Immunological memory induced by genetically transduced tumor cells

Background: Recent studies have demonstrated the usefulness of gene-modified tumor cells for immunotherapy. Using the tumorigenic murine fibrosarcoma, MCA 106, we investigated the effects of localized interferon-γ (IFNg) secretion on tumorigenicity and on long-term memory. Methods: The murine IFNg (MuIFNg) gene was introduced into tumor cells. High and low IFNg-secreting clones were isolated. C57BL/6 mice were injected subcutaneously (s.c.) with either parental (P), high or low IFNg-secreting (H- or L-IFNg) cells, and tumor growth was assessed weekly. Spleens were harvested on different days postinjection (p.i.) to assess in vitro cytolytic activity. In parallel, tissues from injection sites were stained with macrophage-, CD4-, and CD8-detecting antibodies. Mice were injected s.c. with H-IFNg MCA106 tumor. After 150 days the animals were rechallenged s.c. with MCA106P in one leg and with irrelevant syngeneic tumor in the other. Results: Both P- and L-IFNg cells had similar growth, whereas the H-IFNg cells never grew. Only splenocytes from the H-IFNg animals showed in vitro CTL activity persisting until day 30 p.i. Histological data revealed a macrophage and CD4⁺ infiltrate much earlier in the H-IFNg group compared with the P group. Only the irrelevant, syngeneic tumor grew in animals previously injected with H-IFNg cells, whereas both P and irrelevant syngeneic tumors grew in controls. Conclusions: Transduction of MCA106 cells with the MuIFNg gene diminished in vivo tumorigenicity in proportion to the amount of IFNg secreted. Immunization with H-IFNg cells elicited a host response characterized by macrophages and CD4⁺ cells. Long-term tumor-specific memory was seen after immunization with H-IFNg cells.     

The effect of visual deprivation on canine gastric secretion

In 13 dogs with gastric cannulas the acid output per hour was determined after: (a) subcutaneous injection of 0.1 mg histamine (base), (b) subcutaneous injection of 1.0 mg histamine (base), (c) teasing with meat (10 min interval), (d) intravenous injection of 1.0 units/kg of insulin. The pepsin concentration was also determined after the intravenous injection of 1.0 units/kg of insulin. The range and average acid output and pepsin concentration were established for each test condition per dog. Vision was compromised in the dogs by ablation of the orbits, collapse of the orbits, and by occipital cortical lesions. Gastric secretory studies were repeated at intervals over a 4 month period. There was marked inhibition of acid output and pepsin concentration in all dogs for the entire 4 month period to all gastric stimuli.Acknowledgment is made to medical students Alan C. Leshnower, Dennis G. Westmoreland and John M. Eisenberg; to Jan Rubion, University of Tennessee Clinical Research Center, for the pepsin determinations; to Robert H. Murray, Surgical Research Laboratories, VA Hospital, Memphis, Tenn; to Lena Haney for histologic preparations; and to T. Bond for handling the statistical material.Supported in part, by Grant GB-7687 from the National Science Foundation.Supported by General Research Grant FR-05423, NIH, US Public Health Service.Supported by Research Grant FR-00211, US Public Health Service.     

Pseudoaneurysms complicating organ transplantation: roles of CT, duplex sonography, and angiography

In a retrospective study of proved pseudoaneurysms (PAs) in 15 patients with transplanted organs (11 liver, three kidney, one pancreas), the results of computed tomography (CT), duplex sonography, and angiography were reviewed. Of the 15 cases of PA, eight occurred at the arterial anastomosis and seven were nonanastomotic. Three of the eight anastomotic PAs were caused by infection. Of the seven nonanastomotic PAs, four were caused by percutaneous biopsy, two were caused by infection, and one was of undetermined cause. In nine (60%) of the 15 patients the PAs were incidentally detected at imaging studies performed for other reasons. Diagnosis requires a high degree of suspicion. CT was performed in nine cases and duplex sonography in ten. The diagnosis of PA was made with CT in six (67%) patients and with duplex sonography in five (50%). CT and duplex sonography could not enable diagnosis when the PA was small, when the arterial anastomosis was not included in the field of study, or when enhancement with intravenously administered contract material was suboptimal. Angiography depicted the PAs in all 15 patients. In three liver transplant recipients with gastrointestinal tract bleeding, the causative PAs were detected only with angiography.     

Outpatient therapy of intra-abdominal abscesses following early discharge from the hospital

Although percutaneous aspiration and drainage of abdominal abscesses will frequently avert an open surgical procedure, patients remain hospitalized during drainage. The authors treated 9 patients for abscesses using percutaneous drainage catheters and sent them home with the catheter in place. All had an uneventful recovery. An average of $12,050 was saved in each case. The authors suggest that outpatient drainage of abdominal abscesses is significantly less expensive than inpatient treatment, yet does not jeopardize patient care.     

Neuropsychological and linguistic follow-up studies of children with galactosaemia from an unscreened population

Many galactosaemics appear to have neuropsychological and/or linguistic problems in spite of dietary treatment. Because the neonatal screening program in Norway does not include galactosaemia, we have re-examined Norwegian galactosaemics. Of 16 known patients, 8 patients participated in the study. They had been diagnosed between 2 and 11 weeks of age, and were between 9 months and 19 years old at the time of this study. All had very low or 0 activity of galactose-1-phosphate uridyl transferase. As part of the study all were examined neurologically, and had an age-appropriate developmental/IQ test, an ABR and an EEG, and a comprehensive psycholinguistic evaluation. The three youngest patients had normal developmental/IQ tests, while the five older patients had IQ scores in or below low range of normal. The majority had delayed language development and three patients were classified as having verbal dyspraxia. ABR and EEG showed mild pathology in the oldest patient only. Galactosaemia appears to be associated with significant risks of developmental and language delays in this unscreened population.     

Biplane arteriography in ischemia of the lower extremity

A technique for simultaneous bilateral biplane arteriography of the abdomen, pelvis, and lower extremities is described. The biplane views provided clinically significant information in approximately 40% of cases.     

The effect of enterectomy on gastric secretion in dogs with biliary fistulas

Bile was excluded from the gastrointestinal tract of 5 dogs with Heidenhain pouches by total external biliary fistulas. After a major portion of the jejunum and the ileum was resected Heidenhain pouch secretions increased in all instances. The results indicate that the increase in gastric secretion which regularly follows small-bowel resection is independent of the presence or absence of bile in the gastrointestinal tract.Supported by Grant AM-7750 from the US Public Health Service.The opinions expressed in this publication are those of the authors and not necessarily those of the US Air Force Medical Service.