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Biomedical subjects

S Mandelbaum

Publications and source records attributed to S Mandelbaum.

At least 19 recordsLinked to original sources
PubMed2003

Improved therapeutic outcome following combination immunogene vaccination therapy in murine myeloma.

Increasing evidence suggests a role for immunologic vaccination and therapy in the management of minimal residual myeloma. We have previously demonstrated a synergistic effect of combining the Th1 stimulating cytokine IL-12 with the co-stimulatory molecule CD80 in murine myeloma vaccination therapy. We reasoned that the efficacy of such treatment might be further improved by incorporating additional gene products which enhance the function of antigen presenting cells. Studies were therefore conducted with murine myeloma BM1 cells expressing Flt3L (membrane bound or soluble forms) or GM-CSF and the IL-12 x CD80 combination. Single agent and combined therapeutic approaches were explored. All gene-modified BM1 cells, except BM1/IL-12 x CD80, developed tumors when subcutaneously injected into BALB/c mice. As prophylactic tumor vaccines, the combined use of gene-modified BM1/sFlt3L+GM-CSF+IL-12 x CD80 was most effective, providing 100% protection against subsequent parental BM1 tumor challenge. By comparison, only partial protection was observed with any single gene-engineered tumor vaccine. Notably, IL-12 x CD80 coexpressing BM1 cell vaccines were the most effective therapeutic vaccine in a minimal disease model. Such protective vaccination was achieved by stimulation of lymphocyte proliferation and enhancement of cytotoxic lymphocyte activity.

Adjuvants, Immunologic↗
PubMed2001

Tricistronic viral vectors co-expressing interleukin-12 (1L-12) and CD80 (B7-1) for the immunotherapy of cancer: preclinical studies in myeloma.

Synergy between interleukin-12 (IL-12) and B7-1 (CD80) for cancer immunotherapy has previously been demonstrated in animal models of breast cancer, lymphoma, and multiple myeloma. With a view to human clinical application, tricistronic retroviral and adenovirus vectors co-expressing IL-12 (IL-12p40 plus IL-12p35) and CD80 were constructed by utilizing two internal ribosome entry site (IRES) sequences to link the three cDNAs. A murine stem cell virus (MSCV)-based retroviral vector (MSCV-hIL12.B7) utilized distinct IRES sequences from the encephalomyocarditis virus (EMCV) and the foot-and-mouth disease virus (FMCV), whereas Ad5-based adenovirus vectors contained transcriptional units with two EMCV IRES sequences under the control of murine (AdMh12.B7) or human (AdHh12.B7) cytomegalovirus promoters. AdMh12.B7 was found to consistently direct higher levels of IL-12 and CD80 expression than AdHh12.B7 following infection of a number of human tumor cell lines. In preclinical studies, the human myeloma cell line U266 was infected with MSCV-hIL12.B7 and a resulting clonal cell line, U/MSCV-h12.B7, was generated with stable expression of CD80 and secreting IL-12 at 1 ng/24 h/10(6) cells. By comparison, following AdMh12.B7 infection, 81% of infected U266 cells (U/AdMh12.B7) expressed CD80 and secreted IL-12 at 25-50 ng/24 h/10(6) cells. Both engineered myeloma cell lines stimulated enhanced allogeneic mixed lymphocyte proliferation and provoked increases in cytotoxic T-lymphocyte responses and gamma-interferon release from normal donor lymphocytes exposed to parental U266 cells. These results suggest potential clinical utility of AdMh12.B7 in immunotherapy strategies for the treatment of multiple myeloma and other cancers.

Adenoviridae↗
PubMed1997

Treatment of experimental methicillin-resistant Staphylococcus epidermidis endophthalmitis with intravitreal vancomycin and intravitreal dexamethasone.

The use of intravitreal steroids to treat bacterial endophthalmitis remains controversial. The efficacy of intravitreal vancomycin alone (group 1), intravitreal dexamethasone alone (group 2), and a combination of intravitreal vancomycin and dexamethasone (group 3) in the treatment of experimental methicillin-resistant Staphylococcus epidermidis endophthalmitis was evaluated in a rabbit model: 24 h after bacterial inoculation of all eyes, right eyes were treated and left eyes served as infected controls. Vitreal aspirations and grading of vitreal inflammatory reaction were done regularly until sacrifice. Group 2 eyes demonstrated more inflammation histologically than control eyes. Vitreal aspirations demonstrated no growth by 5 days from groups 1 and 3 eyes. Although the clinical appearance was not significantly different between groups 1 and 3, the histologic appearance of group 3 eyes showed less intense intraocular inflammation. Treatment with dexamethasone in the absence of appropriate antibiotics was more harmful than no treatment at all (P < .05). Therapy with both intravitreal vancomycin and dexamethasone results in less inflammation than intravitreal vancomycin alone in this model.

Animals↗
PubMed1994

Biochemical effects of folate-based inhibitors of thymidylate synthase in MGH-U1 cells.

The TS-inhibitory effects induced by a 24-h exposure to the folate-based TS inhibitors CB3717, C2-desamino analogs of CB3717 including D1694, and BW1843U89 were quantitated using the MGH-U1 human bladder carcinoma. The effects of D1694 on the time course of TS inhibition and on intracellular deoxyuridine monophosphate (dUMP) accumulation and deoxyuridine (dUrd) production were evaluated. D1694 and BW1843U89 were the most active TS inhibitors with IC50 values of 2.4 and 0.5 nM, respectively. The C2-desamino C2-methyl dideazafolates were 27-292 times more potent than the parent CB3717 as TS inhibitors. A methyl group at the C2 position of CB3717 had the most dramatic effect, whereas a thiazole substitution for a benzyl added a small benefit and N10 substitution had a limited impact on TS-inhibitory potency and clonogenic survival. There was a significant correlation between the IC50 values for TS inhibition and those for cytotoxic potency obtained for these drugs. LV and thymidine protected cells from these folate-based TS inhibitors. Intracellular dUMP levels following 24 h D1694 (IC50) exposure increased 7-fold. Levels of dUrd effluxing into the media increased up to 4.5 microM following a 24-h exposure to D1694 (IC90). We conclude that (a) C2-desamino C2-methyl dideazafolates are potent TS inhibitors, (b) TS inhibition requires prolonged exposure with these folate TS inhibitors, (c) survival is correlated with inhibition of TS for the folate-based TS inhibitors and (d) the biochemical consequences of TS inhibition include increased dUMP and dUrd levels.

Cell Survival↗
PubMed1992

Photogrammetric analysis of corneal trephination.

We used a high-magnification shadow photogrammetric system to evaluate corneal buttons trephined from human donor globes. Whole eyes were trephined with one of five instruments: nonguarded blades held by hand or placed on a handle, Barraquer-Mateus motorized trephine, Hessberg-Barron suction trephine, or Hanna microkeratotrephine. Corneoscleral buttons were punched with one of three punches: Cottingham, Katena Lieberman guillotine, or a modified Lieberman guillotine with an increased impact force (BPEI 2). The precision (how closely buttons approximated the trephine diameter), accuracy (repeatability), acircularity (deviation from roundness), and straightness (verticality of edges) of cut were calculated from the diameter and edge profile angle measurements of buttons cut by the different instruments. These results were statistically compared. The Hanna microkeratotrephine instrument had the greatest precision and accuracy, least acircularity, and straightest edges. Of the corneal punches evaluated, the Cottingham instrument had the greatest precision; however, the BPEI 2 punch cut with the greatest accuracy and the straightest edges.

Cornea↗
PubMed1990

Potential bacterial contamination in fluorescein-anesthetic solutions.

To determine the ability of fluorescein-anesthetic combination solutions and their applicators to regain sterility, we contaminated four commercially available fluorescein-anesthetic solutions and their dropper tips with inocula of either Pseudomonas species or Staphylococcus species. No organisms could be cultured from Fluress one minute after inoculation of the solution or five minutes after inoculation of the dropper tip. In contrast, organisms were cultured from the other fluorescein-anesthetic preparations for at least one hour after bacterial inoculation into the solution or onto the dropper tip. These differences in the ability of fluorescein-anesthetic solutions to regain sterility after bacterial contamination were statistically significant.

Anesthetics↗
PubMed1990

Granular epithelial keratopathy as an unusual manifestation of Pseudomonas keratitis associated with extended-wear soft contact lenses.

We describe four patients who, using extended-wear soft contact lenses for myopia, abruptly developed ocular irritation and injection associated with elevated granular opacities initially confined to the central corneal epithelium. Cultures of the granular epithelial lesions were positive for Pseudomonas aeruginosa in all patients. Cultures of the contact lenses and lens case solutions grew Pseudomonas species and other gram-negative organisms. All patients responded to discontinuation of lens wear and frequent topical antibiotics. All recovered baseline visual acuity, and three have successfully resumed contact lens wear. These cases document that Pseudomonas keratitis may be manifested as a granular epithelial keratopathy.

Adult↗
PubMed1989

Propionibacterium-associated endophthalmitis after extracapsular cataract extraction. Review of reported cases.

Sixteen cases of previously reported culture-proven Propionibacterium-associated endophthalmitis after extracapsular cataract extraction (ECCE) are reviewed. The inflammation was observed 2 to 10 months after surgery and occurred after laser posterior capsulotomy in four cases. Clinically, it appeared as a chronic iridocyclitis characterized by granulomatous-appearing keratic precipitates (5 cases), hypopyon (10 cases), and a white plaque on the posterior capsule or intraocular lens (IOL) implant (8 cases). Response to corticosteroid treatment was transient. Surgical intervention was required between 1 and 16 months after the inflammation began and included removal of the IOL and capsular bag via the limbus in 7 cases and pars plana vitrectomy in 11. Intravitreal antibiotics were administered in 12 cases. Postoperative visual acuity ranged from 20/20 to count fingers, with 11 of 16 patients recovering visual acuity of 20/40 or better. Propionibacterium-associated endophthalmitis should be suspected if chronic indolent intraocular inflammation develops after ECCE. Intraocular specimens should be obtained and submitted for aerobic and anaerobic culture and cytologic/histopathologic studies. Based on the clinical courses of these patients, recommendations for management are discussed.

Bacterial Infections↗
PubMed1989

Shadow photogrammetric apparatus for the quantitative evaluation of corneal buttons.

We have developed a technique for the accurate, quantitative, geometric evaluation of trephined and punched corneal buttons. A magnified shadow of the frontal and edge views of a corneal button mounted on the rotary stage of a modified optical comparator is projected onto the screen of the comparator and photographed. This process takes approximately three minutes. The diameters and edge profile at any meridian photographed can subsequently be analyzed from the film. The precision in measuring the diameters of well cut corneal buttons is +/- 23 microns, and in measuring the angle of the edge profile is +/- 1 degree. Statistical analysis of inter observer variability indicated excellent reproducibility of measurements. Shadow photogrammetry offers a standardized, accurate, and reproducible method for analysis of corneal trephination.

Calibration↗
PubMed1988

A suction trephine block for marking donor corneal buttons.

We describe a technique to accurately align the circumferences of the donor button and host cornea during penetrating keratoplasty. The donor cornea is trephined on a block into which four narrow, intersecting, equally spaced radial cuts are made. Suction is applied to the donor cornea through the four cuts, resulting in four radial marks in the donor corneal epithelium. Four radial marks are also made in the host cornea before trephination, using a radial keratotomy marker. When the donor button is placed within the recipient opening, the radial marks are aligned and used as guides for the cardinal sutures. This simple technique allows for matching of the donor and host circumferences, even if there is some collapse of the peripheral host cornea and sclera at surgery, and should minimize astigmatism resulting from donor/host misalignment.

Astigmatism↗
PubMed1988

Exogenous fungal endophthalmitis.

The authors report 19 cases of exogenous fungal endophthalmitis managed between 1969 and 1986. These developed after ocular surgery (5 cases), after trauma (6 cases), by intraocular spread from fungal keratitis (4 cases), after therapeutic keratoplasty for keratitis (3 cases), and by spontaneous infection of a filtration bleb (1 case). The diagnosis of endophthalmitis was made from 3 days to 4 months after surgery or trauma. In patients with preexisting keratitis, endophthalmitis was noted 2 weeks to 5 months after the onset of keratitis. Seventeen cases were caused by filamentous fungi; two were caused by yeast. Fusarium (6 cases) and Acremonium (3 cases) accounted for approximately one half of the isolates. Forty-two percent of the patients recovered 20/400 or better acuity (3 of 5 postoperative cases, 4 of 6 trauma cases, and 1 of 4 keratitis cases). The clinical and microbiologic features of these cases are presented, and recommendations for management are offered.

Electroretinography↗
PubMed1987

Noncontact trephination of the cornea using a pulsed hydrogen fluoride laser.

We used a pulsed hydrogen fluoride infrared laser and a specially designed axicon lens to perform circular corneal trephinations in ten eye bank eyes. This noncontact system focused each laser pulse into an annulus on the cornea. Corneal perforation was achieved in seven to nine seconds at a repetition rate of 10 Hz, using a laser output energy of 100 mJ per pulse. A trephination, 90% of corneal thickness, 6.5 mm in diameter, was produced with 70 pulses.

Cornea↗
PubMed1987

Microbial endophthalmitis resulting from ocular trauma.

Twenty-seven cases of culture-positive endophthalmitis that developed after ocular trauma were reviewed. The intraocular culture specimens showed a virulent microbiologic spectrum with Bacillus sp as the most common isolate (8 eyes). The visual prognosis was poor, with only 22% of patients retaining 20/400 or better vision. This level of vision was achieved in 2 of 22 (9%) bacterial cases and in four of five (80%) fungal cases. Retinal detachment (5 cases) or retinal breaks (2 cases) at the time of the initial injury had a uniformly poor visual prognosis. Postoperative retinal detachment not associated with phthisis bulbi occurred in five eyes, three of which had successful retinal reattachment surgery. Delayed onset retinal detachment after successful initial management of traumatic endophthalmitis had a greater frequency of successful retinal reattachment surgery.

Adolescent↗
PubMed1986

Preliminary report on corneal incisions created by a hydrogen fluoride laser.

We created corneal incisions in eye bank eyes with a pulsed hydrogen fluoride infrared laser. This laser was selected because its emission spectrum (2.7 to 3.0 micron) closely corresponds to the absorption peak of water in the infrared region. Short pulses (200 nsec) of hydrogen fluoride laser light focused with a cylindrical lens resulting in radiant exposures of 1.3 J/cm2 at the corneal surface created linear cuts in the cornea with minimal thermal damage adjacent to the incision, suggesting that the pulsed hydrogen fluoride laser may be useful for corneal surgery.

Cornea↗