Search PubMed⌕ Search

Biomedical subjects

K Fried

Publications and source records attributed to K Fried.

At least 91 records · Page 5Linked to original sources

End structure and neuropeptide immunoreactivity of axons in sciatic neuromas following nerve section in neonatal rats.

The formation of neuromas after neonatal nerve injury was studied in rats. In neonatal pups, the sciatic nerve was cut and tightly ligated, and a portion of the distal stump was removed. After 6-10 weeks, a nerve-end neuroma had formed in about 70% of the animals. In the remaining animals the nerve had grown on the side of the ligature. The end structure of the neuroma axons was studied using anterogradely transported WGA-HRP injected into the L5 dorsal root ganglion. HRP labeling occurred in the entire proximal sciatic nerve. In the neuroma, labeled fibers branched profusely and either terminated with minor end swellings or turned in the retrograde direction. Immunohistochemistry showed that the fibers which projected into the neuroma presented a moderate immunoreactivity to substance P and neuropeptide Y and a strong reactivity to calcitonin gene-related peptide. The results show that many sensory and sympathetic sciatic nerve fibers survive chronic axotomy in the newborn and contribute to the formation of nerve-end neuromas. There are, however, important structural differences between adult and neonatally induced neuromas.

Animals↗

Substance P-, CGRP- and NPY-immunoreactive nerve fibers in rat sciatic nerve-end neuromas.

Substance P (SP)-, calcitonin gene-related peptide (CGRP)- and neuropeptide Y (NPY)-immunoreactive nerve fibers were examined in experimental sciatic nerve-end neuromas in the rat with immunohistochemical techniques. At 1-3 days after nerve ligation and section of the sciatic nerve there was an accumulation of SP-like immunoreactivity (SP-LI). Six days after the lesion there was, however, a marked reduction and the neuromas remained virtually depleted from SP-LI at survival times between 8 days and 3 months. CGRP-LI was strong at 1-5 days post-operatively. By 8 days, CGRP-LI was reduced, but a large number of axons were still immunoreactive, and remained immunolabelled up to 3 months. CGRP-LI nerve fibers formed endbulbs, and appeared to grow in both anterograde and retrograde directions. Fine fibers sprouts were first observed at 8 days, but preterminal branching in neuromas aged less than a month was uncommon. At early stages (1-3 days) after ligation, there was a marked accumulation of NPY-LI proximal to the nerve constriction. NPY-LI was reduced from 5 days and on, but many fibers remained NPY-positive and their growth pattern through proximal and distal neuroma segments could be determined. The present results thus may indicate a differential effect of nerve injury on neuropeptide expression: immunohistochemically detectable SP-LI rapidly disappears from sciatic nerve fibers trapped in nerve-end neuromas, but CGRP-LI and NPY-LI remain and are useful as neuroanatomical markers for two subclasses of sprouting axons. Furthermore, the findings suggest that both CGRP and NPY, but not SP, could be involved in ectopic electrical activity in experimental neuromas.

Animals↗

De- and regeneration of axons after minor lesions in the rat sciatic nerve. Effects of microneurography electrode penetrations.

The structural effects of microneurography electrode penetrations were examined in the rat sciatic nerve. Such penetrations always produced restricted peri- and endoneurial lesions, resulting in degeneration of myelinated and unmyelinated axons, as well as in demyelination. The regenerative response was vigorous, and the regenerating axons usually formed a separate region of fascicle. However, restitution was not complete after 9 weeks survival, and in some cases not even after 16 weeks.

Animals↗

Combined retrograde tracing and enzyme/immunohistochemistry of trigeminal ganglion cell bodies innervating tooth pulps in the rat.

Rat trigeminal neurons innervating tooth pulps were retrogradely labelled with fluorogold and analysed enzyme- and immunohistochemically for their content of substance P, calcitonin gene-related peptide, fluoride-resistant acid phosphatase, GM 1 ganglioside, carbonic anhydrase and neurofilament protein. The data showed that both small, medium-sized and large trigeminal neurons were labelled after fluorogold deposition in maxillary molar pulps, with a majority of the cells being medium-sized and large. Less than 2% of the pulpal neurons showed substance P-like immunoreactivity. Fifty-six per cent of the pulpal nerve cells were calcitonin gene-related peptide-positive. These cells were small, medium-sized and large. Only 1% of the fluorogold-labelled cells contained fluoride-resistant acid phosphatase enzyme activity. This paralleled the finding that the pulpal neurons were unstained by Griffonia simplicifolia isolectin I-B4, a plant lectin which preferentially binds to fluoride-resistant acid phosphatase-positive cells. Choleragenoid-like immunoreactivity, which identifies cells with the GM 1 ganglioside receptor, was found in 70% of the fluorogold-labelled pulpal neurons. Approximately 80% of the fluorogold-labelled cells showed RT 97-immunoreactivity. RT 97 labels neurofilament protein and is present in large light primary sensory neurons. No pulpal neurons appeared to contain carbonic anhydrase, as judged from both enzyme- and immunocytochemical observations. The findings suggest that, in the rat, trigeminal tooth pulp neurons, which according to the classical view are nociceptive, form a heterogeneous group of neurons with a minority of small cells which may contain calcitonin gene-related peptide but rarely either substance P or fluoride-resistant acid phosphatase. However, the vast majority of pulpal nerve cells appear to have sizes and cytochemical characteristics which are not generally associated with nociceptive primary sensory neurons.

Acid Phosphatase↗

Cardiovascular, skeletal and ophthalmologic manifestations in patients with Marfan's syndrome.

Cardiovascular, skeletal and ophthalmologic manifestations of Marfan's syndrome were evaluated in 36 patients with Marfan's syndrome, including 22 females and 14 males whose ages ranged from 3 to 70 years. The patients complained mainly of palpitations and chest pain. Mitral clicks and/or systolic murmurs were heard in 31 patients (86%); skeletal findings were found in 35 patients (97%) and ECG T-wave changes in 11 (30%). Chest X-rays showed cardiac enlargement in six patients (17%) and dilatation of the aorta in two (6%). Holter monitoring performed in 21 patients showed only a few premature atrial and ventricular beats in 4, although prolapse of the mitral valve was found in 18 patients. Echocardiography revealed mitral valve prolapse in 32 patients (89%), 21 females (95% of females) and 11 males (79% of males). Aortic root dilatation was found in 19 patients (53%). 11 males (79% of males) and 8 females (36% of females). This study demonstrates the variable clinical expression of Marfan's syndrome and the importance of clinical and noninvasive methods, mainly echocardiography, for its evaluation.

Adult↗

Proportion of unmyelinated axons in rat molar and incisor tooth pulps following neonatal capsaicin treatment and/or sympathectomy.

The occurrence of unmyelinated axons was examined ultrastructurally in rat molar and incisor root pulps of normal rats, of neonatally capsaicin-treated rats, of rats subjected to neonatal capsaicin treatment followed by resection of the superior cervical ganglion and of sympathectomized but otherwise normal rats. Following capsaicin treatment the occurrence of unmyelinated pulpal axons was slightly subnormal. Sympathectomy was largely without effect on the population of unmyelinated axons in tooth pulps of capsaicin-treated rats. In normal rats the proportion of unmyelinated axons in molar pulps was not altered by sympathectomy but it caused a slight decrease in the number of unmyelinated incisor pulpal axons. These findings support the view that most of the unmyelinated axons in rat molar and incisor pulps are sensory, that the parent neurons of these axons differ from nociceptive neurons at other sites by being largely resistant to neonatal capsaicin treatment and that very few unmyelinated tooth pulp axons represent postganglionic efferents.

Adrenergic Fibers↗

End-structure of afferent axons injured in the peripheral and central nervous system.

The end-structure of afferent axons chronically severed in the rat sciatic nerve or dorsal column (DC) was visualized by centrifugal transport of horseradish peroxidase (HRP) or wheatgerm agglutinin conjugated to HRP (WGA:HRP) injected into the L4 or L5 dorsal root ganglion. Nerve regeneration was prevented and neuroma formation encouraged by tightly ligating the cut nerve end. For the first few weeks postoperative, the time during which afferents trapped in a nerve-end neuroma generate their most intense ectopic impulse barrage, the developing neuroma was dominated by swollen terminal end-bulbs. There was some axonal dying-back, retrograde fiber growth, and terminal sprouting, but little preterminal branching. The rich tangle of fine preterminal branches usually thought of in relation to nerve-end neuromas did not elaborate until several months postoperative, a time when the neuroma is relatively quiescent electrically. Afferents cut in the DC, which never develop dramatic ectopic electrical activity, showed morphological peculiarities similar to nerve-end neuromas during the early postoperative period, including retrograde fiber growth and minimal sprouting. They did not, however, go on to form luxuriant branches. These data provide preliminary clues as to the structure of the ectopic impulse-generating mechanism thought to underlie paresthesias and pain associated with peripheral nerve injury.

Afferent Pathways↗

Autosomal dominant carpal tunnel syndrome in a Karaite family.

A clinical examination and a history of 64 members belonging to four generations of a Karaite kindred revealed 11 patients with carpal tunnel syndrome (CTS). Bilateral involvement and early age of onset are salient features. The mutation may be traced in four generations. Hereditary primary CTS may be more prevalent than hitherto suspected.

Adult↗

Nerve growth to tooth buds after homotopic or heterotopic autotransplantation.

Feline permanent incisor tooth buds (bell stage) were autotransplanted to mandibular alveolar sockets (homotopic site) or to the submandibular subcutis or the leg (heterotopic sites). This was done in 34 kittens aged 1-2 months. After survival times of 3-8 months the animals were fixed by glutaraldehyde perfusion. A total of 56 mineralized teeth, which had developed at the recipient sites, were removed, demineralized and processed for light microscopic (LM) general evaluation. Fourty-four teeth, which were judged to be grossly normal in the LM, were selected for electron microscopic (EM) analysis with respect to the occurrence of pulpal nerve fibres. The highest proportion of normal teeth (16 of 16) was obtained from the alveolar site, followed by the submandibular (11 of 14) and hindlimb (17 of 26) sites. Most of the grossly normal grafts possessed pulpal axons (37 of 44). The alveolar grafts were all innervated and exhibited a largely normal appearance qualitatively and in terms of percentage of myelinated fibres. The proportion of innervated pulps was lower among the heterotopic mandibular (10 of 11) and hindlimb (11 of 17) grafts. In addition, signs of nerve fibre degeneration appeared more frequently at the heterotopic sites. On the basis of these findings, and in view of the results of other workers, we conclude that tooth germs are attractive targets for all divisions of the trigeminal nerve and for cutaneous nerves outside the trigeminal system. However, the morphological picture tends to become increasingly abnormal with increasing distance from the normal locus.

Alveolar Process↗

Unmyelinated axons in the feline trigeminal motor root.

The trigeminal motor root was studied in the electron microscope at different proximodistal levels in eight adult cats. Counts at a level halfway between the trigeminal ganglion and the pontine junction showed that the root contains about 9% (n = approximately 300) unmyelinated axon profiles at this level. Small groups of unmyelinated axons occur on both sides of the PNS-CNS border, in the surrounding pia mater, and in perivascular spaces of the CNS compartment. Examination of serial sections from the PNS-CNS transitional region showed that some unmyelinated axons actually cross the PNS-CNS border. The functional significance of these fibres remains unknown.

Animals↗

On nerves and teeth in the lower jaw of the cichlid Tilapia mariae.

The anatomy of the teeth and tooth-related nerves in the lower jaw was examined in the cichlid Tilapia mariae. This was done in order to establish a basis for studies on dental neuroplasticity in a polyphyodont vertebrate. The region of interest was explored in specimens fixed by glutaraldehyde perfusion, and by using X-ray photography, maceration, scanning electron microscopy, gross dissection, and light microscopic examination of serial sections. The results show that the lower jaw carries some 60-65 functional teeth. In addition, numerous replacement teeth and tooth germs in various stages of development are located in a cavity in the dentary bone. Numerous nerve bundles are present in immediate relation to the dental follicles of tooth germs. Unerupted teeth do not contain light-microscopically discernible pulpal axons, but the pulps of functional teeth contain myelinated axons. Both perifollicular and pulpal nerve bundles derive from a nerve plexus, which is formed by branches from r. mandibularis trigemini. This nerve is easily accessible to experimental manipulation, where it courses through the adductor mandibulae muscular complex. Thus, the lower jaw of T. mariae seems to represent a suitable system for the study of tooth-nerve interactions in a polyphyodont species.

Animals↗

Short internodal lengths of canine tooth pulp axons in the young adult cat.

Light-microscopical measurements have been made on teased pulpal nerve fibers from young adult cat canine teeth. In the root canal portion (apical to first branching point) the mean internodal length was approximately 250 micron. In the pulpal chamber portion (coronal to the first branching point) the pulpal nerve fibers had a mean internodal length of approximately 125 micron. A local decrease in internodal length was evident at bifurcations and in preterminal regions. These internodal lengths are shorter than in similarly sized stem axons. The possible functional significance of this difference is discussed.

Animals↗

Structural development of the feline mental nerve.

The qualitative and quantitative structural development of the feline mental nerve (MN), a branch of the inferior alveolar nerve (IAN), was studied by electron microscopy from 40 days postconception (dpc) (about 2 weeks before birth) to 11 years after birth. Myelination was initiated at 40-45 dpc. At 2 months after birth de novo myelination was completed, and the larger myelinated axons had achieved a fully differentiated nodal-paranodal morphology. Size growth of myelinated axons continued until 6 months, when a bimodal size distribution between 1 and 12 months was established. When compared to the IAN, the MN contained a higher proportion of unmyelinated axons. Age-related signs of axon degeneration, which previously were recorded in the IAN, were lacking in the MN. This suggests that senescent IAN axon degeneration is related to dental rather than to cutaneous MN branches.

Aging↗

Genetic microcephaly in a pair of monozygous twins.

A pair of monozygotic female twins with true primary microcephaly is described. The autosomal-recessive nature of the disease is supported by the following: the twins are concordant for the disease; the parents, themselves normal, are related; the reduced skull dimensions were noted at birth; neurologic problems are absent; the karyotype is normal; the gestation and delivery were normal, without any history of influences capable of inducing microcephaly. A detailed dermatoglyphic study is given.

Consanguinity↗

Changes with age in canine tooth pulp-nerve fibres of the cat.

Light microscopical observations have been made on teased pulpal nerve fibres from mandibular canine teeth of cats aged 3 years or more. Both internodal lengths and external fibre diameters appeared to be reduced compared to the young adult. Qualitative myelin sheath changes were commonly observed. These consisted of extremely short, smooth or distorted intercalated internodes, myelin wrinkling, nodal lengthening and formation of myelin ovoids. Features suggesting de-myelination were also present. These findings should be considered when functional aspects of pulpal axons in the ageing tooth are discussed.

Aging↗

Inheritance of idiopathic torsion dystonia among Jews.

Idiopathic torsion dystonia (ITD) has long been considered to be genetically determined, but the pattern of inheritance has been unclear. It has been suggested that inheritance may differ in Jews and non-Jews. In the present study, data gathered in a nationwide survey of ITD in Israel were analysed. Between 1969 and 1980, 47 patients were collected, of whom 40 were of European origin. In these European Jews, the ITD frequency was about 1:23 000 live births, which was five-fold greater than in Jews of Afro-Asian origin. Assuming that all cases fit the same genetic model, an X linked or a simple autosomal recessive model of inheritance did not agree well with our data. An autosomal dominant model with low penetrance could have accounted for our observations and would yield an ITD gene frequency in European Jews of 3 to 4:100 000. In view of the increased ages of their fathers, the isolated cases may have included some new mutations. Multifactorial inheritance was also possible. However, it may be inappropriate to assume that all cases have the same genetic basis, or even that all are inherited.

Dystonia Musculorum Deformans↗