Glomerular targeting of acidic fibroblast growth factor-1 in renal transplanted rats

BACKGROUND: Acidic fibroblast growth factor (FGF-1) functions as a potent hormonal inducer of wound repair mechanisms in vivo. In addition, the involvement of FGF-1 in a number of pathophysiological conditions, including chronic human renal allograft rejection, has been described. Consequently, there is an increasing need to monitor FGF-1 pharmacokinetics and distribution for both therapeutic and diagnostic opportunities. We now describe in vivo imaging and targeting of FGF-1 in renal transplanted rats. METHODS: Sham-operated, syngeneic renal transplanted, and allogeneic renal transplanted rats were imaged using an Anger gamma camera. Renal function was evaluated first by dynamic 99mTc-MAG3 imaging, and subsequently, 99mTc-labeled FGF-1 (99mTc-FGF-1) was imaged after i.v. injection. Microautoradiography of harvested kidneys determined the compartmental localization of 99mTc-FGF-1. RESULTS: 99mTc-MAG3 renal scans were grossly abnormal in the allogeneic renal transplanted rats. In this group, a significant reduction in 99mTc-FGF-1 renal binding was measured by imaging analyses, as compared with renal binding in the sham-operated and syngeneic renal transplanted groups, which were not significantly different. Both groups of renal transplanted rats showed a redistribution of FGF-1 to the glomerular compartment. CONCLUSIONS: 99mTc-FGF-1 serves as a new radiotracer to measure in vivo targeting of the growth factor. Reduced renal binding of 99mTc-FGF-1 in the allogeneic transplanted kidney was consistent with decreased blood flow. Unique glomerular targeting of 99mTc-FGF-1 in the transplanted kidney provides additional evidence supporting a role for this growth factor in the pathogenesis of chronic rejection.     

Gamma camera dual imaging with a somatostatin receptor and thymidine kinase after gene transfer with a bicistronic adenovirus in mice

PURPOSE: To compare two systems for assessing gene transfer to cancer cells and xenograft tumors with noninvasive gamma camera imaging. MATERIALS AND METHODS: A replication-incompetent adenovirus encoding the human type 2 somatostatin receptor (hSSTr2) and the herpes simplex virus thymidine kinase (TK) enzyme (Ad-hSSTr2-TK) was constructed. A-427 human lung cancer cells were infected in vitro and mixed with uninfected cells at different ratios. A-427 tumors in nude mice (n = 23) were injected with 1 x 10(6) to 5 x 10(8) plaque-forming units (pfu) of Ad-hSSTr2-TK. The expressed hSSTr2 and TK proteins were imaged owing to internally bound, or trapped, technetium 99m ((99m)Tc)-labeled hSSTr2-binding peptide (P2045) and radioiodinated 2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl-5-iodouracil (FIAU), respectively. Iodine 125 ((125)I)-labeled FIAU was used in vitro and iodine 131 ((131)I)-labeled FIAU, in vivo. The (99m)Tc-labeled P2045 and (125)I- or (131)I-labeled FIAU were imaged simultaneously with different window settings with an Anger gamma camera. Treatment effects were tested with analysis of variance. RESULTS: Infected cells in culture trapped (125)I-labeled FIAU and (99m)Tc-labeled P2045; uptake correlated with the percentage of Ad-hSSTr2-TK-positive cells. For 100% of infected cells, 24% +/- 0.4 (mean +/- SD) of the added (99m)Tc-labeled P2045 was trapped, which is significantly lower (P <.05) than the 40% +/- 2 of (125)I-labeled FIAU that was trapped. For the highest Ad-hSSTr2-TK tumor dose (5 x 10(8) pfu), the uptake of (99m)Tc-labeled P2045 was 11.1% +/- 2.9 of injected dose per gram of tumor (thereafter, dose per gram), significantly higher (P <.05) than the uptake of (131)I-labeled FIAU at 1.6% +/- 0.4 dose per gram. (99m)Tc-labeled P2045 imaging consistently depicted hSSTr2 gene transfer in tumors at all adenovirus doses. Tumor uptake of (99m)Tc-labeled P2045 positively correlated with Ad-hSSTr2-TK dose; (131)I-labeled FIAU tumor uptake did not correlate with vector dose. CONCLUSION: The hSSTr2 and TK proteins were simultaneously imaged following dual gene transfer with an adenovirus vector.     

Diagnosis and treatment of viral encephalitis

Acute encephalitis constitutes a medical emergency. In most cases, the presence of focal neurological signs and focal seizures will distinguish encephalitis from encephalopathy. Acute disseminated encephalomyelitis is a non-infective inflammatory encephalitis that may require to be treated with steroids. Acute infective encephalitis is usually viral. Herpes simplex encephalitis (HSE) is the commonest sporadic acute viral encephalitis in the Western world. Magnetic resonance imaging of brain is the investigation of choice in HSE and the diagnosis may be confirmed by the polymerase chain reaction test for the virus in the cerebrospinal fluid. In this article, we review the diagnosis, investigations, and management of acute encephalitis. With few exceptions (for example, aciclovir for HSE), no specific therapy is available for most forms of viral encephalitis. Mortality and morbidity may be high and long term sequelae are known among survivors. The emergence of unusual forms of zoonotic encephalitis has posed an important public health problem. Vaccination and vector control measures are useful preventive strategies in certain arboviral and zoonotic encephalitis. However, we need better antiviral therapy to meet the challenge of acute viral encephalitis more effectively.     

The placenta: Immunologic or hemodynamic protector of the fetus?

Complete separation of the maternal and fetal circulation during normal pregnancy has been regarded as an extremely important protective factor from the immunologic standpoint. This hypothesis was tested in outbred rabbits in which a direct maternal-fetal parabiosis was established during the last week of pregnancy by implanting an intact maternal omental pedicle subcutaneously into the fetus. A functional cross-circulation, which developed after 48 hours as evidenced by maternal⁵¹Cr-labeled erythrocytes, led to pathologic changes culminating in fetal death within 70 to 80 hours postoperatively. Hyperacute graft rejection, previously postulated as the etiology of these fetal changes, was ruled out since the same characteristic syndrome occurred in similarly treated inbred fetuses syngeneic with their mothers. This study indicates that the absence of direct vascular intercommunication between mother and fetus at the level of the placenta is clearly necessary for physiologic as well as immunologic reasons.     

A continuously monitored recirculating perfusion system for measuring intestinal absorption

A system was developed for the continuous and simultaneous measurement of water and nutrient (or electrolyte) absorption from the intestine. A recirculating loop (with a reservoir) was kept moving by means of two peristaltic pumps. Water was quantitated by means of a chromogenic nonabsorbed marker and a spectrophotometer. The nutrient (or electrolyte) was present in radiolabeled form and was quantitated by means of a gamma-ray detector. Use of the system was illustrated by the study of²²NaCl and⁷⁵Se-l-selenomethionine. By utilization of a suitable detector, beta-emitting radionuclides may also be used in the perfusing fluid.Supported by U. S. Public Health Service Grants CA06519 and AM09429.