Biomedical subjects

James Lane

Publications and source records attributed to James Lane.

6 recordsLinked to original sources

PubMed2005

A new site-specific integration system for mycobacteria.

Site-specific integration into the mycobacterial chromosome can produce stable transformants useful for understanding pathogenesis. However, gene expression can be problematic at certain sites of integration. We have used the Streptomyces phiC31 integration system to integrate vector DNA into Mycobacterium smegmatis, M. bovis BCG, and M. tuberculosis through site-specific recombination. A single dominant insertion site was found in M. smegmatis, as previously reported. Three different insertion sites were found in M. bovis BCG. In M. smegmatis, integrated vectors appear to be far more stable than episomal plasmids during unselected passage in vitro, although excision products are detectable. Plasmids based on the phiC31 integration system could make useful tools for the study of mycobacterial genetics.

BCG Vaccine↗

PubMed2005

Greater early pancreas graft loss in women compared with men after simultaneous pancreas-kidney transplantation.

BACKGROUND: Gender differences in graft survival has been reported after some types of organ transplantation, but not after pancreas transplantation. This study compares graft survival between women and men after simultaneous pancreas-kidney transplantation (SPK). METHODS: All first time SPK (n = 163) transplants (109 M/54 F) performed between 1989 and 2000 at University of Nebraska Medical Center, where data was available, were analyzed for overall graft and patient survival. Graft failure was then subdivided into early (<6 months), and late (>6 months), and compared between women and men. RESULTS: The 5-yr pancreas and kidney graft survival rates for all SPK recipients was 86% [95% confidence interval (CI) = 81-92%] and 87% (95% CI = 82-93%), respectively. While overall pancreas graft survival in women was similar to men (p = 0.16), early pancreas graft failure was greater in women than men (p = 0.010) with no one cause for failure predominant. There was no gender difference in late pancreas graft failure or in early, or late kidney graft failure in the same recipients. The gender difference was unexplained by differences in age, immunosuppression, body mass index (BMI), or diabetes duration between women and men. CONCLUSIONS: This is the first report of a gender difference in pancreas graft survival after SPK with greater early (<6 months) pancreas graft failure in women than men. With no gender difference in kidney graft failure in the same individuals, gender differences in immune responses are unlikely to be the cause. Multiple variables likely contribute.

Adult↗

PubMed2002

Apolipoprotein E gene polymorphism alters lipids before pancreas transplantation.

BACKGROUND: Pancreas transplantation (PTX) improves lipids in patients with type 1 diabetes mellitus. However, there are patients who have persistent abnormal lipids or develop new hyperlipidemia despite PTX. One factor that may influence the lipid profile is apolipoprotein E (Apo E) genotype. Apo E polymorphism, particularly E2 and E4 alleles, increases the risk of dyslipidemia. Apo E2 has also been found to increase risk of diabetic nephropathy and so may be more prevalent in PTX candidates. METHODS: This study evaluated fasting-lipid profiles in type 1 diabetes patients who were pancreas transplant candidates to prospectively evaluate the impact of Apo E genotype on dyslipidemia before and after PTX. RESULTS: Presence of one or more E4 alleles resulted in higher triglycerides ( =0.0446), lower HDL ( =0.0247), and a higher cholesterol-to-HDL (C/H) ratio ( =0.0405) before PTX when compared with those with E3/3 genotype. After PTX, lipids improved so there was no longer a difference in fasting lipids between patients with an E4 allele and E3/3 genotype. Presence of an E2 allele had no significant impact on fasting lipids before or after PTX. CONCLUSIONS: Presence of an Apo E4 allele worsened HDL, triglycerides, and C/H ratio before PTX compared with those with E3/3 genotype, whereas the presence of an Apo E2 allele had no significant effect on lipids before or after PTX. Thus, Apo E4 has a larger impact than Apo E2 on fasting-lipid profile in PTX candidates, and Apo E gene polymorphism does not worsen lipid dyslipidemia after PTX, despite introduction of immunosuppressant medications known to cause dyslipidemia.

Adult↗

PubMed2002

Carotid intima media thickness decreases after pancreas transplantation.

BACKGROUND: Pancreas transplantation (PTX) improves diabetic microvascular complications, but it is unknown whether PTX alters macrovascular disease. Carotid intima media thickness (IMT) has been shown to correlate with cardiovascular events, so this study was designed to evaluate changes in carotid IMT after PTX. METHODS: Four groups were studied: PTX candidates (n=60); successful PTX recipients (n=89; mean time since PTX=4.0+/-0.3 years); patients with type 1 diabetes but without nephropathy (n=20); and normal controls (n=32). Mean IMT and mean of maximum carotid IMT measurements (mean-max IMT), hemoglobin A1C, serum creatinine, body mass index (BMI), blood pressure, smoking status, use of hypolipidemic medications, and fasting lipids were determined in all groups. RESULTS: Age, gender distribution, and BMI were not different among the groups. Duration of diabetes was also equal between pre- and post-PTX groups. Mean and mean-max IMT were greatest pre-PTX and decreased after PTX (P<0.05) to a value that was not different from controls. Hemoglobin A1C and creatinine decreased, and high density lipoprotein (HDL) increased after PTX (P<0.05), but there were no significant differences in other lipids, BMI, use of lipid lowering agents, blood pressure, or smoking status. CONCLUSIONS: Carotid IMT is lower after PTX, suggesting a reduction in overall cardiovascular risk independent of changes in use of hypolipidemic agents, smoking, blood pressure, BMI, or lipids, except HDL. Improved carotid IMT after successful PTX predicts a reduction in future vascular disease events and suggests that the macrovascular disease of type 1 diabetes is at least partially reversible with improved glucose control.

Adult↗

PubMed2002

Pancreas and kidney transplantation.

Kidney transplantation is preferred over dialysis for management of end-stage renal disease complicating type I or type 2 diabetes, for those who are eligible. Simultaneous pancreas-kidney (SPK) or pancreas after kidney transplantation (PAK) is an important alternative to kidney transplantation alone for type I diabetes patients if the patient is able to withstand the additional risks of these procedures, because of the benefits of glucose control on other diabetic complications. Pancreas transplantation alone (PTA) is most useful for the treatment of debilitating, frequent hypoglycemia complicating type I diabetes, if renal function is adequate. One-year pancreas graft survival is best after SPK (82%) but has significantly improved after both PAK (74%) and PTA (76%). The I-year kidney graft and patient survival rates after SPK are similar to kidney transplantation alone. Pancreas transplantation normalizes glucose beyond what can be achieved with insulin therapy and has been shown to decrease progression of or improve most, if not all, diabetic end-organ complications using current immunosuppression regimens. However, the diabetologist and endocrinologist should remain involved in the care of the pancreas or kidney transplant recipient for treatment of vascular disease risk factors such as dyslipidemia, surveillance of other diabetic complications including foot ulcers, surveillance and treatment of bone loss, and management of hyperglycemia if it recurs.

Diabetic Nephropathies↗

PubMedDate not supplied

What is hypoglycemia in patients with well-controlled type 1 diabetes treated by subcutaneous insulin pump with use of the continuous glucose monitoring system?

OBJECTIVE: To analyze 72-hour interstitial glucose concentrations measured by a glucose sensor in adult subjects. METHODS: We compared glucose levels in 10 patients with type 1 diabetes mellitus (DM-1) and 10 normal control subjects with use of the Medtronic Continuous Glucose Monitoring System (CGMS). Hypoglycemic events identified by the CGMS, the patients, or both were compared in the patients with DM-1. In addition, the results between two glucose sensors placed at similar sites in the same subject were evaluated. RESULTS: Hemoglobin A1c and mean glucose values were higher in the DM-1 group than in the control group (P<0.01), whereas time spent at glucose levels of less than 60, 60 to 79, and 121 to 150 mg/dL were similar between the two study groups. Time spent at glucose levels above 150 mg/dL was greater in the DM-1 group than in the control group (P<0.05). Of the 74 total hypoglycemic events in the patients with DM-1, the sensor and the patient recognized 14%, only the patient recognized 9% (confirmed by readings of <55 mg/dL on a glucose meter), and only the sensor detected 77%. Of note, 41% of the patient-identified symptomatic hypoglycemic events were missed by the CGMS. When one patient with DM-1 and one control subject wore two glucose sensors simultaneously, one and not the other sensor often identified "hypoglycemia," and the correlation was only fair to good by intraclass correlation analysis. CONCLUSION: Many asymptomatic "hypoglycemic events" identified by the CGMS may not be actual hypoglycemia. Hypoglycemia is both overreported and underreported with use of the CGMS. Thus, adjustment of insulin doses to reduce asymptomatic hypoglycemia identified by the CGMS alone may not be warranted.

Adult↗