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PubMed1975

[Investigations on the shape and size of bone-chips produced during boring and grinding (author's transl)].

Examinations of the shape and size of chips produced during boring and grinding of dry macerated and fresh temporal bone by various drills and grinders at different revolutions show that rose trepans mainly scrape fresh bone, producing large rolled-up chips, but knock off dry macerated bone, producing more compact chips of bizarre shape. In either case the chip waste also contains plenty of fine and finest compact chips which are broken off and splinter during the removal or knocking-off of the chips from solid bone. The size of the chip depends on the size of the drill head. Diamond cutting heads produce fine and finest compact bone chips. Bone milling produces plenty of scrapes even from dry macerated temporal bone. The rate of revolutions (10,000-80,000 per min) had no influence on the shape and size of chips. Clinically the scraped chip seems to be the most favourable in the drilling of bone because it causes least damage. The use of a drill head with sharp-edged, intact cutting surfaces seems important for this, with continuous rinsing during the boring process to prevent soiling of the interspaces between the cutters and to ensure full performance in accordance with their construction.

Humans↗
PubMed1995

Distribution of mRNA encoding the FA-CHIP water channel in amphibian tissues: effects of salt adaptation.

A water channel, the frog aquaporin-CHIP (FA-CHIP) was recently cloned from Rana esculenta urinary bladder. The 28.9 kDa encoded protein shows 78.8%, 77.4%, 42.4% and 35.6% identity with rat CHIP28, human CHIP28, rat WCH-CD and gamma-TIP, other members of the new transmembrane water channel family (Aquaporin-CHIP). We have now studied membranes from different frog (R. esculenta) organs employing semiquantitative PCR using FA-CHIP specific primers and an internal standard to quantify the PCR products. The FA-CHIP mRNA was abundantly expressed in the frog urinary bladder, skin, lung and gall bladder, while a lower expression was detected in the colon, liver and oviduct. FA-CHIP mRNA was not detected in the frog kidney, erythrocytes and brain but its expression was observed in the toad (Bufo arenarum) urinary bladder and skin, showing that FA-CHIP is probably a general amphibian water channel. Salt acclimation is known to increase the water permeability of frog and toad epithelia. We have now observed that salt acclimation for 1, 3, 4 or 5 days markedly increased skin and urinary bladder FA-CHIP mRNA expression. It is generally accepted that water permeability is controlled in these tissues by the rate of water channel transfer from subapical vesicles (aggrephores) to the apical membrane. Our results indicate that water permeability is also regulated at the level of the FA-CHIP transcription.

Adaptation, Physiological↗
PubMed2025

Automated chromatin profiling with spa-ChIP-seq uncovers the impacts of condition variations.

Chromatin immunoprecipitation followed by sequencing (ChIP-seq) is widely used to study the genomic localization of DNA-associated proteins. However, conventional protocols include multiple manual steps that can introduce inconsistency and limit scalability, thereby restricting the inclusion of appropriate replicates and controls. Although the introduction of liquid handling platforms has improved reproducibility, most existing efforts have automated only a subset of the workflow, and extending automation to efficiently map non-histone proteins, such as chromatin regulators, remains challenging. Here, we present a fully automated implementation of our previously developed single-pot ChIP-seq protocol (Texari et al. 2021), named spa-ChIP-seq, which enables scalable processing of 8 to 96 ChIP-seq samples from crosslinked cells to sequencing-ready library in approximately three days with an estimated cost of $70 per sample. Benchmarking spa-ChIP-seq against manual ChIP-seq performed in parallel demonstrates comparable signal-to-noise ratio between the two workflows. Using spa-ChIP-seq, we systematically evaluate multiple parameters including shearing and crosslinking conditions, buffer compositions, and the ratio of antibody to cell-number. We find, for the first time to our knowledge, that weaker genomic localization signals are sensitive to changing the antibody to cell-number ratio, whereas the stronger signals remain unaffected. This finding underscores the importance of maintaining consistent antibody-to-cell-number ratio for comparative studies, such as treatment responses or chromatin-QTL mapping. The spa-ChIP-seq protocol is publicly available, including deck setups, operational parameters, and scripts. We envision that this robust, cost-efficient protocol will facilitate high-throughput, reproducible ChIP-seq analyses, supporting large-scale studies of antibody validation, compound screening, population genomics, and diagnostic frameworks.

Journal Article↗
PubMed1982

[On vibration hazards of chipping-hammer operators in an iron foundry. Part 2. Results of the hygienic control].

We previously reported that the working and health conditions of vibrating tool operators in an iron foundry were investigated in 1975 and vibration hazards were observed to occur frequently in workers operating chipping-hammers powered by compressed air. After that, we instituted medical treatment for the afflicted workers and improvement of working conditions in the foundry, and have performed annual medical examinations for four years. In this paper, the course of hygienic control and the change in the medical findings of twenty-four chipping-hammer operators are reported. 1. The following measures were taken to improve the working conditions of chipping-hammer operators and therapy for patients (Table 1): (1) The operating time of vibrating tools, including chipping-hammer, was limited to two hours per day. The casting process was improved to diminish the flashes that are the objects of chipping-hammer operation. For the purpose of reducing the vibration transmitted to the operator, a servo-arm that has a servomechanism for the chipping-hammer was developed and introduced. (2) Infrared lamps in the foundry and air curtains at the doorway were installed for keeping the chipping-hammer operating area warm. A warm room was set up in the foundry for providing warmth during rest periods and protective clothing against the cold was provided. (3) Workers who displayed health disturbances by medical examinations were treated during the cold season from November to April by periodic visits to the clinic or extended hospitalization, or transferred to job without vibration exposure, according to their stage of disease. Preventive treatment with vasodilator and bubble bath was performed in winter for the chipping-hammer operators. 2. In order to estimate the effect of these countermeasures, annual medical examinations were conducted in March 1975, March 1976, April 1977 and March 1978. Such subjective symptoms as Raynaud's phenomenon, finger numbness, finger listlessness, heavy-headedness, forgetfulness, irritability and hearing disorder showed a tendency for improvement, but other complaints did not (Tables 2-4). The improvement of Raynaud's phenomenon is considered to be due not merely to the countermeasures but also to reducing the chance of provocation and therefore the countermeasures should not be overestimated as a factor of recovery of vibration hazards. Of the functional tests, a tendency for improvement was recognized in sensory functions and peripheral circulatory functions, but not in motor functions (Tables 5, 6). However, the course of recovery was not fast and some advanced cases, especially those using chipping-hammers for more than ten years, showed less improvement after hospital treatment (Table 7, Fig. 1). This indicates the importance of hygienic control which enables vibration hazards patients to have early diagnosis and treatment. Furthermore, in order to eradicate the vibration hazards in the cast metal industry, a drastic reform of the finishing process is considered to be necessary.

Adult↗
PubMed1993

The human aquaporin-CHIP gene. Structure, organization, and chromosomal localization.

Aquaporin-CHIP is the first known molecular water channel. Originally identified in red cells and renal tubules, transcripts and proteins related to AQP-CHIP are also expressed in diverse epithelia with distinct developmental patterns. Northern analyses of RNA from several tissues revealed transcripts of 3.1 kilobases and other sizes. The nucleotide sequences of human kidney AQP-CHIP cDNAs are identical to the human bone marrow AQP-CHIP cDNA. The 17-kilobase human AQP-CHIP structural gene was isolated, and restriction maps were constructed and partially sequenced. The TATA consensus sequence is located 87 bp 5' to the translation initiation site, and sequences surrounding the polyadenylation consensus were determined. Four exons were identified corresponding to amino acids 1-128, 129-183, 184-210, and 211-269, separated by introns of 9.6, 0.43, and 0.80 kilobases. Genomic Southern analyses indicated the existence of a single AQP-CHIP gene which was located at human chromosome 7p14 by in situ hybridization. Sequence comparisons of AQP-CHIP and cDNAs of similar proteins from diverse species suggested a common evolutionary origin. At least three of these proteins are now known to function as membrane water pores and are referred to as the "Aquaporins." These genomic AQP-CHIP DNA sequences should permit molecular characterization of the complex patterns of AQP-CHIP expression.

Animals↗
PubMed1996

Demonstration of aquaporin-CHIP in peritoneal tissue of uremic and CAPD patients.

Aquaporin-CHIP is a 28 kD channel forming integral membrane protein. It acts as an osmotically driven, water-selective pore. The presence of aquaporin-CHIP has been demonstrated in the proximal tubule in the kidney and in the pleura, as well as in other tissues. During peritoneal dialysis a dissociation between the transport of water and sodium using hyperosmolar solutions has been reported, suggesting the presence of ultrasmall pores. Water channels, like aquaporin-CHIP, could be the morphological equivalent of these pores. We investigated the possible presence of aquaporin-CHIP in cryo-sections of peritoneal tissue using affinity purified human anti-CHIP IgC (P. Agre, Baltimore, MD). Peritoneal biopsies (omenta) were obtained at catheter insertion in 2 uremic patients with end-stage renal disease, and at catheter reimplantation of 1 patient treated with continuous ambulatory peritoneal dialysis (CAPD) for two years. Peritoneal tissue obtained at autopsy from 1 patient who had been on CAPD for four years, but in whom CAPD had been discontinued for five months, was also studied. Aquaporin-CHIP antiserum specific staining was found in the endothelial cells of the peritoneal capillaries in all patients. No obvious difference in the intensity of staining was seen between uremic and CAPD patients. This demonstration of aquaporin-CHIP in human peritoneal endothelial cells supports the hypothesis of the existence of ultrasmall pores within the peritoneal membrane. These water channels facilitate the transcellular transport of water, induced by an osmotic gradient, in the absence of sodium transport. It may be the explanation for the dissociation of water and sodium transport that occurs during hyperosmolar solutions. Aquaporin-CHIP is present in human peritoneal endothelial cells in both uremic and CAPD patients. Aquaporin-CHIP may be the morphological equivalent of the ultrasmall pores within the peritoneal membrane.

Aquaporin 1↗
PubMed1994

The three-dimensional structure of human erythrocyte aquaporin CHIP.

Water-permeable membranes of several plant and mammalian tissues contain specific water channel proteins, the 'aquaporins'. The best characterized aquaporin is CHIP, a 28 kDa red blood cell channel-forming integral protein. Isolated CHIP and Escherichia coli lipids may be assembled into 2-D crystals for structural analyses. Here we present (i) a structural characterization of the solubilized CHIP oligomers, (ii) projections of CHIP arrays after negative staining or metal-shadowing, and (iii) the 3-D structure at 1.6 nm resolution. Negatively stained CHIP oligomers exhibited a side length of 6.9 nm with four-fold symmetry, and a mass of 202 +/- 3 kDa determined by scanning transmission electron microscopy. Reconstituted into lipid bilayers, CHIP formed 2-D square lattices with unit cell dimensions a = b = 9.6 nm and a p422(1) symmetry. The 3-D map revealed that CHIP tetramers contain central stain-filled depressions about the fourfold axis. These cavities extend from both sides into the transbilayer domain of the molecule leaving only a thin barrier to be penetrated by the water pores. Although CHIP monomers behave as independent pores, we propose that their particular structure requires tetramerization for stable integration into the bilayer.

Aquaporin 1↗
PubMed1994

Examination of rat salivary glands for the presence of the aquaporin CHIP.

The aquaporin CHIP, AQP-CHIP, is a 28-kDa integral membrane protein that functions as a water channel in kidney and red blood cells. We have examined rat salivary glands for the presence of this molecule. In Northern blot analyses an AQP-CHIP cDNA hybridized to rat kidney mRNA approximately 20-fold more than to mRNA from the rat parotid gland. Western blot analyses, using antisera against human AQP-CHIP, showed that AQP-CHIP was present in crude membranes from rat salivary glands to a much lesser extent than in rat kidney membranes. A 2.8 kb cDNA encoding AQP-CHIP was also isolated from an adult rat parotid gland cDNA library. Immunolocalization studies using thin and ultrathin cryosections and light and electron microscopy, however, revealed that no glandular epithelium was labeled. In contrast, significant immunolabeling was present in microvascular endothelial cells. Non-fenestrated endothelia of capillaries and venules exhibited labeling on both their apical and basolateral membranes. The present study demonstrates that AQP-CHIP is not involved directly in fluid secretion from salivary epithelial cells. Further, this study provides strong evidence that AQP-CHIP is an endothelial cell water channel found within salivary gland tissue which may contribute to water permeability in the capillary beds.

Animals↗
PubMed1996

Analysis of ligase chain reaction products amplified in a silicon-glass chip using capillary electrophoresis.

Ligase chain reaction (LCR) is a useful molecular technique for detecting known point mutations. We report the first example of the use of a disposable silicon-glass micro-chip for LCR and the first application of capillary electrophoresis (CE) to analyze samples amplified by LCR in a chip. Silicon-glass chips were manufactured using conventional photolithography and anodic bonding. The chips provide three distinct advantages for LCR: excellent thermal conductivity, a micro reaction volume ( < 10 microliters), and reproducible, low-cost manufacturing. Investigation and quantitation of amplification efficiency of LCR in a chip or in a tube requires an analytical technique that is faster and more convenient than the conventional slab gel methods. Slab gel electrophoresis uses relatively large amounts of sample and is labor-intensive and time-consuming, and thus is unsuitable for the separation and detection of LCR products. In contrast CE requires sample volume (original LCR products) of less than 1 microliter and is therefore well-suited to analysis of the micro-volume reaction mixture from chips. We combined CE with a sensitive laser induced fluorescence (LIF) detection system for the rapid separation and quantitative detection of LCR products amplified from the lacI gene in a silicon-glass chip. Comparative studies were made with LCR between tubes and silicon-glass chips. CE-LIF analysis is ideally suited to examination of micro-LCR amplification with high throughput. The technologies may find medical uses in disease diagnosis and research.

Base Sequence↗
PubMed1998

A fish hepatoma cell line (PLHC-1) as a tool to study cytotoxicity and CYP1A induction properties of cellulose and wood chip extracts.

Cytotoxicity and CYP1A induction properties of celluloses and wood chips were studied with a teleost liver cell line, PLHC-1. Cells were exposed to acetone extracts of celluloses produced using new bleaching techniques (elemental chlorine free, ECF; totally chlorine free, TCF) in two sulphate mills or without any bleaching (unbleached, UB) in a sulphite mill. In another set of exposures, celluloses (ECF and TCF bleached) and wood chips (from pine and birch) were collected from a sulphate mill, extracted with acetone, and the extracts used to treat the cells. After exposure, O-deethylation of 7-ethoxyresorufin (EROD, a measure of cytochrome P4501A (CYP1A) catalytic activity), and total protein content, a measure of cytotoxicity, were assayed. The presence of the CYP1A protein in the exposed cells was assessed by immunoblotting. The cellulose and wood chip extracts were able to cause both cytotoxicity and EROD induction in the PLHC-1 cells. In the exposures conducted with the material from three different mills, the celluloses made of birch were more cytotoxic and more potent inducers of EROD activity than were the celluloses of pine. Further, UB celluloses increased EROD activity and caused cytotoxicity at lower doses than material bleached with modern bleaching techniques. In the exposures made with material from one single mill, there were no clear trends between the celluloses made of pine or birch. Wood chips of pine, however, were more cytotoxic than wood chips of birch. Especially with pine wood chips, cytotoxicity interfered with the induction of EROD activity, thus complicating the evaluation of CYP1A induction. CYP1A protein content was not detected in cells exposed to extracts of celluloses or wood chips, possibly due to low amounts of protein available for the assay. Wood and pulp processing, like bleaching, may change the chemical composition of the raw material in a way that reduces the potency for biological effects of the final product, cellulose. This could explain why both UB celluloses and wood chips were more potent in the cells than ECF or TCF bleached celluloses. In this study the PLHC-1 cell line showed its potential for use in evaluating the biological activity existing in pulp and paper mill products and raw materials. The identity and source of the compounds that were able to affect the PLHC-1 cell line remain to be determined.

Animals↗
PubMed1998

Study IV: concurrent validity of the DSM-IV revised Children's Interview for Psychiatric Syndromes (ChIPS).

OBJECTIVE: To determine validity of the Diagnostic and Statistical Manual of Mental Disorders (4th ed.) (DSM-IV) revised Children's Interview for Psychiatric Syndromes (ChIPS) in inpatient children and adolescents. METHOD: Participants were 47 psychiatric inpatients 6-12 (n = 23) and 12 to 18 years of age (n = 24). ChIPS was administered to all participants. The Diagnostic Interview for Children and Adolescents-Revised-Child Version (DICA-R-C) was administered to 40 participants. Discharge diagnoses were recorded for all participants. Kappas, low base rate kappas, and percentage agreement were used to assess diagnostic agreement between sources for 18 disorders. RESULTS: ChIPS/DICA-R-C kappas could not be calculated for two disorders because of 100% agreement on their absence. Fourteen of 16 kappas were significant (p < 0.05). The remaining 2 of 16 disorders had 98% agreement (kappax = 0.494, p < 0.157). When ChIPS results were compared with discharge diagnoses, sensitivity for each disorder averaged 70%, whereas specificity averaged 84%. When disagreements occurred between all three sources, ChIPS was somewhat more likely than DICA-R-C to agree with discharge diagnoses (27% versus 22%). Analysis were repeated for children and adolescents, then for boys and girls. Boys and children had fewer significant ChIPS and DICA-R-C kappa coefficients compared with girls and adolescents; this appeared to be related to the fewer number of diagnoses they endorsed. ChIPS/clinician agreement was similar for boys and girls as well as for children and adolescents. Administration time was less for ChIPS than for DICA-R-C (p < 0.08). CONCLUSION: Psychometric properties of the DSM-IV revised ChIPS compare favorably with that of other structured interviews. ChIPS appears to work well for adolescents as well as children.

Adolescent↗
PubMed1995

Immunolocalization of aquaporin CHIP in the guinea pig inner ear.

Aquaporin CHIP (AQP-CHIP) is a water channel protein previously identified in red blood cells and water transporting epithelia. The inner ear is an organ of hearing and balance whose normal function depends critically on maintenance of fluid homeostasis. In this study, AQP-CHIP, or a close homologue, was found in specific cells of the inner ear, as assessed by immunocytochemistry with the use of affinity-purified polyclonal antibodies against AQP-CHIP.AQP-CHIP was predominantly found in fibrocytes in close association with bone, including most of the cells lining the bony labyrinth and in fibrocytes lining the endolymphatic duct and sac. AQP-CHIP-positive cells not directly apposing bone include cells under the basilar membrane, some type III fibrocytes of the spiral ligament, fibrocytes of the spiral limbus, and the trabecular perilymphatic tissue extending from the membranous to the bony labyrinth. AQP-CHIP was also found in the periosteum of the middle ear and cranial bones, as well as in chondrocytes of the oval window and stapes. The distribution of AQP-CHIP in the inner ear suggests that AQP-CHIP may have special significance for maintenance of bone and the basilar membrane, and for function of the spiral ligament.

Animals↗
PubMed1996

Selective sampling of yellow prostate chips: a specific method for detecting prostatic adenocarcinoma.

Yellow chips were sought in 206 transurethral resection specimens of prostate. 18 (9%) contained yellow chips, and 46 (22%) prostatic adenocarcinomas were present. Yellow chips showed a specificity of 100% (95% confidence interval, CI 98-100%), a sensitivity of 39% (95% CI 25-55%), and a positive predictive value of 100% (95% CI 82-100%) for prostatic adenocarcinoma. Yellow chips were more easily recognized in poorly fixed specimens. On comparing prostatic adenocarcinomas with or without yellow chips, there was no significant difference in Gleason score or percentage of chips infiltrated by tumour. Complete sampling of prostate chips may be unnecessary, if yellow chips are present and selectively sampled. Naked-eye detection of prostatic adenocarcinoma may be increased by examining the tissue before fixation.

Adenocarcinoma↗
PubMed1994

Human red cell Aquaporin CHIP. II. Expression during normal fetal development and in a novel form of congenital dyserythropoietic anemia.

Channel-forming integral protein (CHIP) is the archetypal member of the Aquaporin family of water channels. Delayed CHIP expression was shown recently in perinatal rat (Smith, B. L., R. Baumgarten, S. Nielsen, D. Raben, M. L. Zeidel, and P. Agre. 1993. J. Clin. Invest. 92:2035-2041); here we delineate the human patterns. Compared with adult, second and third trimester human fetal red cells had lower CHIP/spectrin ratios (0.72 +/- 0.12, 0.94 +/- 0.22 vs 1.18 +/- 0.11) and reduced osmotic water permeability (0.029, 0.026 vs 0.037 cm/s); CHIP was already present in human renal tubules by the second trimester. A patient with a novel form of congenital dyserythropoietic anemia (CDA) with persistent embryonic and fetal globins and absent red cell CD44 protein was studied because of reduced CHIP-associated Colton antigens. Novel CDA red cells contained < 10% of the normal level of CHIP and had remarkably low osmotic water permeability (< 0.01 cm/s), but no mutation was identified in Aquaporin-1, the gene encoding CHIP. These studies demonstrate: (a) unlike rat, human CHIP expression occurs early in fetal development; (b) red cell water channels are greatly reduced in a rare phenotype; and (c) disrupted expression of red cell CHIP and CD44 suggests an approach to the molecular defect in a novel form of CDA.

Adult↗
PubMed2000

Chip is an essential cofactor for apterous in the regulation of axon guidance in Drosophila.

LIM-homeodomain transcription factors are expressed in subsets of neurons and are required for correct axon guidance and neurotransmitter identity. The LIM-homeodomain family member Apterous requires the LIM-binding protein Chip to execute patterned outgrowth of the Drosophila wing. To determine whether Chip is a general cofactor for diverse LIM-homeodomain functions in vivo, we studied its role in the embryonic nervous system. Loss-of-function Chip mutations cause defects in neurotransmitter production that mimic apterous and islet mutants. Chip is also required cell-autonomously by Apterous-expressing neurons for proper axon guidance, and requires both a homodimerization domain and a LIM interaction domain to function appropriately. Using a Chip/Apterous chimeric molecule lacking domains normally required for their interaction, we reconstituted the complex and rescued the axon guidance defects of apterous mutants, of Chip mutants and of embryos doubly mutant for both apterous and Chip. Our results indicate that Chip participates in a range of developmental programs controlled by LIM-homeodomain proteins and that a tetrameric complex comprising two Apterous molecules bridged by a Chip homodimer is the functional unit through which Apterous acts during neuronal differentiation.

Animals↗
PubMed2000

Use of a biodegradable chlorhexidine chip in the treatment of adult periodontitis: clinical and radiographic findings.

BACKGROUND: Previous multi-center trials demonstrated the efficacy of a biodegradable chlorhexidine-gelatin chip (CHX) in reducing probing depth in patients with periodontitis. The present study utilized a subset of subjects from the parent study to determine if the CHX chip was effective in maintaining alveolar bone over a 9-month period. METHODS: Forty-five subjects with at least four 5 to 8 mm pockets, stratified by smoking status, were enrolled in this double-blind controlled, placebo-controlled trial. Control groups received either placebo chip plus scaling and root planing (SRP) or SRP alone. Test group subjects received active CHX chip or SRP alone (to maintain the blind). Standardized radiographs were taken for quantitative digital subtraction radiography at baseline and 9 months. RESULTS: At 9 months, 15% of SRP treated subjects experienced loss of bone in 1 or more sites, no subject treated with active chip plus SRP lost bone (P <0.01). At 9 months, significant differences in the change in probing depth and clinical attachment levels favoring the active chip over SRP alone or SRP plus CHX chip were also observed (P <0.05). CONCLUSIONS: These data indicate that the CHX chip, when used as an adjunct to scaling and root planing, significantly reduces loss of alveolar bone.

Adult↗
PubMed1988

Pharmacokinetics of cis-dichloro-trans-dihydroxy-bis-isopropylamine platinum IV (iproplatinum, CHIP) in patients with normal and impaired renal function and following intraperitoneal administration.

CHIP is a quadrivalent platinum (Pt) complex, introduced clinically as a less toxic alternative to cis-platinum. The drug's major route of excretion is via the kidneys, and in this study the pharmacokinetics of unchanged CHIP, filterable Pt and total Pt have been determined following intravenous administration to patients with a range of renal function. Total Pt and filterable Pt in plasma decayed biexponentially and was fitted to a two-compartment model, whereas unchanged CHIP declined monoexponentially and was best fitted to a one-compartment model, according to Akaike's information criteria. There is a correlation between the unchanged CHIP clearance and 51Cr-EDTA clearance. The pharmacokinetics of CHIP was determined following intraperitoneal (i.p.) administration (dose, 150-300 mg m-2 4 h dwell time) and a regional advantage (peritoneal peak concentration/plasma peak concentration) of approximately 30 fold was seen. It is likely that the dose of CHIP will need to be reduced in patients with impaired renal function, and the use of i.p. CHIP in ovarian carcinoma warrants further study.

Female↗
PubMed1997

Rat sciatic nerve regeneration through a micromachined silicon chip.

The capacity of regenerating nerve fibres to grow through a perforated silicon chip was tested using the silicone chamber model for nerve regeneration. The chips were fabricated as circular membranes, 4 mm in diameter, thickness 60 microns, with a perforated area, 2 mm in diameter, in the centre. Three types of chips were fabricated utilizing anisotropic etching. The chips were glued with silicone adhesive between two halves of silicone rubber tubing (total length 8 mm, inner diameter 1.8 mm, outer diameter 3.0 mm) which was used to bridge a 4 mm gap between the proximal and distal nerve stumps of a transected rat sciatic nerve. The capacity of regenerating nerve fibres to grow through the holes of the chip was analysed by light and scanning electron microscopy after 4 or 16 weeks of regeneration. Furthermore, the muscle contractility force of the gastrocnemius muscle was measured after 16 weeks of regeneration and compared as a percentage of the contralateral uninjured side. Nerves generated through chips with hole diameters of 10 or 50 microns were morphological and functional failures. The nerve structures distal to chips with hole diameters of 100 microns contained many myelinated nerve fibres in a minifascicular pattern after both 4 and 16 weeks of regeneration. The muscle contractility force was 56% of that of contralateral control muscles.

Animals↗