Liver damage preferentially results from CD8(+) T cells triggered by high affinity peptide antigens.

Little is understood of the anatomical fate of activated T lymphocytes and the consequences they have on the tissues into which they migrate. Previous work has suggested that damaged lymphocytes migrate to the liver. This study compares class I versus class II major histocompatibility complex (MHC)-restricted ovalbumin-specific T cell antigen receptor (TCR) transgenic mice to demonstrate that after in vivo activation with antigen the emergence of CD4(-)CD8(-)B220(+) T cells occurs more frequently from a CD8(+) precursor than from CD4(+) T cells. Furthermore, this change in phenotype is conferred only by the high affinity native peptide antigen and not by lower affinity peptide variants. After activation of CD8(+) cells with only the high affinity peptide, there is also a dramatically increased number of liver lymphocytes with accompanying extensive hepatocyte damage and elevation of serum aspartate transaminase. This was not observed in mice bearing a class II MHC-restricted TCR. The findings show that CD4(-)CD8(-)B220(+) T cells preferentially derive from a CD8(+) precursor after a high intensity TCR signal. After activation, T cells can migrate to the liver and induce hepatocyte damage, and thereby serve as a model of autoimmune hepatitis.

Quantification of the Whole Lymph Node Vasculature Based on Tomography of the Vessel Corrosion Casts.

Lymph nodes (LN) are crucial for immune function, and comprise an important interface between the blood and lymphatic systems. Blood vessels (BV) in LN are highly specialized, featuring high endothelial venules across which most of the resident lymphocytes crossed. Previous measurements of overall lymph and BV flow rates demonstrated that fluid also crosses BV walls, and that this is important for immune function. However, the spatial distribution of the BV in LN has not been quantified to the degree necessary to analyse the distribution of transmural fluid movement. In this study, we seek to quantify the spatial localization of LNBV, and to predict fluid movement across BV walls. MicroCT imaging of murine popliteal LN showed that capillaries were responsible for approximately 75% of the BV wall surface area, and that this was mostly distributed around the periphery of the node. We then modelled blood flow through the BV to obtain spatially resolved hydrostatic pressures, which were then combined with Starling's law to predict transmural flow. Much of the total 10 nL/min transmural flow (under normal conditions) was concentrated in the periphery, corresponding closely with surface area distribution. These results provide important insights into the inner workings of LN, and provide a basis for further exploration of the role of LN flow patterns in normal and pathological functions.

Anesthetic management of descending thoracic aortobifemoral bypass for aortoiliac occlusive disease: Our experience.

BACKGROUND: Complete obstruction of the abdominal aorta at the renal artery level is a difficult surgical problem. Aortic clamping and declamping can lead to profound haemodynamic changes, myocardial infarction, ventricular failure or even death may result. These complications are important challenges in anesthetic management of these patients. METHODS: Between August, 2010 and April, 2012, descending thoracic aorta to femoral artery bypass grafting was used to revascularize lower limbs in 11 patients in our institute. The anesthetic management of these patients is described here. Epidural catheter placement was done in T 5-6 or T 6-7 space for post operative pain relief. Induction was done by, Inj. Glycopyrolate 0.2 mg, Inj. Fentanyl 5 µg/kg., Inj. Pentothal sodium 5 mg/kg, Inj. Rocuronium 0.9 mg/kg, IPPV done. Left sided double lumen tube was inserted, Maintenance of Anesthesia was done by O2 + N2 O (30:70). Increments of Vecuronium and Fentanyl were given Monitoring of Heart rate, arterial pressure, central venous pressure were continuously displayed. The available pharmacological agents were used when there is deviation of more than 15% from base line. RESULTS: In our study, inspite of measures taken to control rise in blood pressure during aortic cross clamping, a rise of 90 mm of Hg in one patient and 60-80 mm of Hg in four patients was observed, which was managed by sodium nitropruside infusion. At the end of surgery seven patients were extubated on the operation table. In remaining four patients DLT was replaced by single lumen endotracheal tube and were shifted to ICU on IPPV. They weaned off gradually in 3-5 hours. In our series blood loss was 400 ml to 1000 ml. There was no mortality in the first 24 hours. Postoperative bleeding was reported in one case which was re-explored and stood well. CONCLUSION: The anesthetic technique during aortic surgery is directed at minimizing the hemodynamic effects of cross clamping in order to maintain the myocardial oxygen supply demand ratio.

The effects of spaceflight on mammary metabolism in pregnant rats.

The effects of spaceflight on mammary metabolism of 10 pregnant rats was measured on Day 20 of pregnancy and after parturition. Rats were flown on the space shuttle from Day 11 through Day 20 of pregnancy. After their return to earth, glucose oxidation to carbon dioxide increased 43% (P < 0.05), and incorporation into fatty acids increased 300% (P < 0.005) compared to controls. It is unclear whether the enhanced glucose use is due to spaceflight or a response to landing. Casein mRNA and gross histology were not altered at Day 20 of pregnancy. Six rats gave birth (on Day 22 to 23 of pregnancy) and mammary metabolic activity was measured immediately postpartum. The earlier effects of spaceflight were no longer apparent. There was also no difference in expression of beta-casein mRNA. It is clear from these studies that spaceflight does not impair the normal development of the mammary gland, its ability to use glucose, nor the ability to express mRNA for a major milk protein.

Experimental production of varicocele and its effect on testes.

Parital obstruction of left renal vein leads to production of varicocele in a fairly short period, i.e.; even within a month. Collateral venous channels play an important role in the formation and degree of varicocele. Varicocele has got a depressive effect on the spermatogenesis on the side of varicocele as well as on opposite testes. Leydig cells and interstitial tissue flourish at the expense of gonadal elements. The factors affecting the spermatogenesis are different from those of other tissues of the testes.