Early detection of metastasis by alterations in the cellular immune system in the murine liver and blood

We investigated the reaction of the cellular immune system of liver and blood in the C57BL/6 mouse to a metastasizing Lewis lung carcinoma. The cellular immune system of the liver consists of mature and immature macrophages, B-cells, T-cells including their subpopulations, and natural killer cells, and their percentage frequencies differ significantly from those in the corresponding mononuclear blood cell (MBC) compartment. This suggests that the hepatic immune cells represent a system with autonomous function showing a typical homing of its members. Imminent metastasis to the liver is signalled by impressive alterations in the percentage frequencies of nonparenchymal liver cells (NPLC). There are a dramatic loss of mature macrophages, an increase in immature macrophages, a reduction of T-helper cells leading to a low CD4/CD8 ratio, and an increase in natural killer cells. In the blood, the corresponding precursor cells show comparable changes with a delay of at least 2 days. Early metastasis is accompanied by a significant increase in mononuclear NPLC producing tumour necrosis factor . The alterations in percentage frequencies of the NPLC during tumour metastasis differ markedly from the changes in these cells in the liver during endotoxinaemia.     

Energy turnover and lactate dehydrogenase activity in detrusor smooth muscle from rats with streptozotocin-induced diabetes

Force generation and tissue glucose metabolism were measured in the urinary bladder smooth muscle from rats with streptozotocin-induced diabetes (7–8 wk duration). Bladder wet wt was almost 4–fold higher in the diabetic animals compared with the untreated controls. Morphological analysis showed that the growth was associated with hypertrophy of the smooth muscle component in the bladder wall. Force generation of isolated bladder strip preparations was measured in vitro at different ambient oxygen tensions. Activation of intramural nerves, with electrical field stimulation, induced contractions that were unaffected by reduction of oxygen tension down to Po₂ 100 mmHg for both control and diabetic muscle strips. At zero Po₂ force was reduced by approximately 10–20% in both groups. High-K⁺ solution induced ‘tonic’ contractions that were slightly more inhibited by lowering Po₂. At intermediate Po₂ (between 100 and 20 mmHg) the diabetic muscle gave slightly higher force. At zero Po₂ no significant difference could be detected between strips from control and diabetic animals. Oxygen consumption and lactate production in the preparations were determined at a Po₂ of 290 mmHg and related to the volume of smooth muscle. At zero Po₂ lactate formation increased 3- to 4-fold. The metabolic tension cost was lower at zero Po₂ No differences in basal and contraction related metabolic rates could be detected between the two groups under normoxic and anoxic conditions. The maximal activity of lactate dehydrogenase (LDH) determined in tissue sampIes was about 2-fold higher in the diabetic bladder muscle. This increased enzymatic activity could thus not be correlated with any altered metabolic properties of the smooth muscle in the urinary bladder from diabetic rats.     

Immunohistochemical characterization of an anti-epithelial monoclonal antibody (mAB lu-5)

Summary A mouse monoclonal antibody (mAB lu-5) was prepared using a lung cancer cell line as an antigen. The selected clone produces an IgG with a gamma-1 heavy chain and a kappa-light-chain. Immunohistochemical testing of mAB lu-5 on 117 normal tissue biopsies and 474 tumours revealed reactivity with an intracytoplasmic, formaldehyderesistant antigen present in most epithelial and mesothelial cells, but absent in mesenchymal cells. The antibody can therefore be used as a first order, pan-epithelial marker. It proved also useful for fast tumour diagnosis on frozen sections.     

Thymocyte activating factors from SV40-transformed human embryo fibroblasts

A novel factor was found in the medium conditioned by SV40-transformed human embryo fibroblasts, which stimulate concanavalin A-induced thymocyte DNA synthetic response. This activity was estimated to be 10-15 kD and divided into two activities by ion exchange chromatography. One of them is a protein molecule and the other is a glycoprotein. In addition, these activities are not derived from the growth factors reported previously such as interleukin 2 (Morgan, R., Ruscetti, F. and Gallo, R. C. (1976) Science 193, 1007-1008) and transforming growth factor (De Larco, J. E. and Todaro, G. J. (1978) Proc. Natl. Acad. Sci. U.S.A. 75, 4001-4005).     

Reversibility of artifacts of fluid volume measurements by bioimpedance caused by position changes during dialysis

The effect of temporary position changes, sitting up from supine, on extracellular (ECW) and intracellular (ICW) resistances and fluid volumes calculated from whole body bioimpedance using a Xitron 4200 impedancemeter was investigated on 8 patients during dialysis for a total of 11 tests. It was found that ECW resistance decreased instantaneously by an average of 2.3% when the patient sits up, due to plasma and interstitial fluid shift into the legs which decreases leg resistance, the major contributor to total resistance. This drop in resistance is incorrectly interpreted by the device as an increase in ECW volume which averages 235 ml. But this effect is completely reversible and both ECW resistance and fluid volume rapidly resume their normal course when the patient returns to his initial position. No significant variation in ICW resistance was observed in any of the patients at the position change. We conclude that segmental impedance, which has been proposed to minimize this artifact, is not advisable in dialysis monitoring and that it is simpler to ignore or switch off measurements during the position change so that later data are not affected by it.     

Bone marrow examination for the diagnosis of mycobacterial and fungal infections in the acquired immunodeficiency syndrome.

In a series of 342 bone marrow examinations from 314 patients with human immunodeficiency virus infection, 70 examinations (20%) detected opportunistic mycobacterial or fungal infections. One hundred eleven of the 314 patients had such infections, and, hence, 63% (70/111) were detected by bone marrow examination. Special stains for microorganisms detected 16 (32%) of 50 Mycobacterium avium complex infections, 10 (22%) of 45 Mycobacterium tuberculosis infections, eight (73%) of 11 Histoplasma capsulatum infections, and five (83%) of six Cryptococcus neoformans infections. Bone marrow cultures detected 36 (72%) of the 50 M avium complex infections, 13 (29%) of the 45 M tuberculosis infections, and 63% of the fungal infections. Marrow examination revealed infection in only one of the 70 specimens (1%) collected to evaluate thrombocytopenia alone or hematologic malignancy, but in 69 (25%) of 274 with fever, neutropenia, anemia, or miscellaneous other indications for marrow examination. Granulomas were detected in 102 (30%) of the biopsy specimens, including 71 (64%) of those in cases with mycobacterial or fungal infection. The granulomas showed caseous necrosis in nine cases, all in patients with tuberculosis, and the 27 cases with tuberculosis-associated granulomas tended to show large, tightly cohesive granulomas. The presence of granulomas correlated with opportunistic infection in 82 (80%) of 102 cases. Without granulomas, special stains were positive in only eight (3%) of 240 specimens. These results suggest that (1) bone marrow granulomas are a common and valuable histologic clue to opportunistic infection; (2) without them, special stains may not be a cost-efficient way to diagnose such infection; and (3) bone marrow examination can be a useful method of diagnosing opportunistic mycobacterial and fungal infections in patients with fever, anemia or neutropenia, and underlying human immunodeficiency virus infection.     

Transplantation of cultured fetal human adrenal chromaffin cells to rat brain

Adrenal chromaffin cells, obtained from a therapeutically aborted human fetus of about 11 weeks gestation, were cultured for 3 weeks in vitro and then transplanted to the striatum of rats. Transplanted cells became established through strands of tissue growing into the host striatum. No signs of inflammation or rejection were observed up to the time of sacrifice one month post-transplantation. Histofluorescence examination of the implanted areas showed many clusters of cells having an intensely positive catecholamine fluorescence with some of the cells developing conspicuous processes. This study, showing survival of cultured human adrenal chromaffin cells transplanted into rat brain tissue, might indicate the feasibility of using cultured human material for future human neuronal transplantation studies as a therapeutic measure.