Nanoparticle Transport in Epithelial Cells: Pathway Switching Through Bioconjugation

The understanding and control of nanoparticle transport into and through cellular compartments is central to biomedical applications of nanotechnology. Here, it is shown that the transport pathway of 50 nm polystyrene nanoparticles decorated with vitamin B₁₂ in epithelial cells is different compared to both soluble B₁₂ ligand and unmodified nanoparticles, and this is not attributable to B₁₂ recognition alone. Importantly, the study indicates that vitamin B₁₂‐conjugated nanoparticles circumnavigate the lysosomal compartment, the destination of soluble vitamin B₁₂ ligand. Whereas cellular trafficking of soluble B₁₂ is confirmed to occur via the clathrin‐mediated pathway, transport of B₁₂‐conjugated nanoparticles appears to predominantly take place by a route that is perturbed by caveolae‐specific inhibitors. This data suggests that, following its conjugation to nanoparticles, in addition to dramatically increasing the cellular uptake of nanoparticles, the normal cell trafficking of B₁₂ is switched to an alternative pathway, omitting the lysosomal stage: a result with important implications for oral delivery of nanoparticulate diagnostics and therapeutics.     

Bone marrow transplantation for severe aplastic anemia: has outcome improved?

Bone marrow transplants for severe aplastic anemia were first performed in the 1970s. Transplant regimens, supportive care, and patient selection have changed substantially since then. Our objective was to determine the impact of these changes on transplant outcome. We studied 1,305 recipients of HLA-identical sibling transplants for aplastic anemia between 1976 and 1992, reported to the IBMTR by 179 centers. We compared survival of transplants performed in three intervals (1976 through 1980 [n = 186], 1981 through 1987 [n = 648], and 1988 through 1992 [n = 471]) using Cox proportional hazards regression. Five-year survival (+/-95% confidence interval) increased from 48% +/- 7% in the 1976-1980 cohort to 66% +/- 6% in the 1988-1992 cohort (P < .0001). Risks of graft-versus-host disease (GVHD) and interstitial pneumonia decreased over time, but the risk of graft failure did not. Higher long-term survival resulted primarily from decreased mortality in the first 3 months posttransplantation. Late mortality risks were low and changed little over the intervals studied. In multivariate analysis, changes in transplantation strategies accounted for most but not all of the improved outcome. Use of cyclosporine to prevent GVHD was the most important factor. Changes in patient selection did not seem to explain improved survival. Survival after HLA-identical sibling bone marrow transplantations for aplastic anemia has improved since 1976. Changes in GVHD prophylaxis account for much of this improvement. Other changes may also operate.     

Mesh inguinal herniorrhaphy: a ten-year review

Inguinal herniorrhaphy remains one of the most common surgical operations, with approximately 10 to 20 per cent performed for recurrence. Reviews by specialized hernia centers show mesh repair has a recurrence rate of 0.2 per cent. Detractors of this repair include increased cost, technical difficulty, and risk for infection. The purpose of this study was to compare mesh versus nonmesh inguinal herniorrhaphy at a large teaching institution. From 1985 to 1994, 892 patients underwent primary repair for inguinal hernia at the Veterans Administration Hospital at Memphis, TN. Patients were stratified by repair [Lichtenstein (Mesh), open anterior (Bassini, Marcy, McVay, and Shouldice), laparoscopic (Lap), and preperitoneal (Post)]. Operative time for Mesh repair (111 +/- 2 minutes) was longer than for Bassini or McVay (91 +/- 2 and 98 +/- 2 minutes; P < 0.05), and Lap repairs were longer than all others (192 +/- 16 minutes; P < 0.05). Hospital stay averaged 2.2 +/- 0.1 days for Mesh versus 2.6 +/- 0.1 days for all repairs combined (P = not significant). Mesh patients developed four wound infections (1.0%), none requiring mesh removal, versus nine infections (1.8%) in other groups (P = not significant). One Mesh patient (0.3%) developed recurrence, compared with 16 (3.5%) with open anterior repair (P < 0.01). Inguinal herniorrhaphy using an open mesh repair technique provides superior recurrence rates without increasing risk for infection, length of stay, or technical difficulty.     

Systemic arterial blood pressure and urine protein/creatinine ratio in dogs with hyperadrenocorticism

OBJECTIVE: To determine prevalence and severity of systemic arterial hypertension and proteinuria in dogs with naturally developing hyperadrenocorticism and to determine whether these abnormalities resolve with adequate management of the disease. DESIGN: Case series and cohort study. ANIMALS: 77 dogs with naturally developing hyper-adrenocorticism examined once; 15 dogs examined before and after treatment. RESULTS: Among dogs examined only once, hypertension was diagnosed in 21 of 26 dogs with untreated pituitary-dependent hyperadrenocorticism (PDH), 17 of 21 with inadequately controlled PDH, 8 of 16 with well-controlled PDH, 10 of 10 with an untreated adrenocortical tumor, and 0 of 4 that had undergone adrenalectomy because of an adrenocortical tumor. Untreated dogs and dogs with inadequately controlled PDH had significantly higher blood pressures than did other dogs. Proteinuria was documented in 12 of 26 dogs with untreated PDH, 5 of 16 with inadequately controlled PDH, 3 of 14 with well-controlled PDH, 5 of 8 with an untreated adrenocortical tumor, and 1 of 3 that had undergone adrenalectomy. Dogs with untreated PDH and dogs with an untreated adrenocortical tumor had higher urine protein/creatinine ratios than did dogs with well-controlled PDH. Among dogs evaluated before and after treatment, blood pressure and urine protein/creatinine ratio did not change in 8 dogs with inadequately controlled hyperadrenocorticism, but decreased in 7 dogs with well-controlled disease. CLINICAL IMPLICATIONS: Results suggest that systemic hypertension and proteinuria are common in dogs with untreated hyperadrenocorticism and that successful treatment of hyperadrenocorticism will result in resolution of these abnormalities in many, but not all, dogs.     

Hepatic hemangioma. Analysis of 103 cases. Clinical considerations and imaging methods

Hemangiomas are the most common benign vascular tumor found in the liver. In this study, 103 cases of hepatic hemangiomas were analysed in a retrospective manner. Image aspects such as those seen in ultrassonography, computed tomography, nuclear magnetic resonance and arteriography are discussed. The incidence was higher amongst the female sex, between individuals from 40 to 60 years old, which presented predominantly without symptoms (66%) and localized mainly in the right hepatic lobe (74%). The meaning of those aspects, when adopted, permits the clinicians to differentiate benign from malignant nodular lesions in the liver.     

Medical and psychological aspects of irritable bowel syndrome

To engineer an a non-islet cell capable of glucose-stimulated insulin secretion, a chinese hamster ovary cell line (CHO) was transfected with a mammalian expression vector carrying the human insulin cDNA (pCB/hINS). More proinsulin than insulin was released daily by the stably transformed cell line (CHO-INS). Examination of acid-ethanol extracts confirmed that both insulin and proinsulin were stored. Immunohistochemical analysis of the cells also showed that (pro)insulin was stored. Unlike beta cells, CHO-INS cells did not secrete insulin in response to glucose. To investigate this lack of effect, we examined whether transfection of GLUT2 cDNA, which is ordinarily not expressed in CHO-INS cells, would confer glucose-stimulated insulin secretion. Consequently, we have demonstrated that glucose regulated insulin release occurs in the CHO-INS-GLUT2 cell line and that glucose potentiates the insulin secretory response to non-glucose secretagogues.     

Molded rigid polymer monoliths as separation media for capillary electrochromatography. 2. Effect of chromatographic conditions on the separation

Monolithic columns for capillary electrochromatography have been prepared within the confines of untreated fused-silica capillaries in a single step by a simple copolymerization of mixtures of butyl methacrylate, ethylene dimethacrylate, and 2-acrylamido-2-methyl-1-propane-sulfonic acid (AMPS) in the presence of a porogenic solvent. The use of these novel macroporous monoliths eliminates the need for frits, the difficulties encountered with packed capillaries, and capillary surface functionalization. Since the porous properties of the monolithic materials can be easily tailored through changes in the composition of the ternary porogenic solvent, the effects of both pore size and the percentage of sulfonic acid monomer on the efficiency and the electroosmotic flow velocity of the capillary columns could be studied independently over a broad range. A simple increase in the content of charged functionalities within the monolith leads to an expected acceleration of the flow velocity. However, increasing the pore size leads to a substantial deterioration of the efficiency of the separation. In contrast, monoliths with increasing levels of AMPS in which the pore size remains fixed due to adjustments in the composition of the porogenic solvent show no deterioration in efficiency while maintaining the same increase in flow velocity, thus producing a significant reduction in separation time. Additionally, measurements on monoliths with constant levels of AMPS but different pore sizes suggest that flow velocity may be affected by the flow resistance within the capillary column.     

Effects of chronic administration of alcohol on neural mechanisms of arterial blood pressure regulation]

Metaphor comprehension was studied in schizophrenics as compared to psychiatric and nonpsychiatric controls. Subjects were asked in a two-condition forced-choice response task to detect the metaphor similar or contrary to a proverb with an abstract meaning. Schizophrenic patients were impaired in both conditions. However, the paranoid patients' performances did not differ from psychiatric and nonpsychiatric controls. These results are consistent with the hypothesis that the ability of metaphorizing is preserved in some schizophrenic patients.