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PubMed2002

Cellular mechanisms underlying the long QT syndrome.

QT prolongation is commonly associated with life-threatening torsade de pointes arrhythmias that develop as a consequence of the amplification of electrical heterogeneities intrinsic to the ventricular myocardium. These heterogeneities exist because of differences in the time course of repolarization of the three predominant cell types that make up the ventricular myocardium, giving rise to transmural voltage gradients and a dispersion of repolarization responsible for the inscription of the electrocardiographic T wave. Agents and conditions that reduce net repolarizing current amplify the intrinsic spatial dispersion of repolarization, thus creating the substrate for the development of re-entry. The result is a prolongation of the QT interval, abnormal T waves, and development of polymorphic re-entrant ventricular tachycardia displaying characteristics of torsades de pointes. These conditions also predispose M cells and Purkinje fibers to develop early afterdepolarization-induced extrasystoles, which are thought to trigger episodes of torsades de pointes. Agents that prolong the QT interval but do not increase transmural dispersion of repolarization are not capable of inducing torsades de pointes. The available data suggest that that the principal problem with the long QT syndrome is not long QT intervals but rather the dispersion of repolarization that often accompanies prolongation of the QT interval.

Animals↗
PubMed1994

Dbl and Vav mediate transformation via mitogen-activated protein kinase pathways that are distinct from those activated by oncogenic Ras.

Vav and Dbl are members of a novel class of oncogene proteins that share significant sequence identity in a approximately 250-amino-acid domain, designated the Dbl homology domain. Although Dbl functions as a guanine nucleotide exchange factor (GEF) and activator of Rho family proteins, recent evidence has demonstrated that Vav functions as a GEF for Ras proteins. Thus, transformation by Vav and Dbl may be a consequence of constitutive activation of Ras and Rho proteins, respectively. To address this possibility, we have compared the transforming activities of Vav and Dbl with that of the Ras GEF, GRF/CDC25. As expected, GRF-transformed cells exhibited the same reduction in actin stress fibers and focal adhesions as Ras-transformed cells. In contrast, Vav- and Dbl-transformed cells showed the same well-developed stress fibers and focal adhesions observed in normal or RhoA(63L)-transformed NIH 3T3 cells. Furthermore, neither Vav- or Dbl-transformed cells exhibited the elevated levels of Ras-GTP (60%) observed with GRF-transformed cells. Finally, GRF, but not Vav or Dbl, induced transcriptional activation from Ras-responsive DNA elements (ets/AP-1, fos promoter, and kappa B). However, like Ras- and GRF-transformed cells, both Vav- and Dbl-transformed cells exhibited constitutively activated mitogen-activated protein kinases (MAPKs) (primarily p42MAPK/ERK2). Since kinase-deficient forms of p42MAPK/ERK2 and p44MAPK/ERK1 inhibited Dbl transformation, MAPK activation may be an important component of its transforming activity. Taken together, our observations indicate that Vav and Dbl transformation is not a consequence of Ras activation and instead may involve the constitutive activation of MAPKs.

3T3 Cells↗
PubMed2003

Expression of tubulin beta II in neural stem/progenitor cells and radial fibers during human fetal brain development.

Recent studies revealed that the "radial glia" in fetal rodent brains are dividing neuronal precursor cells. However, in fetal primate brains, this issue remains unclear, with previous reports indicating that radial glia are a specialized form of astroglia. To investigate the relationship between radial fibers (RFs) and neural stem/progenitor cells in the fetal human brain, we generated polyclonal antibodies to human nestin protein and developed a new mAb, KNY-379, by screening for antibodies that immunostained RFs on paraffin-embedded human fetal brain specimens (12 gestational weeks). The immunostaining for KNY-379 antigen and nestin was seen over the RFs in brains at 8 gestational weeks. Furthermore, KNY-379 antigen and nestin were also detected in human neural stem/progenitor cells in neurosphere cultures. At 12 to 15 gestational weeks, the KNY-379 immunostaining of RFs remained in the periventricular zone and the deep part of the intermediate zone, but it also appeared in outgrowing axons in the cortical plate, in the superficial portion of the intermediate zone, and in apical dendrites in the molecular layer. In the later stages of fetal development (18-40 gestational weeks), this antigen remained in the outgrowing axons and dendrites, but was no longer associated with RFs. Expression cloning and immunoblot analysis demonstrated the antigen to be tubulin beta II, which would thus be a good marker for studying RFs and neural stem/progenitor cells in the early developing human brain.

Adult↗
PubMed1987

Muscarinic and nicotinic synaptic activation of the developing chicken iris.

The development of the mechanical characteristics of contraction and the pharmacology of synaptic activation in chick iris and ciliary body were examined from embryonic day 9 through posthatching. The ciliary ganglion-target muscle system has proven to be a useful model for both in vivo and in vitro studies of neuron-target interactions; one such interaction is involved in neuronal cell death, which in the ciliary ganglion occurs from Stage (St) 34 to 40. To understand the mechanism by which cholinergic blocking agents prevent naturally occurring neuronal death in the chick ciliary ganglion (see the following paper, Meriney et al., 1987), it was necessary to determine the effect of these agents on synaptic transmission at target structures during the cell death period. Initially (St 34-36), iris muscle contraction are synaptically mediated via muscarinic ACh receptors (AChRs) on myoepithelial cells, which have the contractile and structural characteristics of smooth muscle. Close apposition of synaptic terminals, similar to that described for mature synapses, was observed on these myoepithelial cells. Subsequently (St 37), the striated muscle fibers that appear are activated by nicotinic receptors, although muscarinic AChRs are also present. Mechanically, this can be seen as gradually changing from a slow-onset contraction, elicited only by 30 Hz stimulation, to a fast-twitch response (St 37-44). Dilator fibers that develop later in the iris (at about St 39) also possess nicotinic and muscarinic receptors. The ciliary body musculature, although not extensively studied, also appears to have dual cholinergic activation during development. The mature iris has predominately striated muscle fibers that have both junctional nicotinic and muscarinic (mostly extrajunctional) AChRs. The dual presence of both receptor types in the same muscle fiber was confirmed with intracellular recordings, in which only the initial portion of the ACh-elicited depolarization was sensitive to alpha bungarotoxin (alpha BTX). In addition, specific muscarinic binding sites were described in the developing, as well as in the mature, iris. The developing chick iris was also shown to contract directly in response to light, this response disappearing after hatching. This unique dual-receptor pharmacology (nicotinic-muscarinic) and light response of a striated muscle may be due to the neural crest origin of these cells.

Animals↗
PubMedDate not supplied

Development of a novel polyimide hollow fiber for an intravascular oxygenator.

The authors have synthesized a novel fluorinated polyimide to develop a membrane material for oxygenators and fabricated polyimide hollow fibers for use in an intravascular oxygenator. A dry/wet phase inversion process has been applied to a spinning process to prepare an asymmetric polyimide hollow fiber. The outer surface of the hollow fiber consists of an ultrathin, dense skin layer, with a calculated apparent thickness of approximately 60 nm. The fiber diameter was 800 microns with a wall thickness of 130 microns. The asymmetric hollow fiber has two advantages because (a) the hollow fiber does not produce plasma leakage due to the dense skin layer of the surface and (b) O2 and CO2 transfer rates through the hollow fiber are enhanced due to the ultrathin skin layer and are significantly larger than those of presently available membrane oxygenators. The blood compatibility of the polyimide hollow fiber without heparinization has been evaluated in vitro. Deformation and aggregation of platelets adherent to the fibers were not observed, and the polyimide suppressed platelet activation. The polyimide significantly reduced the production of anaphylatoxin and also suppressed complement activation.

Carbon Dioxide↗
PubMedDate not supplied

Quantitative analysis of animal model lens anatomy: accommodative range is related to fiber structure and organization.

PURPOSE: The results of a recent study on accommodation in humans and baboons has revealed that lens fiber structure and organization are key components of the mechanism of accommodation. Dynamic focusing involves the controlled displacement and replacement, or realignment, of cortical fiber-ends at sutures as the mechanism of accommodation at the fiber level. This emended explanation of the mechanism of accommodation raises the following question: as the structure of crystalline lenses are only similar, not identical between species, is accommodative amplitude related to differences in the structure and organization of fibers between species? To address this question, we have quantitatively examined the structure and organization of fibers in a number of the more commonly used animal models (mice, cattle, frogs, rabbits and chickens) for lens research. MATERIALS AND METHODS: Lenses (a minimum of 12-18 lenses/species) from mice, cattle, frogs and rabbits were used for this study. Prior to fixation for structural analysis, measurements of the gross shape of the lenses (equatorial diameter, anterior and posterior minor radii [anterior + posterior minor radius = polar axis]) were taken directly through a stereo surgical dissecting microscope equipped with an ocular reticle. Lenses were then prepared for and examined by light (LM), transmission (TEM) and scanning electron microscopy (SEM). Scale computer-assisted drawings (CADs) of lenses and lens fibers were then constructed from quantitative data as described above and from quantitative data contained in micrographs. RESULTS: The differences in fiber structure and organization that effect accommodative range arise early in development and are continued throughout lifelong lens growth. In umbilical suture lenses (avian) secondary fibers develop with almost completely tapered anterior ends (85-90% reduction of their measures of width and thickness at the equator). By comparison, in lenses with line sutures (e.g. frogs and rabbits) secondary fibers develop with just a 50-60% reduction in anterior fiber taper. In lenses with Y sutures (mice and cattle), fiber width taper is only 25-40%. However, in all cases, while the taper of the posterior end width of fibers is just slightly less (approx. 15-20%) than that of anterior ends, posterior end thickness is only reduced by one half that of anterior thickness. CONCLUSIONS: In humans, the mechanism of accommodation at the fiber level involves the controlled realignment of very flattened and flared, rather than tapered fiber-ends at sutures. In this manner, the simultaneous increase in lens thickness and surface curvature in the accommodated state is the result of fiber-ends being overlapped along multiple (9-12) suture branches covering the majority of the anterior and posterior surfaces. The results of this animal study strongly suggest that accommodative range is directly related to quantitative differences in fiber structure and organization in the different suture types. The very broad accommodative range in birds is made possible, at least in part, by the almost complete tapering of fiber-ends at umbilical sutures. In contrast, the essentially negligible accommodative range of animals that have line- and Y-suture lenses is at least partially the result of the fact that these lenses have fibers with very little end taper. Thus, the blunt ends of fibers in line- and Y-suture lenses precludes any significant overlap of end segments to effect accommodation.

Amphibians↗
PubMed2004

Pruning of motor neuron branches establishes the DLM innervation pattern in Drosophila.

During the Drosophila life-cycle two sets of neuromuscular junctions are generated: the embryonic/larval NMJs develop during the first half, followed by the period of metamorphosis during which the adult counterpart is generated. Development of the adult innervation pattern is preceded by a withdrawal of larval NMJs, which occurs at the onset of metamorphosis, and is followed by adult-specific motor neuron outgrowth to innervate the newly developing adult fibers. Establishment of the adult innervation pattern occurs in the context of a broader restructuring of the nervous system, which results in the development of neural circuits that are necessary to carry out behaviors specific to the adult. In this article, we follow development of the dorsal longitudinal muscle (DLM) innervation pattern through metamorphosis. We find that the initial period of motor neuron elaboration is followed by a phase of extensive pruning resulting in a threefold reduction of neuromuscular contacts. This event establishes the adult pattern of second order branching. Subsequent higher order branching from the second order "contact" points generates the characteristic multiterminal innervation pattern of the DLMs. Boutons begin to appear after the pruning phase, and are much smaller than their larval counterparts. Additionally, we demonstrate that the DLM innervation is altered in the hyperexcitable double mutant, ether a go-go Shaker, and that the phenotype is suppressed by the hypoexcitable mutant, nap(ts1). Our results demonstrate that electrical activity regulates the patterning of DLM innervation during metamorphosis.

Animals↗
PubMed1988

Progressive and regressive changes in the nucleus pulposus. Part II. The adult.

The spines of 28 cadavers were studied with magnetic resonance (MR) imaging, correlated with anatomic sections, to characterize the progressive and regressive changes in the nucleus pulposus. Four additional types of nucleus pulposus were identified in this study. The transitional type (type II) of childhood had fibrous tissue that developed near the anulus fibrosus anteriorly or posteriorly. MR images showed a notch of reduced signal intensity in the nucleus pulposus where the fiber was developing. The adult type (type III), which is predominant after age 30 years, had an indistinct boundary between the nucleus pulposus and anulus fibrosus. MR images showed the fibrocartilage in the nucleus pulposus and inner anulus fibrosus as areas of high signal intensity. Adult disks with a tear of the anulus fibrosus (type IIIB) had a lower signal intensity on MR images and slightly reduced disk heights. This type may represent an early stage of degeneration. Degenerated intervertebral disks (type IV) had either dense disorganized fibrous tissue or fluid replacing the normal fibrocartilaginous structure of the nucleus pulposus. MR images showed narrow intervertebral disk spaces with either reduced signal intensity if collagen was present or increased signal intensity if fluid was present. This study suggests that the nucleus pulposus may progress normally through types I, II, and III.

Adult↗
PubMed1989

Degeneration of oxidative muscle fibers in HTLV-1 tax transgenic mice.

The HTLV-1 tax gene under control of the HTLV-1 long terminal repeat (LTR) was introduced into transgenic mice. Previously tax protein expression in the muscle and peripheral nerves of three independent mouse lines was reported. Here the localization of this transgenic protein at a cellular and subcellular level is described. Tax protein was expressed in oxidative muscle fibers that developed severe progressive atrophy. It localized to the cytoplasma where it was associated with structures resembling degenerating Z bands. This pattern of muscle fiber involvement is similar to that observed in human retroviral associated myopathy. This transgenic mouse model suggests that preferential expression of the HTLV-1 viral promoter in oxidative muscle fibers may explain the productive infection of these fibers in HTLV-1 myopathy.

Animals↗
PubMedDate not supplied

Mathematical and experimental analyses of antibody transport in hollow-fiber-based specific antibody filters.

We are developing hollow fiber-based specific antibody filters (SAFs) that selectively remove antibodies of a given specificity directly from whole blood, without separation of the plasma and cellular blood components and with minimal removal of plasma proteins other than the targeted pathogenic antibodies. A principal goal of our research is to identify the primary mechanisms that control antibody transport within the SAF and to use this information to guide the choice of design and operational parameters that maximize the SAF-based antibody removal rate. In this study, we formulated a simple mathematical model of SAF-based antibody removal and performed in vitro antibody removal experiments to test key predictions of the model. Our model revealed three antibody transport regimes, defined by the magnitude of the Damköhler number Da (characteristic antibody-binding rate/characteristic antibody diffusion rate): reaction-limited (Da </= 0.1), intermediate (0.1 < Da < 10), and diffusion-limited (Da >/= 10). For a given SAF geometry, blood flow rate, and antibody diffusivity, the highest antibody removal rate was predicted for diffusion-limited antibody transport. Additionally, for diffusion-limited antibody transport the predicted antibody removal rate was independent of the antibody-binding rate and hence was the same for any antibody-antigen system and for any patient within one antibody-antigen system. Using SAF prototypes containing immobilized bovine serum albumin (BSA), we measured anti-BSA removal rates consistent with transport in the intermediate regime (Da approximately 3). We concluded that initial SAF development work should focus on achieving diffusion-limited antibody transport by maximizing the SAF antibody-binding capacity (hence maximizing the characteristic antibody-binding rate). If diffusion-limited antibody transport is achieved, the antibody removal rate may be raised further by increasing the number and length of the SAF fibers and by increasing the blood flow rate through the SAF.

Antibodies↗
PubMed2004

Axonogenesis in the medaka embryonic brain.

In order to know the general pattern of axonogenesis in vertebrates, we examined axonogenesis in the embryonic brain of a teleost fish, medaka (Oryzias latipes), and the results were compared with previous studies in zebrafish and mouse. The axons and somata were stained immunocytochemically using antibodies to a cell surface marker (HNK-1) and acetylated tubulin and visualized by retrograde and anterograde labeling with a lipophilic dye. The fiber systems developed correlating with the organization of the longitudinal and transverse subdivisions of the embryonic brain. The first axons extended from the synencephalic tegmentum, forming the first fiber tract (fasciculus longitudinalis medialis) in the ventral longitudinal zone of the neural rod, 38 hours after fertilization. In the neural tube, throughout the entire brain two pairs of longitudinal fiber systems, one ventral series and one dorsal or intermediate series, and four pairs of transverse fiber tracts in the rostral brain were formed sequentially during the first 16 hours of axon production. In one of the dorsal longitudinal tracts, its branch retracted and disappeared at later stages. One of the transverse tracts was found to course in the telencephalon and hypothalamus. The overall pattern of the longitudinal fiber systems in medaka brain is similar to that in mouse, but apparently different from that in zebrafish. We propose that a ventral tract reported in zebrafish partially belongs to the dorsal fiber system, and that the longitudinal fiber systems in all vertebrate brains pass through a common layout defined by conserved genetic and developmental programs.

Animals↗
PubMed1983

Acetylcholinesterase in the ventrobasal thalamus: transience and patterning during ontogenesis.

In this study, maturational alterations in acetylcholinesterase-dependent staining of the thalamic ventrobasal complex of rat and mouse were examined. The study was undertaken to address the question of whether this nucleus exhibits transient acetylcholinesterase positivity during its development and whether the enzyme is likely to be synthesized by its immature intrinsic neurons. Also, the patterning due to acetylcholinesterase staining of cells and fibers, and the developmental changes in these patterns, have not been described in earlier work. In contrast to surrounding thalamic nuclei, the ventrobasal complex is acetylcholinesterase-positive at birth. In rat, acetylcholinesterase staining of the ventrobasal thalamus is still more intense than in adjacent nuclei at the end of the first week postnatally. Virtually all somata in the nucleus are filled with dense reaction product at this time. Ultrastructurally, reaction product is associated with the granular endoplasmic reticulum. At this stage, there is a marked difference in intensity of staining between the medial and lateral subdivisions of the nucleus, and patterned clustering of somata within each subdivision is readily appreciated in acetylcholinesterase-stained material. In the second postnatal week, intrinsic acetylcholinesterase activity is progressively lost. By the end of the third postnatal week, the nucleus is quite pale except for one area. In the posterior portion of the lateral subdivision, adjacent to the nucleus reticularis, interconnecting bundles of acetylcholinesterase-positive fibers enter the nucleus. They course medially in the lateral subdivision and break up into a plexus of fine fibers. The development of acetylcholinesterase-dependent staining patterns in the mouse is quite similar, except that histochemically detectable levels of enzyme are substantially lower in the neonatal period. It is concluded that the ventrobasal complex can be distinguished from other thalamic nuclei in regard to earlier onset and/or transience of acetylcholinesterase staining. Ultrastructural observations suggest that virtually all immature ventrobasal neurons are synthesizing acetylcholinesterase. It is suggested that the transient staining for enzyme is due primarily to alteration in synthesis and/or turnover in neurons of the ventrobasal complex. In addition, the acetylcholinesterase staining reveals a patterning of fibers and cells that also undergoes developmental alteration. Evidence is discussed suggesting that axons in the barrels of somatosensory cortex (SmI) are derived from these transiently acetylcholinesterase-positive somata. Consequently, the loss of acetylcholinesterase fiber staining in the barrels, during the third postnatal week (noted previously), may be related to a decrease in synthesis of enzyme in the neuronal somata of the ventrobasal complex.

Acetylcholinesterase↗
PubMed1996

Developmental localization of GAP-43 and olfactory marker protein in rat olfactory bulb transplants.

In an effort to identify and understand the laminar disorganization that occurs in the transplanted (TX) rat olfactory bulb (OB), we examined the development of fiber systems within these TX OBs. One antibody for olfactory marker protein (OMP) was used to identify axons of mature olfactory receptor neurons (ONs) and a second antibody, for a growth-associated protein (GAP-43), provided a marker for all extending or immature fibers. Donor OBs were taken from fetuses on embryonic days 14 or 15 (sperm-positive day is zero) and TX directly into the cavity produced by removal of an OB in 1-day-old hosts of the same strain. After survival times of 1 and 2 weeks and at maturity, adjacent 8 microns paraffin sections from the TX material were examined for OMP and GAP-43 reactivity. Fiber bundles, reactive for OMP, were found within the TX by 1 week post-TX, indicating rapid re-innervation of the donor OB by ONs. The appearance of OMP reactivity gradually shifted from tightly packed, well-defined fiber bundles at 1 week post-TX to a diffuse reticulated pattern of individual fibers emerging from bundles at maturity. The OMP-reactive fiber bundles of the TX OB also contained GAP-43-reactive fibers, but GAP-43 reactivity also extended to other (OMP-negative) bundles and fields. Reactivity for GAP-43 in the TX OB was nearly ubiquitous at 2 weeks post-TX but, as development progressed (in both the TX and normal OB), such reactivity gradually decreased. Thus, while maturation in sensory afferent fiber systems in the TX OB may be delayed, it eventually follows a pattern similar to that in the normal OB, suggesting that factors other than the timing of fiber extension may be responsible for the laminar disorganization of the TX OB.

Animals↗
PubMed1986

[Development of various types of muscle fibers in the quadriceps femoris and the soleus during human ontogenesis].

By means of histological methods for revealing adenosine triphosphatase of myosin (pH 4.6) and succinate dehydrogenase activity, using postmortem material, development of various muscle fibers of the femoral m. quadriceps and m. soleus has been studied in human ontogenesis. The first stage of rearrangements lasts from the 5th-6th month of the uterine development up to 2 years of age and is characterized by formation (from non-differentiated) of oxidative, glycolytic and oxidative-glycolytic fibers. During the period from 2 up to 7-8 years of age the ratio in the types changes slightly, but transversal section size of the muscle fiber increases intensively. Then from 11 up to 17 years of age, together with maximal increment of the fibers transversal section, there is an essential change in the type relation. By the 17th years of age, in the femoral m. quadriceps the part of the fibers with glycolytic type of energy supply increases, while in the m. soleus the oxidative fibers become more numerous. By the 70th years of age in the femoral m. quadriceps relative amount of intermediate fibers increases.

Adenosine Triphosphatases↗
PubMed1998

Expression of myosin heavy chain isoforms during development of domestic pigeon pectoralis muscle.

The pectoralis muscle of birds provides virtually all the power for the downstroke of the wing during flight. In adults it consists almost entirely of FOG (fast-twitch oxidative-glycolytic) and/or FG (fast-twitch glycolytic) fiber types. The aims of this study are to contrast MyHC (myosin heavy chain) transitions occurring within avian FG and FOG fibers during development, and to test the hypothesis that the pectoralis matures before the acquisition of flight. Pectoralis was obtained from pigeons (Columba livia) aged from 13 days in ovo to adult. Monoclonal antibodies generated against chicken MyHC isoforms were used with Western blots and immunocytochemistry. FG and FOG fibers were differentiated using a histochemical method demonstrating NADH (nicotinamide adenine dinucleotide), and "lesser fiber diameters" were quantified. Western blots confirm that the antibodies label pigeon MyHCs. A small number of the fibers are slow type in ovo, but these are quickly restricted in distribution and lost after hatching. In ovo fast-twitch fibers contain a ventricular isoform, and at least two embryonic-neonatal forms (designated E-N103 and E-N165). One week after hatching, fast-twitch fibers can be distinguished by NADH as FG or FOG. At fledging, four weeks after hatching, FG and FOG fibers are smaller than in older birds and E-N103 and E-N165 persist in both fibertypes. E-N103 wanes in all fibers shortly after fledging. E-N165 gradually disappears from FG fibers. Thus, despite pigeons being at adult body mass at fledging, their pectoralis is not fully mature.

Animals↗
PubMed1994

Clearance of refractory ceramic fibers (RCF) from the rat lung: development of a model.

Chronic exposure and postexposure experiments have been recently performed in rats to evaluate the biological responses of inhaled refractory ceramic fibers (RCF) at different concentration levels. The lung burden data in the accessory lobe of the rat lung were collected during and after different exposure and postexposure periods. The size distribution of retained fibers in the lung at different time points was also measured. We used these data to develop a mathematical model of fiber clearance from the rat lung. It was found that the clearance rate did not depend significantly upon fiber size but there was a clear dependence on lung burden. As lung burden increased, the clearance rate was found to decrease. An empirical equation was derived for the clearance rate as a function of lung burden. At low burdens, rats had a retention half-time of about 126 days for RCF compared to a typical half-time of about 60 days for insoluble nonfibrous particles.

Animals↗
PubMed1991

Postnatal changes in the distribution of succinate dehydrogenase activities among diaphragm muscle fibers.

The distributions of oxidative capacities among type-identified muscle fibers in the developing cat diaphragm were examined by quantifying succinate dehydrogenase (SDH) activity using a microdensitometric procedure. Animals were studied during the first six weeks of postnatal development and compared to adults. Muscle fiber SDH activities were initially low during the first 2 postnatal wk, then increased to their highest values between 3 and 6 wk. Thereafter, fiber SDH activities declined to adult values. At each age, the distributions of SDH activities for both type I and II fibers were unimodal. Thus, no objective basis exists for subclassifying type II fibers based on differences in oxidative capacity. Fibers could be subclassified as type IIA, IIB, or IIC based on the acid pH lability of ATPase staining. In neonates, approximately 90% of all fibers were classified as type IIC. Thereafter, the proportion of IIC fibers decreased while the proportions of type I, IIA, and IIB increased. Adult fiber type proportions were reached by 6 wk of age. The SDH activity of type I fibers was generally higher than that of type II fibers at all ages, although there was considerable overlap in the distributions of SDH activities among type I and II fibers. The SDH activity of type IIC fibers was also higher than that of either type IIA or IIB during development. Only in the adult diaphragm was the SDH activity of type IIA fibers higher than that of type IIB. At no age could type IIA, IIB, or IIC fibers be discriminated based solely on differences in oxidative capacity.

Adenosine Triphosphatases↗