A muscle spindle model for primary afferent firing based on a simulation of intrafusal mechanical events.

1. A muscle spindle model for primary afferent firing is presented that contains two components representing a gamma d-dependent (bag1) and gamma s-dependent (bag2/nuclear chain) intrafusal fiber. Each of the intrafusal fibers is composed of a linear elastic element representing the sensory part and a muscle fiber representing the muscular part. 2. The muscular part of the bag1 was modeled as a slow twitch, that of the bag2 as a fast twitch muscle fiber. 3. The sensory regions were linear length transducers, generating a rising depolarization on increasing stretch. The input of both bags was fused by taking the largest depolarization to determine a generator potential. The rate of primary afferent firing depended on this generator potential as well as on its rate of change. 4. To simulate the high sensitivity of muscle spindles to small amplitudes of stretching, a model analogue of cross-bridge fixation (or stiction) has been included in the muscular part of the bag1 fiber. This makes use of one hundred cross-bridge regions that release one after the other, provided a certain breaking force is exceeded. 5. The values of the mechanical parameters that defined the model were selected by a computerized search procedure. 6. The values found by means of this procedure allowed the model to provide an accurate simulation of experimental data on ramp-and-hold stretches (for 6 different stretch velocities under variable conditions of fusimotor activity). 7. On sinusoidal stretches at a frequency of 1 Hz the spindle model responded with about one-half the discharge modulation reported in experimental studies. Its phase advance tended to be slightly lower than that observed for real spindles. 8. Frequency response curves showed the same high sensitivities at high frequencies as those observed in real spindles. 9. Close evaluation of the model compared with experimental results in literature reveal its merits as well as its limitations. Because the model is structural rather than phenomenologic, it provides insight into how intrafusal events may contribute to observed firing properties of real muscle spindles.     

Analysis of saccadic short-term plasticity in three dimensions

The capacity for short-term adaptation is a well-established property of the horizontal (H) and vertical (V) components of saccades. It allows these directional components, which clearly serve the goal of foveation, to maintain their precision even under changing circumstances. Torsional (T) saccade components, on the other hand, which deal with the orientation of the target on the fovea, have hardly been investigated in adaptation experiments. They appear to be severely restricted by Listing's law during fixations and saccades. The main purpose of Listing's law is far from obvious but could be visual or oculomotor. Better knowledge of the adaptive capacity of the saccadic system in the torsional direction could throw new light on the functional significance of this interesting neural strategy. To study short-term plasticity in the torsional components of saccades, binocular 3D-eye positions were measured, using magnetic search foils. Five normal human subjects were instructed to make uni-directional refixation saccades, while they viewed a large visual scene. To induce a change in the torsional component, the complete stimulus was rapidly rotated during these saccades. We thoroughly investigated the torsional responses of the saccadic system, to see if any short-term adaptive response in torsional direction was induced, in which case the notion of a visual purpose for Listing's law would be strengthened. In none of our experiments, however, did we find any clear adaptive response in torsional direction. To further investigate the reliability of this result and to ascertain that our experimental conditions allowed classical gain adaptation, we also did experiments designed to achieve a combination of torsional adaptation and classic gain shortening in one of the directional components. While gain adaptation was very obvious, none of the experiments provided evidence for a short-term effect in torsion. We conclude that our experiments do not support a purely visual basis for Listing's law.     

A comparison of T4:T8 lymphocyte ratio in the periodontal lesion of healthy and HIV-positive patients.

Previous reports describe a characteristic, rapidly progressive, periodontitis that is unique to patients who are seropositive for HIV antibody (Western blot +). The purpose of this study was to compare the T4 and T8 lymphocyte subpopulations in the peripheral blood and periodontal lesions of these HIV patients with those of healthy controls. T-cell subsets in peripheral blood were quantified by flow cytometry. The values from this analysis were used to calculate the peripheral T4:T8 lymphocyte ratio for each patient. Gingival tissue (papilla) was obtained from 8 HIV+ patients and from 6 healthy HIV- control patients during routine gingival surgery. The T-cell subpopulations in the gingival tissue were determined using serial cryostat sections that were labeled with monoclonal antibodies for T4 and T8 cells and developed using an avidin-biotin-peroxidase system. Six sections were taken from each of the 14 tissue specimens (one per patient). The sections were examined at 450 x and the mean number of T4 and T8 cells calculated for each section. These mean values were then used to determine the T4:T8 lymphocyte ratio for each tissue specimen. The peripheral blood analysis revealed a mean serum T4:T8 ratio of (2.07 +/- 0.455) for the controls and (0.58 +/- 0.26) for the HIV patients. The significantly lower T4:T8 ratio in HIV patients is consistent with their diagnosis. Although the results indicated that the mean T4:T8 lymphocyte ratio in the gingiva of controls was highly variable (2.70 +/- 1.344), the gingiva of HIV patients consistently exhibited a complete absence of T-cells.(ABSTRACT TRUNCATED AT 250 WORDS)     

Chlorella virus PBCV-1 replication is not affected by cytoskeletal disruptors.

The majority, if not the entire life cycle, of the large dsDNA-containing algal virus PBCV-1 occurs in localized regions in the cytoplasm. Thirteen drugs that disrupt the cytoskeleton had no effect on PBCV-1 replication at concentrations which inhibited host growth. Therefore, host cytoskeletal elements do not appear to be important in PBCV-1 morphogenesis.     

Pituitary responsiveness to GH-releasing hormone, GH-releasing peptide-2 and thyrotrophin-releasing hormone in critical illness

OBJECTIVE Protein hypercatabolism and preservation of fat depots are hallmarks of critical illness, which is associated with blunted pulsatile GH secretion and low circulating IGF-I, TSH, T4 and T3. Repetitive TRH administration is known to reactivate the pituitary-thyroid axis and to evoke paradoxical GH release in critical illness. We further explored the hypothalamic-pituitary function in critical illness by examining the effects of GH-releasing hormone (GHRH) and/or GH-releasing peptide-2 (GHRP-2) and TRH administration. PATIENTS AND DESIGN Critically ill adults (n=40; mean age 55 years) received two i.v. boluses with a 6-hour interval (0900 and 1500 h) within a cross-over design. Patients were randomized to receive consecutively placebo and GHRP-2 (n=10), GHRH and GHRP-2 (n=10), GHRP-2 and GHRH+GHRP-2 (n=10), GHRH+GHRP-2 and GHRH+GHRP-2+TRH (n=10). The GHRH and GHRP-2 doses were 1μg/kg and the TRH dose was 200μg. Blood samples were obtained before and 20, 40, 60 and 120 minutes after each injection. MEASUREMENTS Serum concentrations of GH, T4, T3, rT3, thyroid hormone binding globulin (TBG), IGF-I, insulin and cortisol were measured by RIA; PRL and TSH concentrations were determined by IRMA. RESULTS Critically ill patients presented a striking GH response to GHRP-2 (mean±SEM peak GH 51±9 μg/l in older patients and 102±2μg/l in younger patients; P=0.005 vs placebo). The mean GH response to GHRP-2 was more than fourfold higher than to GHRH (P=0.007). In turn, the mean GH response to GHRH+GHRP-2 was 2.5-fold higher than to GHRP-2 alone (P=0.01), indicating synergism. Adding TRH to the GHRH+GHRP-2 combination slightly blunted this mean response by 18% (P=0.01). GHRP-2 had no effect on serum TSH concentrations whereas both GHRH and GHRH+GHRP-2 evoked an increase in peak TSH levels of 53 and 32% respectively. The addition of TRH further increased this TSH response < ninefold (P=0.005), elicited a 60% rise in serum T3 (P=0.01) and an 18% increase in T4 (P=0.005) levels, without altering rT3 or TBG levels. GHRH and/or GHRP-2 induced a small increase in serum PRL levels. The addition of TRH magnified the PRL response 2.4-fold (P=0.007). GHRP-2 increased basal serum cortisol levels (531±29nmol/l) by 35% (P=0.02); GHRH provoked no additional response, but adding TRH further increased the cortisol response by 20% (P=0.05). CONCLUSIONS The specific character of hypothalamic-pituitary function in critical illness is herewith extended to the responsiveness to GHRH and/or GHRP-2 and TRH. The observation of striking bursts of GH secretion elicited by GHRP-2 and particularly by GHRH+GHRP-2 in patients with low spontaneous GH peaks opens the possibility of therapeutic perspectives for GH secretagogues in critical care medicine.     

New ways of performing in vivo flow velocity measurements in the basilar artery

The basilar artery is the only large artery in which two flows merge, and this is reflected in the flow downstream. We report quantitative flow — velocity measurements with a phase-based MR technique, i.e. the Fourier velocity encoding method, in the basilar artery of a volunteer. To our knowledge, this has not previously been performed successfully. A comparison is made with the results of flow velocity measurements in the basilar artery with transcranial Doppler ultrasonography; the techniques agreed very well. Although Doppler ultrasonography is still most widely used, no information on the flow rate and the flow velocity distribution in the basilar artery can be provided. MR flow measurement techniques appear promising when detailed information on the flow velocity distribution and flow rate is needed.     

Lipid-associated total parenteral nutrition in patients with severe acute pancreatitis

Biochemical data were studied in 18 patients with severe acute pancreatitis receiving lipid associated with total parenteral nutrition. The mean nonprotein energy intake was 30 kcal/kg/day, with 34-70% of the nonprotein calories as lipid. These parameters were no different between patients who survived and those who died. The mean sum of Ranson criteria was significantly higher in patients who died as compared with those who survived. Plasma triglycerides, glucose, albumin, and the amount of insulin supplementation were related to the severity of the disease and to the outcome. Persistent hypertriglyceridemia, hyperglycemia, hypoalbuminemia, and higher insulin requirements were observed in patients who died in comparison with those who survived and this appeared to be an index of fatal outcome. These abnormalities reflect in part an inability to utilize nonprotein energy, because the measured energy expenditure in relation to intake was lower in the patients who died, despite comparable intakes and expected energy expenditures.     

Coronary artery and saphenous vein graft remodeling: A review of histologic findings after various interventional procedures—part V

Catheter balloon angioplasty is a well accepted form of nonsurgical treatment of acutely and chronically obstructed coronary artery vessels. It is also the centerpiece for various new intervention techniques. Their morphologic effect on the site of obstruction has been termed “remodeling.” Part V of this six-part series focuses on remodeling effects of balloon angioplasty on obstructed young (≤ 1 year) and old (> 1 year) saphenous vein bypass grafts.