Quantitative analysis of spermatogenic DNA synthesis in the rat using a monoclonal anti-5-bromodeoxyuridine antibody

Summary. The utility of the 5-bromodeoxy-uridine (BrdUrd) labelling technique for the quantitative analysis of spermatogenic deoxyribonucleic acid (DNA) synthesis was investigated in the rat. Rat testicles were labelled by a single intraperitoneal injection of 100 mg kg⁻¹ of BrdUrd. The testicles were removed 1 h after injection, fixed in Bouin's fluid and embedded in paraffin. BrdUrd-labelled cells were detected by immunohistochemical staining using a monoclonal anti-BrdUrd antibody. The number of BrdUrd-labelled tubules per total number of tubules (percent L.T.), the number of BrdUrd-labelled cells per total number of tubules (tubular ratio) and the number of BrdUrd-labelled cells per number of Sertoli cells (Sertoli cell ratio in BrdUrd-labelled cells) were calculated as indices of spermatogenic DNA synthesis during each stage of the seminiferous epithelial wave. BrdUrd labelling was found exclusively in the nuclei of spermatogonia and in preleptotene spermatocytes in the seminiferous epithelium. The percent L.T. was generally greater than 50%, except in stages VI, VII and XIV, and the tubular as well as Sertoli cell ratios in BrdUrd-labelled cells was greater than 2.0 and 0.15, respectively, in stages I, II-III, V, VIII, X, and XII. The tubular ratio and Sertoli cell ratio in BrdUrd-labelled cells along the seminiferous epithelial wave had two distinct peaks. The distribution of the tubular ratio using the BrdUrd-labelling technique correlated well with the distribution previously established by measuring tritiated thymidine uptake per tubule. Thus, the BrdUrd labelling technique, which is more efficient than the tritiated thymidine labelling technique, can be used to quantitatively evaluate spermatogenic DNA synthesis.     

A double blind study of the effectiveness of ketotifen in preventing the development of asthma in atopic dermatitis patients

Many asthmatic children have experienced atopic dermatitis in their younger days. As it is very difficult to cure childhood asthma we attempted to determine the anti-allergic drug effects in preventing the development of asthma by using ketotifen on atopic dermatitis patients. The study was designed as a placebo controlled double blind trial of 128 atopic dermatitis patients aged from 2-34 months. 91 patients were given complete analysis in the study, 33 patients were given only a safety rate and 4 patients were dropped. The 91 patients were followed for 52 weeks. Our primary finding was that the development of bronchial asthma was inhibited in the ketotifen group compared to the placebo controlled group with a statistically significant degree (p less than 0.001). We also found that clinical symptoms of atopic dermatitis were significantly improved in the ketotifen group (p less than 0.001). Only 5 patients complained of mild side effects.     

The effects of interferon-beta on phorbol ester or calcium ionophore-induced intercellular adhesion molecule-I expression in epidermal carcinoma cells.

Keratinocyte intercellular adhesion molecule (ICAM)-I expression is induced by interferon (IFN)-gamma. It has been previously reported that IFN-beta suppresses IFN-gamma-induced ICAM-I expression in A431 cells, a human squamous cell carcinoma cell line. In this study, the suppression mechanisms were investigated at the post second messenger level. Both 12-O-tetradecanoylphorbol-13-acetate (TPA) and calcium ionophore (A23187) induce ICAM-I expression in A431 cells. ICAM-I expression induced by either was not suppressed with cotreatment with IFN-beta. Furthermore, IFN-beta did not inhibit the translocation of protein kinase C (PKC) by TPA. It appears that the pathways involved in ICAM-I expression induced by activation of PKC or increased in intracellular Ca++ are not affected by IFN-beta.     

Early gastric cancer manifested as brain metastasis: Report of a case

A case of early gastric cancer, limited to submucosal layer, which was manifested as cerebral metastasis is presented herein. A 47-year-old man was admitted to Nagaoka Chuo General Hospital with convulsions and a disturbance in consciousness, where a computed tomography (CT) scan revealed a cerebral tumor in the left temporal lobe. The resected tumor was identified as a metastatic adenocarcinoma. Further investigation revealed gastric cancer involving the posterior wall of the cardia. At laparotomy, multiple and small metastases of the liver and a jejunal metastasis were found, and a palliative total gastrectomy was performed. The surgical specimen revealed a protruding, poorly differentiated medullary adenocarcinoma, with invasion of the submucosal layer. The patient died 4 months after undergoing the laparotomy. This case report is presented to make clinicians aware of the possibility that early gastric cancers may present as brain metastasis.     

Comparison of circulatory and respiratory responses between supplementary epidural buprenorphine and eptazocine administration during and immediately after total intravenous anesthesia

Opioid supplements are often required in total intravenous anesthesia (TIVA). Most ϰ-opiate receptors are found in the spinal cord, wherea μ-opiate receptors are widespread throughout the brain and spinal cord. Buprenorphine has a strong μ-action with a minute ϰ-action, while eptazocine stimulates ϰ-receptors only. From these, epidural eptazocine is expected to exert strong spinal analgesia by ϰ-stimulation without μ-action, which produces circulatory and respiratory depression. Therefore, the clinical effects of epidural opioids on circulation, respiration, and analgesia were compared. Continuous epidural administration of eptazocine or buprenorphine was combined with TIVA in patients scheduled for elective abdominal surgery. Epidural opioid administration was continued throughout and for 72h after anesthesia. A significant analgesic effect (P<0.01) of epidural eptazocine without circulatory and respiratory depression was observed. With epidural buprenorphine, circulatory and respiratory depression during and immediately after anesthesia were significant (P<0.05). These results suggest that medullary μ-stimulation by an epidural opioid induces circulatory (hypervagotonicity and hypervagosensitivity) and respiratory depression, while ϰ-stimulation produces only minimal effects on circulatory and respiratory systems.     

Microsurgical and magnetic resonance imaging anatomy of the cerebello-medullary fissure and its application during fourth ventricle surgery.

The cerebellomedullary fissure, the only entrance or exit to the fourth ventricle, is surrounded rostrally by the cerebellar tonsils and the biventral lobules and caudally by the medulla oblongata, the tela choroidea, and the lateral recesses. This fissure is an important route in operations on the fourth ventricle. We studied the microsurgical and magnetic resonance imaging (MRI) anatomy of the fissure by using autopsied normal cerebellum. MRI revealed that the fissure is visible as a slit and is indicated by the enhanced choroid plexus and the flocculus. Oriented by the anatomical information thus obtained, we have surgically treated nine patients with a tumor either in or around the fourth ventricle. Preoperative MRI clearly demonstrated the tumors in relation to the cerebellomedullary fissure. It revealed the precise anatomical location and extension of the tumor, not only its inferior extension but also its lateral one. The MRI findings and microsurgical anatomy of the cerebellomedullary fissure were quite useful for the removal of the tumors in the fourth ventricle.     

Hyperthermo-chemo-radiotherapy as a definitive treatment for patients with early esophageal carcinoma.

Ten patients with early stage esophageal carcinoma were treated with hyperthermo-chemo-radiotherapy (HCR) without surgery. The reasons for the inoperability of these patients included medically inoperable unresectable cancers, advanced age, and/or refusal to undergo surgery. The diagnosis of early esophageal carcinoma was determined by esophagograms, endoscopy, and ultrasonography. Squamous cell carcinoma was histopathologically confirmed in each case. Each patient underwent four to nine sessions of hyperthermic treatment combined with external irradiation and chemotherapy using bleomycin; eight of these patients received additional radiation, and two terminated treatment after the HCR therapy. The tumors in all patients showed either a complete response (CR) or a partial response (PR) after HCR therapy; in two patients viable cancer cells remained, but later disappeared after additional radiation. Five patients experienced no local recurrence for 12 to 70 months and are now alive and doing well, three died of other medical conditions without any evidence of esophageal cancer, and two died of recurrent esophageal cancer 20 to 27 months after initial admission. All ten patients tolerated the HCR well without any systemic side effects. However, in two patients, esophageal erosion was recognized endoscopically. HCR therapy therefore deserves serious consideration when treating patients with small malignant lesions of the esophagus who, for various reasons, are unable to undergo surgery.