Broad and potent neutralizing human antibodies to tick-borne flaviviruses protect mice from disease

Tick-borne encephalitis virus (TBEV) is an emerging human pathogen that causes potentially fatal disease with no specific treatment. Mouse monoclonal antibodies are protective against TBEV, but little is known about the human antibody response to infection. Here, we report on the human neutralizing antibody response to TBEV in a cohort of infected and vaccinated individuals. Expanded clones of memory B cells expressed closely related anti-envelope domain III (EDIII) antibodies in both groups of volunteers. However, the most potent neutralizing antibodies, with IC₅₀s below 1 ng/ml, were found only in individuals who recovered from natural infection. These antibodies also neutralized other tick-borne flaviviruses, including Langat, louping ill, Omsk hemorrhagic fever, Kyasanur forest disease, and Powassan viruses. Structural analysis revealed a conserved epitope near the lateral ridge of EDIII adjoining the EDI–EDIII hinge region. Prophylactic or early therapeutic antibody administration was effective at low doses in mice that were lethally infected with TBEV.     

Restoration of Glucose Counterregulation by Islet Transplantation in Long-standing Type 1 Diabetes

Patients with long-standing type 1 diabetes (T1D) may exhibit defective glucose counterregulation and impaired hypoglycemia symptom recognition that substantially increase their risk for experiencing severe hypoglycemia. The purpose of this study was to determine whether intrahepatic islet transplantation improves endogenous glucose production (EGP) in response to hypoglycemia in T1D patients experiencing severe hypoglycemia. We studied longitudinally subjects (n = 12) with ∼30 years, disease duration before and 6 months after intrahepatic islet transplantation using stepped hyperinsulinemic-hypoglycemic and paired hyperinsulinemic-euglycemic clamps with infusion of 6,6-²H₂-glucose and compared the results with those from a nondiabetic control group (n = 8). After islet transplantation, HbA_1c was normalized, and time spent while hypoglycemic (<70 mg/dL) was nearly abolished as indicated by continuous glucose monitoring. In response to insulin-induced hypoglycemia, C-peptide (absent before transplant) was appropriately suppressed, glucagon secretion was recovered, and epinephrine secretion was improved after transplantation. Corresponding to these hormonal changes, the EGP response to insulin-induced hypoglycemia, which was previously absent, was normalized after transplantation, with a similar effect seen for autonomic symptoms. Because the ability to increase EGP is ultimately required to circumvent the development of hypoglycemia, these results provide evidence that intrahepatic islet transplantation can restore glucose counterregulation in long-standing T1D and support its consideration as treatment for patients with hypoglycemia unawareness experiencing severe hypoglycemia.     

Genetic Study of an Indian Family with Cherubism

Cherubism (OMIM : 118400) is an autosomal dominant disorder affecting mainly facial bones leading to disfigurement of face needing medical and surgical attention besides impairing the self esteem of person. At present, there is no medical cure and there is limited indication for surgery in such cases. So, correct diagnosis is of paramount importance to both treating physician and family. Here, the authors report a family with two affected members (mother and daughter) who were tested positive for a known pathogenic mutation and thus offered timely treatment and adequate genetic counseling.     

A study of clinical presentation and delays in management of acute myocardial infarction in community

To assess the medico social demographics of acute myocardial infarction (AMI) in our community we studied 609 patients presenting between January 2008 to December 2008 with a detailed questionnaire in four centres of UP. Medical attention was sought late (> 6 hours) in 316 (51.6%), thrombolysis was obtained in 45.2% (275) and presentation was atypical in 16.3% (99). 36.2% (221) had pre-monitory symptoms of which 68% (150) ignored the same while of 32% (71) who did seek medical attention 47.9% (37) were brushed away as non-cardiac in origin. 20.3% (46/226) of hypertension, 23.2% (43/185) of diabetes and 83.4% (91/109) of hyperlipidaemia was diagnosed post event. We conclude that at least half of patients with AMI do not get definitive therapy, at least one in 10 patients do not have the classical symptoms, reasonable proportion are unaware of their risk factors, and a good majority have pre-monitory symptoms which get overlooked.     

Effect of Smoking and Gender on Pulmonary Function and Clinical Features in Sarcoidosis

Background

The effect of cigarette smoking on the clinical manifestations and progression of sarcoidosis is not well characterized. We sought to determine the effects of smoking in sarcoidosis patients and to evaluate for gender-specific differences.

Methods

We examined the effects of cigarette smoking in 518 patients seen at the Sarcoidosis and Interstitial Lung Disease Center at Wayne State University using radiographic pattern, pulmonary function testing, and clinical features of the disease. We performed a separate analysis to evaluate for gender-specific differences based on smoking history.

Results

We found that smokers had significantly lower FEV₁ and FEV₁/FVC values. Total lung capacity was not significantly different between smokers and nonsmokers, but diffusion capacity for carbon monoxide (DL_CO) was significantly reduced in smokers. Gender-based statistical analysis showed a marked decrease in DL_CO values among female smokers. Smokers were also found to have a higher incidence of extrapulmonary involvement as multivariate regression analysis demonstrated that both smoking and female gender are significantly associated with the development of extrapulmonary manifestations.

Conclusions

Our data indicate that both cigarette smoking and gender are important in shaping the clinical manifestations of sarcoidosis. The nature of the gender difference requires further study and may be related to differences in inflammatory response.