Persistent reversal of diabetes by transplantation of fetal pig proislets into nude mice

Facing the limited availability of human adult and fetal pancreases, fetal pig proislets (pancreatic islet precursors) were investigated in view of several inherent advantages. Six litters of fetuses of mean +/- SE gestational age 75 +/- 3 days were obtained from commercially available farm pigs. Pancreatic tissue was gently digested with collagenase, then a 10-day culture was performed. During culture, fetal proislets showed no insulin response to glucose alone but a significant response to glucose plus theophylline. The insulin content per microgram of DNA in the cultured proislets continuously increased. Histological examination by immunoperoxidase staining showed that, apart from single insulin- and glucagon-positive cells, there were no discrete islets in the pancreatic tissue and the cultured proislets. Diabetes was induced with streptozocin (STZ) in eight nude mice 3-4 wk after proislet transplantation and in another eight nude mice without transplantation. During the initial week, blood glucose levels of mice in both groups increased rapidly. The mean +/- SE peak value of blood glucose levels in the transplanted group was 20.4 +/- 2.0 mM and was 20.1 +/- 1.3 mM in the group without transplantation. Simultaneously, body weight decreased from 29.5 +/- 0.7 to 21.5 +/- 0.9 g and from 27.9 +/- 0.7 to 19 +/- 1 g in the groups, respectively. Afterward, blood glucose levels of mice in the transplanted group gradually decreased, and normoglycemia was achieved in all mice within 50 +/- 13 days after injection of STZ, i.e., 74 +/- 13 days after transplantation. The group without transplantation persistently maintained blood glucose levels greater than 16.7 mM.(ABSTRACT TRUNCATED AT 250 WORDS)     

Differential changes of retina dopamine binding sites and adenylyl cyclase responses following 6-hydroxydopamine treatment.

Both dopamine D1 and D2 receptors are present in rat retina. D1 receptors are positively coupled to adenylyl cyclase, while D2 receptors are negatively coupled. After intraocular administration of the neurotoxin 6-hydroxydopamine (6-OHDA) there is depletion of retinal dopamine by about 90%, as well as a decrease of the number of D1 and D2 receptor binding sites. Following the 6-OHDA lesion, there is an enhancement of the D1 receptor-stimulated accumulation of cyclic-AMP and a loss of D2 receptor-inhibited accumulation of cyclic-AMP. Our results suggest that some of the retinal D2 receptors are coupled to adenylyl cyclase and some are not.     

Isolated complete orbital infarction: a common carotid artery occlusion syndrome

When blood flow through the internal and external carotid arteries is completely interrupted by ipsilateral common carotid artery occlusion, the arterial orbital circulation may be more compromised than the brain supply. We studied a pure and extreme example of this situation in a patient who presented with acute orbital infarction, but no cerebral ischemia on clinical, CT and single-photon emission computerized tomography (SPECT) grounds. Ipsilateral blindness corresponded to retinal, choroidal and optic nerve infarction. The pattern of ophthalmoplegia, with relative sparing of adduction, was more compatible with a muscle than a nerve dysfunction, but a reactive dilated pupil, corneal anesthesia, and orbital pain suggested that the intraorbital branches of the ocular motor nerves and ophthalmic division of the trigeminal nerve were not spared. In addition, signs of widespread ocular ischemia were present. Sequential examinations documented the evolution pattern over 1 year. The absence of an orbital collateral supply from the contralateral external carotid and muscular cervical arteries systems, which contrasted with an adequate middle cerebral artery supply via the contralateral internal carotid artery, may explain this isolated and complete form of orbital ischemia due to common carotid artery occlusion.     

Elimination of malignant clonogenic cells from human bone marrow using multiple myeloid cell-specific monoclonal antibodies and complement.

Single or combined monoclonal antibodies (McAbs) Zh53, Zh820, and Zh2-1 have been used to eliminate malignant clonogenic cells from human bone marrow. The test of cytotoxicity showed that all of these McAbs could express high specific cytotoxic action against HL-60 cells and were selectively complement-dependent cytotoxic to various types of fresh leukemic cells. Clonogenic assay detected that single treatment with antibody and rabbit complement (RC) could reduce clonogenic units of HL-60 cells by more than 2 logs and two treatments reduced clonogenic units by more than 4 logs. However, combination of 2 McAbs could reduce clonogenic units by 4-5 logs. The data suggest that multiple treatments with McAbs and RC or a combination of 2 McAbs are more effective than a single treatment in eliminating clonogenic tumor cells. Treatment of normal human bone marrow with Zh53, Zh2-1 and RC did not produce a loss of normal CFU-GM, but treatment with Zh820 reduced the clonic units of normal CFU-GM by 24%.

     

Delta hepatitis virus infection in China

To assess the prevalence, epidemiological features and prognostic implications of hepatitis D (Delta) in Sichuan Province, The People's Republic of China, 649 sera (515 from HBsAg positive patients and 134 from HBsAg negative subjects) were tested by radioimmunoassay (RIA) for antibody to the hepatitis D virus (anti-HD). Forty-seven sera (7.2%) showed some degree of reactivity. Serial dilutions of these sera indicated that prozoning was not responsible for the equivocal results. Thirty-four of the 47 sera were submitted under code to a second laboratory for independent analysis. According to those results anti-HD antibodies were detected in four of these sera. The overall prevalence of anti-HD in the HBsAg positive patients therefore was 0.8% (4/515). On the basis of clinical, biochemical and histological data 427 HBsAg positive sera were further divided into acute Type B hepatitis, chronic Type B hepatitis, healthy carrier state and hepatocellular carcinoma (HCC) subgroups. Two of 65 (3.1%) anti-HD positive sera belonged to the acute Type B hepatitis group; one of 104 (0.9%), the chronic Type B hepatitis group and one of 246 (0.4%), the healthy carrier group. No antibody was detected in sera from 12 HBsAg positive HCC patients. All HBsAg negative patients were negative for anti-HD antibody. The results of this study indicate that despite a high prevalence of hepatitis B virus infection, positive serology for delta virus is uncommon in Sichuan Province, The People's Republic of China.