Relationship between tumor DNA ploidy and regional lymph node changes in lung cancer.

Seventy-four patients with lung cancer, resected consecutively from April 1989 to August 1990, were divided into (1) 21 with diploid tumors having a single G0/G1 peak and a coefficient of variation (CV) of 4.9 or less, (2) 18 with peridiploid tumors having a single G0/G1 peak and a CV at 5.0 or more, and (3) 35 with aneuploid tumors having multiple G0/G1 peaks. Aneuploid tumors had higher frequencies of lymphatic invasion and metastasis to the mediastinal lymph nodes. To evaluate the relationship between ploidy tumor status and immunologic competence of the regional lymph nodes, histologic findings and the proportion of killer T-lymphocytes were examined in the dissected lymph nodes. Aneuploid tumors had significantly lower proportions of paracortical hyperplasia and killer T-lymphocytes than did diploid and peridiploid ones in the nonmetastatic lymph nodes of N0 and N1 disease. These findings suggest the possibility that a decline in the antitumor competence of these lymph nodes could cause metastasis to the nodes. The recurrence rates were 19% in diploid, 33% in peridiploid, and 54% in aneuploid tumors, and the 2-year survival rates were 87%, 78%, and 44%, respectively. Peridiploid tumors showed intermediate values between diploid and aneuploid in terms of immunologic competence, recurrence rate, and survival. They were assumed to have a different proportion of aneuploid cells than the other two.     

TRANSSYNAPTIC DEGENERATION IN THE INFERIOR OLIVARY NUCLEUS ASSOCIATED WITH PONTINE GLIOBLASTOMA

A case of glioblastoma arising in the pons of a 14-year-old boy in whom transsynaptic degeneration was found in the inferior olivary nucleus is reported. The tumor occupied most of the pons including the tegmental tract and invaded into the midbrain, medulla oblongata, cerebellar peduncles, thalamus, basal ganglia, and meninges. The right inferior olivary nucleus was devoid of the tumorous lesion, but many neurons were severely vacuolated. An im-munohistochemical study using glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE), and S-100 protein was performed. GFAP and S-100 protein were positive in the reactive glia of the nucleus and NSE gave a faint reaction in some degenerated neurons. These degenerative changes found in neurons of the inferior olivary nucleus were considered to be transsynaptic degeneration due to the destruction of the tegmental tract at the pons and of cerebellar peduncles by invasive pontine glioblastoma. ACTA PATHOL. JPN. 35: 1495–1500, 1985.     

β-Adrenergic modulation of the Na+−K+ pump in frog skeletal muscles

Adrenaline markedly increased the ouabain-sensitive 22Na+-efflux by stimulating the Na+-K+ pump in frog skeletal muscle. The facilitatory effects of adrenaline had the following properties. The effects of adrenaline on the ouabain-sensitive Na+-efflux were observed at concentrations greater than 0.1 microM and the magnitude increased with concentration up to 10 microM. At a concentration of 30 microM, adrenaline markedly augmented the ouabain-sensitive Na+-efflux, but other biogenic amines were less effective (noradrenaline and dopamine) or ineffective (histamine and serotonin). The increase of Na+-efflux induced by 1 microM adrenaline was blocked by 3 microM propranolol, but not by 3 microM phenoxybenzamine. The properties of the facilitatory action of adrenaline on the ouabain-sensitive Na+-efflux suggest that beta-adrenoceptors have an important role in modulating the Na+-K+ pump activity in the skeletal muscle membrane. The protein complex localized in excitable membranes, namely the Na+-K+ ATPase-beta-adrenoceptor complex, may be the functional unit which operates the membrane machinery driving the Na+-K+ pump.     

Redox-linked signal transduction pathways for protein tyrosine kinase activation

The signaling for activation of protein tyrosine kinases (PTKs) is usually started by binding of ligands to cell-surface receptors. However, recent evidence suggests the presence of ligand binding-independent signaling pathways that are mediated by oxidative stress. Oxidation and reduction of protein cysteine sulfhydryl (SH) groups may work as a molecular switch to start or to stop the signaling. It is known that oxidation of cysteine SH groups on protein tyrosine phosphatases switches off the action of protein tyrosine phosphatases. This event may not, however, signal for initial autophosphorylation of previously unphosphorylated PTKs, whereas it certainly prevents dephosphorylation of once-phosphorylated PTKs. We have suggested new mechanisms for oxidative stress-mediated PTK activation. First, cell-surface glycosylphosphatidylinositol-anchoring proteins and a phosphoglycolipid/cholesterol-enriched membrane microdomain termed a "raft" can be the direct targets of oxidative stress for inducing their clustering through an S-S-bonded or S-X-S-bonded crosslinking of cell-surface proteins and subsequent activation of raft-associating Src family PTKs. Second, intracellular specific cysteine SH groups on PTK proteins can be another target of oxidative stress for inducing a conformational change necessary for initial activation of PTKs. A possible relationship between cell-surface and intracellular events is that the former frequently induces superoxide production as the second messenger for the latter.     

Clinical application of18F-FUdR in glioma patients — PET study of nucleic acid metabolism

Summary Positron emission tomography was used to investigate the metabolism of nucleic acids by¹⁸F-fluoro-2-deoxyuridine (¹⁸F-FUdR) in 22 patients with gliomas. Sixteen cases of high grade glioma clearly demonstrated a region of high activity with a differential absorption rate (DAR) of 0.64 ± 0.34. Six cases of low grade glioma failed to reveal a positive image of the tumor and the DAR in tumor was 0.21 ± 0.042 (p < 0.01). This PET-¹⁸F-FUdR study succeeded in differentiating high and low grade gliomas from the view point of nucleic acid metabolism.     

TRPA1 contributes to capsaicin‐induced facial cold hyperalgesia in rats

Orofacial cold hyperalgesia is known to cause severe persistent pain in the face following trigeminal nerve injury or inflammation, and transient receptor potential (TRP) vanilloid 1 (TRPV1) and TRP ankylin 1 (TRPA1) are thought to be involved in cold hyperalgesia. However, how these two receptors are involved in cold hyperalgesia is not fully understood. To clarify the mechanisms underlying facial cold hyperalgesia, nocifensive behaviors to cold stimulation, the expression of TRPV1 and TRPA1 in trigeminal ganglion (TG) neurons, and TG neuronal excitability to cold stimulation following facial capsaicin injection were examined in rats. The head‐withdrawal reflex threshold (HWRT) to cold stimulation of the lateral facial skin was significantly decreased following facial capsaicin injection. This reduction of HWRT was significantly recovered following local injection of TRPV1 antagonist as well as TRPA1 antagonist. Approximately 30% of TG neurons innervating the lateral facial skin expressed both TRPV1 and TRPA1, and about 64% of TRPA1‐positive neurons also expressed TRPV1. The TG neuronal excitability to noxious cold stimulation was significantly increased following facial capsaicin injection and this increase was recovered by pretreatment with TRPA1 antagonist. These findings suggest that TRPA1 sensitization via TRPV1 signaling in TG neurons is involved in cold hyperalgesia following facial skin capsaicin injection.     

Non-invasive detection of coronary artery disease by body surface electrocardiographic mapping after dipyridamole infusion

Electrocardiographic changes after dipyridamole infusion (0.568 mg/kg/4 min) were studied in 41 patients with coronary artery disease and compared with those after submaximal treadmill exercise by use of the body surface mapping technique. Patients were divided into three groups; 19 patients without myocardial infarction (non-MI group), 14 with anterior infarction (ANT-MI) and eight with inferior infarction (INF-MI). Eighty-seven unipolar electrocardiograms (ECGs) distributed over the entire thoracic surface were simultaneously recorded. After dipyridamole, ischemic ST-segment depression (0.05 mV or more) was observed in 84% of the non-MI group, 29% of the ANT-MI group, 63% of the INF-MI group and 61% of the total population. Exercise-induced ST depression was observed in 84% of the non-MI group, 43% of the ANT-MI group, 38% of the INF-MI group and 61% of the total. For individual patients, there were no obvious differences between the body surface distribution of ST depression in both tests. The increase in pressure rate product after dipyridamole was significantly less than that during the treadmill exercise. The data suggest that the dipyridamole-induced myocardial ischemia is caused by the inhomogenous distribution of myocardial blood flow. We conclude that the dipyridamole ECG test is as useful as the exercise ECG test for the assessment of coronary artery disease.     

Screening for Gaucher Disease Using Dried Blood Spot Tests: A Japanese Multicenter,Cross-sectional Survey

Objective For patients with Gaucher disease (GD), a rare, inherited lysosomal storage disease, obtaining a definitive diagnosis is currently time-consuming and costly. A simplified screening method to measure the glucocerebrosidase (GBA) activity using dried blood spots (DBS) on filter paper has recently been developed. Using this newly developed screening method, we evaluated real-world GD screening in patients suspected of having GD. Methods This multicenter, cross-sectional, observational study with a diagnostic intervention component evaluated real-world screening in patients suspected of having GD based on their clinical symptoms and a platelet count <120,000/μL. The endpoint was the number of patients with low GBA activity determined using DBS. Results In 994 patients who underwent initial DBS screening, 77 had low GBA activity. The assay was not repeated in 1 patient who was diagnosed as having a high possibility of GD due to clinical symptoms, and a further 21 patients completed the study without undergoing the second assay. Of the remaining 55 patients who had 2 DBS assays performed, 11 had a low GBA activity in both assays. Overall, DBS screening identified 12 (1.2%) patients with a low GBA activity, a proportion consistent with prior screening studies. Conclusion These results suggest that the simplified DBS method was less burdensome to patients, was easily utilized by many physicians, and could be a useful first-tier screening assay for GD prior to initiating burdensome genetic testing.