Regeneration of aged vocal folds with basic fibroblast growth factor in a rat model: a preliminary report

Aged vocal folds have been reported to have dense collagen deposition and decreased hyaluronic acid (HA) in the lamina propria. These characteristics are thought to contribute to vocal problems that occur with age (presbyphonia). To restore better viscoelasticity to aged vocal folds, an intervention that might increase HA and decrease collagen production from aged vocal fold fibroblasts would appear to be a potentially useful approach. Our previous in vitro study has revealed that basic fibroblast growth factor (bFGF) consistently stimulates HA production and decreases collagen production from aged rat vocal fold fibroblasts. The present in vivo study examined the effects of intracordal injection of bFGF into aged rats' vocal folds in terms of restoration of HA and collagen distribution in the lamina propria. We injected bFGF transorally into the lamina propria of (unilateral) vocal folds. The injection was repeated 4 times weekly, and rats were painlessly sacrificed 1 week, 1 month, and 2 months after the final injection. Histologic examination revealed that bFGF significantly increased the HA content of the lamina propria up to 2 months, but showed no effect on collagen, even after 2 months. Because it might take longer for excessive collagen to be degraded, further studies are necessary to clarify the long-term effect on collagen. A drug delivery system for bFGF also needs to be developed to maximize its effect in the future. The present study suggested at least a positive effect of bFGF in restoring the HA content in the aged vocal fold lamina propria.     

Extended observation of the nasal cycle using a portable rhinoflowmeter

OBJECTIVE: Nasal patency varies owing to the effects of humidity, temperature, and exercise. In addition, periodic cycles of congestion and decongestion that alternate between the right and the left side of the nose, which are termed the "nasal cycle," have been observed. The physiologic mechanisms underlying this cycle are not clear. Sympathetic nerves that supply the nose are regulated by the hypothalamus and the vasomotor areas of the brainstem. It is possible that the nasal cycle could be involved in protection against respiratory infection or allergies. Conventional methods of studying the nasal cycle, including rhinomanometry and acoustic rhinometry, impose limitations on the location and timing of evaluation. We studied the nasal cycle using a new portable device for relatively long-term rhinoflowmetry. METHODS: Twenty normal subjects aged 24 to 77 years were fitted with the portable rhinoflowmeter (Rhinocycle, Rhinometrics, Lynge, Denmark) to continuously measure nasal air flow via each nostril over 12 daytime hours. RESULTS: No subject complained of discomfort owing to the device, and 14 of them showed a detectable nasal cycle. The mean nasal cycle duration was 110 minutes, although variation was considerable, even in a single subject. CONCLUSIONS: The portable device proved useful for observing the nasal cycle, and it should be valuable for the general investigation of nasal physiology.     

Inhibitory activity on matrix metalloproteinases and cell-proliferating activity of tissue inhibitor of metalloproteinases-1 (TIMP-1)-contrastive difference between human and bovine TIMP-1s on mouse cell proliferation

Either human or bovine TIMP-1 inhibited matrix metalloproteinase (MMP) activities, such as collagenolytic, gelatinolytic and caseinolytic, expressed by mouse cells as well as those expressed by human cells. Bovine TIMP-1 stimulated the proliferation of both human and mouse cells, but human TIMP-1 only proliferate human cells and not mouse cells indicating that the cell-proliferating activity has more strict species specificity than MMP inhibitory activity. All the results from [(3)H]thymidine incorporation, the phosphorylation of tyrosine-containing cellular proteins and extracellular-signal-regulated protein kinases supported the cell-proliferating properties of both human and bovine TIMP-1s. Human TIMP-1 seems not to bind to TIMP-1 receptors on mouse cells.     

The sensorimotor transformation of cross-modal spatial information in the anterior intraparietal sulcus as revealed by functional MRI

The parietal cortex in monkeys and humans has been shown to play an important role in the transformation of sensory information to motor commands. However, it is still unclear whether in humans, these areas are divided functionally into subregions based on different combinations of sensory and motor modalities. To identify subregions in the parietal cortex involved in the sensorimotor information transformation between different modalities, functional MRI was used to examine brain areas activated during tasks requiring different sensorimotor transformations--i.e., various combinations of eye (saccade) or finger movements triggered by visual or somatosensory cues. We then compared the activations between cross-modal conditions (eye movements triggered by somatosensory cues and finger movements triggered by visual cues) and intramodal (eye movements triggered by visual cues and finger movements triggered by somatosensory cues) conditions. Although the parietal cortex was involved in all tasks regardless of sensorimotor combinations, the only region activated to a greater degree in the cross-modal conditions compared to the intramodal conditions was the anterior portion of the intraparietal sulcus (a-IPS). The results suggest that the a-IPS plays an important role in the sensorimotor transformation of cross-modal spatial information.     

Mitochondrial encephalomyopathies: an update

A genetic classification of the mitochondrial encephalomyopathies includes disorders due to defects of mitochondrial DNA (mtDNA) and disorders due to defects of nuclear DNA (nDNA). Recent progress in mtDNA-related diseases includes: (i) new pathogenic mutations in protein-coding genes, especially those encoding subunits of complex I (ND genes); (ii) the pathogenic nature of homoplasmic mutations, whose expression is regulated by environmental and genetic factors; (iii) increasing interest in the functional and pathophysiological role of haplotypes. Advances in mendelian mitochondrial diseases include: (i) new mutations in genes for complex I subunits; (ii) identification of new mutant ancillary proteins associated with complex IV and complex V deficiencies; (iii) better molecular understanding of disorders due to faulty intergenomic communication, which are associated with multiple mtDNA deletions, mtDNA depletion, or defects of mtDNA translation; (iv) the pathogenic role of alterations of the inner mitochondrial membrane phospholipid components, especially cardiolipin; (v) the emerging importance of defects in mitochondrial motility, fission, or fusion.     

Effects of exercise intensity, posture, pressure on the back and ambient temperature on palmar sweating responses due to handgrip exercises in humans

We have, by using newly developed ratemeters, attempted to examine the effects of exercise intensity, posture, pressure on the skin of the back, and ambient hyperthermic conditions (approximately 30 degrees C) on the 5-s handgrip exercise-mediated responses of active palmar sweating in humans. Thirty-five right-handed male (n=5) and female (n=30) volunteer students (20.2+/-1.3 years old) participated in the present study. Oral explanation of only the isometric handgrip exercise (IHG) caused a rapid and oscillatory response (pre-operational) of active palmar sweating in almost all subjects (10 of 14 subjects). Performing the IHG for 5-s caused a significant increase in active sweating rate (operation-mediated response) in both ipsi- and contra-lateral palmar surfaces of the thumbs of all subjects. The operation-mediated responses of active palmar sweating to the IHG were reproducible, resulting in no habituation. The increase of operation-mediated responses to the IHG was dependent upon exercise intensity (100-25% maximal voluntary contractions). The IHG-mediated ipsi- and contra-lateral responses of active palmar sweating were significantly decreased by changing the body posture from a seated to a supine position or by pressing the skin of the back. Ambient hyperthermic conditions (approximately 30 degrees C) for 60 min also resulted in a significant decrease in the back-pressure-dependent reduction of the operation-mediated responses of active palmar sweating to the IHG. In conclusion, in order to optimize the precision and reproducibility of clinical tests involving palmar sweating responses, it is important that subjects maintain a constant handgrip force and posture and that ambient temperature be kept under normothermic conditions.     

Non-gated fetal MRI of umbilical blood flow in an acardiac twin

Currently, the standard method of diagnosis of twin reversed arterial perfusion (TRAP) sequence is ultrasound imaging. The use of MRI for flow visualization may be a useful adjunct to US imaging for assessing the presence of retrograde blood flow in the acardiac fetus and/or umbilical artery. The technical challenge in fetal MRI flow imaging, however, is that fetal electrocardiogram (ECG) monitoring required for flow imaging is currently unavailable in the MRI scanner. A non-gated MRI flow imaging technique that requires no ECG monitoring was developed using the t-test to detect blood flow in 20 slices of phase-contrast MRI images randomly scanned at the same location over multiple cardiac cycles. A feasibility study was performed in a 24-week acardiac twin that showed no umbilical flow sonographically. Non-gated MRI flow images clearly indicated the presence of blood flow in the umbilical artery to the acardiac twin; however, there was no blood flow beyond the abdomen. This study leads us to conjecture that non-gated MRI flow imaging is sensitive in detecting low-range blood flow velocity and can be an adjunct to Doppler US imaging.     

Expression of tumor necrosis factor-alpha stimulated gene-6 mRNA in cultured human uterine cervical fibroblasts

BACKGROUND: Uterine cervical ripening process is an active biochemical process similar in part to inflammatory reaction. In this process, hyaluronan plays important roles including facilitation of tissue hydration, release of matrix metalloproteinases and migration of inflammatory cells. The activities of hyaluronan are mediated by the hyaluronan binding proteins, hyaladherins. In the present study, we investigated the mRNA expression of tumor necrosis factor-alpha stimulated gene-6 (TSG-6), a member of the hyaladherin family, in cultured human uterine fibroblasts and uterine cervical tissues. METHODS: We developed one-step RT-PCR method for the quantification of TSG-6 mRNA and quantified the expression of TSG-6 mRNA in cultured human uterine fibroblasts, treated with or not proinflammatory cytokines, and TSG-6 mRNA in uterine cervical tissues. RESULTS: We clarified that [1] TSG-6 mRNA was expressed constitutively in cultured human uterine cervical fibroblasts, [2] expression of TSG-6 mRNA was upregulated in a dose dependent manner by proinflammatory cytokines, such as IL-1beta and TNF-alpha, which were key mediators in the cervical ripening process, [3] expression of TSG-6 mRNA in uterine cervices during parturition was significantly (P < 0.05) higher than that in a non-pregnant state. CONCLUSIONS: Our results suggest that TSG-6 might participate in the cervical ripening process.