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M Posner

Publications and source records attributed to M Posner.

At least 55 records · Page 3Linked to original sources
PubMed1993

Preparation of viable tumour cell vaccine from human solid tumours: relationship between tumour mass and cell yield. The Tissue Bank, Pittsburgh Cancer Institute.

Active specific immunotherapy for cancer often requires the use of autologous or allogeneic tumour cells as immunizing antigen. Tumours were obtained for such a protocol. However, estimation of viable cell yield from pre-processed fresh tumour mass was difficult, and initially there did not appear to be a direct relationship between pre-processed tumour mass and viable cells obtained after processing. We therefore analysed all of 293 tumour specimens processed to attempt to discern such a relationship. Of these 137 were melanoma, 14 were sarcoma, 48 were adenocarcinoma, 59 were renal cell carcinoma and 35 were classified as other. A positive correlation was found between pre-processed tumour mass and viable cell yield, with Spearman correlation values varying from r = 0.49 (adenocarcinoma) to r = 0.84 (melanoma). For all tumours the Spearman correlation was r = 0.70 (p = 0.0001). Not surprisingly, the most frequent site of removal associated with bacterial contamination was bowel. In conclusion, this study provides useful curves for predicting viable tumour cell yield from pre-processed tumour mass of given histology.

Adenocarcinoma↗
PubMed1993

Functional and immunologic characterization of human immunodeficiency virus type 1 envelope glycoproteins containing deletions of the major variable regions.

Deletions of the major variable regions (V1/V2, V3, and V4) of the human immunodeficiency virus type 1 (HIV-1) gp120 exterior envelope glycoprotein were created to study the role of these regions in function and antigenicity. Deletion of the V4 region disrupted processing of the envelope glycoprotein precursor. In contrast, the deletion of the V1/V2 and/or V3 regions yielded processed exterior envelope glycoproteins that retained the ability to interact with the gp41 transmembrane glycoprotein and the CD4 receptor. Shedding of the gp120 exterior glycoprotein by soluble CD4 was observed for the mutant with the V3 deletion but did not occur for the V1/V2-deleted mutant. None of the deletion mutants formed syncytia or supported virus entry. Importantly, the affinity of neutralizing antibodies directed against the CD4-binding region for the multimeric envelope glycoprotein complex was increased dramatically by the removal of both the V1/V2 and V3 structures. These results indicate that, in addition to playing essential roles in the induction of membrane fusion, the major variable regions mask conserved neutralization epitopes of the HIV-1 gp120 glycoprotein from antibodies. These results explain the temporal pattern associated with generation of HIV-1-neutralizing antibodies following infection and suggest stratagems for eliciting improved immune responses to conserved gp120 epitopes.

Animals↗
PubMed1992

A double-blind, placebo-controlled study of the safety and efficacy of ipratropium bromide nasal spray versus placebo in patients with the common cold.

Ipratropium bromide (IB) has been found to reduce secretions in the upper respiratory tract; this is accomplished through competitive inhibition of acetylcholine at muscarinic receptors that control rhinorrhea production. This study compared the safety and efficacy of IB with placebo in the symptomatic relief of rhinorrhea in patients with the common cold. Human subjects with symptoms of a common cold, primarily rhinorrhea, were enrolled and treated with either IB (84 micrograms/nostril) or placebo; each was administered as two sprays per nostril, four times a day, for 4 days. Primary efficacy analyses were in-clinic measurements of nasal discharge weights over a 3-hour period after administration on days 1 and 2 and assessment of rhinorrhea symptoms by use of a subjective patient-completed visual analog rating scale. IB significantly reduced rhinorrhea an average of 18% over placebo for days 1 and 2 (p = 0.01). Visual analog scale scores showed an average improvement in rhinorrhea of 22% over placebo (p = 0.001). When patients with relatively minor rhinorrhea (baseline weight of nasal discharge < or = 1.0 gm) were excluded, IB produced an average reduction in nasal discharge of 23% over placebo for days 1 and 2 (p = 0.003).

Adult↗
PubMed1992

Cavernous hemangioma of the adrenal gland.

Cavernous hemangiomas of the adrenal gland are rare. We report on a patient with a left adrenal hemangioma successfully treated by radical excision. The literature pertaining to this interesting pathological condition is reviewed.

Adrenal Gland Neoplasms↗
PubMed1992

A phase II trial of continuous infusion cisplatin and 5-fluorouracil with oral calcium leucovorin in colorectal carcinoma.

Twenty previously untreated patients with advanced colorectal adenocarcinoma were entered on a Phase II trial of 3-day continuous infusion cisplatin (25 mg/m2/day) and 5-fluorouracil (800 mg/M2/day) with oral calcium leucovorin (30 mg/dose) every 6 hours. There were four partial responses (20%) and two complete responses (10%) for a total response rate of 30% (95% confidence limits +/- 20%). Patients received a median of 4.5 cycles of therapy (range 2-9 cycles). Three patients experienced neutropenia; one had a life-threatening infection. One developed neuropathy at 375 mg/M2 cumulative dose. Four patients developed mucositis. Treatment was stopped for one patient with stable disease after 5 cycles because of anorexia and nausea and vomiting; treatment was stopped for four patients because of excessive fatigue. The median duration of responses was 4 months (range 3-6 months). Although this regimen is active, the response rate, cumulative nature of the toxicity, and the requirement for hospitalization led us to conclude that this regimen does not warrant Phase III testing but might be a basis for further Phase II therapeutic trials.

Administration, Oral↗
PubMed1992

Relationship of the human immunodeficiency virus type 1 gp120 third variable loop to a component of the CD4 binding site in the fourth conserved region.

Neutralizing antibodies that recognize the human immunodeficiency virus gp120 exterior envelope glycoprotein and are directed against either the third variable (V3) loop or conserved, discontinuous epitopes overlapping the CD4 binding region have been described. Here we report several observations that suggest a structural relationship between the V3 loop and amino acids in the fourth conserved (C4) gp120 region that constitute part of the CD4 binding site and the conserved neutralization epitopes. Treatment of the gp120 glycoprotein with ionic detergents resulted in a V3 loop-dependent masking of both linear C4 epitopes and discontinuous neutralization epitopes overlapping the CD4 binding site. Increased recognition of the native gp120 glycoprotein by an anti-V3 loop monoclonal antibody, 9284, resulted from from single amino acid changes either in the base of the V3 loop or in the gp120 C4 region. These amino acid changes also resulted in increased exposure of conserved epitopes overlapping the CD4 binding region. The replication-competent subset of these mutants exhibited increased sensitivity to neutralization by antibody 9284 and anti-CD4 binding site antibodies. The implied relationship of the V3 loop, which mediates post-receptor binding steps in virus entry, and components of the CD4 binding region may be important for the interaction of these functional gp120 domains and for the observed cooperativity of neutralizing antibodies directed against these regions.

Animals↗
PubMed1992

Characterization of the cDNA of a broadly reactive neutralizing human anti-gp120 monoclonal antibody.

The F105 mAb, identified in an HIV-1-infected individual, binds to a discontinuous epitope on the HIV-1 gp120 envelope glycoprotein, blocks the binding of gp120 to the CD4 viral receptor, and neutralizes a broad range of HIV-1 isolates. This study reports the primary nucleotide and deduced amino acid sequences of the rearranged heavy and light chains of the mAb F105. This IgG1k mAb uses a VH gene member of the VH4 gene family (V71-4) and is productively rearranged with a D-D fusion product of the dlr4 and da4 germline DH genes and the JH5 gene. This rearranged heavy chain gene expresses the VH4-HV2a idiotope, which is seen in human monoclonal IgM cold agglutinins. The F105 Vk appears to be derived from the Humvk325 germline gene and is rearranged with a Jk2 gene. For both chains, the mutational pattern in the rearranged VH and VL genes is indicative of an antigen-driven process. These studies show that production of a broadly neutralizing anti-HIV-1 antibody that recognizes determinants within the CD4 recognition site of the envelope glycoprotein is achieved by rearrangement of the V71-4 and Humvk325 germline variable region genes along with selected individual point mutations in the rearranged genes.

Amino Acid Sequence↗
PubMed1992

New method of limb deformities correction in children.

A new "bloodless" technique (Ilizarov) was used to correct 36 limb deformities in 29 children. There were six leg length discrepancies, five achondroplasias, four deformed feet, five joint contractures, one rotational deformity of tibia, and in three the apparatus was used as an external fixator after corrective osteotomy. Lengthening was accomplished in 15 of the 16 procedures (93%). Average increase in femur length was 10 cm (32%), in tibial length 7.5 cm (30%), in humerus 11 cm (40%). Bony union was achieved in two out of five pseudoarthroses. Four deformed feet were fully corrected. Joint contractures were corrected in four out of five. The complication rate is as high as in other methods but with the Ilizarov apparatus, longer segments of bone were lengthened and more complex deformities were treated. Complications lessened as experience was gained.

Achondroplasia↗
PubMed1992

Cooperativity of neutralizing antibodies directed against the V3 and CD4 binding regions of the human immunodeficiency virus gp120 envelope glycoprotein.

Human immunodeficiency virus type 1 (HIV-1) infection elicits neutralizing antibodies directed against two discrete regions of the gp120 exterior envelope glycoprotein: the third variable (V3) loop and the CD4 binding region. Monoclonal antibodies directed against these two regions demonstrated additive or, in some cases, weakly synergistic neutralization of HIV-1 infection. Cooperativity in virus neutralization was also observed for some gp120 mutants that, in the absence of anti-V3 loop antibodies, were relatively resistant to neutralization by antibodies directed against the CD4 binding region. Although the binding of some anti-V3 region monoclonal antibodies increased the recognition of the multimeric envelope glycoproteins by anti-CD4 binding antibodies, this enhanced binding was not predictive of the degree of cooperativity observed in virus neutralization. These results suggest that elicitation of both types of neutralizing antibodies should increase the efficacy of vaccine preparations.

Animals↗
PubMed1991

Cyclosporine's effect on functional reserve in the renal allograft.

Thirteen renal allograft recipients (6 patients on cyclosporine/7 patients on azathioprine) participated in a short-term oral protein-loading study to determine the effect of cyclosporine on an allograft's functional reserve. The baseline glomerular filtration rate of the two groups were similar (52 +/- 18 ml/min/1.73 m2 for the azathioprine/conventional therapy (CT) group and 47 +/- 12 ml/min/1.73 m2 for the cyclosporine (CsA) group), as were the baseline effective renal plasma flows (218 +/- 78 ml/min/1.73 m2 and 222 +/- 75 ml/min/1.73 m2, respectively). At 3 hr following the protein load there was an increase in GFR to 66 +/- 28 ml/min/1.73 m2 in the CT group. The GFR (39 +/- 8 ml/min/1.73 m2) of the CsA group at this time was unchanged. The responses in ERPF were similar. No significant difference was found between the two groups baseline RAA profiles (4.7 +/- 3.3 ng/ml/hr (CT) and 4.7 +/- 1.7 ng/ml/hr [CsA]), or those at the third hour (8.1 +/- 8.3 ng/ml/hr (CT) and 3.5 +/- 1.9 ng/ml/hr [CsA]). The data in this study indicate that CsA alters the renal allograft's response to a protein meal. This difference may be related to an altered vasodilatory response. This altered vascular reactivity may be mediated through renin activation and/or other hemodynamic regulators such as prostaglandins.

Adult↗
PubMed1991

Comparison of immune repertoires of Chinese and Philippine patients infected with Schistosoma japonicum.

Chinese and Philippine patients exhibited detectable titers of serum antibodies to Schistosoma japonicum worm and egg antigens. Western blot (immunoblot) data revealed differing antigenic profiles. Antigen inhibition studies showed low and high levels of cross-reactivity with anti-worm and anti-egg antibodies, respectively, derived from both Chinese and Philippine patients. Thus, anti-egg antibodies and egg antigens are more conserved than anti-worm antibodies and worm antigens.

Adolescent↗
PubMed1991

Characterization of a discontinuous human immunodeficiency virus type 1 gp120 epitope recognized by a broadly reactive neutralizing human monoclonal antibody.

While one hypervariable, linear neutralizing determinant on the human immunodeficiency virus type 1 (HIV-1) gp120 envelope glycoprotein has been well characterized, little is known about the conserved, discontinuous gp120 epitopes recognized by neutralizing antibodies in infected individuals. Here, the epitope recognized by a broadly reactive neutralizing monoclonal antibody (F105) derived from an HIV-1-infected patient was characterized by examining the effects of changes in conserved gp120 amino acids on antibody reactivity. The F105 epitope was disrupted by changes in gp120 amino acids 256 and 257, 368 to 370, 421, and 470 to 484, which is consistent with the discontinuous nature of the epitope. Three of these regions are proximal to those previously shown to be important for CD4 binding, which is consistent with the ability of the F105 antibody to block gp120-CD4 interaction. Since F105 recognition was more sensitive to amino acid changes in each of the four identified gp120 regions than was envelope glycoprotein function, replication-competent mutant viruses that escaped neutralization by the F105 antibody were identified. These studies identify a conserved, functional HIV-1 gp120 epitope that is immunogenic in man and may serve as a target for therapeutic or prophylactic intervention.

Amino Acid Sequence↗
PubMed1991

Activating tasks for the study of visual-spatial attention in ADHD children: a cognitive anatomic approach.

The clinical label attention deficit hyperactivity disorder (ADHD) suggests that this syndrome is a disorder of attention. However, the presumed attentional deficits have not been linked either to specific cognitive operations or to specific neural systems. To provide this link, theories of the cognitive anatomy of attention were used to generate hypotheses about specific visual-spatial attentional deficits in children with ADHD. A cued reaction-time test was used to assess covert and overt shifts of attention theoretically linked to two neuroanatomically defined attentional systems in the posterior and anterior parts of the human brain. The early, posterior-based covert shift of attention was found to be normal in ADHD children, but a later, anterior-based overt shift of attention was abnormal as reflected by a significant lateral difference in reaction time. This was interpreted as a failure to sustain focused attention.

Analysis of Variance↗
PubMed1991

Parotid enlargement in children seropositive for human immunodeficiency virus: imaging findings.

We investigated the clinical, immunologic, and imaging features of parotid enlargement in 10 children seropositive for human immunodeficiency virus (HIV) who were infected prenatally. In seven patients, sonography revealed many small hypoechoic areas suggestive of lymphoid infiltration. In three older children, large anechoic areas suggesting lymphoepithelial cysts were present. The lesions probably represent generalized lymphoid infiltration akin to pulmonary lymphoid hyperplasia, although only two of our patients had radiologic evidence of pulmonary lymphoid hyperplasia. Four of five of the children with parotid enlargement who had immunologic studies were phenotypically HLA-DR5, an immunophenotype associated with improved immune response, occurring in less than one in four in the normal population. This suggests that painless parotid enlargement may be a good prognostic sign in HIV-seropositive children. Parotid enlargement was found in 10 HIV-positive children from 6 months to 11 years old. All except one were infected prenatally.

Antibodies, Viral↗
PubMed1991

An immunoregulatory human monoclonal antibody in schistosomiasis japonica.

A series of human monoclonal antibodies were generated using splenocytes from a Chinese patient with chronic schistosomiasis who had undergone splenectomy as part of a portacaval decompression operation. Splenocytes were transformed in bulk culture by Epstein Barr virus and transformants fused with the HMMA 2.11 TG/O cell line. Twenty individual IgG antiworm and egg antibody-producing hybridomas were generated and screened for antigen reactivity by Western blot and for suppression of antigen-induced blastogenesis of murine splenocytes from Schistosoma japonicum-infected animals. Only one IgG clone significantly suppressed (56% P less than 0.05) soluble egg antigen (SEA)-induced blastogenesis. This human monoclonal antibody bound a 50 kD carbohydrate antigen on Western blot analysis, binding both the adult worm and egg antigens of this parasite. The non-regulatory monoclonal antibodies bound this same molecule present in adult worms but not the corresponding molecule in a preparation of soluble eggs. Thus, specific immunoregulatory epitopes can be identified by human monoclonal antibodies generated from patients with chronic disease.

Animals↗
PubMed1991

Ilizarov technique in treatment of congenital hand anomalies. Two case reports.

An Ilizarov apparatus was successfully used in the treatment of a six-year-old child with a radially deviated hand caused by congenital pseudoarthrosis of the distal radius after previous traditional surgery failed. The limb length was restored, the pseudoarthrosis healed, and the deviated hand corrected. A second child, five years old, with Poland's syndrome, had a 90 degrees flexion contracture of the wrist that was treated with the Ilizarov apparatus. The flexion contracture was gradually corrected. It seems that the Ilizarov apparatus can be an important tool in the treatment of complex limb deformities.

Child↗