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PubMedDate not supplied

Suppressive effects on allergic contact dermatitis by short-term fasting.

Fasting alters various hormonal and immune conditions. It has been reported that delayed type immune response to the injection of keyhole limpet hemocyanin was depressed by short-term fasting. In this study, we adopted the computer-assisted image analyzer for histopathological analysis and evaluated the influence of short-term fasting on allergic contact dermatitis induced by 2,4-dinitrofluorobenzene (DNFB). Mice were sensitized by painting of DNFB to the abdomen. After the sensitization, mice were challenged by DNFB painting to the ear. Fasting started 24 hour before (48-hour fasted group) or immediately after (24-hour fasted group) the challenging. Fasting without DNFB treatment did not induce remarkable change of ear thickness, ear tissue, serum albumin, serum total protein, serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase. or serum creatine phosphokinase. In contrast, lasting suppressed the increment of ear thickness in the DNFB-treated group in this study. We could also demonstrate, using the computerized image analyzer, that both lymphocyte infiltration and the edema in the dermis were suppressed in fasted mice treated with DNFB. Further, edema in the dermis was inhibited more strongly in 48-hour fasted mice than in 24-hour lasted mice. These findings indicate that short-term fasting induce histopathological changes in the state of contact dermatitis.

Alanine Transaminase↗
PubMed1998

Slow inactivation does not affect movement of the fast inactivation gate in voltage-gated Na+ channels.

Voltage-gated Na+ channels exhibit two forms of inactivation, one form (fast inactivation) takes effect on the order of milliseconds and the other (slow inactivation) on the order of seconds to minutes. While previous studies have suggested that fast and slow inactivation are structurally independent gating processes, little is known about the relationship between the two. In this study, we probed this relationship by examining the effects of slow inactivation on a conformational marker for fast inactivation, the accessibility of a site on the Na+ channel III-IV linker that is believed to form a part of the fast inactivation particle. When cysteine was substituted for phenylalanine at position 1304 in the rat skeletal muscle sodium channel (microl), application of [2-(trimethylammonium)ethyl]methanethiosulfonate (MTS-ET) to the cytoplasmic face of inside-out patches from Xenopus oocytes injected with F1304C RNA dramatically disrupted fast inactivation and displayed voltage-dependent reaction kinetics that closely paralleled the steady state availability (hinfinity) curve. Based on this observation, the accessibility of cys1304 was used as a conformational marker to probe the position of the fast inactivation gate during the development of and the recovery from slow inactivation. We found that burial of cys1304 is not altered by the onset of slow inactivation, and that recovery of accessibility of cys1304 is not slowed after long (2-10 s) depolarizations. These results suggest that (a) fast and slow inactivation are structurally distinct processes that are not tightly coupled, (b) fast and slow inactivation are not mutually exclusive processes (i.e., sodium channels may be fast- and slow-inactivated simultaneously), and (c) after long depolarizations, recovery from fast inactivation precedes recovery from slow inactivation.

Animals↗
PubMed2006

Prospective study to evaluate the influence of FAST on trauma patient management.

BACKGROUND: Previous studies have concentrated on the accuracy of Focused Assessment with Sonography in Trauma (FAST), but evaluation of whether FAST changes subsequent management has not been fully assessed. METHODS: This prospective study compared 419 trauma admissions in two groups, FAST and no-FAST, for demographics, time of resuscitation, and action after resuscitation. The 194 patients undergoing FAST had their management plan specified before, and confirmed after, FAST was performed to assess for change in management. To ensure scan consistency and to minimize bias, criteria were established to define an adequate FAST. RESULTS: FAST was performed in 194 patients (46%), assessing for free fluid. Management was changed in 59 cases (32.8%) after FAST. Laparotomy was prevented in 1 patient, computed tomography was prevented in 23 patients, and diagnostic peritoneal lavage was prevented in 15 patients. Computed tomography rates were reduced from 47% to 34% and diagnostic peritoneal lavage rates were reduced from 9% to 1%. CONCLUSIONS: FAST plays a key role in trauma, changing subsequent management in an appreciable number of patients.

Adolescent↗
PubMed1998

Origin of slow and fast oscillations of Ca2+ in mouse pancreatic islets.

1. Pancreatic islets exposed to 11 mM glucose exhibited complex variations of cytoplasmic Ca2+ concentration ([Ca2+]i) with slow (0.3-0.9 min-1) or fast (2-7 min-1) oscillations or with a mixed pattern. 2. Using digital imaging and confocal microscopy we demonstrated that the mixed pattern with slow and superimposed fast oscillations was due to separate cell populations with the respective responses. 3. In islets with mixed [Ca2+]i oscillations, exposure to the sarcoplasmic-endoplasmic reticulum Ca2+-ATPase inhibitors thapsigargin or 2,5-di-tert-butylhydroquinone (DTBHQ) resulted in a selective disappearance of the fast pattern and amplification of the slow pattern. 4. In addition, the protein kinase A inhibitor RP-cyclic adenosine 3',5'-monophosphorothioate sodium salt transformed the mixed [Ca2+]i oscillations into slow oscillations with larger amplitude. 5. Islets exhibiting only slow oscillations reacted to low concentrations of glucagon with induction of the fast or the mixed pattern. In this case the fast oscillations were also counteracted by DTBHQ. 6. The spontaneously occurring fast oscillations seemed to require the presence of cAMP-elevating glucagon, since they were more common in large islets and suppressed during culture. 7. Image analysis revealed [Ca2+]i spikes occurring irregularly in time and space within an islet. These spikes were preferentially observed together with fast [Ca2+]i oscillations, and they became more common after exposure to glucagon. 8. Both the slow and fast oscillations of [Ca2+]i in pancreatic islets rely on periodic entry of Ca2+. However, the fast oscillations also depend in some way on paracrine factors promoting mobilization of Ca2+ from intracellular stores. It is proposed that such a mobilization in different cells within a tightly coupled islet syncytium generates spikes which co-ordinate the regular bursts of action potentials underlying the fast oscillations.

Animals↗
PubMed1998

Differential effect of adenosine on anterograde and retrograde fast pathway conduction in patients with atrioventricular nodal reentrant tachycardia.

INTRODUCTION: Several studies have shown that the fast pathway is more responsive to adenosine than the slow pathway in patients with AV nodal reentrant tachycardia. Little information is available regarding the effect of adenosine on anterograde and retrograde fast pathway conduction. METHODS AND RESULTS: The effects of adenosine on anterograde and retrograde fast pathway conduction were evaluated in 116 patients (mean age 47 +/- 16 years) with typical AV nodal reentrant tachycardia. Each patient received 12 mg of adenosine during ventricular pacing at a cycle length 20 msec longer than the fast pathway VA block cycle length and during sinus rhythm or atrial pacing at 20 msec longer than the fast pathway AV block cycle length. Anterograde block occurred in 98% of patients compared with retrograde fast pathway block in 62% of patients (P < 0.001). Unresponsiveness of the retrograde fast pathway to adenosine was associated with a shorter AV block cycle length (374 +/- 78 vs 333 +/- 74 msec, P < 0.01), a shorter VA block cycle length (383 +/- 121 vs 307 +/- 49 msec, P < 0.001), and a shorter VA interval during tachycardia (53 +/- 23 vs 41 +/- 17 msec, P < 0.01). CONCLUSION: Although anterograde fast pathway conduction is almost always blocked by 12 mg of adenosine, retrograde fast pathway conduction is not blocked by adenosine in 38% of patients with typical AV nodal reentrant tachycardia. This indicates that the anterograde and retrograde fast pathways may be anatomically and/or functionally distinct. Unresponsiveness of VA conduction to adenosine is not a reliable indicator of an accessory pathway.

Adenosine↗
PubMed2005

Prospective analysis of the effect of physician experience with the FAST examination in reducing the use of CT scans.

OBJECTIVE: The objective of this study was to examine the effect of ultrasound experience level on emergency physicians' Focused Assessment with Sonography for Trauma (FAST) exam accuracy and emergency physicians' confidence in using FAST findings to assist in managing patients with blunt trauma. METHODS: This prospective, consecutive enrolment study evaluated adult trauma team activation blunt trauma patients. Based on the number of post-training FAST exams carried out, 11 attending emergency physicians were grouped into A (<25 exams, n = 4), B (26-50 exams, n = 4) or C (>50 exams, n = 3). The FAST exam was carried out prior to other diagnostic studies. The emergency physicians were asked to prospectively judge their perception of the need for surgery, abdominal CT or no further tests. All study patients ultimately underwent CT, diagnostic peritoneal lavage or laparotomy. Among each physician group, the number of subsequent CT scans deemed necessary by the emergency physician after a 'normal' FAST was calculated and compared. RESULTS: Accuracy was greatest in group C. Sixty-nine of 80 patients in group A had a normal FAST exam; emergency physicians deemed CT necessary in 68/69 cases (99%; confidence interval [CI] 92-100%). Eighty-two of 98 patients in group C had a normal FAST exam; emergency physicians deemed CT necessary in 19/82 cases (23%; CI 15-34%). Physicians in groups B and C were less likely to order CT after a normal FAST than group A (P < 0.001). CONCLUSIONS: FAST accuracy was greatest among more experienced emergency physicians. A normal FAST exam assisted more experienced emergency physicians with the perceived need to order significantly fewer CT scans than less experienced emergency physicians.

Adult↗
PubMed1994

The influence of fasting on blood glucose, triglycerides, cholesterol, and alkaline phosphatase in rats.

Serum concentrations of glucose, cholesterol, triglycerides, and serum alkaline phosphatase activity were measured over different periods of time of food deprivation in male rats. Thirty percent of non-fasted rat's sera was found to be lipemic. At 16 hours of fasting, glucose levels dropped by 30% compared to the level of the non-fasting control group, and remained at a relatively constant level for up to 48 hours of fasting. Triglyceride concentrations decreased at 16 hours after fasting. Serum cholesterol levels were not changed at any of the fasting periods compared to the non-fasted control group. Alkaline phosphatase activity was decreased at 8 hours of fasting, with further declines in activity of the serum enzyme seen at 16, 24, and 48 hours of fasting. It was concluded that at 16 to 18 hours fasting, a non-absorptive state had been reached in male rats.

Journal Article↗
PubMed1982

The pCa-tension and force-velocity characteristics of skinned fibres isolated from fish fast and slow muscles.

1. Single fast fibres and small bundles of two to six slow fibres were dissected from the myotomal muscles of the cod, Gadus morhua, and the dogfish, Scyliorhinus canicula. Fibres were chemically skinned with the non-ionic detergent Brij 58.2. The isometric tension properties were investigated. Maximal isometric tensions (mean +/- S.E. of mean) were 18.65+/-1.18 (n = 11) and 8.34+/-0.98 (n = 13) N cm(-2) for cod fast and slow fibres, and 18.34+/-0.88 (n = 28) and 8.24+/-0.39 (n = 12) N cm(-2) for dogfish fast and slow fibres respectively. The values are comparable to those observed in mammalian and amphibian skinned fibres. The lower tensions generated by the slow fibres cannot be fully explained on the basis of their lower myofibrillar fractional volume.3. In common with previous studies, a steep sigmoid relationship between pCa and tension was observed. The threshold for tension generation was around pCa 7.2. Half-maximal pCas were 6.08 and 6.42 for cod fast and slow muscle, and 6.41 and 6.50 for dogfish fast and slow fibres respectively. Cod fibres were maximally activated at around pCa 5.18, and dogfish fibres at pCa 5.62.4. Contraction-induced residual tensions were observed in cod fast fibres after return to relaxing solution. This phenomenon is a feature common to many skinned fibre studies, but the mechanism behind it has yet to be resolved.5. The force-velocity characteristics of fast and slow fibres have been investigated (at 8 degrees C).6. Points below 0.6 P(0) on the P-V curves could be fitted to a linear form of the Hill equation. Extrapolated V(max)s were calculated as follows: cod fast fibre V(max) = 1.01 muscle length sec(-1) (Lsec(-1)) (a = 0.21 P(0); b = 0.21 Lsec(-1)). Slow fibre = 0.53 Lsec(-1) (a = 0.28P(0); b = 0.21 Lsec(-1)). Dogfish fast fibre V(max) = 2.34 Lsec(-1) (a = 0.06 P(0); b = 0.14 Lsec(-1)). Slow fibre = 0.67 Lsec(-1) (a = 0.19 P(0); b = 0.13 Lsec(-1)).7. Contraction velocity in cod slow fibres decreased continuously to produce markedly non-linear velocity transients, similar to those reported for amphibian slow fibres.8. The effect of altering Ca(2+) concentration on the shape of the isotonic velocity curve (at low loads) was studied in dogfish fast fibres (0.5-1 degrees C). Contraction velocity decreased continuously during shortening, at both maximal and half-maximal Ca(2+) concentration. The rate of decay of velocity with shortening was greater at low Ca(2+) concentration.

Action Potentials↗
PubMed1999

FAST-2 is a mammalian winged-helix protein which mediates transforming growth factor beta signals.

The mechanisms by which transforming growth factor beta (TGF-beta) and related ligands regulate transcription remain poorly understood. The winged-helix (WH) transcription factor fork head activin signal transducer 1 (FAST-1) was identified as a mediator of activin signaling in Xenopus embryos (X. Chen, M. J. Rubock, and M. Whitman, Nature 383:691-696, 1996). We have cloned a novel WH gene from the mouse which shares many properties with FAST-1. We find that this gene, which we call FAST-2, is able to mediate transcriptional activation by TGF-beta. FAST-2 also interacts directly with Smad2, a cytoplasmic protein which is translocated to the nucleus in response to TGF-beta, and forms a multimeric complex with Smad2 and Smad4 on the activin response element, a high-affinity binding site for FAST-1. Analysis of the sequences of FAST-1 and FAST-2 reveals substantial protein sequence divergence compared to known vertebrate orthologs in the WH family. This suggests that FAST-2 represents a new WH gene related to FAST-1, which functions to mediate TGF-beta signals in mammals. We have also examined the structure of the FAST-2 gene and find that it overlaps with a kinesin motor protein gene. The genes are transcribed in opposite orientations, and their transcripts overlap in the 3' untranslated region.

Activins↗
PubMed1996

Magnetic resonance imaging in epilepsy with a fast FLAIR sequence.

OBJECTIVE: To assess the diagnostic value of the fast FLAIR sequence in patients with epilepsy. METHODS: One hundred and twenty eight patients with epilepsy and 10 control subjects were scanned with the fast FLAIR sequence with 5 mm slices, a coronal gradient echo (GRE) T1 weighted sequence with 1.5 mm slices and spin echo (SE) or fast spin echo (FSE) proton density and T2 weighted sequences with 5 mm slices. All images were compared by an unblinded neuroradiologist and neurologist. Fast FLAIR images of patients with hippocampal sclerosis (HS) and normal control subjects were also evaluated by two blinded independent raters. RESULTS: Fast FLAIR provided a high conspicuity of neocortical damage, hamartomas, dysembryoplastic neuroepithelial tumours, and clear cut hippocampal sclerosis. However, the same information could be obtained from the coronal T1 and T2 weighted images. In three patients fast FLAIR showed a clearly abnormal signal when SE T2 weighted images had not been definitely abnormal. Heterotopia was less conspicuous on fast FLAIR than GRE T1 weighted images. The two blinded raters detected all but one of the patients with clear cut hippocampal sclerosis on fast FLAIR images but missed all borderline cases of hippocampal atrophy and there were two false positives. Clear cut hippocampal sclerosis was more conspicuous on fast FLAIR images than on SE T2 weighted images in most patients, but additional patients were not identified. CONCLUSION: Fast FLAIR has the advantage of identifying neocortical lesions and definite hippocampal sclerosis with a short scanning time and may also demonstrate lesions when other sequences are normal in a limited number of cases. The technique was not useful, however, for identifying mild hippocampal sclerosis or heterotopia.

Clinical Protocols↗
PubMed1984

Myosin light chain phosphorylation in fast and slow skeletal muscles in situ.

The physiological properties of contraction-induced phosphate incorporation into the phosphorylatable light chain (P-light chain) of myosin were examined in fast-twitch white, fast-twitch red, and slow-twitch skeletal muscles in situ. Neural stimulation of rat gastrocnemius muscles between 0.5 and 100 Hz produced an increase in the phosphate content of the P-light chain from the white portion of the muscle, and the rate of P-light chain phosphorylation was frequency dependent. The extent of phosphorylation of P-light chain from the fast-twitch red portion of the gastrocnemius muscle was less. In contrast to fast-twitch skeletal muscle, only high-frequency stimulation (30-100 Hz) produced a small increase in the phosphate content of P-light chain from the slow-twitch soleus muscle. Fast white muscle contained 2.2 and 3.5 times more myosin light chain kinase activity than did the fast red and slow muscle, respectively. The rate of P-light chain dephosphorylation was four times faster in slow muscle than in fast white muscle. Thus the greater extent of phosphorylation of P-light chain in fast-twitch white skeletal muscle fibers may be due in part to the presence of more kinase and less phosphatase activities. Isometric twitch tension potentiation was correlated to the extent of phosphorylation of P-light chain from fast white muscle. The physiological consequences of P-light chain phosphorylation are likely to be of greatest importance in fast-twitch white muscle.

Animals↗
PubMed1975

Prolonged fasting in mice: a more sensitive approach to genetic diabetes.

Effects of two different periods of fasting were studied on glucose tolerance and insulin response to glucose in genetically diabetic KK and nondiabetic C57BL/6J mice. Blood sugar levels of the KK mice did not differ markedly from those of the C57BL/6J mice at the fed state or after 8 h fasting. They were, however, significantly higher in the KK mice when fasted for 18 h. The serum IRI levels, which were at least twice as high in the KK mice, decreased more markedly after 18 h fasting. The KK mice showed impaired glucose tolerance after 8 h fasting, which became more pronounced after 18 h fasting. The insulin response to glucose in the KK mice was not altered after an 8-hour fast; it was, however, diminished greatly after an 18-hour fast. These data suggest that prolonged fasting is necessary to detect the diabetic traits in the KK mice. The C57BL/6J mice showed neither impaired glucose tolerance nor diminished insulin response to glucose at both periods of fasting. Studies with the F1 hybrids (KK male X C57BL/6J female), which carry half of the diabetic genes, suggest that the mode of inheritance of diabetes in the KK mice might be polygenic.

Animals↗
PubMed1975

Determinants of fast- and slow-pathway conduction in patients with dual atrioventricular nodal pathways.

Electrophysiological studies were performed in two patients with documented paroxysmal supraventricular tachycardia and dual atrioventricular (AV) nodal pathways as defined by the atrial extra-stimulus technique. Both patients manifested two ranges of A-H intervals (AV nodal conduction times) at critical cycle lengths, reflecting fast- and slow-pathway conduction. The occurrence of fast- and slow-pathway conduction at the same cycle length depended on a long fast-pathway effective refractory period relative to the spontaneous or driven cycle length. At critical cycle lengths with fast-pathway conduction, a shift to slow-pathway conduction could be induced by a premature atrial impulse falling within the effective refractory period of the fast pathway. Repetitive retrograde concealed conduction to the fast pathway then maintained antegrade slow-pathway conduction. Resumption of fast-pathway conduction was induced with premature atrial impulses falling within the effective refractory periods of both the fast and the slow pathways, allowing recovery of the fast pathway for antegrade conduction. Atrial echoes and AV nodal reentrant paroxysmal supraventricular tachycardia occurred when sufficient slow-pathway delay was achieved to allow recovery of the fast pathway for retrograde conduction.

Atrioventricular Node↗
PubMed1981

"Fast" isomyosins and fiber types in mammalian skeletal muscle.

Immunohistochemical procedures have been used to correlate antigenic differences among fast isomyosins with their specific localization in particular types of rat muscle fibers. Antisera were produced in rabbits against myosins isolated from guinea pig fast-white (tensor fasciae latae) and fast-red (masseter) muscles. After sequential cross-adsorptions on insolubilized heterologous myosins, antibodies mainly directed against heavy chain determinants were obtained. In indirect immunofluorescence assays, these antibodies selectively stained fast-white (type IIB) and fast-red (type IIA) fibers, respectively. Slow-twitch (type I) fibers, which were reactive with antibodies against soleus muscle myosin, were unreactive with anti-fast-myocin antibodies. In addition to these major types of fibers, with unique immunoreactivity, two groups of fibers with double reactivity were identified: 1) fibers reactive with anti-slow-twitch and anti-fast-red antibodies (corresponding to IIC fibers with enzyme histochemistry) and 2) fibers reactive with anti-fast-red and anti-fast-white antibodies. We propose to identify these fibers with the symbols I in equilibrium with IIA and IIA in equilibrium with IIB, respectively, as they may be considered as intermediate and/or transitional stages between the major fiber types. No fibers were reactive with both anti-slow-twitch and anti-fast-white antibodies. Therefore, muscle fibers may change in a sequential manner, from I leads to IIA leads to IIB or in the reverse direction, suggesting an obligatory sequence of gene activation.

Animals↗
PubMed1994

MR imaging of peritoneal disease: comparison of contrast-enhanced fast multiplanar spoiled gradient-recalled and spin-echo imaging.

OBJECTIVE: We performed this study to compare contrast-enhanced fast multiplanar spoiled gradient-recalled (SPGR) MR imaging with unenhanced spin-echo imaging for the detection of benign and malignant peritoneal abnormalities. MATERIALS AND METHODS: We retrospectively reviewed abdominal MR images of 34 patients with proved peritoneal abnormalities, including 21 patients with malignant and 13 patients with benign peritoneal disease. Six additional patients had false-positive interpretations of their MR examinations because of diaphragmatic thickening and enhancement. Unenhanced T1-weighted images, fast spin-echo T2-weighted images, and breath-hold fast multiplanar SPGR images obtained immediately and 10-15 min after IV injection of gadopentetate dimeglumine were available. Images were reviewed for evidence of peritoneal disease by two observers who had no knowledge of the clinical findings. The four types of images were separately evaluated for peritoneal thickening, masses, and abnormal enhancement. The anatomic location, thickness, and pattern of thickening of the peritoneum were noted. Results were correlated with surgical findings or results of percutaneous biopsy. RESULTS: Immediate and delayed contrast-enhanced fast multiplanar SPGR images showed malignant peritoneal tumor in all 21 cases, compared with T1-weighted images, which showed tumor in 11 cases (p < .01), and fast spin-echo T2-weighted images, which showed tumor in 13 cases (p < .01). Enhancement of the peritoneal tumor increased the tumor's conspicuity, particularly on delayed fast multiplanar SPGR images, which were selected as the best sequence for detection of peritoneal tumor in 18 of the 21 cases. The MR findings varied widely from moderately and regularly thickened, enhancing peritoneum to very thick (> 1 cm) and lobular or masslike peritoneal thickening with enhancement. Delayed fast multiplanar SPGR images showed evidence of benign peritoneal disease in all 13 cases compared with immediate fast multiplanar SPGR images, which showed disease in 12 cases (p > .05); T1-weighted images, which showed disease in four cases (p < .05); and fast spin-echo T2-weighted images, which showed disease in only one case (p < .01). In the benign forms of peritoneal disease, the peritoneum was often regular in contour and tended to be thinner than in the cases of malignant peritoneal tumor, in which the peritoneum was generally thicker and more lobular or masslike. However, significant overlap was seen between the MR findings in benign and malignant forms of peritoneal disease. CONCLUSION: Detection of peritoneal abnormalities with MR imaging can be improved by using contrast-enhanced fast multiplanar SPGR imaging. The findings of peritoneal thickening and enhancement are best depicted on delayed images.

Adult↗
PubMed1990

[Electrophysiological properties of fast- and slow-adapting units and their generator potentials of the frog tongue].

The purpose of this study was to determine the stimulus response properties of fast and slow adapting units in the fungiform papillae of the frog tongue. Secondly, fast- and slow- adapting generator potentials were recorded from fast and slow-adapting mechanoreceptors in the single fungiform papilla glossopharyngeal nerve preparations, respectively. Results I. Impulse response properties of fast- and slow-adapting units 1) Most of the fungiform papillae were innervated by both fast- and slow-adapting units. Fast-adapting units evoked 1-4 impulses to each stimulus and the adaptation time was less than 17.5 msec. Slow-adapting units evoked 27.8 +/- 8.0 impulses (range: 11-49 impulses n = 18) during a pressure stimulation of 3 sec, and the adaptation time was 1.64 +/- 0.73 sec (range: 0.53-2.86 sec, n = 18). 2) Threshold, latency and absolute refractory period for fast-adapting units were 7.0 +/- 1.9 microns (range: 3.0-11.8 microns, n = 189), 2.31 +/- 1.29 msec (range: 0.85-6.80 msec, n = 31) and 2.9 +/- 1.0 msec (range: 1.8-5.6 msec, n = 33), respectively. Those for slow-adapting units were 4.6 +/- 1.8 microns (range: 2.0-11.8 microns, n = 152), 13.54 +/- 11.29 msec (range: 2.00-54.00 msec, n = 35) and 6.5 +/- 3.6 msec (range: 1.9-19.6 msec, n = 35), respectively. 3) A fast-adapting unit innervated 5.1 +/- 2.5 fungiform papillae (range: 1-13 fungiform papillae, n = 58) and the receptive area was 0.342 +/- 0.312 mm2 (range: 0.005-1.548 mm2, n = 55). A slow-adapting unit innervated 3.3 +/- 2.0 fungiform papillae (range: 1-12 fungiform papillae, n = 50) and the receptive area was 0.158 +/- 0.144 mm2 (range: 0.006-0.616 mm2, n = 29). 4) Conduction velocity of the fast-adapting unit was 23.0 +/- 3.1 m/sec (range: 15.0-30.6 m/sec, n = 528) and that of the slow-adapting unit was 12.8 +/- 2.2 m/sec (range: 4.4-21.1 m/sec, n = 495). The conduction velocity was calculated from the time necessary to conduct at two different points of the nerve fiber. 5) The upper limits of fast- and slow-adapting units for vibratory stimulation were 62.7 +/- 10.5 Hz (range: 50-80 Hz, n = 15) and 34.5 +/- 9.6 Hz (range: 15-45 Hz, n = 10), respectively. II.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Interaction of PtCl4(Fast Black)2 with hyperthermia.

We are developing complexes of negatively charged PtCl4 with positively charged nuclear dyes as new antitumor agents for use alone and in conjunction with hyperthermia and/or radiation. Elemental analysis has shown that the complex PtCl4(Fast Black)2 is a tight ion pair. In experimentally growing EMT6 cells in vitro, PtCl4(Fast Black)2 killed cells in a log-linear manner which increased as the temperature of the exposures was increased from 37 to 42 degrees C or 43 degrees C. In addition, cell kill was also increased under conditions of low pH (6.45), especially in hypoxic cells treated at elevated temperature. Measurement of intracellular platinum levels after exposure to 25 microM cisplatin or PtCl4(Fast Black)2 demonstrated that platinum levels were between 170- and 200-fold higher after exposure to PtCl4(Fast Black)2. In vivo studies in the FSaIIC murine fibrosarcoma showed, again, that PtCl4(Fast Black)2 killed in a log-linear manner. Treatment of tumors placed in the thigh with 43 degrees C, 30-min hyperthermia immediately following i.p. injection of PtCl4(Fast Black)2 was dose modifying. One hundred mg/kg of PtCl4(Fast Black)2 produced a 4.6-day tumor growth delay which increased to 6.4 days with 43 degrees C, 30-min hyperthermia immediately following i.p. injection of PtCl4(Fast Black)2 was does modifying. One hundred mg/kg of PtCl4(Fast Black)2 produced a 4.6-day tumor growth delay which increased to 6.4 days with 43 degrees C, 30-min hyperthermia (growth delay for hyperthermia alone was 1.4 days), and 500 mg/kg produced a 5.6-day delay which increased to 11.0 days with hyperthermia. In contrast, cisplatin (5 mg/kg) produced a 4.4-day delay which increased to 5.9 days with hyperthermia. PtCl4(Fast Black)2 was well tolerated by animals, and the maximally tolerated dose was approximately 650 mg/kg. This new complex appears quite active as an antitumor agent alone and in conjunction with hyperthermia, and, since other studies have shown it to interact positively with radiation, this agent seems a very appropriate candidate for further development as a clinical anticancer drug.

Animals↗
PubMed1985

Fast and slow nerve growth factor binding sites in human neuroblastoma and rat pheochromocytoma cell lines: relationship of sites to each other and to neurite formation.

We studied (a) the distribution and properties of fast and slow 125I-nerve growth factor (125I-NGF) binding sites in cultured human neuroblastoma (NB) cell lines that were categorized as responsive (N+) or unresponsive (N-) to NGF by neurite outgrowth, (b) whether fast or slow sites mediate actions of NGF, and (c) whether NGF-mediated conversion of fast to slow sites occurs in human NB and pheochromocytoma PC 12 cells. In human NB SH-SY5Y cells, the slow sites were trypsin resistant and binding was of high affinity. Loss of binding to the slow sites had a half-time of 25 to 30 min at 37 degrees C and was very slow at 4 degrees C. In contrast, the fast sites were trypsin sensitive and binding was of lower affinity; its dissociation half-time was less than 1 min at 4 degrees C and 37 degrees C. The association rate constants of both sites were about 0.8 to 1.2 X 10(7) M-1 sec-1. Some human NB cells had both fast and slow sites. The N+ human NB lines SH-SY5Y and LA-N-5 had only slow sites. Despite the virtual elimination of fast sites by trypsin in NB MC-IXC cells, remaining slow sites could still efficiently bind 125I-NGF. These observations showed that fast sites are not required for slow site binding, neurite outgrowth, or other demonstrated actions of NGF in some NB cells. In PC 12 cells, 125I-NGF initially bound to fast sites was not directly transferred to slow sites as required for NGF-mediated conversion. The association rate constants of fast and slow sites in PC12 cells were both about 2 X 10(7) M-1 sec-1. The association kinetics were consistent with simple bimolecular reactions in both NB and PC12 cells. The combined evidence in NB and PC12 cells did not support the hypothesis of NGF-mediated conversion of fast to slow sites.

Animals↗