Hyperthyroidism is accompanied by significant dysfunction of both proximal and distal skeletal muscles. The purpose of this study was to quantitate the degree of muscle weakness in newly diagnosed patients with Graves' disease and to assess the response to treatment. Ten patients were prospectively studied with objective measures of strength and endurance of proximal and distal muscles while hyperthyroid (stage I), after 2 weeks of propranolol (stage II), and about 6 months later when euthyroid (stage III). Propranolol treatment for 2 weeks resulted in a subjective decrease in weakness, which was accompanied by a statistically significant improvement in grip strength (P less than 0.01), shoulder strength (P less than 0.02), and grip endurance (P less than 0.01) but not shoulder endurance. Muscle function further improved and attained control levels when the patients were chemically and clinically euthyroid. In contrast, a control group subjected to the same muscle testing protocol before and after 1 week of propranolol treatment showed no improvement in grip, shoulder strength, or shoulder endurance but had decreased grip endurance (P less than 0.01) and increased subjective weakness. These results confirm that muscle weakness commonly is associated with hyperthyroidism and can be quantitatively profound. In contrast to the effects of beta-blockade in normal controls, propranolol partially improves muscle weakness in thyrotoxic patients. We conclude that thyroid hormone and catecholamines in concert mediate the muscle dysfunction of hyperthyroidism.

The interaction of Legionella micdadei with human polymorphonuclear neutrophils (PMNs) and serum was investigated to determine their roles in host defense against this organism. Serum and PMNs from normal donors having no antibody to L micadei were used. PMNs phagocytized once-agar-passaged (74.6% +/- 6.5%) and twice-agar-passaged (87.3% +/- 1.0%) L micdadei less (P less than 0.05) than L micdadei passaged multiple times on agar (97.5% +/- 1.0%) or Staphylococcus aureus (98.3% +/- 0.5%). Under the same conditions, no phagocytosis of Legionella pneumophila occurred. Use of heat-inactivated serum abolished phagocytosis. PMN killing of once-agar-passaged (1.5% +/- 1.5%) and twice-agar-passaged (0) L micdadei was less (P less than 0.001) than that of L micdadei passaged multiple times on agar (88.6% +/- 4.0%) or S aureus (96.8% +/- 0.5%). L micdadei was not killed by fresh serum, although, in contrast to L pneumophila, it was opsonized by C3. Thus virulent L micdadei is phagocytized, but not killed, by human PMNs, with complement being the major opsonin.

We have recently shown that LegioneUla micdadei is ingested, but not killed, by human neutrophils. Herein we investigate the role of human monocytes in defense against this organism. Serum and monocytes from normal donors having no detectable antibody to L. micdadei were used. Egg-passaged L. micdadei organisms multiplied inside these monocytes with a peak growth of 2 log units within 12 h. No growth occurred when monocytes were omitted or when sonicated monocytes were used. Electron microscopy 18 h after infection revealed these organisms to be intracellular in normal-appearing phagosomes. When the input multiplicity of L. micdadei was greater than 1 CFU per monocyte, no intracellular growth occurred. When egg-passaged Legionella pneumophila organisms were used, intracellular organisms were found in phagosomes studded with ribosomes at the same time period. Peak intracellular growth of L. pneumophilia occurred by 48 h. L. micdadei activated the complement system and was opsonized by C3. However the use of complement-depleted (heatinactivated) serum as the opsonic source had no effect on the bacterium's ingestion or growth in the monocyte. Thus, L. micdadei multiples in human monocytes. This entry and growth is independent of antibody or complement. The intracellular locations of L. micdadei and L. pneumophila differ, suggesting different mechanisms for the survival of these two organisms in the monocyte.

Consistent chromosomal translocations involving the c-myc cellular oncogene and one of the three immunoglobin loci are typical for human Burkitt's lymphoma, induced mouse plasmacytoma (MPC) and spontaneously arising rat immunocytoma (RIC). Another plasma cell malignancy, multiple myeloma (MM), arising spontaneously in the ageing C57BL/KaLwRij mice, was investigated in order to see whether the MM cells contain c-myc abnormalities of the MPC or RIC type. Rearrangement of the c-myc oncogene was found in the bone marrow cells only in 5T2 MM transplantation line in a mouse of the 24th generation and in none of the seven other MM of the 5T series which were of earlier generations. Since the mouse 5T MM resembles the human MM very closely, including the absence of consistent structural c-myc oncogene abnormalities, it can serve as a useful experimental model for studies on the aetiopathogenesis of this disease. Images Figure 2 Figure 3

Abstract. Intravenous (i.v.) injection of mice with lipopolysaccharide (LPS), and the proteolytic enzymes trypsin and proteinase, mobilizes pluripotent haemopoietic stem cells (CFU-s) as well as granulocyte-macrophage progenitor cells (GM-CFU) and the early progenitors of the erythroid lineage (E-BFU) from the haemopoietic tissues into the peripheral blood. We investigated the involvement of the complement (C) system in this process. It appeared that the early mobilization induced by LPS and other activators of the alternative complement pathway, such as Listeria rnonocytogenes (Lm) and zymosan, but not that induced by the proteolytic enzymes, was absent in CS-deficient mice. The mobilization by C activators in these mice could be restored by injection of CS-sufficient serum, suggesting a critical role for CS.