Indium-labeled presensitized T cells for diagnosis of graft rejection.

The aim of this experiment was to test a safe, noninvasive method for necessary, accurate diagnosis of early allograft rejection. Heart-lung allograft was performed heterotopically using Brown Norway (BN) rats as the donor and Lewis (LEW) rats as the recipient. T cell suspensions were prepared from lymphnodes of specifically sensitized LEW rats that had acutely rejected full-thickness BN skin graft. Cell count was adjusted 50 x 10(6) cells/ml. The suspension was incubated in vitro with 111I oxide (1 m Ci-ml). An aliquot of labeled cell suspension containing 40 x 10(6) cells and a total radioactivity of 200 mCi was administered intravenously to each animal 3 and 6 days after heart-lung transplant. The traffic of T cells was followed in vivo and in isolated organs under large field view gamma camera. The gamma camera revealed radioactivity on the graft starting Postoperative Day 5 when the heart was actively beating; no radioactivity was revealed at the site of the isografted organs. The histology showed mild to moderate cellular infiltration parallel to the grade of radioimaging intensity. The injection of indium-labeled presensitized T cells was able to detect the rejection process in an early phase when there are no clinical symptoms of rejection and/or the rejection cascade can be reversed. These results suggest that a similar method can be used in human organ transplantation for early diagnosis of rejection.     

Experimental autoimmune thyroiditis in transplanted isologous tissue and attempts to produce parathyroid lesions

Strictly inbred guinea-pigs immunized with isologous thyroid extract in complete Freund's adjuvant consistently developed thyroiditis in intramuscular transplants of isologous thyroid tissue, with reactions at least as severe as those seen in their in situ thyroid glands. Normal isologous thyroid tissue accurately reflected the severity of the systemic thyroiditis within 2 weeks after transplantation into a previously immunized guinea-pig. There was no correlation between the intensity of the histological reaction of experimental autoimmune thyroiditis and the absolute amount of thyroid tissue present in an immunized guinea-pig.

Control animals without antigen–adjuvant immunization failed to demonstrate any thyroiditis after multiple thyroid isografts alone. Parallel immunization procedures with isologous parathyroid tissue extracts failed to produce any parathyroiditis or thyroiditis.

The finding that the cellular reactivity of thyroid autoimmunity is an anatomically generalized phenomenon adds to the similarity of the process to other forms of delayed hypersensitivity such as homotransplantation immunity. Accessible transplants of specific target tissue may be used to monitor the natural course of experimental autoimmune disease or the effect of attempts to modify it.

     

Identification of a new locus for autosomal dominant non-syndromic hearing impairment (DFNA7) in a large Norwegian family

Hereditary hearing impairment affects about 1 in 1000 newborns. In most cases hearing loss is non-syndromic with no other clinical features, while in other families deafness is associated with specific clinical abnormalities. Analysis of large families with non-syndromic and syndromic deafness have been used to identify genes or gene locations that cause hearing impairment. The present report describes a large Norwegian family with autosomal dominant non-syndromic, progressive high tone hearing loss with linkage to 1q21-q23. A maximum LOD score of 7.65 (theta = 0.00) was obtained with the microsatellite marker D1S196. Analysis of recombinant individuals maps the deafness gene (DFNA7) to a 22 cM region between D1S104 and D1S466. The region contains several attractive candidate genes. This report supports the idea of extensive genetic heterogeneity in hereditary hearing impairment and represents the first localization of a deafness gene in a Norwegian family.      

Multiple cerebral metastases: detectability with Gd-DTPA-enhanced MR imaging

Sixteen patients with suspected cerebral metastases were studied with magnetic resonance (MR) imaging before and after the intravenous administration of 0.1 mmol/kg of gadolinium diethylenetriaminepenta-acetic acid. The images were interpreted blindly by two neuroradiologists; all clinical, radiologic (computed tomographic and MR imaging), and pathologic data were reviewed to arrive at a final "best diagnosis," which was then compared with the prior blinded interpretations. Of seven patients found to have multiple metastases, six (86%) had at least one tumor nodule depicted by postinfusion MR imaging that was missed by one or both observers on review of preinfusion images alone. Lesions missed on preinfusion studies were usually small nodules hidden by or not detected next to regions of high-signal edema thought to be related to the adjacent tumor nodule. The authors believe that contrast enhancement improves detection of metastatic foci with MR imaging and that the findings indicate broader implications for the detection of multiple lesions from other causes.     

CLINICO-EPIDEMIOLOGICAL ALGORITHM FOR PREDICTING SYSTEMIC ARTERIAL HYPERTENSION AT HIGH ALTITUDE THROUGH MATHEMATICAL MODELLING

A population based hybrid design combining element of cohort and cross-sectional approach was used to develop a simple clinical algorithm to predict individual probability of developing hypertension (systolic BP > 140 mm Hg and/or diastolic BP > 90 mmHg). 3615 soldiers initially normotensive at the time of induction into high altitude, were studied by systematic random sampling. Multiple logistic regression analysis showed a high significant association between hypertension and age, body mass index (BMI), tobacco smoking and alcohol consumption. Using the constant/coefficient values obtained from the logistic model and the receiver operating characteristics (ROC) curve analysis, the following predictive rule was developed – To the age in years, add (BMIx 3.86); also add 5.53 if he is a smoker; and add 19.81 if he consumes alcohol. If the total exceeds 142, the individual is at high risk of developing hypertension. This algorithm carries a sensitivity of 68.2% and specificity of 78.5%.KEY WORDS: Hypertension, High altitude     

Mouse-to-rat testicle transplantation

This report details mouse-to-rat testicular transplantation with immediate revascularization. Donor preparation involved grafting a long segment of aorta and inferior vena cava (IVC) containing the testicular artery and vein. The graft aorta and IVC were anastomosed to the rat aorta and IVC, respectively. Vasovasostomy was completed and the scrotal epithelia were anastomosed to draw the graft toward the host scrotal sac. Twenty-nine of 53 transplants were determined to be viable. Histologically, 6- to 18-hr-old grafts displayed moderate to minimal polymorphonuclear neutrophil (PMN) infiltrates. Ischemia set in somewhere between 18-24 hr postoperatively. Beyond 24 hr the grafts displayed progressive infiltration of PMN and perivascular and intertubular lymphocytes, disorganization of the germinal epithelium, and cessation of spermatogenesis.