests that the protease inhibitors, as well as dbcAMP and PLC, may modulate HLA-DR expression at a post-translational site as well as during IFN-gamma signal transduction. These results suggest that trypsin-like protease activity may be required for cellular HLA-DR antigen expression following exposure to IFN-gamma.

Administration, Topical↗
PubMed1989

Short-term keloid treatment in vivo with human interferon alfa-2b results in a selective and persistent normalization of keloidal fibroblast collagen, glycosaminoglycan, and collagenase production in vitro.

Two intralesional injections of interferon alfa-2b (1.5 million U per injection) into a progressively enlarging keloid resulted in a 41% reduction in its area. Fibroblasts cultured from the keloid before and 9 days after the initial injection were compared with fibroblasts cultured from the patient's normal skin with respect to proliferation and production of connective tissue matrix components and collagenase. There were no significant differences in the in vitro doubling times of keloidal fibroblasts before (p greater than 0.2) and after (p greater than 0.5) treatment with interferon alfa-2b, as well as of normal fibroblasts, in subconfluent cultures. Multiple passages of keloidal fibroblasts before interferon alfa-2b therapy assayed as confluent cultures produced more collagen (171%, 187%, and 204%), more glycosaminoglycans (153% and 141%), and less collagenase (26% and 31%) than the patient's own normal fibroblasts. In contrast, keloidal fibroblasts after interferon alfa-2b therapy persistently produced normal or subnormal amounts of collagen (107%, 73%, and 64%) and glycosaminoglycans (97% and 96%) and normalized levels of collagenase activity (96% and 86%). Normal amounts of fibronectin were produced by keloidal fibroblasts before and after treatment with interferon alfa-2b.

Cell Division↗
PubMed1989

Differential regulation of collagen, glycosaminoglycan, fibronectin, and collagenase activity production in cultured human adult dermal fibroblasts by interleukin 1-alpha and beta and tumor necrosis factor-alpha and beta.

In order to clarify the role played by immunologically derived cytokines in dermal connective tissue synthesis and degradation, we investigated the effect of human recombinant (hu-r) interleukin (IL) 1-alpha and beta, hu-r tumor necrosis factor (TNF)-alpha and beta, hu-r IL 2, and hu-r granulocyte-macrophage colony-stimulating factor (GM-CSF) on the production of collagen, glycosaminoglycan, fibronectin, and collagenase activity by three lines of cultured human adult dermal fibroblasts. Our results show that 24-72 h treatment of confluent fibroblast cultures with IL 1-alpha or beta or TNF-alpha or beta causes concentration (1 to 1 X 10(4) U/ml) dependent increases in collagen, glycosaminoglycan, and collagenase activity production, but decreases in fibronectin production. In contrast, treatment with IL 2 and GM-CSF had no effect on fibroblast functions. The data show that IL 1-alpha and beta and TNF-alpha and beta differentially regulate fibroblast functions, and that increases in catabolic functions like collagenase activity production are more than tenfold greater than increases in anabolic functions like collagen production. When these results are considered along with other reports, they suggest that IL 1 and TNF may play predominately a catabolic role in situ during dermal fibrotic responses by directly inhibiting fibronectin production and indirectly causing the degradation of collagen and glycosaminoglycan by significantly increasing dermal fibroblast elaboration of collagenase and proteoglycanase activities.

Adult↗
PubMed1989

Pentoxifylline inhibits normal human dermal fibroblast in vitro proliferation, collagen, glycosaminoglycan, and fibronectin production, and increases collagenase activity.

Fibroblasts from normal human adult skin were cultured in vitro in the presence and absence of different concentrations of pentoxifylline or a pentoxifylline analog, A81-3138 (10(-1)-10(3) micrograms/ml). Similar concentration dependent reductions in normal proliferation of fibroblasts in fetal calf serum-driven subconfluent cultures were detected following treatment with pentoxifylline or A81-3138. Fibroblasts assayed as confluent cultures produced sub-normal amounts of collagen, glycosaminoglycans (GAGs), and fibronectin in a fashion dependent upon the concentration of pentoxifylline. In contrast, fibroblasts exposed to pentoxifylline elaborated double the collagenase activity produced by normal, untreated fibroblasts. The reduced proliferation and reduced synthetic activities were not due to a lethal toxic effect on fibroblasts by pentoxifylline and A81-3138, nor was the reduction in collagen synthesis simply due to an inability to secrete newly synthesized intracellular collagen. Unlike pentoxifylline-induced inhibition of collagen and fibronectin production, which was detected only in cultures supplemented with serum, pentoxifylline inhibits, to a similar degree, both constitutive and serum-driven production of GAGs. The addition of IL1 beta (2.5 and 10.0 U/ml) to serum-driven fibroblast cultures resulted in greater proliferation, which was inhibitable by the presence of pentoxifylline and A81-3138 as anti-fibrotic agents in certain disorders of fibrosis.

Cell Division↗