The response of Golgi tendon organs to single motor unit contractions

1. Cross-correlation analysis has been used to quantify the responses of cat soleus tendon organs to repetitive twitch contractions of: (a) different motor units within the muscle, (b) single motor units at different muscle lengths, and (c) single motor units when the pulse-train pattern of stimulation delivered to the motor unit axon was altered. 2. Ib afferents were observed which responded to each of several hundred successive motor unit twitches with identical numbers of spikes and with relatively invariant latencies. 3. The present results show that tendon organs are sensitive to subtle alterations in motor unit twitch wave form and amplitude, and that this sensitivity is reflected in the precise timings of their afferent discharge. 4. Examination of these tendon organ responses indicates that the forces produced by single motor units couples to the receptor capsule are well above threshold. Calculations based on these results, and earlier soleus motor unit and muscle fibre data, suggest that the absolute force threshold for tendon organs may be as little as 4 mg, which is less than the estimated minimum twitch force generated by individual soleus muscle fibres. 5. Considering the number of tendon organs in a muscle, and the likelihood that every motor unit is connected with at least one receptor, the sensitivity of tendon organs ensures that every twitch of every motor unit will be reflected in the population of afferent signals projecting to the spinal cord.     

Electrocardiographic abnormalities in hypothyroidism before and after exercise

Eleven men and 50 women with severe hypothyroidism were studied. All patients had a serum PBI less than 3.0 mug/100 ml, 131I 24 hours uptake less than 13% and a a photomotogram contraction and half relaxation time of 380 msec or more. Before exercise the mean +/- SE heart rate was 68.39 +/- 3.26/min, the PR interval 17.08 +/- 0.37 csec, the QRS voltage (sum of the QRS amplitude in leads I, II and III) 16.44 +/- 0.89 mm (10mm = 1.0 mV) and the T wave amplitude 0.06 +/- 0.15 mm. A significant correlation (p less than 0.05) existed between the PBI values and the QRS voltage. Following exercise there was a significant acceleration of the heart rate (+ 23.39/min, p less than 0.001), shortening of the PR interval (-0.66 csec, p less than 0.02) and T wave elevation (+ 0.40 mm, p less than 0.001). ST segment changes were not observed in any case. Replacement treatment in 7 cases resulted in a significant change in the resting heart rate (+ 11.86/min. p less than 0.025), PR interval (-3.28 mm, p less than 0.025) and T wave height (+ 2.50 mm, p less than 0.01). These findings suggest that exercise may be used in the differentiation between hypothyroidism and coronary heart disease. The theoretical importance of these findings is also discussed. An increase in cardiac energy demands during exercise may be the cause for some of the ECG changes observed on exertion.     

Systemic lupus erythematosus in children: the complex problems of diagnosis and treatment encountered in 101 such patients at the Mayo Clinic

Between 1945 and 1970, 101 children (86 girls and 15 boys) with systemic lupus erythematosus were evaluated at the Mayo Clinic. Only 9 children were less than 9 years old at the time of diagnosis. The most frequent presenting complaint was arthralgia; fever, fatigue, and a "butterfly" malar rash also were common. Renal involvement, found in more than 76 per cent of patients, was a prognostically poor sign. The overall survival of children with renal involvement is improved by the use of adequate steroid therapy.     

Atraumatic retrieval of the proximal end of a severed digital flexor tendon

A suction catheter technique is suggested as the next procedure of choice when proximal digital "milking" with wrist flexion fails to deliver the proximal end of the flexor tendon severed within the digital sheath.     

Synthesis and biological properties of novel pyridinioalkanoyl thiolesters (PATE) as anti-HIV-1 agents that target the viral nucleocapsid protein zinc fingers

Nucleocapsid p7 protein (NCp7) zinc finger domains of the human immunodeficiency virus type 1 (HIV-1) are being developed as antiviral targets due to their key roles in viral replication and their mutationally nonpermissive nature. On the basis of our experience with symmetrical disulfide benzamides (DIBAs; Rice et al. Science 1995, 270, 1194-1197), we synthesized and evaluated variants of these dimers, including sets of 4,4'- and 3,3'-disubstituted diphenyl sulfones and their monomeric benzisothiazolone derivatives (BITA). BITAs generally exhibited diminished antiviral potency when compared to their disulfide precursors. Novel, monomeric structures were created by linking haloalkanoyl groups to the benzamide ring through -NH-C(=O)- (amide) or -S-C(=O)- (thiolester) bridges. Amide-linked compounds generally lacked antiviral activity, while haloalkanoyl thiolesters and non-halogen-bearing analogues frequently exhibited acceptable antiviral potency, thus establishing thiolester benzamides per se as a new anti-HIV chemotype. Pyridinioalkanoyl thiolesters (PATEs) exhibited superior anti-HIV-1 activity with minimal cellular toxicity and appreciable water solubility. PATEs were shown to preferentially target the NCp7 Zn finger when tested against other molecular targets, thus identifying thiolester benzamides, and PATEs in particular, as novel NCp7 Zn finger inhibitors for in vivo studies.     

Proteolytic specificity of Lactobacillus delbrueckli subsp. bulgaricus influences functional properties of mozzarella cheese

Low-moisture part-skim Mozzarella cheeses were manufactured from 2% fat milk and aged for 21 d. Treatments included cheeses made with one of three different strains of Lactobacillus delbrueckii ssp. bulgaricus in combination with a single strain of Streptococcus thermophilus. A fourth, control treatment consisted of cheeses made with only S. thermophilus. Although total proteolytic ability of these strains, as indicated by the o-phthaldialdehyde analysis, was similar in each of the three strains of L. bulgaricus, these strains exhibited different proteolytic specificities toward the peptide, alpha(s1)-CN (f 1-23). On the basis of their alpha(s1)-CN (f 1-23) cleavage patterns and a previously described classification, these strains were assigned to the groups I, III, and V. The objective of this study was to investigate the influence of lactobacilli proteolytic systems, based on specificity toward alpha(s1)-CN (f 1-23), on functionality of part-skim Mozzarella cheese. Moisture, fat, protein, salt-in-moisture, and moisture in nonfat substances content of cheeses made with groups I, III, and V strain were similar. Control cheese had a lower moisture content than did other treatments. Significant differences were observed in functional properties between cheeses manufactured using groups III and V strains. Cheeses made with groups I and III strains were similar in their meltability, hardness, cohesiveness, melt strength, and stretch quality. Meltability and cohesiveness increased with age, while melt strength and stretch quality decreased with age for all cheeses. Additionally, HPLC showed that total peak areas of water-soluble peptides derived from cleavage of alpha(s1)-CN (f 1-23) by different strains of lactobacilli could be highly correlated to meltability and stretch characteristics of cheeses made with those strains.     

Noninterferometric quantitative phase imaging with soft x rays

We demonstrate quantitative noninterferometric x-ray phase-amplitude measurement. We present results from two experimental geometries. The first geometry uses x rays diverging from a point source to produce high-resolution holograms of submicrometer-sized objects. The measured phase of the projected image agrees with the geometrically determined phase to within +/-7%. The second geometry uses a direct imaging microscope setup that allows the formation of a magnified image with a zone-plate lens. Here a direct measure of the object phase is made and agrees with that of the magnified object to better than +/-10%. In both cases the accuracy of the phase is limited by the pixel resolution.     

The HIV-inactivating protein, cyanovirin-N, does not block gp120-mediated virus-to-cell binding

Concentrations of the potent, HIV(human immunodeficiency virus) inactivating protein, cyanovirin-N (CV-N), which completely inhibit HIV-1 infectivity, do not block the binding of soluble CD4-receptor (sCD4) to HIV-1 lysates nor the attachment of intact HIV-1 virions to several target T-cell lines. Furthermore, in contrast to the known disassociative effects of sCD4 on viral envelope glycoproteins, treatment of HIVRF with high concentrations of CV-N results in complete viral inactivation but without apparent shedding of gp120 or other ultrastructural changes. These results are consistent with the view that the virucidal effects of CV-N result from interference with step(s) in the fusion process subsequent to the initial binding of the virus to target cells.     

Exploring structure-activity relationships around the phosphomannose isomerase inhibitor AF14049 via combinatorial synthesis

Phosphomannose Isomerase (PMI) has been shown by genetic methods to be an essential enzyme in fungal cell wall biosynthesis. The PMI inhibitor AF14049 was discovered as an unanticipated side product from high-throughput library screening against the enzyme from C, albicans. Solid-phase synthetic methods were developed and a series of libraries and discrete analogs synthesized to explore SAR around AF14049.