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Biomedical subjects

A Weinberg

Publications and source records attributed to A Weinberg.

At least 91 records · Page 5Linked to original sources
PubMed1997

Do intact viral particles survive excimer laser ablation?

OBJECTIVE: To determine if intact and potentially infectious viral particles can withstand excimer laser ablation and possibly pose a health hazard to medical personnel. METHODS: Excimer laser ablation of fibroblasts infected with attenuated varicella-zoster virus was performed. The laser plume was collected for polymerase chain reaction analysis and viral culture. RESULTS: While viral DNA was detected in the material trapped from the laser plume, live virus could not be demonstrated to have survived ablation. CONCLUSIONS: Attenuated varicella-zoster virus does not seem to survive excimer laser ablation. However, we recommend the use of safety precautions such as wearing a mask during the procedure. Further research is necessary to determine if other viruses could possibly remain infectious despite exposure to excimer laser radiation.

DNA, Viral↗
PubMed1997

Presence of the T-cell activation marker OX-40 on tumor infiltrating lymphocytes and draining lymph node cells from patients with melanoma and head and neck cancers.

BACKGROUND: The OX-40 antigen is a cell surface glycoprotein in the tumor necrosis factor receptor family that is expressed primarily on activated CD4+ T cells. Selective target organ expression of the OX-40 receptor on autoantigen specific T cells has been found in autoimmune disease. In order to evaluate whether OX-40 is expressed on T cells from patients with nodal-draining carcinomas, OX-40 expression was assessed in tumor infiltrating lymphocytes (TILs), draining lymph node cells (DLNCs), and/or peripheral blood lymphocytes (PBLs) of 13 patients with head and neck squamous cell carcinomas and 9 patients with melanomas. METHODS: Cell phenotype was determined by fluorescence cell analysis using a monoclonal antibody to human OX-40, and CD4+ T cell lymphokine production was determined by reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: Expression of the OX-40 receptor was found in as many as 31% of the TILs and as many as 28% of the DLNCs tested. Conversely, no OX-40 expression was found in PBLs. In addition, CD4+ T cells isolated from DLNCs (but not from TILs or PBLs) secreted a Th1 pattern of cytokines (IL-2, gamma interferon). Co-culture of autologous CD4+ TILs with an MHC class II+ melanoma cell line transfected with OX-40 ligand cDNA resulted in T cell proliferation and in vitro tumor regression. CONCLUSIONS: These findings suggest that OX-40+ CD4+ T cells isolated from tumors and their adjacent draining nodes may represent a tumor-specific population of activated T cells capable of mediating tumor reactivity. These cells may play an exploitable role in future trials of immunotherapy.

CD4-Positive T-Lymphocytes↗
PubMed1997

A multivariable risk factor analysis of the portoenterostomy (Kasai) procedure for biliary atresia: twenty-five years of experience from two centers.

OBJECTIVE: The authors investigated risk factors for failure after portoenterostomy for biliary atresia using univariate and multivariable methods. SUMMARY BACKGROUND DATA: Kasai's portoenterostomy has gained worldwide acceptance as the initial surgical therapy for infants with biliary atresia. Although extended survival has been achieved for many patients, factors influencing outcome have not been defined clearly. METHODS: The authors analyzed risks for failure in 266 patients treated from 1972 to 1996 by the Kaplan-Meier product limit estimate and Cox proportional hazards model. Failure was defined as death or transplant. RESULTS: Age at surgery, surgical decade, and anatomy of atretic bile ducts were identified as independent risk factors. Five-year survival was 49% and median survival was 15 years when bile drainage was achieved. Sixty-five patients had liver transplants. Mean age at transplant was 5.4 years. CONCLUSIONS: The outcome after portoenterostomy for biliary atresia is determined by age at surgery and anatomy of the atretic extrahepatic bile ducts. Liver transplant will salvage patients with failed Kasai with 10-year posttransplant survival of 71%.

Adolescent↗
PubMed1997

Lipoproteins of Treponema denticola: their effect on human polymorphonuclear neutrophils.

The presence of lipoproteins and lipooligosaccharides in Treponema denticola, an oral spirochaete associated with periodontal diseases, was investigated. T. denticola ATCC 35404 and the clinical isolate GM-1 were metabolically labeled with [3H]-cis-9-octadecenoic acid and extracted with the non-ionic detergent Triton X-114. The extract was phase separated, precipitated with acetone and delipidated to remove non-covalently bound lipid (dLPP). In T. denticola ATCC 35404, sodium dodecyl sulfate polyacrylamide electrophoretic separation followed by autoradiography showed [3H]-cis-9-octadecenoic acid incorporation in bands with apparent molecular masses of 14, 20, 26, 31, 38, 72 and 85 kDa and a broad band running from 113 kDa to the top of the gel. This last band resolved into a 53 kDa [3H]-cis-9-octadecenoic acid band upon heating for 10 min, at 100 degrees C. The structural relationship of the outer sheath major oligomeric polypeptide of strain ATCC 35404 and the 53 kDa protein was demonstrated immunologically. Antibodies against the 113 kDa component of the oligomer cross-reacted with the 53 kDa protein. Proteinase K degraded the [3H]-cis-9-octadecenoic acid bands with the exception of the 14 kDa. The 14 kDa was also the major [3H]-fatty acid labeled compound found in the water phase following phenol-water extraction of whole T. denticola ATCC 35404 cells. This compound was purified from the water phase by gel filtration followed by hydrophobic chromatography. Chemical analysis showed that hexadecanoic acid was the predominant fatty acid bound to T. denticola lipoproteins. In the GM-1 strain [3H]-cis-9-octadecenoic acid incorporation was observed in the 116 kDa and 14 kDa bands. dLPP from strain ATCC 35404 caused an enhanced (0.8-8 micrograms/ml) luminol dependent chemiluminiscence (LDCL) effect in human polymorphonuclear neutrophils (PMN) which could be related to protein concentration. The addition of dLPP to PMN together with FMLP at submaximal concentration (1 microM) resulted in a synergistic activation of LDCL. At 21 micrograms/ml, dLPP also induced lysozyme release by the PMN at approximately 30% of the release induced by the chemotactic peptide at 1 microM. In addition, dLPP (21 micrograms/ml) increased additively the release of lysozyme caused by 1 microM FMLP. The release of beta-glucuronidase was not affected. The modulation of neutrophil activity was abolished by preincubation of dLPP with proteinase K. The purified 14 kDa had no effect on either LDCL or exocytosis of lysosomal enzymes of PMN. These data strongly suggest that T. denticola possesses several lipoproteins including outer sheath major oligomeric polypeptides (113-234 kDa) and a lipooligosaccharide of molecular mass of 14 kDa. In addition, an enriched lipoprotein fraction from this oral spirochaete modulates oxygen dependent and independent mechanisms for controlling microorganisms by human PMN.

Antibodies↗
PubMed1997

Role of fimbriae in Porphyromonas gingivalis invasion of gingival epithelial cells.

Porphyromonas gingivalis is a periodontal pathogen capable of invading primary cultures of normal human gingival epithelial cells (NHGEC). Involvement of P. gingivalis fimbriae in the invasion process was examined. Purified P. gingivalis 33277 fimbriae blocked invasion of this organism into NHGEC in a dose-dependent manner. DPG3, a P. gingivalis fimbria-deficient mutant, was impaired in its invasion capability approximately eightfold compared to its parent, strain 381. However, adherence of the mutant was only 50% reduced compared to the parent. Biotin labeling of NHGEC surface proteins revealed that two fimbriated strains, but not DPG3, bound a 48-kDa NHGEC protein. Adhesin-receptor interactions, such as fimbriae binding to a 48-kDa NHGEC surface receptor, may trigger activation of eukaryotic proteins involved in signal transduction and/or provoke the generation of surface P. gingivalis molecules required for internalization.

Bacterial Adhesion↗
PubMed1996

Myelin basic protein specific T-helper cells induce experimental anterior uveitis.

Immunopathological changes in the eyes were examined in Lewis rats after active and passive induction of experimental autoimmune encephalomyelitis (EAE) with myelin basic proteins (MBP) at various stages of EAE. The onset of anterior uveitis (AU) coincided with hind limb paralysis, but uveitis persisted after clinical signs of EAE had subsided. A mild form of uveitis was characteristic for the majority of rats. The changes within the iris and ciliary body consisted of an accumulation of inflammatory cells lining the anterior surface of iris, the trabecular meshwork, and, in some cases, within the ciliary body and the aqueous humor. A similar histopathological picture was observed when rats were injected with the secondary encephalitogenic determinant for Lewis rats, MBP peptide 87-99. Flow cytometry analysis of T cells from the anterior segment of the inflamed eyes after immunization with MBP revealed the presence of CD4+ cells exclusively expressing V beta 8.2 and OX-40 markers. Our data suggest that MBP are encephalitogenic and uveitogenic in Lewis rats and that the V beta 8.2-positive T cells in the eye represent encephalitogenic T cells. Many of those T cells were distributed in the iris and the anterior chamber. These findings indicate that these MBP-specific T cells may play a critical role in EAE as well as in AU.

Animals↗
PubMed1996

Clinicopathologic correlations in acute retinal necrosis caused by herpes simplex virus type 2.

The acute retinal necrosis syndrome is a rapidly progressive and potentially devastating disease. A case of acute retinal necrosis developed in an immunocompetent man, Presumably due to the stress, trauma, or immunomodulation related to a craniotomy for a parasellar craniopharyngioma. Vitrectomy and endoretinal biopsy were performed. Polymerase chain reaction studies of the vitreous revealed herpes simplex virus type 2 as the cause, which has not been previously well documented. Results of cerebrospinal fluid antibody studies were also consistent with the diagnosis. Results of cytology and histopathologic examination demonstrated extensive retinal destruction and mononuclear cell infiltration. Sloughing of the inner retina was evidenced by the presence of retinal vascular remnants in the vitreous cytology specimen. As is characteristic of this disease, the visual outcome of this patient was poor.

Adult↗
PubMed1996

A novel tumor-derived mediator that sensitizes cytokine-resistant tumors to tumor necrosis factor.

Therapeutic successes following treatment of murine tumors with tumor necrosis factor-alpha (TNF) have not been easily applied to clinical oncology because the concentrations of TNF required in humans induces systemic toxicity. This has led us to identify mediators which could sensitize tumors to the effects of TNF, permitting administration of lower doses and possible realization of the therapeutic potential of this cytokine. Our study reports the ability of a novel cytokine, endothelial-monocyte-activating polypeptide II (EMAP II), to sensitize initially resistant murine and human tumors to TNF-induced regression employing a murine model. Recombinant (r) EMAP II was purified from Escherichia coli transformed with a plasmid expressing mature EMAP II. The B16 melanoma, raised in C57BL/6 mice, or a human fibrosarcoma (HT-1080), grown in immunocompromised mice, was injected intratumorally with either vehicle or rEMAP II/heat-treated EMAP II (50-100 micrograms) followed by systemic TNF/heat-treated TNF (5 micrograms) and assessed for tumor volume, hemorrhage, and histologic appearance. Both the B16 melanoma and the HT-1080 human fibrosarcoma underwent thrombohemorrhagic and acute inflammatory changes concomitant with regression or significantly slowed growth after administration of intratumor EMAP II followed by systemic TNF. Omission or inactivation of either cytokine abrogated this effect. These results demonstrate that local treatment of certain tumors with EMAP II results in enhanced susceptibility to TNF-mediated induction of thrombohemorrhage and regression.

Animals↗
PubMed1996

Improved detection of varicella zoster infection with a spin amplification shell vial technique and blind passage.

BACKGROUND: Among the methods available for the diagnosis of varicella zoster virus (VZV) infections, only tissue culture yields an isolate available for antiviral susceptibility testing or pathogenesis studies. However, conventional tube tissue culture (TC) has a low sensitivity. OBJECTIVE: To increase the recovery rate of VZV in tissue culture. STUDY DESIGN: Clinical specimens submitted for VZV isolation were processed by TC and rapid shell vial (SV) techniques followed by a blind passage (BP). For SV, two incubation times and two mAbs, directed against viral-early or immediate-early antigens, were compared. RESULTS: Isolation of VZV using the SV stained at 72 h postinoculation was more sensitive (88-96%) than TC (50-67%), or the SV technique at 48 h (66-70%). It was also more rapid than TC (9.6 days). The comparison of mAbs yielded similar results in SV. Blind passage of SV at 7 days postinoculation further increased detection. CONCLUSIONS: SV combined with BP is the method of choice for VZV isolation.

Journal Article↗
PubMed1996

Lupus anticoagulant and protein S deficiency in children with postvaricella purpura fulminans or thrombosis.

OBJECTIVE: The objective of this study was to determine the cause of purpura fulminans, disseminated intravascular coagulation, or thrombosis in seven children with varicella. All children were found to have a lupus anticoagulant and acquired protein S deficiency. Thrombosis in five children was associated with presumed or documented infection with streptococcus. STUDY DESIGN: Coagulation tests included determinations of the activated partial thromboplastin time, the prothrombin time, the dilute Russell viper venom time, the prothrombin F 1 + 2 fragment, the C4b-binding protein (C4b), total and free protein S antigen, and clotting activities of factors II, V, VII, and X and of protein C and protein S. Autoantibodies to phospholipids, cardiolipin, and protein S were determined in enzyme-linked immunosorbent assays. RESULTS: All children had a lupus anticoagulant and acquired protein S deficiency. Thrombosis in five children was associated with presumed or documented infection with streptococcus. All children transiently expressed free protein S deficiency, elevated levels of IgG, IgM, or both binding to protein S, the lupus anticoagulant, and increased concentration of the F 1+2 fragment. Four children also had antiphospholipid or anticardiolipin antibodies. In one child a purified IgG fraction cross-reacted with both protein S and a specific varicella antigen. CONCLUSIONS: A subset of children with varicella infection, some of whom are coinfected with streptococcus, are prone to development of a lupus anticoagulant and an autoantibody to protein S, which results in acquired free protein S deficiency. Such children are at risk of having life-threatening thrombotic events.

Antibodies, Antiphospholipid↗
PubMed1996

Activation of coagulation and fibrinolytic pathways in patients with left ventricular assist devices.

Left ventricular assist devices have provided successful supportive therapy for patients awaiting cardiac transplantation for extended periods of time. Although thromboembolic events have complicated support with these devices, the HeartMate left ventricular assist device developed by Thermo Cardiosystems, Inc., Woburn, Massachusetts, was specifically designed with a textured blood-contacting surface to minimize this risk. Clinical experience with this device has been encouraging, inasmuch as minimal thromboembolic complications have occurred despite the absence of anticoagulation. The coagulation and fibrinolytic pathways in these individuals were investigated to better understand the hematologic status of patients treated with the Thermo Cardiosystems device. Despite apparently normal prothrombin and activated partial thromboplastin times, as well as platelet counts, evidence of significant thrombin generation and fibrinolysis was present. To eliminate underlying cardiac failure as the responsible factor for these abnormalities, we made similar measurements in patients with end-stage heart failure who were not supported by an assist device or anticoagulation. These measurements revealed no evidence of thrombin generation or fibrinolysis. These data demonstrate that patients supported with a left ventricular assist device, while successfully sustained without systemic anticoagulation, nevertheless have evidence of activation of coagulation. These phenomena appear to be related to the presence of the device rather than to the underlying cardiac abnormalities. Although procoagulant and fibrinolytic pathways are apparently balanced in these patients, these data underscore the potential for the development of bleeding or thrombosis in clinically relevant settings.

Adolescent↗
PubMed1996

Prevention, Identification, and Successful Transvaginal Repair of Bladder Injuries During Laparoscopic-Assisted Vaginal Hysterectomy

A retrospective review of laparoscopic-assisted vaginal hysterectomies performed at a medium-size community hospital revealed eight bladder injuries from December 1991 through December 1995. The preoperative indications varied widely, as did the operating physicians. All of the injuries occurred in the vaginal dissection portion of the procedures and all were identified and repaired during the initial surgery. The first six cases involved vaginal repair with interposition of a fat pad when possible between the bladder suture line and the vaginal cuff. The last two included laparoscopic-directed placement of omentum between these two layers. All of the patients did well and had no further complications. Since these injuries tend to occur at the bladder neck, identification of the ureteral orifices is critical to a successful repair.

Journal Article↗
PubMed1996

NK recognition of cytomegalovirus-infected endothelial cells depends on viral replication and MHC class I expression.

Cytomegalovirus (CMV) infection has been associated with graft rejection in solid organ transplantation and with graft-versus-host disease in marrow transplantation. We hypothesized that CMV-infected endothelial cells play an important role in the rejection process, because of their strategic localization at the interface with the host immune system and their ability to modulate T cell function. To study the effect of CMV infection on cell-mediated cytotoxicity against endothelial cells, peripheral blood mononuclear cells (MNC) were incubated with CMV-infected umbilical vein endothelial cells (CMV-UVEC) or mock-infected controls (M-UVEC) and lysis measured by [3H]leucine release. MNC lysed only CMV-UVEC to a maximum of 23% at E:T 20:1. Lysis was not affected by CD3+ cell depletion, but was abolished by CD16+ cell depletion, indicating that NK cells were the effectors. The kinetics of the NK-mediated lysis of CMV-UVEC paralleled the time course of CMV antigen expression. Furthermore, ganciclovir treatment of CMV-UVEC cultures decreased both specific antigen synthesis and NK-mediated lysis. This indicated that NK might recognize either a viral antigen or a cellular antigen modulated by CMV infection. Treatment of CMV-UVEC with F(ab)2 fragments of human polyclonal anti-CMV antibodies failed to inhibit NK cytotoxicity. In contrast, F(ab)2 fragments of MB40.5, a murine MAb reactive with a conserved epitope on the human MHC class I, significantly decreased lysis, proving that NK lysis of CMV-UVEC is an MHC class I-dependent function. To determine whether CMV-UVEC lysis was dependent solely on upregulation of MHC class I, MNC were incubated with CMV-UVEC mixed with uninfected UVEC. There was no competition for NK-target recognition sites, indicating that NK lysis required an interaction with an MHC class I antigen modified by viral infection. Antibodies against IFN-alpha or -beta did not block NK cytotoxicity against CMV-UVEC. Our findings provide a working frame for further evaluation of cellular immune responses to CMV infection.

Antigens, Viral↗
PubMed1996

Donor-to-host transmission of Mycoplasma hominis in lung allograft recipients.

Mycoplasma hominis is a significant pathogen in immunocompromised hosts, particularly organ transplant recipients. We describe two recipients of lung allografts from the same donor who had M. hominis pleuropulmonary infection during the immediate postoperative period. The most likely source of infection in these cases was the donor's respiratory tract. The slow-growing pinpoint colonies formed by M. hominis on routine bacterial culture medium may be easily overlooked and should be subcultured to mycoplasmal medium for definitive identification. The recommended management of this infection consists of drainage and antimicrobial therapy with tetracycline, clindamycin, or a fluoroquinolone. This report highlights the potential for M. hominis to be transmitted from donor to recipient during organ transplantation.

Adult↗
PubMed1996

Mobile rRNA methylase genes coding for erythromycin resistance in Actinobacillus actinomycetemcomitans.

We found that 17 (68%) of 25 Actinobacillus actinomycetemcomitans isolated from periodontally diseased sites had MICs of erythromycin > or = 8 mg/L. The isolates were hybridized with five rRNA methylase genes and gene mobility was determined. Twenty-four (96%) of 25 isolates hybridized with one or more rRNA methylase genes. Representative isolates were able to transfer erythromycin resistance to Haemophilus influenzae and Enterococcus faecalis recipients. The transconjugants were shown to carry rRNA methylase genes by DNA probe hybridization and had MICs of erythromycin 32 to 256 mg/L.

Aggregatibacter actinomycetemcomitans↗