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Biomedical subjects

G Kaplan

Publications and source records attributed to G Kaplan.

At least 19 recordsLinked to original sources
PubMed1992

Novel responses of human skin to intradermal recombinant granulocyte/macrophage-colony-stimulating factor: Langerhans cell recruitment, keratinocyte growth, and enhanced wound healing.

Recombinant granulocyte/macrophage-colony-stimulating factor (rGM-CSF), prepared from Chinese hamster ovary (CHO) cells and Escherichia coli, was administered to 35 patients with the borderline and polar lepromatous forms of leprosy by the intradermal and subcutaneous routes at doses of 7.5-45.0 micrograms/d for 10 d. With each of these doses and routes, increases in the number of circulating eosinophils were noted. After the intradermal injection, the local skin sites demonstrated zones of roughening and micronodularity that appeared within 24-48 h and persisted for more than 6 d. Reinjection of sites led to enhanced areas of epidermal reaction. GM-CSF prepared from CHO cells was a more potent inducer of this effect. GM-CSF given by the subcutaneous route, at higher doses, failed to initiate these changes. At the microscopic level, the epidermis became thickened (+75%) with increased numbers and layers of enlarged keratinocytes. These contained increased numbers of ribosomes and prominent nucleoli, and were imbedded in a looser meshwork of the zona Pellucida. The modified keratinocytes remained MHC class II antigen negative throughout the course of the response. A major change in the dermis was the progressive accumulation of CD1+, Birbeck granule-positive cells. These Langerhans were recognizable at 48 h after intradermal injection and reached maximum numbers by 4 d. During this period the number of epidermal Langerhans cells remained relatively constant. No increment in dermal Langerhans cells occurred when GLM-CSF was injected by the subcutaneous route. No appreciable increase in the numbers of T cells and monocytes was noted, and granulocytes and eosinophils were largely present within the dermal microvasculature. 4-mm punch biopsies taken from injected sites and adjacent controls were compared in terms of the rapidity of wound healing. 22 of 26 sites demonstrated more rapid filling and hemostasis, whereas four were equivalent to controls. We conclude that rGM-CSF, when introduced into the skin, leads to enhanced keratinocyte growth, the selective recruitment of Langerhans cells into the dermis, and enhanced wound healing of the prepared site. There was no evidence of an enhanced cell-mediated response to Mycobacterium leprae, and bacillary numbers remained unchanged.

Adolescent↗
PubMed1992

Prolonged treatment with recombinant interferon gamma induces erythema nodosum leprosum in lepromatous leprosy patients.

10 patients with borderline and lepromatous leprosy were selected for a prolonged trial with recombinant interferon gamma (rIFN-gamma). Patients received 30 micrograms intradermally for six injections over a 9-d period, and then either 100 micrograms intradermally every 1 mo for 10 mo or every 2 wk for 5 mo (total, 1.2 mg). Erythema nodosum leprosum (ENL) was induced in 60% of the patients within 6-7 mo, as compared with an incidence of 15% per year with multiple drug therapy alone. The mean whole-body reduction in bacterial index over the first 6 mo was 0.9 log units. Cutaneous induration at the intradermal injection sites of greater than or equal to 15 mm predicted the development of a subsequent reactional state. Monocytes obtained from patients receiving the lymphokine demonstrated an increased respiratory burst and a 2.5-5.1-fold increase in tumor necrosis factor alpha (TNF-alpha) secretion in response to agonists. Patients in ENL had an even higher release of TNF-alpha from monocytes as well as high levels of TNF-alpha in the plasma (mean, 2,000 pg/ml). Thalidomide therapy was required to treat the systemic manifestations of ENL. Control of toxic symptoms with thalidomide was associated with a 50-80% reduction in agonist-stimulated monocyte TNF-alpha secretion. IFN-gamma enhanced the monocyte release of TNF-alpha by 3-7.5-fold (agonist dependent) when added to patient's cells in vitro, and this could be suppressed by the in vitro addition of 10 micrograms/ml of thalidomide.

Erythema Nodosum↗
PubMed1992

Case report 728: Desmoplastic fibroma.

A 69-year-old woman with a 25-year history of recurrent sciatica presented with an expanding lytic lesion of the right side of the first sacral vertebra. Histological examination proved the lesion to be a DF. DF is usually diagnosed in young patients and is very rarely located in the spine and sacrum. The growth rate of the tumor was presumed to be very low because it had not progressed from radiological studies performed 9 years previously. The clinical, radiological, and pathological features of DF are described, and the differential diagnoses are discussed. The most difficult problem is to distinguish DF from a low-grade fibrosarcoma or chordoma.

Aged↗
PubMed1992

Rational immunotherapy with interleukin 2.

Interleukin 2 (IL-2), a T lymphocyte product released upon antigen stimulation, has been used for cancer therapy in high doses for more than five years. More recently, its potential as a stimulant of cell-mediated immunity in infectious diseases, particularly those caused by intracellular microbes, has become appreciated. Drawing on the extensive information available as to the structure, cellular and molecular effects of IL-2, this review focuses on its use in patients with lepromatous leprosy and AIDS in low, physiologic doses. The data indicate that IL-2 is effective in stimulating cell-mediated immunity without systemic toxicity.

Humans↗
PubMed1992

Cystic fibrosis genotyping by direct PCR analysis of Guthrie blood spots.

In the United States the most common cystic fibrosis (CF) alleles known are F508, G551D, G542X, R553X, and N1303K. These mutations comprise approximately 85% of U.S. CF alleles, and their detection along with analysis of XV-2C and KM-19 restriction fragment length polymorphisms (RFLPs) can enable the determination of CF status. To facilitate studies for determining CF carrier status, we developed methods to detect each of these mutations and RFLPs by direct PCR amplification of dried blood spots collected on newborn screening (Guthrie) cards. Following collection, samples were protected from contamination by individual plastic bags. One-mm2 segments of filter paper were added directly to 100-microliters PCR reactions containing 1/16 mM spermidine. Three initial cycles at 96 degrees C, then 55 degrees C, for 3 min were performed to free DNA and minimize inhibition by other related materials. Next, 1 unit of Taq polymerase was added and a 2-min extension was carried out at 72 degrees C, followed by 33 amplification cycles using denaturing, annealing, and extension temperatures and times optimal for each primer set. Then, 35 microliters of each reaction was run on 8% acrylamide gels directly or 1% agarose gels following digestion; genotypes were inferred by ethidium bromide staining of gels. Guthrie blood spots of 250 CF probands and their parents were screened and the frequencies of all five mutations as well as the XV-2C KM-19 RFLP haplotypes were determined.(ABSTRACT TRUNCATED AT 250 WORDS)

Alleles↗
PubMed1992

Effect of cutaneous cell-mediated immune response to rIFN gamma on Mycobacterium leprae viability in the lesions of lepromatous leprosy.

1. Studies were carried out to determine the effect of intra-dermal injections of recombinant human interferon-gamma (rIFN gamma) on the viability of Mycobacterium leprae. Twenty-three untreated and 4 treated multibacillary patients, 12 with lepromatous leprosy (LL) and 15 with borderline lepromatous leprosy (BL), were selected for intradermal administration of rIFN gamma or PPD. Treated patients (LL and BL) had received multi-drug therapy according to the recommendations of the World Health Organization, i.e., rifampicin (600 mg/month), dapsone (100 mg/day) and clofazimine (50 mg/day and 300 mg/month) for 1-4 months. Three daily doses of 10 or 30 micrograms rIFN gamma induced local induration and mononuclear leucocyte accumulation. Bacteria isolated from a punch biopsy of the site 21 days after lymphokine administration were injected into mouse foot pads and evaluated for viability and growth. 2. The local response to rIFN gamma (specific activity 2 x 10(7) units/mg protein) induced a delay or total inhibition of M. leprae growth in the mouse foot pad, indicating that the cellular response to the antigen reduced local M. leprae viability. The extent of reduction in viability depended on the dose of rIFN gamma injected and the extent of local induration induced by the lymphokine. With a vigorous cell-mediated immune response growth was fully inhibited. 3. A similar but less extensive effect on M. leprae viability was observed in response to the local injection of 5 units in 0.1 ml of purified protein derivative of tuberculin (PPD).

Animals↗
PubMed1992

Utility of internal markers to improve the accuracy of cystic fibrosis genotype analysis.

DNA diagnostic tests often utilize restriction endonuclease digestion of PCR-amplified portions of genes under analysis. When partial digestion occurs, the resulting patterns may lead to error in diagnosis. To overcome such potential errors in cystic fibrosis testing, we have developed internal markers that can increase the precision and reliability of genotype assignments.

Cystic Fibrosis↗
PubMed1991

[Magnetic resonance imaging of fluorosis and stress fractures due to fluoride].

Osteocondensation of the spine and stress fractures of the appendicular bones are observed under treatment with sodium fluoride or after long-term drinking of Vichy Saint-Yorre spring water. Five patients with a mean total dose of fluoride intake of 24.7 g (9-66) were studied with MR imaging. Two of them had a diffuse osteocondensation; MRI showed a low signal intensity in the vertebrae on T1 and T2-weighted images. MRI was performed in an asymptomatic patient who was being treated with sodium fluoride for 16 months; it revealed a heterogenous low signal intensity in the pelvis and femoral metaphysis. Two patients experienced stress fractures; MRI demonstrated a linear area of very low signal intensity surrounded by an area of decreased signal intensity on T1-weighted images and high signal intensity on T2-weighted images. MRI of fluorosis shows a non specific low signal intensity linked to a densifying image on the standard radiograph or an area of high technetium-99m intake on bone scan.

Aged↗
PubMed1991

The systemic influence of recombinant interleukin 2 on the manifestations of lepromatous leprosy.

14 patients with lepromatous leprosy received twice daily injections of 10 micrograms recombinant interleukin 2 (rIL-2), by the intradermal route, in the skin of the back for 8 d (total dose, 160 micrograms). Lymphokine administration was accomplished without drug toxicity, or the development of acute nerve damage. The majority of patients developed nontender axillary lymphadenopathy during the course of treatment. Local injection sites showed progressively larger zones of induration, peaking at 24 h and persisting for many days. Early 12-h reactions were of a macular, erythematous nature and exhibited an increasingly striking diurnal variation. The morning injection sites were three- to fourfold larger in diameter than those placed in the evening (9 am to 9 pm). Systemic manifestations of intradermal rIL-2 administration were noted. Peripheral blood T cells, including CD4+ and CD8+ phenotypes, increased 2-2.5-fold and NK cells increased sixfold. Elevations in [3H]TdR incorporation into peripheral blood mononuclear cells occurred to a variety of mycobacterial antigens, but not to those of Mycobacterium leprae. Within 2 wk, biopsies at sites far removed from the back showed increased infiltration of mononuclear cells in 12 of 14 patients. Immunocytochemistry revealed the presence of newly emigrated CD4+ T cells, monocytes, and dermal CD1+ Langerhans cells. Endothelial cells of small dermal vessels expressed major histocompatibility complex class II determinants on their surface. Transmission electron microscopy of these specimens revealed markedly enlarged endothelial cells with many surface projections extending into the lumen as well as extravasating lymphoid cells. The numbers of acid-fast M. leprae in the peripheral sites were examined by slit smear and in biopsies of matched leprosy lesions taken before and after IL-2 administration. Within 2 mo, slit smears showed a 0.5 log or greater reduction in 12 of 14 patients, with a mean for all patients tested of 0.5 log units. Biopsy specimens showed a 1 log unit or greater reduction in the bacterial index (B.I.) in 6 of 14 patients. Historical controls in this Nepalese population showed a 0.5 log unit reduction after multidrug therapy over a period of 12 mo. Thus, after 8 d of IL-2 injections, a fivefold reduction in B.I. was observed during the first 2 mo of the study. Antibody levels against M. leprae phenolic glycolipid 1 (PGL-1) and lipoarabinomanan B were markedly elevated after IL-2 injections, while PGL-1 antigen levels were reduced. We conclude that the administration of rIL-2 has had a significant effect in decreasing the total body burden of M. leprae.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1991

Thalidomide selectively inhibits tumor necrosis factor alpha production by stimulated human monocytes.

Thalidomide selectively inhibits the production of human monocyte tumor necrosis factor alpha (TNF-alpha) when these cells are triggered with lipopolysaccharide and other agonists in culture. 40% inhibition occurs at the clinically achievable dose of the drug of 1 micrograms/ml. In contrast, the amount of total protein and individual proteins labeled with [35S]methionine and expressed on SDS-PAGE are not influenced. The amounts of interleukin 1 beta (IL-1 beta), IL-6, and granulocyte/macrophage colony-stimulating factor produced by monocytes remain unaltered. The selectivity of this drug may be useful in determining the role of TNF-alpha in vivo and modulating its toxic effects in a clinical setting.

Blood Proteins↗
PubMed1991

A growing spectrum of surgical disease in patients with human immunodeficiency virus/acquired immunodeficiency syndrome. Experience with 120 major cases.

One hundred twenty major general surgical procedures were performed on 88 adult patients harboring the human immunodeficiency virus. Fifty-eight (48%) of the procedures were performed on patients who fulfilled the criteria for acquired immunodeficiency syndrome. The patients were predominantly male (94%). Single risk factors included homosexuality (73% of cases), intravenous drug abuse (8%), and previous blood transfusions (8%). Four patients (5%) had multiple risk factors; risk factors were denied by seven patients (8%). The mean age at surgery was 41.6 years (range, 22 to 67 years). Surgical conditions that rarely affect the population without the human immunodeficiency virus presented diagnostic challenges. Altered physiologic responses to even routine conditions were observed. Thirty-day morbidity rates for emergency (group A) and elective (group B) procedures were 19% and 9%, respectively. This included seven surgical deaths (13%) in group A and one in group B (2%). Patients undergoing 92 of 112 procedures (82%) not associated with surgical mortality were followed up. Patients who were dead at follow-up had mean procedure-survivals of 19 weeks (group A) and 21 weeks (group B) for 33 procedures. Those who remained alive had a mean procedure-survival of 86 weeks for 59 procedures. No single prognosticator could be correlated with outcome, although the combination of hypoalbuminemia with a history of opportunistic infection(s) was associated with short survival. Emergency and elective procedures can be performed in the patient with human immunodeficiency virus/acquired immunodeficiency syndrome with acceptable morbidity and mortality. Procedures are indicated to extend patient life or to improve quality of life.

Acquired Immunodeficiency Syndrome↗