A novel lamina lucida component of epithelial and endothelial basement membranes detected by LH39 monoclonal antibody.

The murine monoclonal antibody, LH39 was characterized in this study and appeared to bind to a novel basement membrane epitope. This antigen was expressed in the epithelial basement membrane of human tissue derived from all three germ cell layers and in basement membranes surrounding small blood vessels within the stroma of all organs examined. LH39 antigen could be first detected in fetal skin at the dermo-epidermal junction at 7 weeks estimated gestational age but was not present in the dermal vasculature until 16 weeks. When tested against tissue from a range of lower mammalian species, LH39 antigen appeared to be primate-specific. The epithelial basement membrane zone in organotypical cultures, where there is de novo synthesis of basement membrane components, contained abundant LH39 antigen in contrast to other basement membrane components, type IV collagen, laminin, and type VII collagen. Ultrastructural localization of LH39 epitope, using immunogold electron microscopy on unfixed freshly frozen tissue, was to the lamina lucida. No cross-reactivity could be detected between LH39 and laminin, fibronectin, and collagens I, III, IV, and V using the ELISA assay. In vitro studies with a range of proteolytic enzymes suggested that the antigen was non-collagenous in nature. LH39 precipitated a polypeptide with a molecular weight of 185 kD from extracts of metabolically labelled cultured keratinocytes, and polypeptides of 185 and 200 kD from the culture medium. The tissue distribution of LH39 antigen suggested that it may be an epitope within anchoring filaments. Potential applications of this antibody include the study of benign and malignant human vascular disorders, diseases and tumours associated with angiogenesis, epithelial neoplasms, and conditions of tissue regeneration and repair, such as wound healing.     

Quantifying arbitrary magnetic susceptibility distributions with MR.

Magnetic susceptibility, as a physical property of materials, plays important roles in many physical, chemical, engineering, and medical applications. Its quantification becomes of significant interest when MRI becomes a commonly used technique in biomedical applications. A general method is presented here for quantifying arbitrary magnetic susceptibility distributions in a localized region on the basis of first principles of magnetic induction field distributions in space. A proof of the concept was demonstrated by computer simulations. The study establishes the methodological basis for quantitative magnetic susceptibility imaging with MR.     

Trends and Predictors for Vagotomy When Performing Oversew of Acute Bleeding Duodenal Ulcer in the United States

Background In the era of Helicobacter pylori treatment, the role of vagotomy in bleeding duodenal ulcers is debatable. National outcomes were evaluated to determine the current surgical treatment and use of vagotomy for bleeding duodenal ulcers. Methods Data from the Nationwide Inpatient Sample (NIS) were used from years 1999 to 2003. Patients were selected using diagnostic codes for acute duodenal ulcer bleed and procedure codes for simple oversew of a bleeding ulcer and vagotomy. Data were analyzed using multiple linear and logistic regression. Results Between 1999 and 2003, 100,931 patients with an acute bleeding duodenal ulcer were identified. Over time, there was a decrease in the number of acute bleeding ulcers (p = 0.027) and a decrease in the number of vagotomies (p = 0.027). A high co-morbidity index [odds ratio (OR), 0.60, p = 0.017], operation in the Midwest (OR 0.50, p < 0.001) and operation in the West (OR 0.68, p = 0.034) were predictive of no vagotomy during surgery for a bleeding duodenal ulcer. Conclusions A vagotomy is not commonly performed during surgical treatment of an acute bleeding duodenal ulcer. This variation in practice was not fully explained by patient characteristics. We must seek new evidence to determine the safety of combined medical and surgical management of this clinical problem. Presented at DDW/SSAT May 20–24, Los Angeles, California.     

Cognitive deficits in progressive supranuclear palsy, Parkinson's disease, and multiple system atrophy in tests sensitive to frontal lobe dysfunction.

Groups of patients with idiopathic Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy or Steele-Richardson-Olszewski syndrome, matched for overall clinical disability, were compared using three computerised cognitive tests previously shown to be sensitive to frontal lobe dysfunction. On a test of planning based on the Tower of London task, all three groups were impaired, but in different ways. The groups with palsy and Parkinson's disease were slower in the measure of initial thinking time, whereas the group with multiple system atrophy was only slower in a measure of thinking time subsequent to the first move, resembling patients with frontal lobe damage. On a test of spatial working memory, each group showed deficits relative to their matched control groups, but the three groups differed in their strategy for dealing with this task. On a test of attentional set shifting, each group was again impaired, mainly at the extradimensional shifting stage, but the group with Steele-Richardson-Olszewski syndrome exhibited the greatest deficit. The results are compared with previous findings in patients with Alzheimer's disease or frontal lobe damage. It is concluded that these basal ganglia disorders share a distinctive pattern of cognitive deficits on tests of frontal lobe dysfunction, but there are differences in the exact nature of the impairments, in comparison not only with frontal lobe damage but also with one another.     

Severity of disability and duration of disease in rheumatoid arthritis.

A longitudinal sample of patients with rheumatoid arthritis (RA) from Santa Clara County, CA was analyzed. Severity was measured with the Disability Index from the Health Assessment Questionnaire (HAQ). First, 6 cohorts were created of women and men with 0 to 10, > 10 to 20, and > 20 years of duration of illness in 1981. Experiences of the 6 cohorts were studied from 1981 to 1989. For both sexes, and both samples which alternately included and excluded the deceased, persons with > 20 years of duration experienced faster deterioration than those with < 20 years. Second, multiple regression models were estimated which treated the Disability Index as the dependent variable. In the regression models, the Disability Index worsened more quickly for women than men, for persons with few rather than many years of education, and for older than younger persons. Regression models which excluded an intercept term suggested a unique "S" shaped curve that described the Disability Index and duration relation.     

Turning behaviour induced by injection of muscimol or picrotoxin into the substantia nigra demonstrates dual GABA components.

Injection of the GABA agonist muscimol into rat caudal substantia nigra caused contralateral turning, whereas injection into the rostral substantia nigra caused ipsilateral turning. The GABA antagonist picrotoxin had the opposite effect. These findings support the hypothesis that GABA has dual actions in the substantia nigra. Ipsilateral turning induced by injection of muscimol into rostral nigra was abolished by haloperidol pretreatment, indicating the involvement of dopaminergic mechanisms. Haloperidol pre-treatment did not prevent turning induced by muscimol injected into the caudal nigra, supporting the existence of a non-dopaminergic nigral output system.