Antitumor effects of oral administration of an interferon-inducing pyrimidinone,Bropirimine, on murine renal-cell carcinoma

Bropirimine [2-amino-5-bromo-6-phenyl-4-(3H)-pyrimidinone] is a low-molecular-weight compound that acts as an inducer of interferon in several animal species. Experiments were designed to explore the possibility of using this drug for the treatment of renal-cell carcinoma (RCC). Euthymic BALB/c mice were inoculated with murine RCC (Renca) cells and given graded doses of Bropirimine p.o. for 5 consecutive days beginning on day 1 following tumor inoculation. These mice were killed and tumors were excised on day 21. Bropirimine significantly (P<0.01) inhibited the tumor growth at a daily dose of 1,000 or 2,000 mg/kg. No adverse effect or toxicity was noted at 1,000 mg/kg, and at 2,000 mg/kg there was only a marginal body-weight reduction without any other appreciable side effect. In addition to the inhibition of tumor growth, there was a small yet significant (P<0.05) increase in the duration of survival (in days) in the Bropirimine-treated animals. When the treatment was delayed to begin on day 6 following tumor inoculation, Bropirimine did not suppress tumor growth in euthymic mice, pointing to the importance of the timing of the treatment. In athymic nude BALB/c mice lacking T-cells or T-cell function, Bropirimine also inhibited tumor growth (P<0.01). The antitumor effect of this drug was abolished by pretreatment with anti-asialo GM1 serum, which eliminated natural killer (NK) activity in euthymic mice. In vivo treatment with Bropirimine augmented the cytotoxicity of lymphocytes isolated from the spleens or lungs of the tumor-bearing mice, which were active against Renca and YAC-1 cells in vitro. This activity was NK-cell-dependent as judged on the basis of the results of the in vitro complement-dependent cytotoxicity assay. Since Bropirimine induced interferon (IFN)-/ production, significantly (P<0.05) elevating its serum concentration, and since this drug mimics the effects of IFN-/, it seemed likely that the Bropirimine-induced NK cell augmentation we found was mediated by IFN-/. These results suggest that Bropirimine, a booster of NK activity, may have potential as an adjunct to other therapeutic modalities in the treatment of human RCC.     

PCNA immunostaining combined with AgNOR staining in esophageal squamous cell carcinoma to identify patients with a poor prognosis

Immunostaining of the proliferating cell nuclear antigen (PCNA) provides important information about cell kinetics and is easily performed on routinely obtained formalin-fixed, paraffin-embedded materials. We report herein the results of a retrospective study on PCNA staining in esophageal cancer undertaken to determine its significance. As this study indicated that immunoreactivity was preserved in specimens fixed within 24 h, only 31 specimens from surgical patients were available for this investigation. The mean PCNA index of the patients without invasion to the adventitia (35.7±17.9) was significantly lower than that of those with invasion to the adventitia or neighboring structures (49.7±14.5), while the PCNA index did not correlate with other clinicopathologic parameters such as histologic type, lymph node metastases, or prognosis. However, when an analysis of PCNA staining was combined with an analysis of argyrophilic nucleolar organizer region (AgNOR) staining, a correlation with prognosis was found. In fact, seven patients with a high PCNA index (44) and AgNOR count (6) had a significantly poorer prognosis than the remaining 22 (P=0.0014), and six of these seven patients died within 2 years. These results indicate that this combined evaluation may be useful for the identification of patients with a poor prognosis among those undergoing surgery for esophageal squamous cell carcinoma.     

Renal cell carcinoma in a patient with malignant lymphoma: a case report

We herein report a case of renal cell carcinoma coexisting with malignant lymphoma. A 69-year-old male complained of an obstruction of the right nasal cavity due to a solid tumor in the paranasal sinuses. A biopsy of the tumor revealed diffuse, large cell and B cell type non-Hodgkin lymphoma. At the same time, just before the patient was scheduled to receive therapy, a left renal cell carcinoma was found. He therefore underwent a left radical nephrectomy.     

Coronary artery bypass grafting in two patients with single coronary artery

We experienced two patients with single coronary artery who underwent CABG using arterial grafts successfully. In two patients coronary angiography demonstrated a single coronary artery which was originated in left coronary sinus and was bifurcated to LAD and LCx, and then RCA branched off proximal LAD, passing in front of the right ventricular out flow tract (Sharbaugh Type L-IIa). To the first patient, a 52-year-old man who had angina on exertion due to long stenosis of RCA, CABG to RCA using RITA was carried out. To the second patient, a 57-year-old man who had inferior myocardial infarction due to 90% stenosis of proximal LAD, CABG to RCA using RITA and LAD using LITA was carried out. Single coronary artery without additional congenital cardiac anomalies may lead to myocardial ischemia, necessitating CABG as coronary reconstructions.     

A case of traumatic aneurysm of innominate artery with occlusion of right subclavian artery

A 42-year-old woman with history of chest blunt trauma from an automobile accident 250 days earlier had suffered easy fatigability of the right upper extremity. She had difference of blood pressure between upper extremities, 94/60 mmHg in the right and 126/70 mmHg in the left. Chest CT showed dilation of the innominate artery which compressed the trachea. Aortography showed an aneurysm of the innominate artery and occlusion of the right subclavian artery at its origin. The aneurysm of the innominate artery was resected and replaced with a 6 mm Dacron graft with aid of the external shunt. The right subclavian artery was also reconstructed with same graft. The aneurysm of the innominate artery should be suspected as a rare complication in blunt trauma of the chest.     

A case of ABO-incompatible renal transplant patient with non-insulin-dependent diabetes mellitus; long-standing observation of serial glomerular change by protocol biopsy

A 41-yr-old patient with non-insulin-dependent diabetes mellitus (NIDDM), before and after ABO-incompatible renal transplant, is reviewed using serial protocol biopsy. Although she recovered from delayed hyperacute rejection (DHAR) immediately post-transplantation, her graft function deteriorated gradually. A mild acute transplant glomerulitis, noted at the 155th day post-transplantation, progressed to pronounced chronic transplant glomerulopathy over 5 yr. In the specimen of the last biopsy, at 5 yr post-transplantation, glomeruli demonstrated an exudative hyaline lesion, which was characteristic of diabetic nephropathy in addition to chronic transplant glomerulopathy. Therefore, we made a diagnosis of this glomerular lesion as chronic transplant glomerulopathy complicated by diabetic glomerulopathy. Considering the result of this case, the protocol biopsy is a useful procedure to diagnose an accurate cause of graft dysfunction in individual cases. It is concluded that the protocol biopsy is apparently useful for the detection of various pathological processes occurring in allograft and may contribute to a strategy for improvement of graft survival.     

Temporal changes in airway protective reflexes elicited by an endotracheal tube in surgical patients anaesthetized with sevoflurane

In order to elucidate temporal changes in airway reflex responses to prolonged tracheal intubation, 14 patients anaesthetized with sevoflurane were studied. In each spontaneously breathing patient with an endotracheal tube in place, the end-tidal concentration of sevoflurane was slowly decreased from the initial value of 1.3% until signs of airway irritation were observed. The value of end-tidal sevoflurane concentration at which the airway reflexes occurred (T(ar)) and the types of airway reflex response elicited at onset of airway reflex response were determined during the periods immediately before (presurgical period) and after surgery (post-surgical period), with an interval ranging from 2 to 7 h between the two periods. There was no significant difference in the values of T(ar) between the presurgical period (0.6 +/- 0.3%, mean +/- SD) and the post-surgical period (0.7 +/- 0.1%). There was a considerable difference in the type of airway reflexes elicited during the two different periods; the initial responses during the presurgical period were the apnoeic reflex and/or forceful expiratory efforts, whereas the initial response during the post-surgical period, in the majority of patients, was the swallowing reflex. Our results indicate that there may be adaptation mechanisms responsible for temporal changes in airway protective reflexes after prolonged endotracheal intubation in surgical patients.     

Laparoscopic bowel resection for early colon cancer

Following the successful introduction of laparoscopic cholecystectomy, many reports confirming the feasibility of using laparoscopy for bowel resection and predicting that it would be advantageous in terms of its minimal invasiveness have been published. In the context of cancer treatment, however, the feasibility of lymphadenectomy, the risk of recurrence, and survival have emerged as major concerns. Even though mucosal cancer (Tis) can be treated by endoscopic resection (ER), when this is not possible open surgery (OS) must be performed. In patients with T1 cancer, tumors showing slight submucosal layer invasion (sm 1) can be treated in the same way as Tis (in cancer) cancers. But 5% to 10% of patients with T1 cancer have massive submucosal layer invasion (sm 2-3) with paracolic lymph node metastasis. At least partial bowel resection with paracolic lymphadenectomy is considered necessary for T1 (sm 2-3) cancers in principle. In summary, laparoscopic local excision of Tis cancers that are endoscopically unresectable and laparoscopically assisted partial resection with paracolic lymphadenectomy for T1 cancers have become accepted because local excision and partial resection with paracolic lymphnedectomy are fairly simple to perform laparoscopically. Therefore as a strategy for the treatment of early colorectal cancer (CRC), minimally invasive laparoscopic bowel resection (LBR) has been positioned between endoscopic resection (ER) and open surgery (OS). While the difficulty of performing radical lymphadenectomy is considered one of the greatest obstacles to the introduction of laparoscopic bowel resection (LBR) for the treatment of advanced colorectal cancer (CRC), early colon cancer is a good indication for laparoscopic bowel resection.     

Dandy-Walker syndrome successfully treated with cystoperitoneal shunting--case report

A neonate presented with Dandy-Walker syndrome manifesting as a large posterior cranial fossa cyst, aplasia of the lower cerebellar vermis, and elevation of the confluence of the sinuses but without hydrocephalus. A cystoperitoneal shunt was placed at one month after birth. The cyst diminished in size, and marked development of the cerebellar hemispheres and descent of the confluence of sinuses were observed, but not vermis development. The primary pathology of Dandy-Walker syndrome is posterior cranial fossa cyst formation due to passage obstruction in the fourth ventricle exit area and aplasia of the lower cerebellar vermis. The first choice of treatment in patients with Dandy-Walker syndrome in whom the cerebral aqueduct is open is cystoperitoneal shunt surgery, regardless of the presence or absence of hydrocephalus.     

The expression of Ca2+/calmodulin-dependent protein kinase I in rat retina is regulated by light stimulation

Ca2+/calmodulin-dependent protein kinase I (CaM-kinase I) in rat retina was analyzed by immunohistochemical analysis, Western blot analysis and kinase activity assay. Western blot analysis revealed two immunoreactive bands similar to those detected in the brain. Developmental studies revealed that CaM-kinase I expression increased in accordance with postnatal development. Expression of CaM-kinase I in the retinas of rats raised in the complete darkness markedly decreased. CaM-kinase I activity assay supported these findings. Synapsin I was shown to be a possible intrinsic substrate of CaM-kinase I in rat retina. These results elucidated that CaM-kinase I is expressed in the retina and may play an important role in the retinal functions and that the expression of CaM-kinase I is regulated by light stimulation.