1. Myoblasts from expanded primary cultures were implanted into cryodamaged soleus muscles of adult BALB/c mice. One to four months later isometric tension recordings were performed in vitro, and the male donor cells implanted into female hosts were traced on histological sections using a Y-chromosome-specific probe. The muscles were either mildly or severely cryodamaged, which led to reductions in tetanic muscle force to 33 % (n = 9 muscles, 9 animals) and 70% (n = 11) of normal, respectively. Reduced forces resulted from deficits in regeneration of muscle tissue as judged from the reduced desmin-positive cross-sectional areas (34 and 66 % of control, respectively). 2. Implantation of 106 myogenic cells into severely cryodamaged muscles more than doubled muscle tetanic force (to 70% of normal, n = 14), as well as specific force (to 66% of normal).Absolute and relative amounts of desmin-positive muscle cross-sectional areas were significantly increased indicating improved microarchitecture and less fibrosis. Newly formed muscle tissue was fully innervated since the tetanic forces resulting from direct and indirect (nerve-evoked) stimulation were equal. Endplates were found on numerous Y-positive muscle fibres. 3. As judged from their position under basal laminae of muscle fibres and the expression of M-cadherin, donor-derived cells contributed to the pool of satellite cells on small-and largediameter muscle fibres. 4. Myoblast implantation after mild cryodamage and in undamaged muscles had little or no functional or structural effects; in both preparations only a few Y-positive muscle nuclei were detected. It is concluded that myoblasts from expanded primary cultures -unlike permanent cell lines -significantly contribute to muscle regeneration only when previous muscle damage is extensive and loss of host satellite cells is severe.

In order to gain further insight into the signal transduction pathway concerning gravitropism, we studied the expression profiles of mRNA in etiolated sunflower (Helianthus annuus L.) seedlings. Differential-display reverse transcriptase PCR product assayed by capillary electrophoresis revealed the small GTPase Ran, regulating nuclear import and export of proteins. Parallel analysis of inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) release by a highly advanced system of metal-dye detection combined with high-performance liquid chromatography provided evidence that the second messenger Ins(1,4,5)P3 is modulated by changes of the gravity vector. Investigations by fast clinorotation and sounding rockets established a positive correlation between the Ins(1,4,5)P3 level and the expression rate of Ran mRNA during simulated and real microgravity. Since an asymmetric distribution of auxin during graviresponse is suggested to induce differential cell elongation, additional information on the perception and transduction pathways was achieved by auxin stimulation experiments. While we were able to demonstrate an auxin-dependent production of Ins(1,4,5)P3, the expression of Ran mRNA was not affected by auxin. Finally, besides the phosphoinositide system as one element of the signal transduction chain linking graviperception to graviresponse, a Ran-mediated interaction model of extracellular microgravity signal perception and intercellular transduction pathway is proposed.

Amyloidosis is a rare disease with an incidence of only 16.6 per 100,000 patients per year. A high grade of clinical suspicion is required to suspect an atypical cause of left ventricular hypertrophy or new-onset heart failure. A transthoracic echocardiogram (TTE) is the initial evaluation that may yield clues pointing towards an etiology of cardiac amyloidosis. Due to the subjective nature of TTE interpretations, suspicion for cardiac amyloidosis may be missed. Once suspicion arises, additional tests, such as serum and urine electrophoresis and technetium-99m pyrophosphate myocardial perfusion imaging, can further aid in establishing a diagnosis. The pathophysiology in transthyretin amyloidosis (ATTR) involves the misfolding of the transthyretin/prealbumin protein, which leads to an inherent propensity to aggregate. These proteins can accumulate in the extracellular space between cardiac myocytes, which may thicken sections of the heart, leading to ventricular restriction. Here, we explore the case of an 83-year-old man with chronic, treatmentresistant heart failure with preserved ejection fraction, New York Heart Association class III, who presented with multiple ruptured bullae in the bilateral lower extremity, leading to a new diagnosis of ATTR cardiac amyloidosis.

No abstract