[Ultrasound-guided erector spinae plane block combined with pregabalin for post-herpetic neuralgia].

Objective: To analyze the clinical effect of ultrasound-guided erector spinae block combined with pregabalin on post-herpetic neuralgia (PHN) in the elderly. Methods: Sixty patients with post-herpetic neuralgia from January 2018 to January 2019 in the Department of Pain, First Affiliated Hospital of Bengbu Medical College were selected. The patients were divided into two groups according to the random number table (n=30): group C and ultrasound-guided erector spinae block (ESPB) group. Group C was treated with the oral drug pregabalin. ESPB group was treated with ultrasound-guided erector spinae block combined with oral drug pregabalin. The digital rating scale (NRS) score, sleep quality score (QS), total pregabalin dosage, and correlation during treatment were recorded before and after treatment at 1, 2, 3, 4, 6, and 8 weeks after treatment. Results: Four weeks after treatment, the scores of NRS and QS in ESPB group were 2.00(2.00-3.00) and 1.00(1.00-2.00) respectively, which were significantly lower than those in group C 3.00(3.00-4.00) and 2.00(2.00-3.00). The differences were statistically significant (Z=-2.318,-2.533, all P<0.05). The dosage of pregabalin in ESBP group was 1.73(1.65-1.99)g, less than that in group C 7.28(7.28-7.28)g, and the difference was statistically significant (Z=-4.916, P<0.05). The NRS score and QS score of ESPB group at the 8th week of follow-up were 2.50(2.00-4.00) and 1.00(0.00-2.00), respectively, which were significantly lower than those of group C 4.00(3.00-4.00) and 1.00(1.00-2.00). The difference was statistically significant (Z=-2.426,-2.691, all P<0.05). The significant effective rate of ESPB group was 70.0%, which was significantly better than that of group C (36.7%). The difference was statistically significant (χ(2)=6.694, P<0.05). Adverse reactions were mild in both groups. Conclusion: Ultrasound-guided erector spinae block can effectively alleviate the pain of elderly patients with PHN in the chest, significantly reduce the dosage of oral drugs, improve the sleep quality of patients, and have higher safety.

[Experimental observation of hyperbaric oxygen combined with radioactive seed implantation in the treatment of nude mice bearing esophageal squamous cell carcinoma].

Objective: To investigate the effect and mechanism of hyperbaric oxygen combined with radioactive seed implantation in the treatment of esophageal squamous cell carcinoma. Methods: Subcutaneous tumor model of esophageal squamous cell carcinoma using TE-8 cells was established. Tumor bearing Balb/c(nu/nu) mice (60 mice) were divided into four groups, Cont group that treated with normal oxygen level, HBO group that treated with hyperbaric oxygen, RSI group that treated with radioactive seed implantation, and HBO+ RSI group that treated with hyperbaric oxygen combined with radioactive seed implantation. Tumor volume ratio and mean survival time of tumor bearing mice were observed. Pathological changes of tumor tissue after treatment were observed by hematoxylin eosin (HE) staining. Enzyme linked immunosorbent assay kit was used to detect oxidative stress. Apoptosis related proteins were detected by Western blot. Results: After treatment, the tumor volume ratio of HBO+ RSI group was 3.51±0.80 and was significantly lower than that of Cont group, HBO group, and RSI group (P<0.05). The mean survival time of HBO+ RSI group tumor bearing mice was 62 d and was significantly longer than that in Cont group, HBO group, and RSI group (P<0.05). HE staining showed that the pathological changes of tumor tissues were most obvious in HBO+ RSI group. After treatment, the MDA and Bax levels in nude mice of HBO+ RSI group were significantly higher than those in Cont group, HBO group and RSI group, but the levels of GSH, SOD and Bcl-2 were significantly lower than those of Cont group, HBO group and RSI group (P<0.05). Conclusion: Hyperbaric oxygen combined with radioactive seed implantation could slow tumor growth and increase survival time of tumor bearing mice. The possible mechanism is that hyperbaric oxygen combined with radioactive seed implantation can improve the oxidative stress response and the expression of apoptosis protein in tumor bearing nude mice.

[Phase â ¡ clinical trial of PD-1 inhibitor combined with chemotherapy for locally advanced resectable oral squamous cell carcinoma].

Objective: To explore the effectiveness and safety of programmed death 1(PD-1) inhibitory combined with chemotherapy as a neoadjuvant therapy for locally advanced resectable oral squamous cell carcinoma. Methods: This study was a randomized controlled phase Ⅱ trial. Patients recruited from Tianjin Medical University Cancer Institute and Hospital from July 2021 to February 2023 were randomly divided into two groups in a 1∶1 ratio: the experimental group (Toripalimab combined with albumin paclitaxel and cisplatin) and the control group (albumin paclitaxel and cisplatin); patients in both groups underwent three cycles of neoadjuvant therapy. After completion of neoadjuvant therapy, patients were evaluated and subsequent surgical treatment was performed. According to the completion of treatment, the analysis was conducted on both the full analysis set and the protocol set. The effectiveness and safety of treatments were evaluated. SPSS 20.0 software was used for statistical analysis. Results: A total of 41 cases with oral cancer were enrolled, including 26 males and 15 females, aged between 34 and 74 years old. There were 23 cases in the experimental group and 18 cases in the control group. A total of 23 cases completed neoadjuvant therapy and surgery according to the protocol. Experimental group and control group showed respectively the complete response rates of 1/19 and 0/17, the partial response rates of 13/19 and 8/17, the stage-down rates of 4/19 and 3/17, the pathologic complete response rate of 8/14 and 2/9, with no statistically significant differences in individual rates between two groups (P>0.05). The major pathological response rate of 13/14 in experimental group was higher than that of 2/9 in control group (P<0.05). The incidence of grade 3-4 adverse reactions related to treatment was low in both groups (4/23 vs. 3/18, χ2=0.13, P=0.72), and the most common serious adverse reactions in the experimental group were granulocyte deficiency and electrolyte disorder. There were no adverse reactions that affected subsequent surgical treatment or caused death, and the safety and tolerability were good. The median follow-up time was 15 months, and the one-year disease-free survival rate of the experimental group was higher than that of control group (92.86% vs. 77.78%, χ2=0.62, P=0.42), with a relative decrease of 87% in the risk of disease progression or death (P=0.029). For patients with programmed death-ligand 1(PD-L1) protein expression combined positive score≥20, the experimental group showed higher major pathological response rate than control group (5/5 vs. 0/4, P=0.03). Conclusion: The neoadjuvant therapy of immunotherapy combined with chemotherapy can improve the pathological remission of oral squamous cell carcinoma and the long-term survival benefits and the prognosis of patients.

Herbaceous Dominant the Changes of Normalized Difference Vegetation Index in the Transition Zone Between Desert and Typical Steppe in Inner Mongolia, China.

Asymmetric responses of aboveground net primary productivity (ANPP) to precipitation were identified as a signal to predict ecosystem state shifts at temperate grassland zones in Inner Mongolia, China. However, mechanism studies were still lacking. This study hypothesized that the enhanced growth and newly emerged herbaceous after increased precipitation resulted in the highest asymmetry at the transition zone between desert and typical steppe. We monitored the responses of the normalized difference vegetation index (NDVI) of different species to precipitation events using un-manned aerial vehicle technology to test this hypothesis. NDVI and species richness were measured twice at fixed points in July and August with a time interval of 15 days. Results showed that: (1) From July to August, NDVI in the transition zone increased significantly after precipitation (P < 0.05), but NDVI in both the desert and typical steppe showed a non-significant change (P > 0.05). (2) In the transition zone, NDVI increases from the shrub and herbaceous contributed to 37 and 63% increases of the site NDVI, respectively. (3) There was a significant difference in species richness between July and August in the transition zone (P < 0.05), mainly caused by the herbaceous (Chenopodiaceae, Composite, Convolvulaceae, Gramineae, Leguminosae, and Liliaceae), which either emerged from soil or tillers growth from surviving plants. This study demonstrated that herbaceous dominant the changes of NDVI in the transition zone, which provides a scientific basis for the mechanism studies of ANPP asymmetric response to precipitation and warrants long-term measurements.

LncRNA RPPH1 predicts poor prognosis and regulates cell proliferation and migration by repressing P21 expression in gastric cancer.

OBJECTIVE: The purpose of this study was to explore the expression and biological functions of long non-coding ribonucleic acid (lncRNA) ribonuclease P RNA component H1 (RPPH1) in gastric cancer (GC), and to analyze the correlations of lncRNA expression with the clinical features and prognosis of GC patients. PATIENTS AND METHODS: The relative expression of RPPH1 in tissue specimens from 60 GC patients was measured via quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR), and the correlations of RPPH1 expression with tumor-node-metastasis (TNM) stage, lymph node metastasis, etc. in GC patients were analyzed. Then, qRT-PCR was performed to detect the relative expression level of RPPH1 in GC cells. Moreover, colony formation assay, 5-Ethynyl-2'-deoxyuridine (EdU) staining, wound-healing assay, and transwell assay were employed to investigate the influence of RPPH1 on GC cell functions. After interfering in the expression of RPPH1, the changes in p21 (CDKN1A, cyclin dependent kinase inhibitor 1A) expression were determined through qRT-PCR and Western blotting. RESULTS: It was shown in qRT-PCR assay results that the expression of RPPH1 was upregulated in 60 cases of GC tissues. Statistical analysis revealed that RPPH1 expression was positively correlated with the TNM stage, lymph node metastasis, and infiltration depth in GC patients. Besides, highly expressed lncRNA RPPH1 suggested poor prognosis of GC patients. Based on the results of qRT-PCR assay, the expression of RPPH1 in GC cells was upregulated. After interfering in RPPH1 expression, both colony formation assay and EdU staining indicated that the proliferative capacity of GC cells was repressed. Furthermore, it was manifested in the results of wound-healing and transwell assays that the migratory and invasive abilities of GC cells were weakened. Finally, the qRT-PCR and Western blotting assay results demonstrated that p21 expression was upregulated after interfering in the expression of RPPH1 in GC cells. CONCLUSIONS: The expression of lncRNA RPPH1 is upregulated in GC, suggesting that the prognosis of the patients is poor. Highly expressed RPPH1 promotes the proliferation and metastasis of GC cells by regulating p21 expression.

The bovine desmocollin family: a new gene and expression patterns reflecting epithelial cell proliferation and differentiation.

We have discovered a third bovine desmocollin gene, DSC3, and studied expression of all three desmocollin genes, DSC1, 2, and 3, by Northern blotting, RT-PCR and in situ hybridization. DSC1 is strongly expressed in epidermis and tongue papillae, showing a "skin"-type pattern resembling that previously described for keratins 1 and 10. Expression is absent from the epidermal basal layer but appears in the immediate suprabasal layers and continues uniformly to the lower granular layer. In tongue epithelium, expression is suprabasal and strictly localized to papillae, being absent from interpapillary regions. In other epithelial low level DSC1 expression is detectable only by RT-PCR. The distribution of Dsc1 glycoproteins, detected by an isoform-specific monoclonal antibody, closely reflects mRNA distribution in epidermis and tongue. DSC2 is ubiquitously expressed in epithelia and cardiac muscle. In stratified epithelia, expression appears immediately suprabasal, continuing weakly to the lower granular layer in epidermis and to just above half epithelial thickness in interpapillary tongue, oesophageal, and rumenal epithelia. DSC3 expression is restricted to the basal and immediately suprabasal layers in stratified epithelia. In deep rete ridges DSC expression strikingly resembles the distribution of stem, transit-amplifying, and terminally differentiating cells described by others. DSC3 expression is strongly basal, DSC2 is strong in 5-10 suprabasal layers, and then weakens to be superseded by strong DSC1. These results suggest that desmocollin isoform expression has important functional consequences in epithelial proliferation, stratification, and differentiation. The data also provide a standard for nomenclature of the desmocollins.

2Hz-electroacupuncture attenuates heroin-seeking behaviors via adjusts CB1-Rs and CB2-Rs expression in relapse-relevant brain regions of heroin self-administration rats.

Opiate addiction has a high rate of relapse. The accumulating evidence shows that electroacupuncture (EA) may be effective for the treatment of opiate relapse. However, the change of expression of CB1-Rs and CB2-Rs involve in 2Hz EA anti-relapse pathway is still unclear. To explore the changes of expression of CB1-Rs and CB2-Rs, heroin self-administration (SA) model rats were adopted and treated using 2Hz EA. The expressions of CB1-Rs and CB2-Rs were observed using immunohistochemistry method. The results showed that, compared with the control group, active pokes in the heroin-addicted group increased, while the active pokes decreased significantly in 2Hz EA group compared with heroin-addicted group. Correspondingly, the expression of CB1-Rs in prefrontal cortex (PFC), hippocampus (Hip), nucleus accumbens (NAc) and ventral tegmental area (VTA) all increased significantly while the expression of CB2-Rs in those relapse-relevant brain regions decreased obviously in heroin-addicted group when compared with the control group. In addition, the expression of CB1-Rs obviously decreased in the 2Hz EA group while the expression of CB2-Rs in those relapse-relevant brain regions increased significantly when compared with the heroin-addicted group. It indicated that 2Hz EA could attenuate the heroin-evoked seeking behaviors effectively. The anti-relapse effects of 2Hz EA might be related to the decrease of CB1-Rs and increase of CB2-Rs expression in relapse-relevant brain regions of heroin SA rats.

Resonance Raman study of sirohydrochlorin and siroheme in sulfite reductases from sulfate reducing bacteria.

Soret-excited resonance Raman (RR) spectra are reported for the sirohemes in the oxidized and Cr11(EDTA)-reduced forms of both desulforubidin from D. baculatus (DSR) and the low molecular weight sulfite reductase from D. vulgaris (1SIR) and for sirohydrochlorin in the oxidized form of desulfoviridin from D. gigas (DSV). Several patterns in the RR spectra of these enzymes can be utilized as signatures for the siroheme/sirohydrochlorin moiety. The active site for DSR and 1SIR consists of a siroheme exchange-coupled to a [4Fe-4S]2+ cluster. Upon addition of Cr11(EDTA), the active center of DSR and 1SIR undergoes a one-electron and two-electron reduction, respectively. The RR spectra of DSR suggest that the siroheme iron is high spin and 5-coordinate in the oxidized enzyme and probably remains high spin and 5-coordinate upon reduction. The iron in the siroheme of oxidized 1SIR changes from a low spin and probably 6-coordinate configuration to a high spin, 5-coordinate complex upon two-electron reduction of the active site. Close similarities between the RR spectral features of the two-electron-reduced assimilatory sulfite reductases from E. coli and from D. vulgaris (1SIR) are discussed.

The determination of the pKa of histidine residues in proteins by Raman difference spectroscopy.

Sensitive Raman difference spectroscopy was used to monitor the protonation and deprotonation of histidine residues in apo-transferrin. We have shown previously that the behavior of small molecules and/or small molecular groups bound to proteins or other large macromolecules can be studied by Raman difference spectroscopy (Yue, K.T. et al. (1989) J. Raman Spectrosc. 20, 541-545). Using this method, we have measured the Raman difference spectra of human transferrin at different pH values with respect to pH 8.9, titrating its various histidine residues. About 12 +/- 2 of the 19 residues were titrated. The pH difference spectrum of transferrin obtained is very similar to that of histidine in solution, but with clear differences in the 1200-1400 cm-1 region. A titration curve with pKa of 6.08 +/- 0.01 fit the data of histidine in solution and a value of 6.56 +/- 0.02 was found for the average value of the 12 histidine residues inside transferrin. The technique has enough sensitivity at present to monitor a single histidine residue in a 130 kDa molecule and to determine the titration curve of one residue in a 40 kDa protein.

X-ray absorption and resonance raman spectroscopy of human myeloperoxidase at neutral and acid pH.

Myeloperoxidase (MPO), an important enzyme in the oxygen-dependent host defense system of human polymorphonuclear leukocytes, utilizes hydrogen peroxide to catalyze the production of hypochlorous acid, an oxidizing bactericidal agent. While MPO shows significant sequence homology with other peroxidases and this homology is particularly striking among the active-site residues, MPO exhibits unusual spectral features and the unique ability to catalyze the oxidation of chloride ions. We have investigated the MPO active-site with X-ray absorption (XAS) and resonance Raman (RRS) spectroscopies at neutral pH and also at the physiological acidic pH (pH approximately 3) and have compared these results with those of horseradish peroxidase (HRP). At pH 7.5, XAS results show that the iron heme active site is 6-coordinate where the distal ligand is likely nitrogen or oxygen, but not sulfur. The heme is distorted compared to HRP, other peroxidases, and heme compounds, but at pH approximately 3, the distal ligand is lost and the heme is less distorted. RRS results under identical pH conditions show that the skeletal core-size sensitive modes and v3 are shifted to higher frequency at pH approximately 3 indicating a 6- to 5-coordination change of high spin ferric heme. In addition, a new band at 270 cm(-1) is observed at pH approximately 3 which is consistent with the loss of the sixth ligand. The higher symmetry of the heme at pH approximately 3 is reflected by a single v4 mode in the (RRS) spectrum. HRP also loses its loosely associated distal water at this pH, but little change in heme distortion is observed. This change suggests that loss of the distal ligand in MPO releases stress on the heme which may facilitate binding of chloride ion.

Resonance Raman study on the iron-sulfur centers of Desulfovibrio gigas aldehyde oxidoreductase.

Resonance Raman spectra of the molybdenum containing aldehyde oxidoreductase from Desulfovibrio gigas were recorded at liquid nitrogen temperature with various excitation wavelengths. The spectra indicate that all the iron atoms are organised in [2Fe-2S] type centers consistent with cysteine ligations. No vibrational modes involving molybdenum could be clearly identified. The features between 280 and 420 cm-1 are similar but different from those of typical plant ferredoxin-like [2Fe-2S] cluster. The data are consistent with the presence of a plant ferredoxin-like cluster (center I) and a unique [2Fe-2S] cluster (center II), as suggested by other spectroscopic studies. The Raman features of center II are different from those of other [2Fe-2S] clusters in proteins. In addition, a strong peak at ca. 683 cm-1, which is not present in other [2Fe-2S] clusters in proteins, was observed with purple excitation (406.7-413.1 nm). The peak is assigned to enhanced cysteinyl C-S stretching in center II, suggesting a novel geometry for this center.

Direct evidence of the metal-free nature of sirohydrochlorin in desulfoviridin.

We have obtained direct evidence that the majority of the sirohydrochlorin chromophore in the dissimilatory sulfite reductase desulfoviridin from Desulfovibrio gigas, is not associated with any metal. The evidence comes from resonance Raman measurements of native and deuterated samples of desulfoviridin. The breathing mode v4 (or v4*) at 1336 cm-1 in the native enzyme is downshifted to 1326 cm-1 upon deuteration. This mode is not sensitive to deuteration if a metal is present at the center of the chromophore inside protein or in solution. The results also establish the existence of exchangeable core hydrogen(s) at the pyrrolic nitrogen(s).

Glucose-induced oxidative stress in vascular contractile cells: comparison of aortic smooth muscle cells and retinal pericytes.

Free radical-mediated damage to vascular cells may be involved in the pathogenesis of diabetic vasculopathy. The aim of this study was to compare the extent of glucose-induced oxidative stress in both vascular smooth muscle cells (VSMCs) and pericytes and the effect on antioxidant enzyme gene expression and activities. Porcine aortic VSMC and retinal pericytes were cultured in either 5 or 25 mmol/l glucose for 10 days. Intracellular malondialdehyde (MDA) was measured as a marker of peroxidative damage, and mRNA expression of CuZn-SOD, MnSOD, catalase, and glutathione peroxidase (GPX) were measured by Northern analysis. Glutathione (GSH) was also measured. There was a significant increase in MDA in VSMCs in 25 mmol/l glucose (1.34 +/- 0.11 vs. 1.88 +/- 0.24 nmol/mg protein, 5 vs. 25 mmol/l D-glucose, mean +/- SE, n = 15, P < 0.01), but not in pericytes (0.38 +/- 0.05 vs. 0.37 +/- 0.05 nmol/mg protein, n = 11). There was a significant decrease in GSH in both cell types (VSMC, 1.40 +/- 0.13 vs. 0.69 +/- 0.12 nmol/mg protein, n = 15, P < 0.001; pericytes, 1.97 +/- 0.17 vs. 0.94 +/- 0.16 nmol/mg protein, n = 11, P < 0.001). mRNA expression of CuZnSOD and MnSOD was increased only in VSMCs (by 58.5 +/- 8.1 and 41.0 +/- 6.9%, respectively, n = 8, P < 0.01). CuZnSOD protein was increased by approximately 120% (P < 0.00001). None of the antioxidant enzyme activities was altered between 5 and 25 mmol/l glucose in either cell type. Both MnSOD activities and GSH concentrations were higher in pericytes compared with VSMC under basal (5 mmol/l) conditions (P < 0.05 and P < 0.02, respectively). These results demonstrate glucose-induced reduction of GSH in both cells, but only in VSMC is there evidence of oxidant damage in the form of lipid peroxidation, implying significant differences in intracellular responses to glucose between contractile cells in the macro- and microvasculature.

Constraint-based assembly of tertiary protein structures from secondary structure elements.

A challenge in computational protein folding is to assemble secondary structure elements-helices and strands-into well-packed tertiary structures. Particularly difficult is the formation of beta-sheets from strands, because they involve large conformational searches at the same time as precise packing and hydrogen bonding. Here we describe a method, called Geocore-2, that (1) grows chains one monomer or secondary structure at a time, then (2) disconnects the loops and performs a fast rigid-body docking step to achieve canonical packings, then (3) in the case of intrasheet strand packing, adjusts the side-chain rotamers; and finally (4) reattaches loops. Computational efficiency is enhanced by using a branch-and-bound search in which pruning rules aim to achieve a hydrophobic core and satisfactory hydrogen bonding patterns. We show that the pruning rules reduce computational time by 10(3)- to 10(5)-fold, and that this strategy is computationally practical at least for molecules up to about 100 amino acids long.

Folding proteins with a simple energy function and extensive conformational searching.

We describe a computer algorithm for predicting the three-dimensional structures of proteins using only their amino acid sequences. The method differs from others in two ways: (1) it uses very few energy parameters, representing hydrophobic and polar interactions, and (2) it uses a new "constraint-based exhaustive" searching method, which appears to be among the fastest and most complete search methods yet available for realistic protein models. It finds a relatively small number of low-energy conformations, among which are native-like conformations, for crambin (1CRN), avian pancreatic polypeptide (1PPT), melittin (2MLT), and apamin. Thus, the lowest-energy states of very simple energy functions may predict the native structures of globular proteins.

Predicting the structures of 18 peptides using Geocore.

We describe an extensive test of Geocore, an ab initio peptide folding algorithm. We studied 18 short molecules for which there are structures in the Protein Data Bank; chains are up to 31 monomers long. Except for the very shortest peptides, an extremely simple energy function is sufficient to discriminate the true native state from more than 10(8) lowest energy conformations that are searched explicitly for each peptide. A high incidence of native-like structures is found within the best few hundred conformations generated by Geocore for each amino acid sequence. Predictions improve when the number of discrete phi/psi choices is increased.

Principles of protein folding--a perspective from simple exact models.

General principles of protein structure, stability, and folding kinetics have recently been explored in computer simulations of simple exact lattice models. These models represent protein chains at a rudimentary level, but they involve few parameters, approximations, or implicit biases, and they allow complete explorations of conformational and sequence spaces. Such simulations have resulted in testable predictions that are sometimes unanticipated: The folding code is mainly binary and delocalized throughout the amino acid sequence. The secondary and tertiary structures of a protein are specified mainly by the sequence of polar and nonpolar monomers. More specific interactions may refine the structure, rather than dominate the folding code. Simple exact models can account for the properties that characterize protein folding: two-state cooperativity, secondary and tertiary structures, and multistage folding kinetics--fast hydrophobic collapse followed by slower annealing. These studies suggest the possibility of creating "foldable" chain molecules other than proteins. The encoding of a unique compact chain conformation may not require amino acids; it may require only the ability to synthesize specific monomer sequences in which at least one monomer type is solvent-averse.

A case of pemphigus vulgaris showing reactivity with pemphigus antigens (Dsg1 and Dsg3) and desmocollins.

Both pemphigus vulgaris antigen (PVA; Dsg3) and pemphigus foliaceus antigen (PFA; Dsg1) are members of the desmoglein subfamily of the cadherin supergene family. Another desmosomal cadherin, desmocollin, is occasionally recognized by certain pemphigus sera. We present a 38-year-old Japanese male who showed clinically and histopathologically typical features of pemphigus vulgaris, whose sera reacted with all PVA, PFA, and desmocollins using immunoblotting of both human epidermis and bovine snout epidermis. Studies using domain-specific fusion proteins of PFA and PVA suggested that this patient's serum reacted with the intracellular domain of PFA and the extracellular domain of PVA, the latter of which seems to be responsible for initiating the skin lesion. The patient's serum showed reactivity with human desmocollin and was shown to react with bovine Dsc2 fusion protein, further suggesting the significance of anti-desmocollin autoantibodies in pemphigus. These results indicate that certain pemphigus cases may produce antibodies against multiple antigen molecules, although the complex mechanism of the production of autoantibodies remains to be elucidated.

Effect of oral aspirin on "ecto-ATPase" activity of washed human platelets.

Aspirin is a potent inhibitor of the platelet release reaction and the accompanying second phase of platelet aggregation. The platelet release reaction is an active, energy-dependent process which appears to require ATP. Eight men ingested 0.32 gm of aspirin daily for 7 days. Although the second phase of 1.7 micron ADP-induced platelet aggregation was absent after aspirin ingestion, the "ecto-ATPase" activities of washed human platelet suspensions were not significantly different before and after ingestion of aspirin. This suggests that the effect of aspirin on the second phase of platelet aggregation is not mediated through inhibition of "ecto-ATPase".

Effect of aspirin on exercise-induced angina.

Suspecting that platelet thromboemboli could play a role in the pathogenesis of myocardial ischemia, we did a random-order, double-blind, crossover study of the effect of the platelet aggregation inhibitor, aspirin, on treadmill exercise-induced angina in 13 men with coronary artery disease. Although collagen-induced platelet aggregation and the second phase of adenosine diphosphate (ADP)-induced platelet aggregation were significantly decreased and the rate of disaggregation of ADP-induced platelet aggregates was significantly increased after 650 mg aspirin in buffered solution, there was no delay in onset of exercise-induced angina, change in heart rate-blood pressure product at onset of angina, or change in S-T segment depression at onset of angina. Regardless of whether the patients had received placebo or aspirin on the preceding day, treadmill exercise until angina was followed by no changes in platelet aggregation or disaggregation, platelet count in blood or platelet-rich plasma, or of the plasma concentration of nonesterified fatty acids.