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Biomedical subjects

B Berman

Publications and source records attributed to B Berman.

At least 109 records · Page 6Linked to original sources

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↗

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↗

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↗

Changing physician test ordering in a university hospital. An intervention of physician participation, explicit criteria, and feedback.

To decrease inappropriate test ordering by medical house staff in a university hospital, we examined the feasibility of an intervention that involved physicians in developing explicit criteria for ordering four specific tests and incorporated feedback of tests ordered. We implemented a time series design with measures at 12 and six months before, during, and three weeks after the intervention. During the intervention, orders for initial or admission chest roentgenograms decreased by 22% and repeated orders for routine urinalyses, chest roentgenograms, and leukocyte differential counts decreased by 23%, 30%, and 46%, respectively, compared with the six-month preintervention period. Orders for prothrombin time and/or partial thromboplastin time did not fall. After the intervention, most test ordering remained at the intervention level. These preliminary results suggest that this intervention may be effective and not overly costly.

Blood Coagulation Tests↗

Halo giant congenital melanocytic nevus: in vitro immunologic studies.

We have assessed in vitro humoral and cell-mediated immune reactions of a patient with a giant congenital melanocytic nevus that showed clinical and histologic evidence of spontaneous regression. Nevus cell-specific antibody was detected in the patient's serum, which was cytotoxic to epidermal cells isolated from the pigmented nevus and specifically to cells of a human melanoma line in a complement-dependent fashion. The presence of epidermal Langerhans cells, known to be antigen-presenting cells, was required for nevus cell-specific activation of the patient's T lymphocytes. Antibody-independent inhibition of melanoma cell growth was detected by the use of the patient's mononuclear cells. Therefore both humoral and cell-mediated immunity may be involved in nevus cell rejection and halo formation.

Child↗

Gait analysis of cerebral palsy children before and after rhizotomy.

Over the past decade, selective posterior rhizotomy has been used successfully to reduce spasticity in patients with cerebral palsy. Although clinical evaluation of these patients revealed functional improvement following surgery, more objective analysis of the outcome of this surgery was sought. Kinematic gait analysis of 14 patients with spastic cerebral palsy was performed before and after selective posterior rhizotomy. Measurements of stride length, thigh range of motion, knee range of motion, average speed of walking, and cadence were made. Statistically significant increases in stride length, thigh range and knee range were found. Average speed was increased and cadence was virtually unchanged. These results corroborate clinical findings of improvement in gait of spastic patients with cerebral palsy following selective posterior rhizotomy.

Adolescent↗

Fatal pancreatitis presenting with subcutaneous fat necrosis. Evidence that lipase and amylase alone do not induce lipocyte necrosis.

We report a case of fatal pancreatitis heralded by the presence of cutaneous panniculitis without abdominal pain or other stigmata of the disease. Although cutaneous fat necrosis has been associated with pancreatitis, it is unusual as the presenting complaint of this relatively common disease. In vitro evidence suggests that human pancreatic amylase or lipase alone is not responsible for the observed panniculitis.

Acute Disease↗

Epidermal Langerhans cell density in patients with pulmonary malignancies and chronic obstructive pulmonary disease.

To evaluate the relationship between ELC density and pulmonary malignancies, as reported in previous investigations, we examined the nonsun-exposed epidermis of 18 patients with pulmonary cancer (CA) not receiving immunosuppressive therapy, 20 patients with chronic obstructive pulmonary disease (COPD-S), and 10 patients with COPD receiving glucocorticosteroid (GCS) therapy (COPD + S). The ELC density was not significantly different between lung tumor patients (1024 +/- 167) and COPD-S (1072 +/- 200, p less than 0.4) control patients, and we found no significant correlation between ELC density and tumor cell type, presence or absence of metastases, tumor stage, or present smoking status. Although we did detect that systemic GCS therapy significantly reduced the ELC density in COPD + S patients (910 +/- 211, p less than 0.05); use of inhaled or chronic low dose (less than or equal to 20 mg daily) GCS did not appear to significantly alter ELC density. In addition, anergy to epicutaneous dinitrochlorobenzene in CA and COPD + S patients positively correlated with a reduction in ELC density, suggesting a possible functional deficit arising from the numerical change. Further investigation is needed to elucidate whether factor(s) other than a reduction in ELC density are involved in the anergic state.

Adult↗

Cerebral palsy spasticity. Selective posterior rhizotomy.

We have performed selective posterior rhizotomies on 60 children with cerebral palsy. The procedure involves lumbar laminectomy with stimulation of the rootlets (fascicles) of the second lumbar to the first sacral posterior roots bilaterally; those rootlets associated with an abnormal motor response, as evidenced by sustained or diffused muscular contraction, are divided leaving intact rootlets associated with a brief localized contraction. The patients were between 20 months and 19 years of age representing all degrees of physical handicap and ranging from profoundly retarded to normal intelligence. Follow-up has been from 1 to 5 years. Each child was assessed pre- and postoperatively and graded in the following categories: muscle tone, power, sitting, standing, walking, upper limb function, and speech. The patients whose function improved most dramatically following rhizotomy were purely spastic and intelligent, were significantly more affected by spasticity in the lower than the upper limbs, had some degree of forward locomotion, and could side-sit independently. Patients with severe athetosis or marked contractures improved least.

Adolescent↗

Persistence of a reduced-collagen-producing phenotype in cultured scleroderma fibroblasts after short-term exposure to interferons.

Transient exposure to inflammation-associated, fibroblast-stimulatory factors appears to initiate fibrosis by inducing the persistently activated phenotypes displayed by fibroblast cultures derived from scleroderma skin and other fibrotic tissues. To determine whether one class of fibroblast-inhibitory factors, the interferons (IFNs), plays a role in terminating fibrosis by acting as persistent fibroblast deactivators, we inhibited (40-60%) the growth and collagen production of normal dermal fibroblasts and hypercollagen-producing scleroderma fibroblasts by short-term exposure to IFN-alpha, beta, or gamma. During subsequent subculture in the absence of IFNs, the growth and collagen production of normal fibroblasts and the growth of scleroderma fibroblasts increased to untreated control levels after two to three passages. In contrast, collagen production by scleroderma fibroblasts remained inhibited for at least five passages (18 cell doublings) and was not further suppressed by subsequent IFN exposure. These data suggest that IFNs may help terminate fibrosis by suppressing persistently activated fibroblast functions.

Cell Division↗

Establishment of a clinical teaching associates breast examination program for medical students.

A program was designed to instruct medical students on how to obtain a history pertinent to breast abnormalities and to perform a breast examination. The use of clinical teaching associates provides direct student instruction and critiques during the examination. In addition, students are taught how to instruct patients in the breast self-examination and to properly document breast abnormalities. Such a program should be considered for incorporation in all physical diagnosis courses as well as in residency training programs and seminars for practicing physicians.

Breast↗

Intralesional recombinant alpha-2 interferon for the treatment of patients with condyloma acuminatum or verruca plantaris.

We conducted a multicenter double-blind study comparing human recombinant intralesional alpha-2 interferon (IFN) and placebo in 237 patients with the clinical diagnosis of condyloma acuminatum or verruca plantaris. A single wart on each patient was injected with 0.1 mL containing 10(6) IU of IFN, 10(5) IU of IFN, or placebo three times weekly for three weeks, and the response to treatment was followed up for 12 weeks. Among 91 of the 114 patients with condyloma acuminatum who completed the study, complete clearing of the treated wart occurred in 16 (53%) of 30 patients receiving 10(6) IU of IFN compared with six (19%) of 32 receiving 10(5) IU of IFN and four (14%) of 29 receiving placebo. In the group of 100 patients with plantar warts, there was no apparent benefit associated with interferon administration. Seven patients (3%) had treatment discontinued due to adverse reactions. Intralesional alpha-2 IFN is of benefit in the treatment of a single condyloma; its role in the treatment of multiple lesions remains to be clarified. Its role in the treatment of verruca plantaris, where no response was seen, also remains to be clarified.

Adult↗

Gamma interferon is the lymphokine and beta interferon the monokine responsible for inhibition of fibroblast collagen production and late but not early fibroblast proliferation.

Human peripheral blood mononuclear cells activated with concanavalin A (Con A) or lipopolysaccharide (LPS) produce, respectively, lymphokines (LK) of 50,000 Mr or monokines (MK) of 20,000 Mr that inhibit the growth and collagen production of cultured human dermal fibroblasts. Because antigenic typing of the antiviral activity of these LK and MK preparations revealed that LK contained mainly gamma interferon (IFN-gamma), and MK, primarily IFN-beta, we investigated if any of the fibroblast-inhibiting activities could be attributed to human IFN. Unlike LK and MK, which act within 24 h to inhibit the growth of subconfluent foreskin and adult dermal fibroblasts, samples of purified, natural derived IFN-alpha, -beta, and -gamma and recombinant DNA-derived IFN-alpha 2 and -gamma were ineffective inhibitors at 24 h and required 48-72 h to significantly inhibit growth. However, all IFN did mimic LK/MK action in causing concentration-dependent inhibition of collagen production by confluent fibroblast microcultures. Furthermore, the collagen production-inhibiting activity of Con A-induced LK supernatant and its 50,000 Mr fraction was completely suppressed by 10(3) neutralizing U/ml of either polyclonal or monoclonal antibody to IFN-gamma, while polyclonal antibodies to IFN-alpha and -beta had no effect. Similarly, the collagen production-inhibiting activity of LPS-induced MK supernatant and its 20,000 Mr fraction was suppressed by polyclonal anti-IFN-beta but not by anti-IFN-alpha or -gamma. Anti-IFN failed to reverse early-acting LK or MK growth-inhibiting activities. These data suggest collagen production-inhibiting LK and MK are IFN-gamma and IFN-beta, respectively, and that early acting, growth-inhibiting LK and MK are not IFN.

Cell Division↗