Ethanol Feeding Causes Inactivation of Both State 1 and State 2 Rat Hepatic Asialoglycoprotein Receptors

Previous studies have shown that ethanol feeding in rats causes inactivation and redistribution of ˜50% of the total asialoglycoprotein receptors (ASGPRs) in hepatocytes (Tworek et al., J. Biol. Chem. 271:2531, 1996), and that two equal populations of hepatic ASGPRs mediate ligand uptake and processing via two functionally different pathways (Weigel in Glycoconjugates: Composition, Structure and Function , Marcel Dekker, 1992, p. 421). The purpose of this study was to determine if ethanol feeding causes preferential inactivation of only one of these two ASGPR populations, which have been designated state 1 and state 2 ASGPRs. The state 2, but not state 1, ASGPRs are inactivated in isolated hepatocytes by a variety of drugs and inhibitors. State 2 ASGPRs can also be inactivated in permeable cells by ATP treatment and then reactivated by treatment with fatty acyl coenzyme As. In the present study, permeable cell assays for state 2 ASGPR inactivation and reactivation were used to assess whether hepatocytes from ethanol-fed rats contain inactive state 2 ASGPRs. The results show that preferential inactivation of one ASGPR population does not occur after ethanol feeding. That inactive ASGPRs could not be reactivated by treatment with palmitoyl-coenzyme A to a greater extent in ethanol-fed versus control cells indicates there is not a larger pool of inactivated state 2 ASGPRs in treated cells. We conclude that ethanol feeding causes equal inactivation of both state 1 and state 2 ASGPRs. Ethanol feeding may represent the first treatment found to inactivate state 1 ASGPRs.     

Left ventricular fibroma in an aged patient: Report of a case

We report herein the case of a 77-year-old man with a left ventricular tumor originating from the papillary muscle of the left ventricular wall, in whom a successful tumor resection with mitral valve replacement was performed. The pathological diagnosis of the tumor was confirmed as cardiac fibroma. His postoperative course was uneventful and he is currently well with no signs of recurrence 2 years after surgery.     

Intracerebral penetration of carteolol hydrochloride in rats

To elucidate the penetrability of carteolol, a β-adrenoceptor antagonist (β-blocker) into the brain of rats, intracerebral and serum concentrations of the compound were determined in male rats receiving single or repetitive oral administration of carteolol hydrochloride at 30 mg/kg. The time-course of the intracerebral concentration of carteolol following single IV administration of the compound at 10 and 30 mg/kg was also studied in male rats. A high-performance liquid chromatography method was used to determine the intracerebral and serum concentrations. Following single oral dosing, the intracerebral concentration of carteolol reached a maximum of 0.074 μg/g at 2 h postdosing and declined with a half-life of 3.7 h, and the C_max and AUC of carteolol in the brain were 12.5% and 19.8% of those in serum. The intracerebral and serum concentrations of carteolol were determined in male rats receiving repetitive oral dosing of the compound once daily for 7 days. The concentration of carteolol in the brain and serum at 1 h postdosing varied within a range of 0.059–0.091 μg/g and 0.321–0.443 μg/ml, respectively, throughout the dosing period, showing no changes in the penetrability of the compound into the brain due to repeated dosing. The concentration of carteolol in the brain and serum increased in a dose-dependent manner in rats receiving a single IV administration of the compound. The elimination half-life of carteolol in the serum and brain was 0.6–0.8 h and 1.3–1.7 h, respectively, in rats following single IV dosing of the compound. The half-life in the brain was about twice as long as that in the serum. The brain to serum concentration ratio was 0.306:0.499. From the above results, it was concluded that carteolol is distributed from the circulation to the brain with low penetrability. Received: 30 October 1996/Final version: 16 December 1996     

Allogeneic cell stimulation enhances cytomegalovirus replication in the early period of primary infection in an experimental rat model.

BACKGROUND: Cytomegalovirus (CMV) diseases commonly occur in allograft recipients in the early post-transplant period. However, factors responsible for the high incidence of CMV diseases during this period are not yet fully defined. METHODS: Wistar-Furth (WF; RT-1(u)) rats were inoculated with 10(4) plaque-forming units (PFU) of rat CMV (RCMV) intraperitoneally, and then transplanted with allogeneic lungs from Dark Agouti (DA; RT-1avl) rats or stimulated with 10(7) mitomycin C-treated spleen cells from DA rats by daily sub-cutaneous injections for 2 weeks. No immunosuppressive agent was used. Naive WF rats and WF rats grafted with syngeneic lungs or cells were used as controls. The level of RCMV replication in rats was assessed by infectious virus titers in tissues. RESULTS: The virus titers in salivary glands of allogeneic and syngeneic lung graft recipients were significantly higher than in naive WF rats. The level of RCMV replication in rats stimulated with allogeneic spleen cells was significantly higher than in the syngeneic recipient rats: virus titers in the salivary gland of allogeneic and syngeneic recipients reached 4.61 +/- 0.33 and 4.00 +/- 0.37 log(10) PFU/g tissue, respectively, at 14 days post-infection (p = 0.015). The augmented viral replication in allogeneic recipients was confirmed by an increase in the number of RCMV antigen-positive macrophages present in tissue sections of the salivary gland. CONCLUSIONS: Acute lung allograft rejection and allogeneic spleen cell stimulation enhance CMV replication in the salivary gland of rats. Various responses to allogeneic antigens occurring in the process of acute allograft rejection could be risk factors for post-transplant CMV replication and infection.     

A surgical case of combined valvular disease complicated by absent right superior vena cava and persistent left superior vena cava.

A 74-year-old man with combined valvular disease with a recent cerebral infarction was admitted. While undergoing thorough examination for valvular disease, absent right superior vena cava (RSVC) and persistent left superior vena cava (PLSVC) were recognized. Chest X-ray film suggested a right arch protrusion, and CT and venogram confirmed the diagnosis. During surgery, replacement of the mitral and aortic valves and annuloplasty of the tricuspid valve were performed. A blood draining cannula was inserted in retrograde fashion from the coronary sinus into the PLSVC, without any difficulties in the tricuspid valve repair. Due to bradycardic atrial fibrillation, we believed that it would be difficult to insert an endocardial electrode postoperatively, hence myocardial electrode was placed in the right ventricular wall. Absent RSVC combined with PLSVC is very rare, and a patient who underwent combined valve surgery with this rare anatomical abnormality is herein presented.     

Inferior vena cava thrombus after retroperitoneal lymphadenectomy for testicular tumor

A rare case of a thrombus in the inferior vena cava (IVC) after retroperitoneal lymphadenectomy for a testicular tumor is reported. A computed tomograph performed after the operation incidentally showed a filling defect in the IVC. However, it was impossible to decide whether the defect was due to an ordinary or a neoplastic thrombus. For this reason, a thrombectomy was performed, and postoperatively it was diagnosed as an ordinary thrombus. The cause of thrombi found only in the IVC is reviewed and the indication for thrombectomy is discussed.     

The usefulness of CEA as an indicator for early detection and a guide to the treatment of recurrent gastric cancer

The usefulness of carcinoembryonic antigen (CEA) as an indicator for recurrence and a guide to the treatment was evaluated from a retrospective analysis of 88 patients with recurrent gastric cancer. Sixty-two of these patients (70.5 per cent), 25 of whom had a preoperative positive assay, and 37 a negative assay, had elevated levels of CEA after disease progression. Averaged CEA level in patients with liver metastasis was significantly higher (872 ng/ml) than in those with peritoneal metastasis (68 ng/ml), with lymph node metastasis (103 ng/ml) or with local metastasis (93 ng/ml) (p<0.01). An elevation of CEA was found prior to the clinical manifestation of recurrence, and the average lead time was 4 months. In 25 patients with a lead time of more than 4 months, survival time after CEA elevation was 13.3 months, which was longer than the 6.5 months of 28 patients with less than 4 months. Thirty-seven of the 88 patients were treated after recurrence. The average survival period after the detection of recurrence was 9.4 months in patients with surgical treatments followed by chemotherapy, 5.9 months in those with chemotherapy alone and 3.8 months in those with surgery alone. The average survival period of 26 patients with positive CEA assays in recurrence was 5.1 months longer than of patients with negative assays. This fact suggested that early detection of recurrence followed by various treatments, in the elevated CEA group, contributes to favorable results.     

Treatment of established osteoporosis with 1α (OH) vitamin D3 and low dose intermittent elcatonin (eel calcitonin derivative)

In addition to estrogen widely used all over the world for the prevention of postmenopausal osteoporosis, calcitonin and vitamin D derivatives are commonly employed to treat established osteoporosis at higher age in Japan. In order to critically assess the usefulness of vitamin D derivatives and calcitonin alone or in combination on the advancement of vertebral deformity at higher age, 32 osteoporotic patients with vertebral deformity with the mean age of 79 were randomly divided into 4 groups with indistinguishable age and severity of the vertebral deformity. Group 1 served as the control without specific medications for osteoporosis. Group 2 was treated with 10 units elcatonin (eel calcitonin derivative) injected intramuscularly twice a week. Group 3 was given 0.75 to 1.5μg/day 1α (OH) vitamin D₃ orally. Group 4 was given a combination of treatments used in Groups 2 and 3. In the lateral X-ray film of the spine taken prior to the test and every 6 months thereafter, the shape of the vertebral body T₈ through L₄ was monitored by measuring the anterior, central and posterior heights. Decrease of the vertebral height ratio; anterior or middle height/posterior or adjacent intact posterior height, by more than 20% of the original value or from above to below 0.80 both appeared to be inhibited during administration of 1α (OH) vitamin D₃. Such effect seems to be augmented by simultaneous administration of elcatonin. Actual decrease of vertebral height ratio values and the per cent fall from the original value significantly less in Groups 3 and 4 than in Group 1. Development of vertebral deformity assessed by the changes of the vertebral height thus appears to decrease during treatment with 1α (OH) vitamin D₃ especially together with calcitonin in established osteoporosis.     

Type-II collagen gene expression is transiently upregulated in experimentally induced degeneration of rabbit intervertebral disc

To clarify phenotypic alterations of intervertebral disc cells during the repair process, we cloned partial type-II collagen cDNA from rabbits and analyzed the level of expression of type-II collagen mRNA in disc degeneration. An animal model was created by surgical denucleation of rabbit intervertebral discs through, an extraperitoneal approach. Eight animals each from an experimental and a control group were killed at 2, 4, 8, or 16 weeks postoperatively, and the disc samples were used for this study. Round chondrorcyte-like cells that filled the herniated space showed intense signal of type-II collagen mRNA and significant pericellular immunostaining of type-II collagen but no clear staining of type-I collagen. Northern. blot analysis revealed that the expression of type-II collagen mRNA of the repair disc cells was transiently increased at 4 weeks postoperatively. The cells were able to change their morphology in response to mechanical stimulation by surgical denucleation and to induce a significant increase in the gene expression of type-II collagen at an early phase of disc degeneration. The present results indicate the transient enhancement of repair activity in the degenerative process of injured fibrocartilage.