Antithromin activity following blockade of the reticuloendothelial system, splenectomy and partial removal of the liver

The level of antithrombins II, III and IV decreased in proportion to the extent of intervention in destruction or removal of a part of the liver in rats. Destruction of the spleen led to depression, and removal--to activation of antithrombin IV. Back of the reticuloendothelial system caused a lesser fall of the antithrombin level than partial hepatectomy. The spleen is supposed to produce antithrombin IV inhibitor.     

Phagocytic activity in stressed mice: effects of alprazolam

To evaluate the possible role of ethnicity in susceptibility to filarial infection, a comparative study of the prevalence of filarial infection was initiated in an endemic village inhabited by two ethnic populations of mainlanders and tribals. An age and sex matched sampled population of 591 mainlanders and 106 tribals was studied by detailed clinical and parasitological (60 mm3 blood) examinations. Sera collected from both population groups (26 each) matched for clinical stage of infection were analysed for humoral immune responses such as antifilarial IgG, circulating filarial antigen and immune complex level. The overall prevalences of clinical disease and infection in both mainlanders (34.18 and 14.4%) and tribals (25.47 and 17.9%) were comparable. However, both annual average adenolymphangitic attack rate (1.77 year-1) and the prevalence of chronic filarial disease (22.6%) amongst tribals were significantly lower. No true elephantiasis was observed in tribals. No significant difference was observed in their humoral immune response, although the antifilarial antibody of IgG class in all stages of filarial infection was lower in tribals than in mainlanders. The results did not reveal any difference in susceptibility to filarial infection in the ethnic groups. The paucity of progressive lesions observed in tribals possibly reflects a difference in the anatomy of lymphatics or genetic or immunoregulatory mechanisms, that needs further study.     

Effect of endotoxin-induced shock on the reticuloendothelial system. Phagocytic activity and DNA-synthesis of reticuloendothelial cells following endotoxin treatment

There was a marked decrease in the RES phagocytic activity during the first 12 hours after injection of high concentrations of endotoxin in rats. Phagocytic activity then increased considerably, reaching maximum values on days 3 to 5 and it was still higher than in control animals 20 days later. Parallel studies on 3H thymidine incorporation showed a significant increase in the rate of DNA-synthesis of reticulum cells of the liver during the 5 days period following endotoxin injection. Peak values were obtained on day 2 when the number of labelled cell were 50 times higher than in the controls. A likely reason for the increased DNA-synthesis is a repair of RES following endotoxin induced damage but it may also represent an endotoxin induced proliferation of reticulum cells that may at least partly account for the enhanced phagocytic activity.     

Serum phospholipase A2 in patients after splenectomy

Phospholipase A2 values increase in serum in various inflammatory states, infections, and postoperatively in surgical patients. Several organs, including the liver and spleen have been suggested as sources of circulating phospholipase A2. The purpose of the present work was to examine the possible role of the spleen as a source of elevated serum concentrations of phospholipase A2 after surgery. Pre- and postoperative serum samples of patients undergoing splenectomy were studied for group I phospholipase A2, group II phospholipase A2, and C-reactive protein mass concentrations and catalytic activity concentration of phospholipase A2. The catalytic activity concentration of phospholipase A2 and the mass concentrations of group II phospholipase A2 and C-reactive protein increased postoperatively (8.08 +/- 1.40 U/l vs. 3.96 +/- 0.89 U/l (mean +/- SEM) for phospholipase A2 catalytic concentration (p < 0.03), and 154.8 +/- 32.1 micrograms/l vs. 47.5 +/- 14.7 micrograms/l (mean +/- SEM) for group II phospholipase A2 mass concentration (p < 0.02, n = 7). The mass concentration of group I phospholipase A2 remained unchanged. The catalytic concentration of phospholipase A2 correlated well with the mass concentration of group II phospholipase A2 (p < 0.001, r = 0.846, n = 43). The concentration of C-reactive protein correlated well with the mass concentration of group II phospholipase A2 (p < 0.001, r = 0.566, n = 43) in serum. The results indicate that group II phospholipase A2 is released into the circulation after splenectomy, and the spleen seems not to be the source of circulating group II phospholipase A2.     

Oxygen consumption and ATPase activity in the corneal epithelium of rabbits with alloxan induced hyperglycemia

PURPOSE: To more fully investigate the effect of hyperglycemia on the aerobic metabolism of the corneal epithelium. METHODS: Corneal epithelial oxygen uptake rates and adenosine triphosphatase (ATPase) activities were measured in alloxan-induced diabetic and control rabbits over a 10 week period. RESULTS: A transient reduction in epithelial oxygen uptake rate was seen at week 1. A chronic 14% reduction in oxygen consumption occurred after 6 weeks of hyperglycemia. Epithelial ouabain-sensitive ATPase activity was unaffected by 10 weeks of hyperglycemia. Epithelial ouabain-insensitive ATPase activity decreased 14% after 10 weeks of hyperglycemia. CONCLUSIONS: Ten weeks of hyperglycemia in the alloxan induced diabetic rabbit was associated with a 14% decrease in corneal oxygen uptake, a 14% decrease in corneal epithelial ouabain-insensitive ATPase activity and no change in corneal epithelial ouabain-sensitive ATPase activity. The Crabtree effect may help explain some of the clinical signs seen in the diabetic cornea as well as explaining why diabetic patients can wear contact lenses with minimal clinical problems.     

2-Chlorodeoxyadenosine treatment after splenectomy in patients who have myelofibrosis with myeloid metaplasia

2-Chlorodeoxyadenosine (2-CdA) is a purine nucleoside analogue with therapeutic activity in low-grade lymphoproliferative disorders. In addition, 2-CdA has a potent myelosuppressive effect, and it has been shown to be toxic to malignant myeloid cells both in vitro and in vivo. In this pilot study we treated nine patients who had advanced myelofibrosis with myeloid metaplasia (MMM) and progressive hepatomegaly or symptomatic thrombocytosis after therapeutic splenectomy. 2-CdA was administered at 0.05-0.1 mg/kg/d for 7 d for one to five treatment cycles. A reduction in liver size associated with marked improvement in fatigue and control of thrombocytosis and leucocytosis was achieved in seven of the nine patients (78% response rate). In four of the seven responding patients the reduction in liver size was durable (4-28 months) and was associated with a decrease in serum alkaline phosphatase levels. However, no patient had improvement in anaemia, and two of the seven initially responding patients have since died of acute leukaemia or progressive disease. Improvement in bone marrow fibrosis was noted in two of five available post-treatment marrow examinations. Toxicity was mainly myelosuppression, which was severe in two patients. 2-CdA may be considered a palliative therapeutic agent after splenectomy in noncytopenic patients with MMM who have progressive hepatomegaly or extreme thrombocytosis.     

Effect of naloxone on the bladder activity of rabbits with acute spinal injury

BACKGROUND: Naloxone enhances bladder activity in patients with chronic spinal cord injury. However, there are few reports on naloxone for bladder morbidity in acute spinal cord injury. METHODS: We performed a prospective, controlled study of the effects of naloxone on bladder function in rabbits with and without surgical transection of the spinal cord at the 10th thoracic vertebra. Acute and chronic stages of injury were defined according to bladder function. Naloxone was given intravenously at both stages, and intrathecally at the acute stage. Bladder activity was monitored by cystometry. Blood concentrations of methionine-enkephalin were measured by radioimmunoassay. RESULTS: Spinal cord injuries were acute 1 or 2 days after surgery, and chronic after 1 or 2 weeks. Bladder capacity significantly decreased after 0.01 mg of intravenous naloxone in uninjured control rabbits, and after 0.03 mg of intravenous naloxone in rabbits with chronic-phase injuries. During the acute-injury phase, 0.3 mg of intravenous naloxone, or 0.02 mg of intrathecal naloxone, was necessary to evoke the micturition reflex. No significant changes in blood enkephalin levels were seen before or after spinal cord injury. CONCLUSION: In rabbits with acute spinal cord injury, intrathecal naloxone evoked the micturition reflex at a much lower dose than did intravenous naloxone. Intrathecal naloxone promises to become a new therapy for the acute stage of spinal cord injury for active recovery of bladder function, and could replace current therapy.     

Lactogenic activity in the serum of rabbits during pregnancy and early lactation

The levels of lactogenic activity in the serum of rabbits during pregnancy and early lactation have been determined. The accuracy and sensitivity of the radioreceptor assay used were increased by several technical improvements. Lactogenic activity remained low throughout pregnancy and increased at parturition; the highest values were reached on day 5 of lactation. No lactogenic activity was detected in placental extracts of rabbits, suggesting that the lactogenic activity measured in the serum is solely of pituitary origin. These results are discussed in relation to the main stages of development of rabbit mammary glands.     

Rapid nuclear translocation and increased activity of cyclin-dependent kinase 6 after T cell activation

To elucidate the roles of cyclin-dependent kinase 6 (cdk6) in T cells, we examined its intracellular localization, kinase activity, and associated proteins in the Jurkat T lymphoblastoid cell line. Jurkat cells had a high level of cdk6, which was associated with cyclin D3, but not cyclin D2, the member of the cyclin D family. When stimulated by a combination of PHA and anti-CD28 mAb, cdk6 activity was up-regulated, as measured by an in vitro kinase assay using recombinant, truncated retinoblastoma tumor suppressor gene protein (Rb protein) as substrate. Activation was most prominent when cells were stimulated with the combination of PHA and anti-CD28, although significant increases were detected after stimulation with PHA alone. The combination also resulted in maximal activation of c-Jun kinase and IL-2 production. Costimulation resulted in a rapid translocation of cdk6 to the nucleus, as demonstrated by both confocal immunofluorescence microscopy and biochemical fractionation techniques. Cdk6 activation and nuclear translocation were also observed after stimulation of Jurkat cells using the anti-CD28 Ab in combination with a mAb to CD3 (OKT3). Furthermore, nuclear translocation was observed in normal human T lymphocytes isolated from peripheral blood and stimulated in vitro with PHA. Two potential endogenous cdk6 substrates (with apparent molecular masses of 75-80 and 55-60 kDa), which were immunoprecipitated with cdk6 and phosphorylated in the in vitro kinase assay, were also identified. These data demonstrate the rapid activation and intracellular translocation of cdk6, implicating this kinase in early signal transduction events in T cells.     

Graded functional activation in the visuospatial system with the amount of task demand

Immunocompromised hosts have defects in their immune system that make them at risk of developing a variety of infections. In addition, these persons may develop a wide variety of noninfectious disease processes that involve the lung. These disorders may be caused by the underlying disease process. This may be seen with the development of metastatic disease from the underlying neoplasm, or it may represent the development of a malignancy secondary to therapy, as is seen with posttransplant lymphoproliferative disease. The abnormalities may be a result of the therapy used to treat the patients, as is seen with radiation injury to the lung and drug toxicity. Pulmonary edema may occur and be from a wide variety of causes. All of these disease processes may simulate an infectious process and must be differentiated from infection to allow proper therapeutic intervention.     

Alpha 2-macroglobulin of rabbits inhibits the habutobin activity

We have investigated whether alpha 2-macroglobulin (alpha 2M) of rabbits inhibits the activity of habutobin, a thrombin-like enzyme from Trimeresurus flavoviridis venom. Rabbit alpha 2M was purified with ultracentrifugation, gel filtration on Sepharose 6B and ion exchange chromatography on DEAE-Sephacel. Inhibitory effects of rabbit alpha 2M on habutobin was determined by the fibrin forming activity, digestion of A alpha chain of fibrinogen, and the release of fibrinopeptide A from fibrinogen. As a results, purified alpha 2M showed a single band with high molecular weight, around 800,000 mol. wt by means of polyacrylamide gel electrophoresis using PhastSystem. Besides inhibiting amidolytic and caseinolytic activity of porcine trypsin, it has inhibited the activity of habutobin: that is, in the presence of rabbit alpha 2M, fibrin forming activity of habutobin was decreased and habutobin-induced digestion of A alpha chain was inhibited. In addition, rabbit alpha 2M reduced habutobin-induced release of fibrinopeptide A from rabbit fibrinogen.     

Phagocytic activity by guinea-pig peritoneal macrophages and human peripheral leukocytes irradiated in vitro (author's transl)

A dose/effect curve for phagocytic activity of guinea-pig peritoneal macrophages and human peripheral leukocytes was determined ranging from anti-inflammatory to immunosuppressive doses. The nitroblutetrazolium reduction test was used stimulating the phagocytes by latex microspheres. A significant enhancement of phagocytic activity by low doses of gamma radiation was observed in guinea-pig macrophages.     

Abdominal wound tumor recurrence after open and laparoscopic-assisted splenectomy in a murine model

PURPOSE: The cause of abdominal wall tumor recurrences after laparoscopic surgery for cancer remains unknown. A recent study from our laboratory using a murine splenic tumor model suggests that poor surgical technique (i.e., crushing of the tumor) and not the CO2 pneumoperitoneum is responsible for port wound tumors. However, in that experiment no actual laparoscopic procedure or manipulation was performed. The purpose of the current study was to determine the rate of abdominal wound tumors after laparoscopic-assisted splenectomy performed via a CO2 pneumoperitoneum vs. open splenectomy using the mouse splenic tumor model. METHODS: To establish splenic tumors, female BALB/c mice (N=72) were given subcapsular splenic injections of a 0.1-ml suspension containing 10(5) C-26 colon adenocarcinoma cells via a left flank incision at the initial procedure. Eight days later, animals were randomized into one of two groups: 1) laparoscopic-assisted splenectomy, or 2) open splenectomy. Laparoscopic-assisted splenectomy animals had three laparoscopic ports placed and then underwent laparoscopic mobilization of the spleen under a CO2 pneumoperitoneum followed by extracorporeal splenectomy via a subcostal incision. Group 2 animals underwent open splenectomy via a subcostal incision after three port incisions were made in the same locations as for laparoscopic-assisted splenectomy mice. The incision was closed after 20 minutes in both groups. Ten days later, the mice were killed and inspected for abdominal wall tumor implants. The experiment was performed via two separate trials. RESULTS: When results of the two trials were combined, there was no significant difference in the incidence of animals in each group with at least 1 port tumor (open, 21 percent; laparoscopic-assisted splenectomy, 33 percent; P=0.14). However, the overall incidence of port site tumors (number of ports with tumors/total number of ports for each group) was significantly higher in the laparoscopic-assisted splenectomy group than in the open group (20 vs. 7 percent; P=0.01). The subcostal incisional tumor recurrence rate was also higher in the laparoscopic-assisted splenectomy group (50 vs. 21 percent; P=0.02). as was the perioperative mortality rate (21 vs. 7 percent; P=0.08). Results of the two individual trials were also considered separately. The incidence of port wound tumors decreased significantly from the first to the second laparoscopic-assisted splenectomy trial (36 vs. 9 percent; P=0.003), although the incidence of tumors at the subcostal incision and the mortality rate for the two laparoscopic-assisted splenectomy group trials were not significantly different. The open group tumor incidences did not change from trial to trial. CONCLUSIONS: Overall, significantly more port and incisional tumors were noted in the laparoscopic-assisted group. Although not statistically significant, mortality rate of the laparoscopic-assisted group was higher than the open group. The reasons for these findings are unclear. Laparoscopic mobilization was quite difficult and required excessive splenic manipulation, which may have liberated tumor cells from the primary tumor and facilitated port tumor formation. With increased experience, less manipulation was required to complete mobilization. Of note, the incidence of port tumors in the laparoscopic-assisted splenectomy group decreased significantly from the first to the second trials; therefore, it is possible that surgical technique is a factor in port tumor formation. However, the persistently high tumor incidence at the subcostal incision site argues against the hypothesis that the second trial's laparoscopic mobilizations were less traumatic. The CO2 pneumoperitoneum may also be a factor. Further studies are warranted to clarify these issues.     

Loss of ATP diphosphohydrolase activity with endothelial cell activation

Quiescent endothelial cells (EC) regulate blood flow and prevent intravascular thrombosis. This latter effect is mediated in a number of ways, including expression by EC of thrombomodulin and heparan sulfate, both of which are lost from the EC surface as part of the activation response to proinflammatory cytokines. Loss of these anticoagulant molecules potentiates the procoagulant properties of the injured vasculature. An additional thromboregulatory factor, ATP diphosphohydrolase (ATPDase; designated as EC 3.6.1.5) is also expressed by quiescent EC, and has the capacity to degrade the extracellular inflammatory mediators ATP and ADP to AMP, thereby inhibiting platelet activation and modulating vascular thrombosis. We describe here that the antithrombotic effects of the ATPDase, like heparan sulfate and thrombomodulin, are lost after EC activation, both in vitro and in vivo. Because platelet activation and aggregation are important components of the hemostatic changes that accompany inflammatory diseases, we suggest that the loss of vascular ATPDase may be crucial for the progression of vascular injury.