Biomedical subjects
Publications and source records attributed to K Fried.
The etiology of idiopathic intussusception is unknown. Occurrence of intussusception in more than one patient in a same family is rare. A familial predisposition is suspected. We present a family in which the two children suffered from intussusception with recurrence in the youngest sibling and review the literature.
A Bedouin family with two girls affected by severe congenital contractural arachnodactyly (CCA) is described. The girls were double second cousins. One of the girls also had ambiguous genitalia, an anomaly not generally associated with this disorder. The two children were both the product of first-cousin Bedouin parents from the same family. It is possible that both sets of parents were heterozygous for CCA; thus the infants may have been homozygous for CCA, which is usually an autosomal dominant condition. No instance of homozygous CCA has previously been reported. This family suggests genetic heterogeneity in CCA and that, in some rare families, the mode of inheritance may be autosomal recessive.
Thyroglossal duct cysts are common congenital abnormalities or developmental field defects, usually detected in early childhood. Despite their frequent occurrence, familial patterns are rare. We report on two new families with thyroglossal duct cysts. In the first family three siblings were involved, while in the second one, father and son were affected. This trait may be autosomal recessive or possibly multifactorial, as the first family would indicate, and also autosomal dominant, as the second family would suggest.
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Expression of neurotrophins and neurotrophin receptors was examined with in situ hybridization and immunohistochemical techniques 10 days to 6 weeks after ventral or dorsal funiculus spinal cord lesions in adult rats and cats, lesions that have previously been shown to allow axon regrowth. Strongly elevated levels of trkB mRNA were seen in the scar tissue formed in the white matter after both types of lesions. Only small increases were detected for nerve growth factor, brain-derived neurotrophic factor, neurotrophin 3, neurotrophin 4, trk, and trkC mRNA in response to the injuries. trkB protein-like immunoreactivity was increased in the regions that showed elevated levels of trkB mRNA. EM localized this immunoreactivity to neurons, astrocytes, and leptomeningeal cells. Neurofilament immunolabeling and axonal tracing demonstrated that nerve fibers in the scar tissue were concentrated to areas that showed strong trkB protein-like immunoreactivity. The findings implicate a role for neurotrophin receptors in axonal sprouting and glial reactions in the injured spinal cord.
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A test for determining N-acetylator metabolic phenotype has been developed using caffeine as a probe drug. A spot sample of urine is taken, and the unextracted urine is then analysed by micellar electrokinetic capillary chromatography. Phenotype is determined from the peak-area ratio of urinary 5-acetylamino-6-formylamino-3-methyluracil to 1-methylxanthine. Phenotype assignments using this method were compared with those made using a standard high-performance liquid chromatography assay, with good agreement between the two methods. The advantage of the capillary electrophoresis analysis is that no sample extraction is necessary, resulting in a total analysis time of around 20 min, and removing a potential source of error.
Neuropeptide Y (NPY)-like immunoreactivity was examined by fluorescence immunohistochemistry in rat sciatic neuromas, L5 dorsal root ganglias (DRGs) and L5 dorsal roots 1-3 weeks after chronic nerve injury. Anterograde tracing demonstrated that a large number of NPY-positive neuroma fibers were sensory. These fibers were mostly large diameter axons, in line with the finding that a majority of NPY-immunoreactive neurons in the DRG were medium- to large-sized neurons which showed immunoreactivity to the neurofilament antibody RT 97. In dorsal roots NPY immunoreactivity was strong after sciatic neuroma formation. Dorsal rhizotomy and ligation, on the other hand, did not induce NPY immunoreactivity at any of the sites examined.
GAP-43-like immunoreactivity in developing and mature incisor and canine tooth pulp nerve fibers in the cat was examined with fluorescence immunohistochemistry and pre-embedding immunogold electron microscopy. As expected, pulpal and periodontal nerve fibers in primary teeth aged 2-3 weeks showed strong immunoreactivity. Double-labeling experiments demonstrated that 50-70% of primary pulpal GAP-43-positive nerve fibers showed CGRP-like immunoreactivity. However, in adult permanent teeth the vast majority of pulpal nerve fibers also displayed intense GAP-43-like immunoreactivity both when surrounding pulpal blood vessels and in the subodontoblast/odontoblast region. There was a high degree (90-95%) of simultaneous expression of GAP-43-like immunoreactivity and CGRP-like immunoreactivity in adult permanent pulps. Immunogold GAP-43 labeling was mainly associated with the cytoplasmic side of axonal membranes. However, occasional examples of immunolabeled Schwann cells were also found. High levels of GAP-43 in normal mature permanent pulpal nerves may facilitate neural plasticity after dental wear or injury.
The distribution of laminin-like immunoreactivity in adult normal and denervated cat mandibular tooth pulps was studied by the use of fluorescence microscopy and pre-embedding immunogold electron microscopy. Immunoreactivity to collagen IV was also assessed in order to distinguish basement membranes. In normal pulps, light-microscope laminin-like immunoreactivity was strong along blood vessels and Schwann cell sheaths, and a faint immunoreactivity was seen also in the odontoblast layer. Electron microscopy confirmed the laminin-like immunoreactivity of endothelial and Schwann cell basement membranes at all pulpal levels. In the odontoblast layer and the predentine, nerve-like structures lacking basement membranes but possessing strong membrane laminin-like immunoreactivity were encountered. In addition, a clear-cut laminin-like immunoreactivity of plasma membranes of the somata and processes of odontoblasts was seen. Observations on denervated pulps as well as pulps in which nerve regeneration had taken place did not reveal any changes in the pattern of laminin-immunoreactivity in basement membranes or odontoblasts. Distribution of collagen IV-like immunoreactivity was very similar to laminin-like immunoreactivity in basement membranes of blood vessels and Schwann cells, and appeared unaffected by denervation. The odontoblasts and nerve-like profiles in the odontoblast layer were devoid of collagen IV-like immunoreactivity. We propose that odontoblast-associated laminin could be of significance as guidance for regenerating terminal pulpal nerve fibers to appropriate targets.
Spinal motoneurons have a capability to regenerate CNS-type axons after intramedullary lesions in the adult cat. Regrowing axons have been traced through CNS-type scar tissue in the ventral funiculus of the spinal cord and into adjacent ventral root fascicles. This scar tissue, which appears to support and sustain regenerating axons, has been shown to have a persistent defect in the blood-brain barrier. It has been suggested that the blood-brain barrier may play a vital role in CNS regeneration by regulating the access of blood-borne trophic factors to the lesion area. In the present study, the binding of antibodies to the human nerve growth factor receptor in the cat spinal cord was examined with immunohistochemical methods 2 days to 8 weeks after a ventral funiculus lesion. The results show that, while no neurons in the ventral horn of the control material contained nerve growth factor receptor-like immunoreactivity as revealed by fluorescence microscopy, affected motoneurons expressed nerve growth factor receptor after ventral funiculus lesion. Nerve growth factor receptor-like immunoreactivity associated to both capillaries and interstitium was present in the scar tissue. Electron microscopic examination of sections labelled with the immunogold-silver method showed that perivascular nerve growth factor receptor-like immunoreactivity was located exclusively to non-pericytic perivascular cells. These cells were abundant in the expanded capillary perivascular spaces adjacent to the traumatic lesion. Similar cells, with or without relation to blood vessels, were observed in the scar tissue and in the pia mater. In a separate set of specimens it was observed that a ventral funiculus lesion combined with ventral root avulsion, which removes denervated PNS tissue, resulted in an expression of nerve growth factor receptor-like immunoreactivity which was similar to the one observed after ventral funiculus lesion only. The results of the present study show that affected motoneurons and cells in the scar tissue express nerve growth factor receptor after ventral funiculus lesion which implies that neurotrophic factors related to nerve growth factor may be of importance for the regenerative response.
Aging of cat tooth pulp nerves involves ultrastructural changes, and changes in the expression of some neuropeptides and in the expression of the receptor for nerve growth factor. Electron microscopy of old pulps demonstrates loss and degeneration of unmyelinated and myelinated axons, as well as demyelination. Immunohistochemical findings show a marked age-related decrease in pulpal calcitonin-gene related peptide- and substance P-like immunoreactivity, and a reduction in nerve growth factor receptor-like immunoreactivity. Changes in neuropeptide expression are not entirely due to loss of nerve fibers, since most aging pulps contain nerve growth factor receptor-positive fibers which lack neuropeptide-like immunoreactivity. The changes reported here parallel the observation that there is an age-related reduction in sensitivity to pulpal stimulation, but may also contribute to the development of oral sensory phenomena such as neuropathic pain. Moreover, the senescent transformation of pulpal nerves probably affects hemoregulation of the pulp, and may thus have consequences for pulpal extraneuronal tissue.
Three bedouin children with mitochondrial myopathy due to cytochrome c oxidase deficiency presented with progressive muscle weakness, failure to thrive, proximal renal tubular acidosis, and lactic acidemia leading to death. Two died by age 5 months and one by age 16 months. Cytochrome c oxidase was markedly reduced in skeletal muscle extracts of all three. Three other children of the same family with most probably the same metabolic aberration are also described. We suggest an autosomal recessive inheritance for this lethal mitochondrial myopathy.
The distribution of nerve growth factor receptor (NGF receptor)-like immunoreactivity in pulps of developing primary and mature permanent cat canine teeth was examined, by use of a monoclonal antibody against NGF receptor detected by fluorescence immunohistochemistry and pre-embedding immunocytochemical light- and electron microscopy. Both primary and permanent pulps contained a vast number of NGF receptor-like immunoreactive nerves. Immunolabelling appeared to be localized both to axons and Schwann cells. In addition, many blood vessel walls in immature primary tooth pulps showed NGF receptor-like immunoreactivity, in contrast to permanent pulps where blood vessels rarely were NGF receptor-immunoreactive. Double-labelling immunofluorescence experiments revealed that in the permanent pulp a majority of the NGF receptor-positive nerves also showed calcitonin gene-related peptide (CGRP)-like immunoreactivity, and many showed substance P-like immunoreactivity. However, nerve fibers with neuropeptide Y-like immunoreactivity lacked NGF receptor-like immunoreactivity. In developing primary tooth pulps fewer NGF receptor-positive nerves were CGRP-like immunoreactive or substance P-like immunoreactive, as compared to the permanent pulp. Neuropeptide Y-like immunoreactive nerve fibers were not detected in the primary tooth pulp. The results suggest a role for nerve growth factor in both developing and mature sensory nerves of the tooth pulp.
Injured sensory axons with endings trapped in a nerve-end neuroma become a source of abnormal impulse discharge and neuropathic pain. We have examined the ultrastructure of such endings anterogradely transported WGA-HRP and freeze-fracture replication, with emphasis on the postinjury period during which the abnormal neural discharge is maximal. Most axons ended in a terminal swelling, depleted of myelin but surrounded by Schwann cell processes. These 'neuroma endbulbs' were richly packed with membrane-bound organelles, and had a smoothly undulating surface with (in neuromas of several weeks standing) a moderate number of short filopodia. Massive sprouting did not occur until several months postinjury. Both p- and e-faces of endbulb axolemma had larger intramembranous particles, on average, than corresponding internodal membrane of control axons. This change, interpreted as indicating remodelling of axolemmal channel (and perhaps receptor) content, may be related to the abnormal electrical behavior of neuroma afferents.
The levels of 5-hydroxytryptamine and tachykinin neuropeptides substance P, neurokinin A, neurokinin B and neuropeptide K were measured in the spinal cord of rats treated by intraventricular injection of the selective serotonergic neurotoxin 5,7-dihydroxytryptamine. The spinal cord levels of 5-hydroxytryptamine as measured by high performance liquid chromatography with electrochemical detection decreased by more than 90% in the ventral and dorsal cord compared to controls. The levels of substance P as measured by radioimmunoassay were significantly reduced (66%, P less than 0.01) in the ventral lumbar cord only. In this region, neurokinin A, neurokinin B and neuropeptide K levels were determined by combined high performance liquid chromatography and radioimmunoassay. The neurotoxin treatment also caused a significant reduction of neurokinin A (72% reduction, P less than 0.01) and a non-significant reduction of neuropeptide K, but virtually no change in the neurokinin B level. Immunohistochemical studies of the ventral lumbar cord of sham-operated animals showed immunoreactivity for 5-hydroxytryptamine as well as for substance P and neurokinin A in nerve fibres around motor neurons. In neurotoxin-treated rats this region was devoid of immunohistochemically detectable substance P- and neurokinin A-positive fibres and showed very sparse or no 5-hydroxytryptamine immunoreactivity. We conclude that among the tachykinins both neurokinin A and substance P, but probably not neurokinin B, co-exist with 5-hydroxytryptamine in nerve terminals in the rat ventral spinal cord.
The peripheral reorganization of pulpal nerves after tooth injury was studied, in the rat, with anterograde horseradish peroxidase tracing techniques, and combined retrograde Fluorogold tracing and immunohistochemistry was employed to examine the effects of inferior alveolar nerve lesions or tooth injury on some cytochemical characteristics of pulpal trigeminal ganglion nerve cells, namely content of substance P, calcitonin gene-related peptide and the ganglioside GM1 (binding subunit of cholera toxin), as well as affinity to RT 97 (antibody to neurofilament protein) and the lectin Griffonia simplicifolia isolectin I-B4. Anterograde horseradish peroxidase tracing demonstrated that pulpal nerves either disappear or reinnervate novel targets after loss of pulpal tissue. There were no obvious signs of neuroma formation. Retrograde Fluorogold labelling with immunohistochemistry showed that after inferior alveolar nerve lesions with subsequent regeneration, a much higher proportion of Fluorogold cells (15%) were substance P-positive compared to normal (2%). In addition, 3% of the cells were Griffonia simplicifolia isolectin I-B4-positive. Such cells were very rare in controls. Proportions of calcitonin gene-related peptide-, GM1- and RT-97-positive cells were normal. After tooth lesions, the proportions of Fluorogold-positive substance P-, Griffonia simplicifolia isolectin I-B4-, GM1- and RT 97-labelled cells were similar to controls, while the proportion of calcitonin gene-related peptide-positive neurons was reduced. The results show that pulpal deafferentation may change the long-term cytochemical characteristics of affected trigeminal ganglion neurons.
The distribution of nerve growth factor receptor (NGFr)-like immunoreactivity and of calcitonin gene-related peptide (CGRP)-like immunoreactivity was studied in nerve fibers of the spinal and medullary dorsal horn of the monkey and the cat, using double-labelling immunohistochemistry with polyclonal CGRP antiserum and a monoclonal antibody against human NGFr. In both species there was an extensive distribution overlap between NGFr-LI and CGRP-LI. However, lack of NGFr-LI in many CGRP-immunoreactive axons suggests that not all CGRP-positive primary afferent fibers possess NGFr.