c Granulomatous liver lesions from AI-42. day 13 after transplantation and steroid pulse therapy was conducted due to elevated concentration of serum creatinine at day 18 after transplantation. Twenty days after transplantation, mycophenolate mofetil was FOXO4 stopped due to diarrhea lasting 11?days. Kidney biopsy was performed under general anesthesia at day 69 after kidney transplantation due to elevated serum creatinine (1.6?mg/dl), and rejection Allopregnanolone was confirmed on kidney biopsy. Chest radiographs were performed and pulmonary infiltrates were observed (Fig.?2a). On necropsy, nodular lesions in the lung, spleen, and liver were observed (Fig.?2b-d). Granulomatous lesions containing central caseous necrosis were observed on H&E stained lung tissue slides (Fig.?2e-g), and AFB were identified on the lung slide (Fig.?2h and ?andi).i). Lung tissue samples were negative on PCR for detection of or NTM. Open in a separate window Fig. 2 Gross and histological lesions in a cynomolgus monkey who underwent allograft kidney transplantation suspected to have tuberculosis (Case #2). a Chest radiograph: note the presence of infiltrate. b Granulomatous Allopregnanolone lung lesions from AK-09. c Granulomatous spleen lesions from AK-09. d Granulomatous liver lesions from AK-09. e Granuloma with central caseous necrosis in lung tissue (AK-09, H&E, 12.5). f Central caseation in a granuloma, magnification of the blue area in e (AK-09, H&E, 200). g Various inflammatory cells, magnification of the area in e (AK-09, H&E, 200). h, i Acid-fast bacilli (or NTM. Open in a separate window Fig. 4 Gross and histological lesions in a cynomolgus monkey who underwent allograft islet transplantation suspected to have tuberculosis (Case #4) during euthanasia after PCR confirmation of tuberculosis in AK-08. a Lung from AI-42. b Granulomatous mesenteric lesions from AI-42. c Granulomatous liver lesions from AI-42. d Acid-fast bacilli (or NTM. Results from serial TSTs of the 26 new monkeys were also all negative. Open in a separate window Fig. 5 SMC screening program for the prevention and control of tuberculosis in nonhuman primates. SMC: Samsung Medical Center, Allopregnanolone TST: tuberculosis skin testing, PCR: polymerase chain reaction, NHP: nonhuman primates Discussion During quarantine, all monkeys had TB antibody tests and PCR for with blood samples; these results were all negative. Still, suspected tuberculosis lesions were observed during the transplantation study. Four monkeys with nodular lesions localized to the respiratory tract, suspected to be tuberculosis, demonstrated no coughing, dyspnea, or other clinical signs. The severity of the respiratory signs is variable between species and strain; rhesus monkeys tend to develop overt respiratory signs more frequently than cynomolgus monkeys [12]. According to a textbook on non-human primates, monkeys often die with no relevant clinical history or clinical signs [13]. On chest radiographs from one monkey, pulmonary infiltrates were observed. According to one report, tuberculosis may present with a weak radiological contrast in non-human primates compared with other species due to the rareness of calcified tubercles [14]. A few AFB were identified on slides from the lung or liver in all four monkeys with nodular lesions. infection usually has very small numbers of AFB in tissue compared with complex infection [12]. Two of four monkeys were PCR positive and the others were PCR negative. PCR tests have a specificity close to 100%, but the sensitivity is variable [15]. Many reports revealed that transplant recipients show negative sputum smear results and negative or indeterminate TST or Quantiferon tests despite active disease and atypical clinical presentations [16]. Most monkeys in Allopregnanolone the zone for transplantation study were given immunosuppressants and underwent transplant surgery. Immunosuppression can interfere with cell-mediated immunity and may interfere with gamma interferon production (Quantiferon) and TST results. Furthermore, most of the animals shared a surgery.

c Granulomatous liver lesions from AI-42