Additive effects of CD59 expression in Gal knockout mice in vitro but not in an ex vivo model

Abstract: Transgenic expression of the human complement regulatory molecule CD59 in mice and genetic deletion of the major xenoantigen galactose α 1,3 galactose (Gal KO) each resulted in partial protection of spleen cells from lysis by human serum. These protective effects were additive when the two genetic modifications were combined. However, when the effects of these genetic modifications were examined in an ex vivo model in which mouse hearts were perfused with human plasma, it was Gal KO which was the modification which determined protection. CD59 expression alone was not protective and CD59 expression in combination with Gal knockout did not result in a significant additional increase in protection over and above that provided by Gal knockout alone. The likely explanation for this discrepancy between the in vitro and ex vivo data is that the H2-K^b promoter used to drive CD59 expression results I in substantially less expression on endothelium than on spleen cells.     

Automatic discrimination of myoelectric signals via parallel cascade identification

It has recently been shown that it is possible to discriminate accurately among myoelectric signals underlying different muscle contraction types, specifically elbow flexion and extension and forearm pronation and supination. It was reported that once a number of distinctive features had been extracted from the myoelectric signals, a neural network could be trained to distinguish the contraction types with an impressively high accuracy. In the present paper, we show that a technique known as parallel cascade identification can be used to construct classifiers that can also accurately, differentiate the contraction types. The use of parallel cascades has the benefit of dispensing with the need for feature extraction, so that raw myoelectric signal data can be used directly. In addition, very little data are required to train the parallel cascades to distinguish accurately novel incoming myoelectric signals. Results of using parallel cascades to distinguish foream pronation, supination, and elbow flexion are presented.     

Loss of cables, a novel gene on chromosome 18q, in ovarian cancer.

Cables, a cyclin-dependent kinase (cdk) interacting protein, has recently been identified and mapped to human chromosome 18q11. Cables appears to be primarily involved in cell cycle regulation and cell proliferation. Overexpression of Cables in Hela and other cell lines inhibits cell proliferation and tumor formation. We hypothesize that loss of Cables expression is associated with ovarian cancer. To test our hypothesis, we examined Cables expression in the four most common subtypes of ovarian carcinomas: serous, endometrioid, mucinous, and clear cell. In addition, mucinous and serous borderline tumors were also included. Loss of Cables expression was observed at high frequency in ovarian serous (11 of 14 cases, 79%) and endometrioid (5 of 10 cases, 50%) carcinomas. In contrast, strong Cables staining was detected in all clear cell carcinomas (10 cases) and mucinous tumors (5 carcinomas and 5 borderline tumors). The majority of serous borderline tumors (11 of 14 cases, 79%) showed positive Cables staining, with the rest showing focal loss of Cables expression. Furthermore, RT-PCR revealed the lack of Cables mRNA in a human ovarian cancer xenograft. No correlation was noted between loss of Cables and histologic grade, tumor stage, and survival. In conclusion, our results indicate that loss of Cables is common in ovarian serous and endometrioid carcinomas and imply that Cables may be involved in the pathogenesis of these two types of ovarian carcinomas.     

Josephine Goldmark (1877–1950): A Biographic Sketch

Josephine Goldmark was one of those remarkable early-twentieth-century American women who, while seeking independence and fulfillment in their own lives, devoted themselves to humanitarian causes and social reform. She was deeply involved in efforts to improve working conditions for women and children. Her work led her into the arena of nursing, especially public health nursing, where she contributed significantly to the development of the profession.     

Species- and sex-specific variations in binding of ochratoxin A by renal proteins in vitro

The mycotoxin ochratoxin A (OTA) is a potent renal carcinogen in rodents and induces renal fibrosis in pigs. Furthermore, OTA has been associated with the development of renal tumors and nephropathies in humans. Large species- and sex-differences are observed in sensitivity toward OTA-mediated toxicity and carcinogenicity, yet neither the mechanism(s) resulting in OTA toxicity nor the reasons for the observed species- and sex-specificities are known. This paper investigated variations in OTA handling viz binding to renal proteins which could possibly explain the observed differences in OTA susceptibility in vivo and in vitro. The results obtained via a modification of a standard receptor-binding assay demonstrated the presence of at least one homogeneous binding component in renal cortical homogenates from pig, mouse, rat and humans. This component was shown to bind OTA in a specific and saturable manner. A range of compounds selected for their affinity for steroid receptors and/or for various known organic anion transporters were employed in a competition assay to answer the question whether this homogenous OTA binding component represents a steroid-like receptor component or one of the known organic anion transporters of the kidney. Although many of the compounds were able to compete with OTA for protein-binding, the competition patterns displayed a distinct species specificity and did not correspond to the competition patterns associated with presently known organic anion transporters of the kidney in the mouse, rat or human. The data thus suggests the presence of a new organic anion transporter or more likely, a cytosolic binding component of unknown function with high affinity and capacity for OTA binding in humans, rats, mice and possibly pigs.     

Acquired and innate resistance to the haemoflagellate cryptobia salmositica in sockeye salmon (Oncorhynchus nerka)

Juvenile sockeye salmon (Oncorhynchus nerka, Fulton River stock) were protected from otherwise lethal challenges with the haemoflagellate Cryptobia salmositica by acclimation to elevated water temperatures (20 degrees C). Fish treated in this manner displayed increased immunity to C. salmositica and yielded plasma showing enhanced lytic activity against the parasite. The acquired lytic activity was antibody- and complement-mediated. In contrast, a stock of naive O. nerka from Weaver Creek, previously identified as having a high innate resistance to the lethal effects of C. salmositica, also had plasma factors that destroyed the parasite in vitro. This anti-Cryptobia activity also involved complement because 1) it resulted in lysis of the parasite, 2) it was heat-labile (40 degrees C for 20 min), and 3) it was largely removed from the plasma by substances capable of activating (binding) complement by the classical pathway (an antigen:antibody complex of Renibacterium salmoninarum and its specific antibody) and the alternate pathway (Escherichia coli lipopolyssacharide). The complement-mediated lysis associated with innate resistance was apparently the result of activation by the alternate pathway because it occurred in fish lacking antibodies against the parasite. The reaction was unusual in that a long incubation period (about 2 days) was required for maximum lysis of the parasite. At least one component of the innate lytic system depended on disulphide bonds because lytic activity was destroyed by 2-mercaptoethanol.     

Intra-operative quick insulin assay to confirm complete resection of insulinomas guided by selective arterial calcium injection (SACI)

Background and aims Insulinomas are rare endocrine disorders. Pre-operatively, conventional imaging techniques often fail to localise the tumor. In addition, due to the lack of quick insulin assays, intra-operative confirmation of complete resection was impossible until recently. Materials and methods Six patients with biochemical evidence of an insulinoma underwent pre-operative localisation studies and selective arterial calcium injection (SACI). In addition, insulin was measured before surgery and every 10–15 min after resection of the tumor using a quick insulin assay. Results Pre-operative localisation studies identified the tumor correctly as follows: endosonography: three of four, magnetic resonance imaging: two of four and SACI: six of six. Tumors in the head and body were enucleated while those in the tail were resected (n = 2, each). Those three patients, in whom magnetic resonance imaging and/or endosonography could localise the tumors pre-operatively, underwent laparoscopic surgery while the remaining three patients underwent open surgery. Intra-operatively, insulin dropped to normal levels within 20 min in all cases. After a follow-up of 0.8–3 years, all patients remained biochemically cured. Conclusions Pre-operatively, SACI appears to be a very sensitive localisation technique and may be most helpful in guiding the surgeon if conventional imaging techniques fail to localise the tumor. Complete removal of an insulinoma can be reliably predicted using a quick insulin assay. This paper was presented at the 2nd Biennial Meeting of the European Society of Endocrine Surgeons (ESES), May 18–20, 2006, Krakow, Poland.     

Prevalence of dietary supplement use in adults with chronic renal insufficiency.

OBJECTIVE: There are currently no studies that have investigated dietary supplement use in the chronic renal insufficiency (CRI) population. The objectives of this study were to determine the prevalence of dietary supplement use in a sample of adults with CRI and to examine whether the prevalence of dietary supplement use was higher in the earlier stages of CRI. DESIGN AND SETTING: Cross-sectional survey conducted at an outpatient nephrology clinic. PATIENTS: Adults (n = 100) with varying degrees of CRI. INTERVENTION: Interview-administered questionnaire. MAIN OUTCOME MEASURES: The questionnaire contained questions related to the use of dietary supplements, attitudes, and beliefs about dietary supplements, as well as medical and demographic data including gender, age, body weight, smoking status, concurrent chronic conditions, prescribed medications, serum creatinine, estimated glomerular filtration rate (GFR), etiology of CRI, income, and education level. RESULTS: The prevalence of dietary supplement use was 45%, with the most frequent use occurring in subjects with a mild to moderate degree of renal insufficiency. There were no significant differences in gender, age, body mass index, smoking status, number of concurrent chronic conditions, number of prescribed medications, income, or education level between supplement users and supplement nonusers. Further analysis of dietary supplement use showed that the number of supplements used ranged from 1 to 5 or more supplements per day, with an overall total of 36 different supplements. Dietary supplement users were significantly more concerned with their health than were supplement nonusers. The most frequent sources of supplement information were physicians and printed material; however, 75% of the dietary supplement users desired further information about their dietary supplements. CONCLUSION: This is the first study to investigate the use of dietary supplements in adults with CRI, and it provides valuable information for health care professionals regarding the dietary supplement use of their patients with CRI.     

Anomalous head posture with early-onset homonymous hemianopia

PURPOSE: We have noted the frequent finding of an ipsilateral head turn in children with early-onset homonymous hemianopia. We report a series of patients with these findings and propose a theory to explain this association. METHODS: Ten patients with early-onset homonymous hemianopia and anomalous head posture were examined. Head computed tomography and magnetic resonance imaging confirmed a cerebral lesion as the cause of the hemianopia in all patients. RESULTS: All patients had onset of central nervous system disease prenatally or before age 18 months. A head turn toward the visual field defect with a gaze preference contralateral to the visual field defect was present in all patients. CONCLUSIONS: Early-onset homonymous hemianopia should be included in the differential diagnosis of anomalous head posture.