We made direct noninvasive magnetic measurements of hepatic iron stores with a specially designed superconducting quantum-interference-device (SQUID) susceptometer in 20 normal subjects and in 110 patients with liver disease, iron deficiency, hereditary hemochromatosis, or transfusional iron overload. Magnetic in vivo measurements of liver non-heme iron were closely correlated with chemical in vitro measurements in liver-biopsy specimens (r = 0.98, P less than 10(-5) up to 115 mumol per gram of liver tissue (wet weight) or more. Magnetically determined storage-iron concentrations were below 6.0 mumol per gram in iron-deficient patients and normal men and premenopausal women, but they were raised (9.7 to 31.4 mumol) in 12 of 67 patients with liver disease and were greatly increased (22.9 to 117.7 mumol) in patients with untreated hereditary hemochromatosis or transfusional iron overload. Magnetic measurements of iron stores provide a new quantitative technique for early detection of hereditary hemochromatosis and for rapid evaluation of treatment regimens for transfusional iron overload.

Rectal cancer (RC) is a challenging disease to treat that requires chemotherapy, radiation, and surgery to optimize outcomes for individual patients. No accurate model of RC exists to answer fundamental research questions relevant to individual patients. We established a biorepository of 32 patient-derived RC organoid cultures (tumoroids) from patients with primary, metastatic, or recurrent disease. RC tumoroids retained molecular features of the tumors from which they were derived, and their ex vivo responses to clinically relevant chemotherapy and radiation treatment correlate well with responses noted in individual patients' tumors. Upon engraftment into murine rectal mucosa, human RC tumoroids gave rise to invasive rectal cancer followed by metastasis to lung and liver. Importantly, engrafted tumors closely reflected the heterogenous sensitivity to chemotherapy observed clinically. Thus, the biology and drug sensitivity of RC clinical isolates can be efficiently interrogated using an organoid-based, in vitro platform coupled with endoluminal propagation in animals.

Summary The cytoplasmic granules (lysosomes) of leucocytes are highly reactive in situ, undergoing explosive rupture during phagocytosis, and relatively radiosensitive in the isolated state. The possibility that these properties might be related to membrane sulfhydryl groups was investigated by standard the binding of 203Hg‐labelled HgCL2 and p‐chloromercuribenzenesulfonate to granules isolated from rabbit peritoneal‐exudate neutrophils. Leucocyte lysosomes had a maximum mercury‐binding capacity of 1·92×10−7moles/mg. protein (7·5 × 10−17 moles per “average” granule), p‐chloro‐mercuribenzenesulfonate binding at 6·6 × 10−4 M was similar to this figure, but at lower concentrations binding of the mercurial was approx. 25% less than that of mercury. Binding of p‐chloromercurihenzenesulfonate was influenced by the physical state of the preparations as well as by the ionic composition of the suspending medium. Isolated granules were highly sensitive to mercury and p‐chloromencuribenzenesulfonate, undergoing rapid disruption upon incubation at 28° in the presence of low concentrations of these agents. At high concentrations of mercury (but not of p‐chloromercuribenzeuesulfonate) the granules became increasingly resistant to rupture. Lysosomes were more sensitive to gammaradiation when they were irradiated in the presence of 10 −5 M HgCl2, indicating that sulfhydryl groups may be involved in the rupture of the granules by radiation.

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