THE EXPRESSION OF THE fms GENE AND THE GENE PRODUCT IN THYROID TUMOR

The amplification of the fms gene DNA was investigated in 5 human thyroid tumors. No significant amplification or rearrangement was observed in tumor DNA. The expression of the fms gene product was also investigated in 20 thyroid tumor tissues embedded in paraffin using a polyclonal antibody to the fms oncogene product immunohistochemically. Ten out of 20 samples showed clearly positive, 6 out of 20 were weakly positive but 4 out of 20 were negative. Therefore, the fms oncogene might play an important role for thyroid carcinogenesis, and it might also be of possible importance for understanding the mechanism of thyroid carcinogenesis

CD44 is a physiological E-selectin ligand on neutrophils

The selectin family of adhesion molecules and their glycoconjugated ligands are essential for blood polymorphonuclear neutrophil (PMN) extravasation into inflammatory and infectious sites. However, E-selectin ligands on PMNs are not well characterized. We show here that CD44 immunopurified from G-CSF–differentiated 32D cells or from peripheral blood PMNs binds specifically to E-selectin. In contrast, CD44 extracted from bone marrow stromal or brain endothelial cell lines does not interact with E-selectin, suggesting cell-specific posttranslational modifications of CD44. PMN-derived CD44 binding activity is mediated by sialylated, α(1,3) fucosylated, N-linked glycans. CD44 enables slow leukocyte rolling on E-selectin expressed on inflamed endothelium in vivo and cooperates with P-selectin glycoprotein ligand–1 to recruit neutrophils into thioglycollate-induced peritonitis and staphylococcal enterotoxin A–injected skin pouch. CD44 extracted from human PMNs also binds to E-selectin. Moreover, we demonstrate that CD44 is hypofucosylated in PMNs from a patient with leukocyte adhesion deficiency type II, suggesting that it contributes to the syndrome. These findings thus suggest broader roles for CD44 in the innate immune response and uncover a potential new target for diseases in which selectins play a prominent role

Dehydrogenation of Conjugated Cholic Acid by Escherichia coli

7α-Dehydrogenation of taurocholic acid and glycocholic acid by Escherichia coli (E. coli) was examined in aerobic and anaerobic culture conditions. Bile acids in the culture medium of E. coli were extracted, separated into free, glycine-conjugate and taurine-conjugate fractions by piperidinohydroxypropyl dextran gel column chromatography, hydrolyzed in alkali and analyzed by gas-liquid chromatography. Both conjugated cholic acids were dehydrogenated to the corresponding 3α,12α-dihydroxy-7-oxo-5β-cholan oic acid without deconjugation and no deconjugation of both conjugated cholic acid was detected in aerobic cultures. But there was little transformation in anaerobic cultures. These data suggest that conjugated cholic acids are taken up by E. coli in an aerobic culture as conjugate forms, dehydrogenated without deconjugation and excreted from the cell as conjugate forms

A Case of Streptobacillus moniliformis Infection with Cutaneous Leukocytoclastic Vasculitis

A 71-year-old man presented with a high fever, polyarthralgia, petechiae and palpable purpura accompanied by livedoid change on his legs and feet. Histopathological findings of the purpura revealed perivascular infiltration of neutrophils, mononuclear cells, and nuclear debris, and extravasation of red cells mainly in the upper dermis: all signs consistent with leukocytoclastic vasculitis. Small vessel thrombi, which are characteristic features of septic vasculopathy, were also observed. Direct immunofluorescence showed negative results. Blood culture revealed the growth of gram-negative bacilli. Subsequently, 16S rRNA sequencing of DNA confirmed the organism as Streptobacillus moniliformis, which is the causative pathogen of rat-bite fever. He had frequently encountered wild rats in his house although there was no evidence of rat bite on his body. Empiric therapy with intravenous administration of ceftriaxone in combination with azithromycin hydrate led to a prompt resolution of the symptoms. Precise history-taking related to contact with rats and detection of skin eruptions suggestive of leukocytoclastic vasculitis on the extremities, especially on the feet, can be clues to Streptobacillus moniliformis infection. Familiarity with its cutaneous features is important for early diagnosis; the evidence herein may also help in understanding its underlying pathogenesis

The Amphibious Mudskipper: A Unique Model Bridging the Gap of Central Actions of Osmoregulatory Hormones Between Terrestrial and Aquatic Vertebrates

Body fluid regulation, or osmoregulation, continues to be a major topic in comparative physiology, and teleost fishes have been the subject of intensive research. Great progress has been made in understanding the osmoregulatory mechanisms including drinking behavior in teleosts and mammals. Mudskipper gobies can bridge the gap from aquatic to terrestrial habitats by their amphibious behavior, but the studies are yet emerging. In this review, we introduce this unique teleost as a model to study osmoregulatory behaviors, particularly amphibious behaviors regulated by the central action of hormones. Regarding drinking behavior of mammals, a thirst sensation is aroused by angiotensin II (Ang II) through direct actions on the forebrain circumventricular structures, which predominantly motivates them to search for water and take it into the mouth for drinking. By contrast, aquatic teleosts can drink water that is constantly present in their mouth only by reflex swallowing, and Ang II induces swallowing by acting on the hindbrain circumventricular organ without inducing thirst. In mudskippers, however, through the loss of buccal water by swallowing, which appears to induce buccal drying on land, Ang II motivates these fishes to move to water for drinking. Thus, mudskippers revealed a unique thirst regulation by sensory detection in the buccal cavity. In addition, the neurohypophysial hormones, isotocin (IT) and vasotocin (VT), promote migration to water via IT receptors in mudskippers. VT is also dipsogenic and the neurons in the forebrain may mediate their thirst. VT regulates social behaviors as well as osmoregulation. The VT-induced migration appears to be a submissive response of subordinate mudskippers to escape from competitive and dehydrating land. Together with implications of VT in aggression, mudskippers may bridge the multiple functions of neurohypophysial hormones. Interestingly, cortisol, an important hormone for seawater adaptation and stress response in teleosts, also stimulates the migration toward water, mediated possibly via the mineralocorticoid receptor. The corticosteroid system that is responsive to external stressors can accelerate emergence of migration to alternative habitats. In this review, we suggest this unique teleost as an important model to deepen insights into the behavioral roles of these hormones in relation to osmoregulation

Daily low-dose cisplatin and concurrent thoracic irradiation for poor-risk patients with unresectable non-small-cell lung cancer.

A pilot study was conducted to assess the efficacy and feasibility of daily low-dose cisplatin with concurrent thoracic irradiation for clinically unresectable non-small-cell lung cancer (NSCLC). Patients with inoperable NSCLC who had poor risk factors such as advanced age, poor performance status, poor lung function, or concomitant active malignancy were entered into the study. Low-dose cisplatin (6 mg/m2) was administered daily before concurrent thoracic irradiation (2 Gy/day; total dose of 60 Gy) was given. Twenty-five patients were registered. The majority of the patients had either stage IIIA (24.0%) or stage IIIB (60.0%) disease. Fifteen patients (60.0%) completed the planned treatment. Both chemotherapy and radiotherapy were stopped in 3 patients (12.0%) due to poor response, and 7 patients (28.0%) partly received radiotherapy alone as a result of their toxicity response. The proportion of total administered dose to planned dose was 90.9% for chemotherapy and 99.3% for radiotherapy, which were comparable to those in previous studies for LA-NSCLC patients without poor risk factors. Grade 3 leukopenia and neutropenia developed in 14 patients (56.0%) and 10 patients (40.0%), respectively, but grade 4 toxicity was not encountered. Grade 3 pneumonitis and esophagitis were observed in 4 patients (16.0%) and 2 patients (8.0%), respectively. The overall response rate was 60.0%. The median survival time was 22 months, and the 2-year survival rate was 50.3%. Daily low-dose cisplatin and concurrent thoracic irradiation were well tolerated even by poor-risk patients with NSCLC, and showed a therapeutic efficacy similar to that for good-risk patients.</p