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Biomedical subjects

D Palmer

Publications and source records attributed to D Palmer.

At least 19 recordsLinked to original sources
PubMed2025

HLA-E and NKG2A Mediate Resistance to BCG Immunotherapy in Non-Muscle-Invasive Bladder Cancer.

Bacillus Calmette-Guérin (BCG) is the first-line therapy for high-grade non-muscle-invasive bladder cancer (NMIBC), yet many patients experience recurrence due to immune evasion. We identify HLA-E and NKG2A as mediators of adaptive resistance involving chronic activation of NK and T cells in BCG-unresponsive tumors. Prolonged IFN-γ exposure enhances HLA-E and PD-L1 expression on recurrent tumors, accompanied by the accumulation of NKG2A+ NK and CD8 T cells. HLA-Ehigh tumor cells preferentially cluster near CXCL12-rich stromal regions with dense effector cell presence, underscoring a spatially segregated tumor architecture. Although cytotoxic lymphocytes retain effector potential, their activity is restrained by HLA-E/NKG2A and PD-L1/PD-1 pathways located in their immediate neighborhood within the bladder tumor microenvironment. These data reveal a spatially organized immune escape program that limits anti-tumor immunity. Our findings support dually targeting NKG2A and PD-L1 checkpoint blockade as a rational, bladder-sparing strategy for patients with BCG-unresponsive NMIBC.

BCG-unresponsive↗
PubMed1991

Generation and characterization of an HLA-DR alpha-specific monoclonal antibody using L-cell transfectants expressing human and mouse class II major histocompatibility dimers.

Among the HLA-DR-specific monoclonal antibodies (mAbs) that have been characterized previously, there is a marked shortage of DR alpha chain-specific mAbs which stain unfixed cells. This may result from the high degree of sequence similarity between the alpha 1 domains of HLA-DR and H-2E leading to a state of cross-tolerance to DR alpha in H-2-expressing mice. BALB/b (E-negative) mice were immunized with DR1-transfected mouse L cells. The chain specificity of the resulting DR-specific mAb was determined using a panel of transfectants expressing hybrid mouse/human class II heterodimers. A DR alpha-specific mAb was generated which was capable of immunoprecipitating DR alpha beta dimers and inhibiting the anti-DR alloresponse of human T-cell clones. The present study demonstrates that, with the selection of a suitable recipient strain, transfectants can be useful in the generation and definition of chain-specific mouse mAbs.

Animals↗
PubMed1989

Formation of a cryogel during processing of cell-free plasma.

Automated plasmapheresis devices are being integrated into many modern plasma procurement programs. Owing to the use of a different concentration and type of anticoagulant, the recovered plasma differs in pH and citrate levels from that obtained by manual plasmapheresis or whole blood donation. Recently, fractionators noted the recovery of a sticky, gelatinous fraction (cryogel) during thawing of cell-free (CF) plasma, along with reduced recovery of factor VIII:C (FVIII:C) in the cryoprecipitate fraction. Following their manufacturing procedures, it was established that the cryogel fraction of CF plasma is enriched in FVIII:C, fibrinogen, and fibronectin, as compared to cryoprecipitate from CPDA-1 plasma. Cryogel formation was not significantly affected by pH or citrate adjustment of the recovered plasma, by the use of polycarbonate or nylon filter membranes, or by the filter wetting agent polyvinylpyrrolidone (PVP). Furthermore, passage of CPDA-1 plasma through the polycarbonate filter did not alter cryoprecipitate quality. However, cryogel formation from CF plasma was reduced significantly by 1) slow thawing at 4 degrees C rather than quick thawing at 20 and 0 or 20 and 4 degrees C, 2) the use of 1:16.6 sodium citrate rather than 1:12.5 ACD-A, or 3) the addition of intact platelets, platelet lysate, membranes, or cytosol to CF plasma before freezing. The data suggest an important and, indeed, essential role of platelet constituents in the formation of both cryoprecipitate and cryogel during the low-temperature purification of plasma proteins.

Blood Platelets↗
PubMed1988

In vitro activity of florphenicol.

Florphenicol was active at a lower concentration than chloramphenicol against over half of 234 recent clinical bacterial isolates. The majority (98%) of the isolates were inhibited by florphenicol at a concentration of 8 mg/l or less. Florphenicol was particularly effective against chloramphenicol resistant strains of Haemophilus influenzae. Klebsiella aerogenes and Bacteroides spp. Florphenicol was bacteristatic for salmonellae and Escherichia coli but bactericidal for Haemophilus influenzae. Florphenicol was slightly more active than chloramphenicol against Chlamydia trachomatis, Mycoplasma hominis and Mycoplasma pneumoniae but less active against Ureaplasma urealyticum.

Chloramphenicol↗
PubMed1988

Effect of lumbar puncture on flow of cerebrospinal fluid.

The rate at which isotopes descend from the cisterna magna to the lumbar subarachnoid space is highly variable. In monkeys, with and without previous lumbar puncture, transit time was measured. In animals with a previous lumbar puncture, transit times were 10 to 120 minutes; in monkeys without a previous lumbar puncture, transit times were 120 to 180 minutes. In experimental studies of cerebrospinal fluid circulation, the effect of lumbar puncture must be controlled.

Animals↗
PubMed1988

Effect of perioperative myocardial infarction on survival of postcardiotomy patients supported with ventricular-assist devices.

Ventricular-assist devices (VAD) have increased survival in patients with postcardiotomy shock, but the predictors of success need to be elucidated. We evaluated 45 patients treated with centrifugal (n = 18) or pulsatile (n = 27) VAD for postcardiotomy cardiogenic shock to determine the effect of perioperative myocardial infarction (PMI) on survival. The patients ranged in age from 15 to 72 years (mean age, 55.1 years). VAD support was left ventricular in 29, right ventricular in seven, and biventricular in nine, and the flow-rate range was 1.6-5.2 l/min (mean rate, 3.97 l/min) for 0.2-22 days (mean time, 4.1 days). PMI was determined by analysis of postoperative electrocardiogram (EKG), enzyme levels, or at necropsy. PMI was considered "possible" if there were either EKG or enzyme level changes, and "definite" if there were EKG and enzyme level changes or necropsy evidence. Of the 45 patients, 19 were successfully weaned from ventricular assistance; 12 were discharged (Group 1), and seven died (Group 2); the remaining 26 patients could not be weaned from VAD support (Group 3). In Group 1, one patient had a definite PMI, and three had a possible PMI. Among the 33 nonsurvivors (Groups 2 and 3), 24 patients had PMI by necropsy examination. Definite PMI was much more common in nonsurvivors (72.7%) than in survivors (8.3%) (p less than 0.05). However, Group 2 nonsurvivors were weaned despite PMI in 100% of cases. These data suggest that, although PMI is a strong negative determinant of survival in postcardiotomy patients, it cannot be considered a contraindication because it does not preclude myocardial recovery.

Adolescent↗
PubMed1985

Immunoperoxidase study of adenovirus pneumonia in dogs.

The pathology of adenovirus pneumonia in 16 dogs is described. Clinically, these dogs had been severely ill, with severe dyspnoea and listlessness, but only faint coughing. Histopathological lesions could be associated directly with the presence of adenovirus antigens in the lungs of these dogs by using an unlabelled immunoperoxidase technique on paraffin tissue sections. The lesions were focal and located in alveoli and bronchioles. Infected cells were mostly alveolar macrophages and less frequently type 1 and 2 pneumocytes and bronchiolar epithelial cells. Infiltrating neutrophils and lymphocytes were not observed to be infected. This type of pneumonia appears to be a fairly well defined clinical and pathological entity in kennel dogs.

Adenoviridae Infections↗
PubMed1978

Stimulation of mucus and nonparietal cell secretion by the E2 prostaglandins.

The effects of prostaglandin E2 (PGE2), 15-methyl prostaglandin E2 (15M), and 16,16-dimethyl prostaglandin E2 (16DM) on gastric mucus and nonparietal cell secretion in rats were measured. Alcian blue binding was used as a measure of gastric mucus. Applied topically, all three agents stimulated nonparietal cell secretion, and PGE2 and 16DM stimulated the secretion of mucus, increasing the fraction in the gastric contents but not that adherent to the mucosa. Topical 15M did not stimulate the production of mucus. Given intranveously, all three agents increased the amount of mucus in the gastric contents without altering the amount of mucus bound to the mucosa. The prostaglandins had no effect on nonparietal cell secretion when given intravenously. These effects could be relevant to the ability of the E2 prostaglandins to protect the gastric mucosa from damage.

Administration, Topical↗
PubMed1977

Secretion of parathyroid hormone by abnormal human parathyroid glands in vitro.

The secretory response of abnormal parathyroid glands obtained surgically from eleven patients with primary and secondary hyperparathyroidsm was tested in vitro. Short term flask studies were used to measure release of parathyroid hormone (PTH) at high (3.0 mM) and low (0.5 mM) calcium. Of eight adenomas, all but one showed increased release of hormone when exposed to low calcium ("responsive to calcium"), the degree of stimulation at three hours ranging from 15 to 209%. By comparison, two normal human glands were stimulated an average of 180%. Glands from three patients with secondary hyperplasia were also responsive to calcium. Thus, parathyroid glands from patients with primary and secondary hyperparathyroidism were characterized by a spectrum of responsiveness to calcium, and absolute "autonomy" was unusual. Even at high calcium concentrations, hormone release persisted at a low but definite level ("basal secretion"). The total number of functioning parathyroid cells is therefore a principal determinant in the oversecretion of PTH in hyperparathyroidism.

Adenoma↗