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Biomedical subjects

C Hildebrand

Publications and source records attributed to C Hildebrand.

At least 55 records · Page 3Linked to original sources

Immunohistochemical and electron microscopic demonstration of nerve fibres in relation to gingiva, tooth germs and functional teeth in the lower jaw of the cichlid Tilapia mariae.

Immunohistochemistry revealed the presence of numerous neurofilament (NF)-like immunoreactive axons in relation to gingiva and dental follicles surrounding mineralizing tooth germs. The gingival nerve fibres frequently approached the prospective papilla of early tooth primordia. Electron microscopic (EM) analysis revealed the presence of bundles of unmyelinated axons immediately below the epithelial-proprial junction of the gingiva. Bundles of nerve fibres were also present in the border zone between the prospective papilla of bud-stage tooth germs and surrounding mesenchyme and in close proximity to blood vessels of the follicles surrounding older tooth germs, but no axons were observed within the emerging dental papilla. In the individual functional tooth, a bundle of NF-like immunoreactive nerve fibres entered the apical part of the pulp forming a subodontoblastic plexus at mid-pulpal levels. EM analysis showed that the apical bundle consisted of many unmyelinated and a few myelinated axons invested by Schwann cell processes. The subodontoblastic plexus contained unmyelinated axons only. Thin, axon-like profiles were also seen in predentinal tubules. Nerve fibres were not observed at pulpal horn levels and in the ligamentous attachment. It is concluded that both immature and mature parts of the lower-jaw dentition of the cichlid T. mariae are innervated and that the microscopic anatomy of this innervation is partly similar to the pattern seen in developing and adult mammals.

Animals↗

Teeth and tooth nerves.

(1) Although our knowledge on teeth and tooth nerves has increased substantially during the past 25 years, several important issues remain to be fully elucidated. As a result of the work now going on at many laboratories over the world, we can expect exciting new findings and major break-throughs in these and other areas in a near future. (2) Dentin-like and enamel-like hard tissues evolved as components of the exoskeletal bony armor of early vertebrates, 500 million years ago, long before the first appearance of teeth. It is possible that teeth developed from tubercles (odontodes) in the bony armor. The presence of a canal system in the bony plates, of tubular dentin, of external pores in the enamel layer and of a link to the lateral line system promoted hypotheses that the bony plates and tooth precursors may have had a sensory function. The evolution of an efficient brain, of a head with paired sense organs and of toothed jaws concurred with a shift from a sessile filter-feeding life to active prey hunting. (3) The wide spectrum of feeding behaviors exhibited by modern vertebrates is reflected by a variety of dentition types. While the teeth are continuously renewed in toothed non-mammalian vertebrates, tooth turnover is highly restricted in mammals. As a rule, one set of primary teeth is replaced by one set of permanent teeth. Since teeth are richly innervated, the turnover necessitates a local neural plasticity. Another factor calling for a local plasticity is the relatively frequent occurrence of age-related and pathological dental changes. (4) Tooth development is initiated through interactions between the oral epithelium and underlying neural crest-derived mesenchymal cells. The interactions are mediated by cell surface molecules, extracellular matrix molecules and soluble molecules. The possibility that the initiating events might involve a neural component has been much discussed. With respect to mammals, the experimental evidence available does not support this hypothesis. In the teleost Tilapia mariae, on the other hand, tooth germ formation is interrupted, and tooth turnover ceases after local denervation. (5) Prospective dental nerves enter the jaws well before onset of tooth development. When a dental lamina has formed, a plexus of nerve branches is seen in the subepithelial mesenchyme. Shortly thereafter, specific branches to individual tooth primordia can be distinguished. In bud stage tooth germs, axon terminals surround the condensed mesenchyme and in cap stage primordia axons grow into the dental follicle.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

The smart card: an ideal tool for a computer-based patient record.

Over the past decades, technology has advanced in all areas. Medical documentation, however, has not altered considerably. This means that medical care is often below standard. This article tries to point out how healthcare could benefit from a computer-based medical record. It also discusses the use of a medical smart card as a computer-based patient record--exemplified by the European DIABCARD-project which develops a chip card for persons with diabetes.

Computer Security↗

Invasion of the rat ventral root L5 by putative sympathetic C-fibers after neonatal sciatic nerve crush.

The present study examines the occurrence of C-fibers in lumbar ventral roots after sciatic nerve crush in neonatal and adult rats. Electron microscopic analysis showed that the number of C-fibers in the ventral root L5 increased significantly on the lesion side after neonatal but not adult sciatic nerve crush and that the number of C-fibers was higher in the ventral root L5 on the unoperated side compared to this root in normal control rats. In order to determine whether the new C-fibers in the L5 root on the lesion side are sensory or sympathetic we made immunohistochemical studies on roots from neonatally crushed rats. We found that there was no obvious lesion side/contralateral side or operated rat/control rat difference with respect to the occurrence and general configuration of axons with substance P-, calcitonin gene-related peptide- or vasoactive intestinal polypeptide-like immunoreactivity. However, the occurrence of axons with tyrosine hydroxylase-like immunoreactivity appeared clearly higher in the ventral root L5 on the lesion side compared to the unoperated side in neonatally crushed rats. Moreover, these axons seemed to be more numerous also in the ventral root L5 on the unoperated side compared to normal control rats. No lesion side/contralateral side or operated rat/control rat differences were seen in the ventral root L4. We propose that the ventral root L5 is invaded by putative sympathetic C-fibers after sciatic nerve crush lesions in newborn rats.

Age Factors↗

Cellular and extracellular components at nodes of Ranvier in rat white matter.

Rat CNS nodes of Ranvier were investigated by electron microscopy and immunohistochemistry. Nodes along thin callosal axons possess tiny node gaps containing few or no astrocytic processes. Nodes along thick spinal axons exhibit spatious node gaps containing relatively few irregularly arranged astrocytic processes. Antibodies against HNK-1, chondroitin sulfate, tenascin or NSP-4 do not label small nodes but stain large nodes. We conclude that rat CNS fibers do not exhibit a strict relation between nodal complexity and fiber size comparable to that found in rat PNS fibers.

Animals↗

Functional properties and nodal spacing of myelinated fibers in developing rat mental and sural nerves.

While the postnatal length growth of the largest internodes in the rat sural nerve (SN) is proportional to nerve elongation, in the developing inferior alveolar nerve (IAN), early postnatal myelin sheath remodelling allows internodal lengthening to exceed the growth rate of the whole nerve. To assess the functional consequences of ongoing myelin sheath remodelling in a developing nerve, we examined the physiological properties of the mental nerve (MN), a cutaneous IAN branch and the SN during maturation. In addition, the nodal spacing and the microscopic anatomy of the nodes in the two nerves were studied. The youngest MNs and SNs (2 weeks) exhibited comparable sensitivities to K(+)-channel blockade with 4-aminopyridine (4-AP), although myelin sheath remodelling was more frequent in the MNs. Subsequently, myelin sheath remodelling ceased in both nerves but the MNs exhibited a greater sensitivity to 4-AP. Large fibers in adult MNs and SNs had a similar nodal anatomy but the former had shorter internodes. Thus, myelin sheath remodeling, per se, does not appear to be a determinant of 4-AP sensitivity in mammalian myelinated fibers. Rather, sensitivity to potassium channel blockade is more likely mediated at the internodal or molecular level.

4-Aminopyridine↗

Sensory C-fibers in rat ventral roots are capsaicin-insensitive and they do not mediate extravasation from pial vessels.

Mammalian ventral roots and pia mater contain sensory C-fibers, some of which exhibit a substance P- and/or calcitonin gene-related peptide (CGRP)-like immunoreactivity. At some locations, sensory axons containing these neuropeptides evoke peripheral plasma protein extravasation after antidromic electrical stimulation. Such axons usually disappear following treatment of neonatal rats with capsaicin. The purpose of the present study is to find out if afferent C-fibers in the rat ventral roots L4 and L5 are capsaicin-sensitive, and if antidromic stimulation of these fibers elicits extravasation in the root and/or the ventral pia mater. The results show (1) that the number of C-fibers in these ventral roots is unaffected by neonatal capsaicin treatment, as seen in the electron microscope; (2) that the occurrence and general configuration of axons with substance P- and CGRP-like immunoreactivity do not appear abnormal in neonatally capsaicin-treated rats, as revealed by fluorescence microscopy on longitudinal frozen sections; (3) that Evans blue albumin is not extravasated in the ventral root or pia mater after electrical ventral root stimulation or following systemic injection of capsaicin. We conclude, that ventral root afferents are functionally different from otherwise similar afferents at other locations.

Animals↗

Shoulder region of the rat: anatomy and fiber composition of some suprascapular nerve branches.

BACKGROUND: The pathophysiology of chronic supraspinatus tendinitis is not fully understood. This may be due to the scarcity of experimental studies on this issue. METHODS: In search for a system suitable for experimental analysis, the present study describes the relevant gross anatomy of the rat shoulder region (dissection), and examines the fiber composition of relevant supra-scapular nerve branches (electron microscopy, selective denervations). RESULTS: The rat shoulder region is similar to the human shoulder in terms of gross anatomy. The average suprascapular nerve (SSC) is derived mainly from the spinal cord segment C5 and contains 3,435 axons, 74% of which are unmyelinated. The supraspinatus branch (SSP) contains 627 fibers. Of the SSP fibers, 52% are myelinated, including 32% motor and 20% sensory axons. Of the C-fibers in the SSP 16% are sympathetic efferents and 32% are sensory. Many of the latter disappear after neonatal capsaicin treatment. The SSC emits a subacromial articular branch (ART), with some 260 axons, about 90% of which are unmyelinated. The myelinated ART fibers are sensory, and of the unmyelinated ones about 24% are sympathetic efferents and 66% are afferents. The latter resist neonatal capsaicin treatment. CONCLUSIONS: In view of the anatomy of the supraspinatus muscle, of the subacromial space, and of relevant nerves, the rat shoulder should be appropriate for experimental studies on inflammatory conditions in the subacromial space.

Animals↗

Morphological heterogeneity of rat oligodendrocytes: electron microscopic studies on serial sections.

The microanatomy of ensheathing and early myelinating rat oligodendrocytes was analyzed through electron microscopic examination of serial sections. The study included cells in the spinal cord (SC) ventral funiculus and the corpus callosum (CC), containing early myelinating, prospective large axons and late myelinating, prospective small axons, respectively. The results show that ensheathment commences fetal day (F) 19 in the SC and 12 days postnatally (P12) in the CC. By then, multipolar SC and CC oligodendrocytes provide axons with uncompacted cytoplasmic sheaths. The average number of axons ensheathed by each such cell was 7 in the SC and 13 in the CC. The mean diameter of the ensheathed axons was 0.69 micron in the SC and 0.36 micron in the CC. The formation of compact myelin had clearly been initiated at birth in the SC and at P17 in the CC. At that stage, the mean number of myelinated axons per analyzed oligodendrocyte was 3 in the SC and 15 in the CC. The mean diameter of the myelinated axons was 1.02 micron in the SC and 0.54 micron in the CC. These observations show that myelin-related rat oligodendrocytes are morphologically heterogeneous. It also seems that this heterogeneity is related to time of onset of myelination and prospective axon diameter. Further, the data suggest that some oligodendrocytes reduce the number of sheaths initially elaborated before formation of compact myelin.

Animals↗

Evidence for a neural influence on tooth germ generation in a polyphyodont species.

It has been suggested that nerve endings emanating from the dental nerve plexus of the jaw might be involved in the formation of tooth germs. In the present study we examine the effect of unilateral denervation on the formation of tooth germs in the lower jaw of a polyphyodont teleost--the cichild Tilapia mariae. Repeated inspection of the lower jaw dentition in normal animals over a period of about 300 days showed that the functional time of an average individual tooth is 101 days. In operated animals, the functional time was normal on the unoperated side, but on the denervated side tooth turnover ceased about 100 days after surgery. Radiographic plates from lower jaw specimens revealed that mineralized replacement teeth were present on the unoperated side, but not on the denervated side, 300 days after denervation. Light microscopic examination of semi-thin transverse sections from decalcified plastic-embedded lower jaws showed that soft-tissue tooth primordia and nerves were lacking on the denervated side, while present within the undisturbed half-jaw. It is concluded that the local presence of mandibular nerve branches is necessary for the formation of tooth germs in the lower jaw of the cichlid T. mariae.

Animals↗

Functional projection of sensory lateral plantar and superficial peroneal nerve axons to glabrous and hairy skin of the rat hindfoot after sciatic nerve lesions.

The functional regeneration of C-fibers mediating polymodal nociception and low-threshold mechanoreceptive axons in the lateral plantar nerve (LPN) and the foot branch of the superficial peroneal nerve (fSPN) was evaluated in normal rats and 3 months after unilateral sciatic nerve crush or neurotomy and suture. The area covered by low-threshold mechanoreceptors (LTMs) was tested through gentle mechanical skin stimulation and recording from the relevant nerve. In regenerated animals the glabrous skin area with functional LPN-related LTMs was severely reduced following a crush lesion. Functional receptors of that type were absent after neurotomy and suture. The hairy skin area with fSPN-related LTMs was smaller than normal, particularly following neurotomy and suture. The distribution of polymodal C-fibers was tested through stimulation-induced extravasation of Evans blue albumin (EBA). In the glabrous LPN skin domain the area showing EBA extravasation did not return to normal after any of the lesion types. However, in the hairy fSPN skin area the distribution of EBA extravasation appeared largely normal following both injuries. We conclude that polymodal nociception reappears to a greater extent than low threshold mechanosensitivity, and that both modalities regenerate better in hairy skin than in glabrous skin.

Animals↗

Fiber composition of the lateral plantar and superficial peroneal nerves in the rat foot.

This study examines the fiber composition of two nerves projecting to the rat hindpaw: the lateral plantar nerve (LPN), which innervates plantar glabrous skin and some plantar muscles, and the foot branch of the superficial peroneal nerve (fSPN), which projects to dorsal hairy skin. The LPN contains 872 (33%) myelinated axons with a size range of 1-7 microns and a peak at 4 microns. Some 200 of the myelinated axons are muscle efferents. There are 1,969 (67%) C-fibers. After neonatal capsaicin treatment, the number of C-fibers in the LPN is 61% below the normal level, but it is not significantly different from control levels after chemical sympathectomy with guanethidine. The fSPN is composed of 470 (20%) myelinated axons with a size range similar to that in the LPN. Virtually all myelinated fibers are sensory. There are 1,791 (80%) C-fibers. In neonatally capsaicin-treated animals, the occurrence of C-fibers is 65% below control levels. In chemically sympathectomized animals, the number of C-fibers in the fSPN is normal. This description of the fiber composition of the LPN and the fSPN in the rat provides a basis for future experimental studies.

Animals↗

A chip card for patients with diabetes.

DIABCARD provides the specification for the core of a Chip Card Based Medical Information System (CCMIS) for the treatment of patients with chronic diseases. It will provide an instrument for assessing health care services, improve the links between health care providers and set up communication between the different levels of health care. It will therefore improve the quality of care and thus the life of patients with chronic diseases. DIABCARD concentrates on diabetes at the moment, the concept of the diabetes chip card will, however, be extendable to other chronic diseases.

Chronic Disease↗

Different effects of 4-aminopyridine on regenerated cutaneous and muscular rat sciatic nerve branches.

Developing and regenerated myelinated rat dorsal and ventral root fibers respond differently to the fast potassium channel blocking agent 4-aminopyridine (4-AP). To pursue this issue further, we made unilateral sciatic nerve crushes in adult rats. Sural (SN) and lateral gastrocnemius (LGN) nerve branches were collected 4-6 months later, for physiological and morphological examination. Regenerated and control nerves in Ringers solution showed generally similar compound action potential (CAP) waveforms, but CAPs of regenerated SNs and LGNs in 4-AP were markedly different. While regenerated SNs showed a prominent late CAP negativity with a "rippled" appearance and markedly compromised recovery properties, the CAP and recovery properties of regenerated LGNs were minimally changed. Light and electron microscopic examination of SN and LGN fibers failed to reveal any features obviously related to the observed physiological differences. We conclude, that the effect of 4-AP on regenerated cutaneous afferents differs from its action on regenerated muscular afferents and efferents. This physiological diversity lacks obvious structural correlates.

4-Aminopyridine↗

Axonal regeneration in an articular branch following rat sciatic nerve lesions.

This study examines the outcome of axonal regeneration in the posterior articular nerve of the adult rat knee joint (PAN), after sciatic nerve lesions. Some animals had previously been subjected to chemical sympathectomy with guanethidine. In crushed cases the number of myelinated PAN axons was 50% above control level. The occurrence of C-fibers was doubled, mainly due to an increased number of sympathetic efferents. In neurotomy/suture cases the number of myelinated fibers was clearly elevated, but the number of C-fibers was close to normal. Most C-fibers were sensory. Similar, but less marked, post-regeneration abnormalities were seen in the nerve to the lateral gastrocnemius muscle. The sural nerve exhibited moderately increased numbers of myelinated and unmyelinated fibers in crushed cases. In neurotomy cases, the myelinated axons had increased and the C-fibers had decreased in number. The size distribution of myelinated PAN axons was less abnormal in crushed cases than after neurotomy, like in the other nerves. These results show that the outcome of axon regeneration in an articular branch of the lesioned rat sciatic nerve differs from that in non-articular branches, and suggest that joints may become hyperinnervated by C-fibers after nerve crush lesions.

Animals↗

A short-term clinical evaluation of L-697,661, a non-nucleoside inhibitor of HIV-1 reverse transcriptase. L-697,661 Working Group.

BACKGROUND: The non-nucleoside reverse transcriptase inhibitors are novel antiretroviral agents with selective activity in vitro against human immunodeficiency virus type 1 (HIV-1). They act through direct inhibition of reverse transcriptase and are not incorporated into DNA. METHODS: We evaluated a pyridinone non-nucleoside reverse transcriptase inhibitor, L-697,661, in separate six-week double-blind trials in patients with HIV-1 infection whose CD4 counts ranged from 200 to 500 cells per cubic millimeter (68 patients) or less than 200 cells per cubic millimeter (67 patients). Eligible patients were randomly assigned to receive L-697,661 orally in one of three doses (25 mg twice a day, 100 mg three times a day, or 500 mg twice a day) or zidovudine (100 mg five times a day). Clinical and laboratory assessments were performed weekly. Viral isolates were obtained from a subgroup of patients before and after treatment and were evaluated for in vitro sensitivity to L-697,661. RESULTS: Both L-697,661 and zidovudine were well tolerated. Transient increases in CD4 counts were noted in the patients with fewer than 200 CD4 cells per cubic millimeter who received the two higher doses of L-697,661, but not in those who received the lowest dose or zidovudine. Patients who received L-697,661 had rapid, dose-related decreases in plasma p24 antigen levels. However, this response virtually disappeared after six weeks in some patients receiving L-697,661, coincidently with the emergence of resistant viruses. This change in susceptibility was more frequent among patients receiving the higher doses of L-697,661 and was associated with amino acid substitutions at positions 103 and 181 in the HIV-1 reverse transcriptase gene. CONCLUSIONS: L-697,661 is safe and well tolerated and has significant dose-related activity against HIV-1. However, resistant strains of the virus emerge rapidly and may limit the effectiveness of non-nucleoside reverse transcriptase inhibitors as monotherapy for HIV-1 infection.

Adult↗

Routes of putative afferent axons in rat lumbosacral ventral roots and pia mater.

Unmyelinated sensory axons occur in mammalian ventral roots. On this basis the law of Magendie has been questioned. With few exceptions, the current ideas on the routes that these axons might follow have been based on electron microscopic examination of transverse sections, and evidence obtained through electrophysiological experiments or tracer studies. The purpose of the present study is to examine putative afferent rat ventral root axons, which have been visualized directly by immunohistochemical labelling. After immunolabelling of axons containing substance P or calcitonin gene-related peptide in longitudinal sections from the ventral roots L4-S1, and in wholemount pia mater-rootlet preparations, fluorescent fibres were searched for in the microscope. The results show that some immunolabelled axons end blindly in the root, while others shift to the pia mater, or make U-turns. Some axons make irregular 'zigzag' deviations or branch. No immunoreactive axons were seen entering the spinal cord via the ventral roots. These observations support the view that the law of Magendie is valid.

Animals↗