Mechanism of histamine release by alpha-chymotrypsin from isolated rat mast cells.

Alpha-chymotrypsin (CT) was modified chemically and physically by the treatments with diisopropyl fluorophosphate, L-(1-tosylamide-2-phenyl) ethylchloromethylketone, hydrogen peroxide and heat. After these treatments, CT lost or decreased both the enzymic activity and ability of releasing histamine from rat mast cells. Ca++ was essential for histamine release by CT, while it enhanced only slightly the enzymic activity. Process of histamine release by CT could be separated into two stages: CT-dependent but not Ca++-dependent, and Ca++-dependent but not CT-dependent. The activated state of mast cells produced by CT decayed rapidly at 37 degrees C in the absence of Ca++, but these cells responded to Ca++ by adding CT once again, suggesting reconstitution of cell membrane structure affected by CT. Isoproterenol, epinephrine, prostaglandin E1, and dibutyryl-cyclic AMP (0.01-0.1 mM) did not inhibit release of histamine induced by CT. Neither theophylline (0.01-0.1 mM) alone nor the combinations of these cyclic AMP-active agents with theophylline inhibited the release of histamine. But, in the presence of papaverine (0.01-0.1 mM) a marked, dose-dependent inhibition was observed. These data suggest that 1) release of histamine by CT from rat mast cells is causally related to its hydrolytic activity, 2) this activity causes a reversible change on mast cell membrane which probably facilitates Ca++-influx through the cell membrane, and 3) there are subtle differences among CT, compound 48/80 and antigens concerning the effect of cyclic AMP-active agents in histamine-releasing mechanisms in mast cells.     

Projections from the parietal cortex to the brain stem nuclei in the cat, with special reference to the parietal cerebro-cerebellar system

Direct projections from the anterior portions of the parietal cortex of the cat to the brain stem nuclei, especially those sending fibers to the cerebellum, were investigated by the Nauta-Gygax and Fink-Heimer methods. Following unilateral lesions of the anterior portions of the middle suprasylvian and/or lateral gyri, a significant amount of pericellular degeneration was found almost entirely ipsilaterally in the rostral levels of the red nucleus and its vicinities, and in the pontine nuclei. Projection fibers to the pontine nuclei appeared to extend over several longitudinal, columnar zones in the pontine gray. Fibers from the anterior portion of the lateral gyrus were observed mainly in the paramedian and lateral nuclei, and those from the middle suprasylvian gyrus in the ventral, paramedian and lateral nuclei. Degeneration in the nucleus reticularis tegmenti pontis of Bechterew was slight, and found bilaterally with ipsilateral predominance. The significance of the anterior portion of the parietal cortex of the cat as a link of cerebro-cerebellar loops was discussed.     

Effect of steroid on antiemetic for side effect of anticancer chemotherapy

The side effect of anticancer agents such as nausea and vomiting frequently interrupt chemotherapy. To reduce these side effects, 5-hydroxytryptamine (5-HT3) receptor antagonist or metoclopramide is administered combined with steroid. In this study, we examined the effect of 5-HT3 receptor antagonist on the frequency of nausea and vomiting in a male cancer patient treated with/without steroid. This patient in his sixties had esophageal cancer (stage IV). He was administered nedaplatin 100 mg/day for 1 day and then 5-fluorouracil (5-FU) 750 mg/day for 5 days combined with radiotherapy (60 Gy) as one cycle of this chemotherapy. In the first cycle, 5-HT3 receptor antagonist was administered, and in the second, the antagonist was administered after treatment with steroid. The blood levels of total bilirubin, GOT, GPT, BUN, Cre, Na, K and Cl were stable normally during both cycles of the chemotherapy, indicating that the hepatopathy and nephropathy which cause nausea and vomiting did not occur in these periods. The frequency and period of the nausea and vomiting were one-third decreased, respectively, by the combination of 5-HT3 receptor antagonist and steroid.     

Recent perspectives second-line chemotherapy for breast cancer

The recent development of chemotherapeutic agents for breast cancer will be reviewed. The paradigm shift from CMF to anthracycline containg regimens +/- taxanes in an adjuvant setting may be considered to decide the sequence of recommended chemotherapy for metastatic breast cancer. Recurrent breast cancer patients who never have undergone anthracycline-containing regimens should be treated with anthracycline regimens. Patients who have already received only an anthracycline-containing regimen in adjuvant therapy will be treated with taxane with or without capecitabine. For patients already having received both anthracycline and taxanes, capecitabine monotherapy will be indicated as a first-line treatment. Physicians will choose the best treatment option among chemotherapeutic agents for patients with distant metastasis.     

A case of anal fistula cancer probably developing from intraluminal dissemination of rectal cancer

A 63-year-old man with a history of anal fistula was admitted to our hospital because the anal pain didn't disappear after the operation. On digital examination, a hard mass measuring 3.0 cm in diameter was found at the anal canal. Biopsy of the mass showed moderately differentiated adenocarcinoma. Colonoscopy revealed another rectal cancer at 15 cm from anal verge. Biopsy of the tumor also showed moderately differentiated adenocarcinoma, resembling the anal canal tumor. Because the histological findings of both tumors were nearly identical, we considered that cancer cells from the rectal cancer had been implanted and developed the metastatic tumor in the anal fistula. The patient underwent anterior resection for the rectal cancer, and a local resection for the anal canal cancer. Immunohistochemical staining for Ki-67, p53, Muc2, CD10, CK-7, and CK-20 revealed similar patterns in both tumors. Additionally, genetic analysis for p53, K-ras, and MSI revealed similar patterns in both tumors. We may suggest from these results that cancer cells from the rectal cancer had been implanted and developed the metastatic tumor in the anal canal.