Arterial pressure-flow relations in the awake standing dog.

The transient circulatory changes following paced heart rate increase are reported from 133 trials with 6 unanesthetized dogs with chronically implanted monitoring devices for heart rate, cardiac output, aortic blood pressure, and mean right atrial pressure. In 62 trials with 2 of the dogs, pulmonary artery, and left ventricular end-diastolic pressure, as well as left ventricular dP/dt were also studied. The sequence of changes in pressures and flows is analyzed in terms of probable underlying mechanisms, particularly with respect to the nature of vascular resistances. The rise in aortic pressure and flow during the first 3 s of paced heart rate increase, before arterial stretch receptor reflexes become active, is more consistent with an effective downstream pressure of about 49 mmHg, presumably at the arteriolar level, than with an effective downstream pressure close to 0 mmHg at the right atrial level. In the pulmonary circulation where vascular reflex effects are less prominent, the pattern of pulmonary arterial pressure and flow for the entire 30 s of observation is consistent with an effective downstream pressure of 9 mmHg, presumably at the alveolar or pulmonary arteriolar level, rather than at the level of the left ventricular end-diastolic pressure.     

Bacteriophages in autoimmune disease and other inflammatory conditions

There are several autoimmune diseases and other inflammatory conditions where an infectious aetiology is suggested by the epidemiology, clinical course and pathological findings. Many candidate bacteria and viruses have been considered as potential aetiological agents but mostly without firm proof. Bacteriophages are viruses that infect bacteria and may be found wherever bacteria are located, but would not be detected unless specifically sought. They have not previously been considered to be pathogens. Bacteriophages are immunogenic and therefore could play a role in the pathogenesis of autoimmune and other inflammatory diseases by acting as antigens on epithelial surfaces, bound to antibody as immune complexes, through molecular mimicry or possibly as superantigens.     

Detection of pathogenic Yersinia enterocolitica by using congo red-magnesium oxalate agar medium.

A Congo red-magnesium oxalate agar medium was developed to detect expression of virulence-associated calcium dependency and Congo red absorption in Yersinia enterocolitica. Of the 157 pathogenic serotypes tested, 119 (75.8%) were positive; 98% of nonpathogenic serotypes and strains of three other Yersinia species were negative.     

Studies on the mechanism of interferon action: Characterization of polysome-associated cellular RNAs modified by interferon

A recent publication indicated that certain polysome-associated RNA species are altered in interferon-treated cells. The present data show that these RNA species are poly(A)-containing mRNAs, RNAs without a poly(A)-rich region and tRNAs. In addition, we show that in polyacrylamide gels in aqueous medium as well as in nonaqueous medium (formamide) the mRNAs from interferon-treated cells migrate more slowly than do control cell mRNAs, suggesting that the interferon mRNAs are slightly larger than normal. Transfer RNAs from interferon-treated cells, on the other hand, move more slowly than control tRNAs in aqueous medium, but not in formamide, suggesting that the difference in mobility in tRNAs is associated with factors other than size.     

Microtubules are required for cytokeratin aggresome (Mallory body) formation in hepatocytes: an in vitro study

Mallory bodies are cytokeratin-ubiquitin aggresomes that form in hepatocytes in many different chronic liver diseases. One of the key components in aggresome formation, not yet investigated in Mallory body formation, is the role of microtubules. An in vitro tissue culture assay is required to test for microtubule involvement in Mallory body formation so that Mallory body formation can be observed in the presence or absence of microtubule-disrupting agents. In this report, a new model of in vitro Mallory body formation was developed, which uses cultured hepatocytes isolated from drug-primed mice. When hepatocytes were incubated in the presence of antimicrotubule agents, they failed to form Mallory bodies. It is concluded that intact microtubules are required for Mallory body formation.     

Cephalometric analyses and flow-volume loops in obstructive sleep apnea patients

Fifteen patients with obstructive sleep apnea syndrome (OSAS) and 10 controls were studied. Polygraphic monitoring during sleep confirmed the presence or absence of OSAS. Ten OSAS patients and five controls had cephalometric analysis and 12 OSAS patients and five controls had a flow-volume loop study during wakefulness. Seven OSAS patients were submitted to both analyses. Flow-volume loops were unable to detect extrathoracic airway obstruction in six out of 12 OSAS patients. One control was found with positive results. Six out of seven subjects with positive flow-volume loops were overweight (greater than or equal to 30% ideal weight). Cephalograms were very useful in demonstrating mandibular deficiencies in OSAS patients. The length of the soft palate and the position of the hyoid bone, together with the measurement of the posterior airway space, are criteria of great interest in OSAS patients. Cephalometric analysis is recommended in all OSAS patients scheduled for surgical procedure. None of these tests, however, whether alone or in combination, is capable of identifying all cases of OSAS.     

B cell precursors are decreased in senescent BALB/c mice, but retain normal mitotic activity in vivo and in vitro

The numbers of phenotypic (sIg- Ly5[220]+) and functional B cell precursors were significantly reduced in the bone marrow of senescent (22-24 months old) BALB/c mice when compared to their young (2-4 months old) cohorts. Little alteration in the numbers of B cell precursors occurred during the first 12 months of life in this strain. In contrast, an accelerated loss of B cell precursors between 15 and 18 months of age was observed. In particular, the levels of small Ly5(220)+ B cell precursors were decreased with advanced age, although a decline in numbers of large sIg- Ly5(220)+ B cell precursors was also evident. The percentages of large sIg- Ly5(220)+ B cell precursors in (S + G2/M) stages of cell cycle were similar (e.g., 60-80%) in aged and young BALB/c mice. Importantly, Ly5(220)+ pre-B cells from both young and aged BALB/c mice, either present in vivo or derived from Ly5(220)- cells in vitro, were capable of proliferation in response to rIL-7. These observations suggest that the aging process results in a progressive decline in the numbers of pre-B cells; however, this apparently is not due to failure of B lineage precursor cells to respond to growth mediators either in vivo or in vitro.     

Amelioration of established Sendai viral pneumonia in the nude mouse using a monoclonal antibody to the virus fusion protein.

The pathological effect of parainfluenza type I (Sendai virus) is known to be a bronchopneumonia, which becomes a chronic pneumonia in the immunodeficient athymic (nude) mouse. The severity of this established chronic pneumonia can be dramatically altered by providing the nude mouse with humoral monoclonal antibodies which are neutralizing, and are directed against the fusion protein, of the virus. The alveolitis, which is a significant part of the pathology, is suppressed due to a reduction (greater than 90%) in the number of virus-infected alveolar macrophages present in the alveoli. This clearly identifies the infected alveolar macrophage as the primary effector cell in the pathogenesis of alveolitis caused by parainfluenza virus type I. The implications of using virus-neutralizing monoclonal antibodies, which have little immunomodulatory toxicity, in the treatment of viral pneumonias are discussed.