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Background: Tamm-Horsfall protein and human serum albumin are common urinary proteins that show uncertain inhibitory action on the crystallization of calcium oxalate monohydrate., Materials and Methods: Batch experiments on crystal nucleation, growth, and aggregation were performed using purified Tamm-Horsfall protein and albumin before and after enzymatic removal of sialic acids from the proteins., Results: At a concentration of 100 nM, both Tamm-Horsfall protein and albumin promoted the time of crystal nucleation by 18.4% and 8.9%, respectively, relative to the control. However, both of the proteins exerted an inhibitory effect on crystal growth, with the IC(50) being 7.27 nM for Tamm-Horsfall protein and 37.5 nM for albumin. The inhibition of crystal aggregation was 81.82% by Tamm-Horsfall protein 100 nM but only 54.55% at 50 nM after enzymatic removal of the sialic acid. Instead of increasing the inhibition, the effect was changed to promotion after an increase in the concentration of Tamm-Horsfall protein to more than 500 nM for native protein and to more than 100 nM for the enzymatic digest. Albumin showed little change after enzymatic treatment and maintained a maximal inhibitory effect of 72.73% on crystal aggregation when the concentration reached to 100 nM., Conclusion: Because the promotion of nucleation could lessen the subsequent saturation of a calcium oxalate solution, it is concluded that Tamm-Horsfall protein and albumin show an overall effect of inhibition on crystallization in vitro. The inhibitory effect of Tamm-Horsfall protein is partly related to sialic acid.

Introduction: Oxalate in urine can cause tubular cellular damage by the production of free radicals. Then, cell death and cellular debris may promote the retention of calcium oxalate crystals and finally the formation of stones. The two most abundant urinary proteins, Tamm-Horsfall protein (THP) and albumin, were tested for the effects of antioxidants., Materials and Methods: By using xanthine-xanthine oxidase reaction, purified THP and albumin were tested for the inhibitory effect. OD(295) was used as a spectrophotometric method to measure the production of uric acid during the reaction., Results and Conclusions: Both proteins can inhibit the reaction of xanthine oxidase on xanthine, although the effect was decreased after enzymatic deglycosylation of sialic acid. Albumin has an IC(50) of 10.7 nM in native condition and 11.9 nM after deglycosylation, whereas THP has 69.6 nM in native condition and 102.0 nM in deglycosylated condition. The data indicates that THP and albumin have an antioxidant effect. Sialic acid in THP has partly an inhibitory effect and is associated with calcium oxalate formation. Studies have indicated that further investigation of the role of free radicals in the formation of urolithiasis and of sialic acid in protein function is needed., (Copyright 2001 S. Karger AG, Basel)

Abnormal function of p53 is commonly associated with various cancer formations. High-grade and late-stage bladder cancers have been reported to have mutated or become inactive p53 when using immunohistochemical stains. Recently, p53 codon 72 polymorphism was extensively studied to determine the risk factors responsible for cancer formation. There was a general population of codon 72 sequence polymorphism of the wild type p53. A single base change from G to C caused the alteration of amino acid residue 72 from arginine to proline. The arginine form is considered to be a significant risk factor in the development of cancer. However, various reports had indicated discrepancies with regard to this polymorphism; some showed no significant difference between the control and cancer groups, while other series were associated with high risks in the proline form homozygotes. To resolve the undefined distribution of this polymorphism in bladder cancers, 58 patients with bladder cancer were enrolled onto this study. When checked using the Chi-squared test (P = 0.952) there were no differences between the control subjects and bladder cancer patients in the distribution of polymorphism. However, proline form homozygotes were more frequently found in the invasive group than the non-invasive group by Fisher's exact test (25% and 2.9%, respectively, P < 0.001). More than 70% of the non-invasive bladder cancers were the arginine form homozygotes. This result is consistent with those reported for hepatocellular carcinoma that showed a history of chronic liver disease and proline form homozygotes in a report by Yu et al. Our data suggest that proline form homozygotes are associated with invasive bladder cancer.

Background: A previous study by Britz-Cunningham et al (N Engl J Med, 1995) indicated that a mutation of the connexin 43 (CX43) gap junction gene might be responsible for Ivemark syndrome. Ser364Pro substitution (TCA-->CCA) is the most common mutation located in the cytoplasmic tail domain of CX43. This domain may be an important part of the conductance channel of the gap junction. It may, therefore, result in heart anomalies and situs inversus during embryonic development, resulting in Ivemark syndrome., Methods: We investigated 10 patients with Ivemark syndrome, 10 healthy individuals, one patient with Kartagener syndrome and one with polysplenia and situs inversus but without heart anomaly for this mutation. Seminested polymerase chain reaction (PCR) was performed using a DNA template from DNA extracted from peripheral blood cells. Direct sequencing was done after purification of the second round of PCR products. Then, the sequence was compared with the last 402 bp of the cDNA-coding region of CX43., Results: No base changes were found in the patients with Ivemark syndrome or other patient groups at the previously reported CX43 residues of Thr326, Gln352, Ser364, Ser365 and Ser373., Conclusions: The results indicate that Ser364Pro mutation of CX43 did not exist in the 10 Taiwanese patients with Ivemark syndrome. Other genes responsible for the Ivemark syndrome should be further investigated.

Putative fossil embryos and larvae from the Precambrian phosphorite rocks of the Doushantuo Formation in Southwest China have been examined in thin section by bright field and polarized light microscopy. Although we cannot completely exclude a nonbiological or nonmetazoan origin, we identified what appear to be modern cnidarian developmental stages, including both anthozoan planula larvae and hydrozoan embryos. Most importantly, the sections contain a variety of small (

Annexin V belongs to a family of eukaryotic calcium-dependent membrane-binding proteins. The calcium-binding sites at the annexin-membrane interface have been investigated in some detail; however, little is known about the functional roles of highly conserved interfacial residues that do not coordinate calcium themselves. In the present study, the importance of tryptophan 185, and threonine or serine at positions 72, 144, 228, and 303, in rat annexin V is investigated by site-directed mutagenesis, X-ray crystallography, and functional assays. The high-resolution crystal structures of the mutants show that the mutations do not cause structural perturbations of the annexin molecule itself or disappearance of bound calcium ions from calcium-binding sites. The assays indicate that relative to wild-type annexin V, loss of the methyl substituent at position 72 (Thr72-->Ser) has no effect while loss of the hydroxyl group (Thr72-->Ala or Thr72-->Lys) causes reduction of membrane binding. Multiple lysine substitutions (e.g., Thr72,Ser144,Ser228,Ser303-->Lys) have a greater adverse effect than the single lysine mutation, suggesting that in annexin V the introduction of potentially favorable electrostatic interactions between the lysine side chains and the net negatively charged membrane surface is not sufficient to overcome the loss of the hydroxyl side chains. Replacement of the unique tryptophan, Trp185, by alanine similarly decreases membrane binding affinity. Taken together, the data suggest that the side chains mutated in this study contribute to phospholipid binding and participate directly in intermolecular contacts with phospholipid membrane components.

Sponge remains have been identified in the Early Vendian Doushantuo phosphate deposit in central Guizhou (South China), which has an age of approximately 580 million years ago. Their skeletons consist of siliceous, monaxonal spicules. All are referred to as the Porifera, class Demospongiae. Preserved soft tissues include the epidermis, porocytes, amoebocytes, sclerocytes, and spongocoel. Among thousands of metazoan embryos is a parenchymella-type of sponge larvae having a shoe-shaped morphology and dense peripheral flagella. The presence of possible amphiblastula larva suggests that the calcareous sponges may have an extended history in the Late Precambrian. The fauna indicates that animals lived 40 to 50 million years before the Cambrian Explosion.

An RF network and a dual-tuned surface coil are described for obtaining proton-decoupled, NOE enhanced 19F spectra from a whole body clinical imager operating at 1.5 Tesia. The network removes 19F frequency noise from the decoupler transmitter, and prevents preamplifier saturation from high-level decoupling signals. Proton decoupling of 19F spectra was optimized using a sample of urine containing 5-fluorouracil (5-FU) and its catabolite fluoro-beta-alanine (FBAL). Proton-decoupled 19F spectroscopy in vivo is demonstrated by obtaining both nonlocalized spectra and spectra localized with three-dimensional chemical shift imaging from the liver of patients undergoing 5-FU chemotherapy.

Simultaneous acquisition of 1H-decoupled 31P and 19F 3D CSI is demonstrated in the liver of a patient undergoing 5-fluorouracil chemotherapy. Both 31P and 19F shared the same voxel size (64 or 27 ml), bi-level 1H-decoupling and 0.35 s TR. The measurements were done in a 1.5 Tesla clinical imager with three radio-frequency (RF) channels and a triple-tuned surface-coil. The overall MRI and MRS examination time was under 90 min. Simultaneous acquisition of 31P and 19F permits localized study of the influence of hepatic metabolism on the uptake and catabolism of fluoropyrimidine drugs without extra measurement time or higher SAR.

We applied 1H-decoupling and nuclear Overhauser enhancement to obtain well-resolved 31P magnetic resonance spectra accurately localized to 20 soft tissue sarcomas in vivo, using three-dimensional chemical shift imaging. Fifteen spectra had large phosphomonoester signals (21% of total phosphorus) that contained high amounts of phosphoethanolamine (compared to those of phosphocholine) but no signals from glycerophosphoethanolamine, and glycerophosphocholine was detected in only four cases. Prominent nucleoside triphosphates (52% of phosphorus) and low inorganic phosphate (10% of phosphorus) indicated that a large fraction of these 15 sarcomas contained viable cells, and this impression was confirmed histologically in 13 of the sarcomas. High-resolution in vitro 31P spectra of extracts of surgical specimens of four of the sarcomas studied in vivo and six additional sarcomas confirmed the in vivo assignments of metabolites and revealed considerable inter- and intratumoral variations of metabolite concentrations associated with histological variations in the relative amounts of cells and of matrix materials or spontaneous necrosis. Seven sarcomas, all high grade with pleomorphic or round cells rather than spindle cells, contained an unidentified phosphodiester signal in vivo; its absence in the extract spectra indicates that it may be from an abnormally mobile membrane component. We have documented a means to obtain new information about in vivo metabolism in human sarcomas and to provide a basis on which to examine the uses of 31P magnetic resonance spectroscopy in the clinical management of sarcomas.

Proton decoupling and nuclear Overhauser effect (NOE) enhancement significantly improve the signal-to-noise ratio and enhance resolution of metabolites in in vivo 31P MRS. We obtained proton-decoupled, NOE-enhanced, phospholipid-saturated 31P spectra localized to defined regions within the normal liver using three-dimensional chemical shift imaging. Proton-decoupling resulted in the resolution of two major peaks in the phosphomonoester (PME) region, three peaks in the phosphodiester (PDE) region and a diphosphodiester peak. In order to obtain molar quantitation, we measured the NOE of all hepatic phosphorus resonances, and we corrected for saturation effects by measuring hepatic metabolite T1 using the variable nutation angle method with phase-cycled, B1-independent rotation, adiabatic pulses. After corrections for saturation effects, NOE enhancement, B1 variations and point spread effects, the following mean concentrations (mmol/l of liver) (+/-SD) were obtained: [PME1] = 1.2 +/- 0.4, [PME2 + 2,3-DPG] = 1.1 +/- 0.1, [Pi + 2,3-DPG] = 2.8 +/- 0.5, [GPEth] = 2.8 +/- 0.7, [GPChol] = 3.5 +/- 0.6 and [beta-NTP] = 3.8 +/- 0.3. T1 and NOE enhancement were strongly correlated (r = 90), and indicated that the fractional contribution of 1H-31P dipolar relaxation to total 31P relaxation is minimal for NTPs, moderate for PMEs and high for PDEs in liver. Proton-decoupling and NOE enhancement permit one to obtain more information about in vivo metabolism of liver than previously available and should enhance the utility of 31P MRS for the study of hepatic disorders.

Simultaneous multivoxel 31P and 19F 3D localized NMR spectroscopy is demonstrated on a phantom and in the liver of patients undergoing bolus-infusion 5-fluorouracil chemotherapy. The 19F and 31P spectra were localized with 8 x 8 x 8 3D chemical-shift imaging, with both nuclei sharing the same field of view and voxel size (27 and 64 ml in phantom and liver, respectively) using a 1.5-Tesla clinical imager with two RF channels and a dual-tuned surface coil. The repetition time (TR = 0.26 s) and Ernst nutation angles (theta E = 32 degrees for 19F, 28 degrees for 31P) were chosen to optimize the signal-to-noise ratio (SNR) per-unit time for the 0.5- to 2-s T1 range of the 19F and 31P metabolites of interest. The overall examination time, including tuning, imaging, shimming and dual-nuclear spectroscopy, was under 90 min. Simultaneous acquisition of 31P and 19F spectra will permit the study of the influence of hepatic and/or tumor metabolism on the uptake and catabolism of fluoropyrimidine drugs with no extra measurement time.

The use of 31P MRS in clinical cancer research has been hampered by both poor anatomic localization of spectra and poor resolution of overlapping signals. We found that accurate localization using 3D chemical shift imaging and improved resolution using 1H-decoupling and nuclear Overhauser-enhancement (NOE) increased signal-to-noise and permitted resolution of separate components within phosphomonoester (PME) and phosphodiester (PDE) regions. Fifty-three cancers of different types (lymphoma, sarcoma, adenocarcinoma) had the following common features: (1) phosphoethanolamine the dominant PME; (2) glycerophosphoethanolamine and -choline rarely detected; (3) a broad PDE signal probably from membrane phospholipids; and(4) prominent nucleoside triphosphates. 1H-decoupling with NOE-enhancement permitted us to obtain new information about in vivo metabolism in human cancers; generate new hypotheses and help guide development of experimental models appropriate to test them; and provide a firm basis with which to examine clinical uses of 31P MRS.

This paper examines the potential and limitations of peak area quantitation of biological NMR spectra using principal component analysis (PCA), including its requirement for prior knowledge. The principles of the method are presented without in-depth mathematical treatment. PCA is illustrated for simulated data, 31P NMR spectra obtained consecutively over 1-2.5 days from perfused Rat-2 cells metabolizing the choline analogue phosphoniumcholine (Chop) and in vivo proton-decoupled, NOE-enhanced, three-dimensional CSI localized 31P NMR spectra of the liver of healthy volunteers. The results show that PCA can be used to quantitate strongly overlapping peaks without prior knowledge of the peak shapes or positions and to reconstruct spectra with significantly reduced noise variance. Two major limitations of PCA are presented: (1) PCA cannot separate peaks whose intensities are well correlated; (2) PCA is sensitive to differences in chemical shift and line-width of peaks between spectra. The discussion focuses on what knowledge of the biological and spectroscopic features of the samples and the principles of PCA is necessary for peak area quantitation via PCA.

The development of clinical applications of 19F magnetic resonance (MR) spectroscopy of 5-fluorouracil (5-FU) has been limited by the inability to localize 19F spectra to specific regions of interest, making it difficult to quantitate drug and metabolite concentrations accurately. To develop methodology for quantitation, we studied the liver of patients receiving rapid bolus i.v. injections of 5-FU. In serial studies, 5-FU disappeared from the liver within 17-26 min, and its catabolite, alpha-fluoro-beta-alanine (FBAL), rose to reach a plateau after 40 min. A high peak level of fluoro-ureido-propionic acid preceded that of FBAL in only one patient, and dihydrofluorouracil was never observed. During the plateau, we obtained MR imaging-directed 19F MR spectra localized using three-dimensional chemical shift imaging. The spin-lattice relaxation time of FBAL in liver, measured using a variable nutation angle method, was 1.6 +/- 0.2 s (mean +/- SD; n = 5). The concentration of FBAL at 60 +/- 10 min after injection was 1.0 +/- 0.2 mm in liver (mean +/- SD; n = 7). This amount represents approximately 20% of the injected dose and 1.4 times the initial hepatic 5-FU concentration. Our approach may permit one to obtain molar concentrations of fluoropyrimidine metabolites simultaneously in hepatic cancers and surrounding liver, and it helps expand pharmacokinetic modeling of fluoropyrimidine catabolism.

Development of biological and clinical uses of in vivo 31P magnetic resonance spectroscopy has been hampered by poor anatomic localization of spectra and poor resolution of overlapping signals within phosphomonoester and phosphodiester regions of the spectrum. We applied 1H-decoupling and nuclear Overhauser enhancement to improve resolution of 31P magnetic resonance spectra accurately localized to 21 non-Hodgkin's lymphomas (NHL) by using three-dimensional chemical shift imaging. All 21 spectra had large phosphomonoester signals (26% of total phosphorus) that contained high amounts of phosphoethanolamine relative to phosphocholine. There were no signals from glycerophosphoethanolamine or glycerophosphocholine but only a broad signal from membrane phospholipids in the phosphodiester region (20% of phosphorus). Prominent nucleoside triphosphates (47% of phosphorus) and low inorganic phosphate (7% of phosphorus) indicate well-perfused tissue with viable cells. Mean intracellular pH was 7.23. These characteristics were similar in all grades and stages of NHL. By analogy with recently reported studies in cell lines in vitro, we hypothesize that the pattern of phospholipid metabolites observed in NHL in vivo is partly a manifestation of sustained activation of phospholipase C or D. The techniques we implemented permitted us to obtain more information about in vivo metabolism of NHL than has heretofore been available. This information is important for the establishment of appropriate experimental models and provides a basis from which to examine potential clinical uses of 31P magnetic resonance spectroscopy.

The radula of the limpet, Cellana toreuma, consists of a continuous series of teeth in various stages of iron biomineralization. The major iron-binding protein of the limpet's iron-containing granule (siderosome) has been purified and identified as ferritin. Limpet ferritin has a M(r) of 575 kDa and can be resolved into two bands by SDS-PAGE analysis, with respective M(r)s of 26 and 21 kDa. The partial N-terminal amino acid sequences of these two subunits were confirmed, and antisera against them were respectively generated. The specifity of these two antisera shows no difference between them. By using transmission electron microscopy and immunogold staining techniques the following two events were revealed: (1) in the superior epithelial cell of the radula, ferritin was disassembled through autophagy or heterophagy before exocytosis; (2) of the limpet ferritin, at least the 26-kDa subunit was found to pass through the microvilli, resulting in the accumulation of iron in the extracellular tooth chamber and the formation of goethite needles. Intracellular ferritin being translocated to the extracellular environment is discussed in the text.

Magnetoreception by honeybees (Apis mellifera) is demonstrated by such activities as comb building and homing orientation, which are affected by the geomagnetic field. In other magnetoreceptive species, iron oxide crystals in the form of magnetite have been shown to be necessary for primary detection of magnetic fields. Here it is shown that trophocytes, which are apparently the only iron granule-containing cells in honeybees, contain super-paramagnetic magnetite. These cells are innervated by the nervous system, which suggests that trophocytes might be primarily responsible for magnetoreception. Electron microscopy also shows cytoskeletal attachments to the iron granule membrane.

In this paper, we apply a quasi-one-dimensional unsteady nonlinear fluid model to study human pulmonary circulation. Eighteen generations of blood vessels composed of the branching arterial, capillary and venous distensible vessel segments make up the complete pulmonary circulation. The numerical result gives satisfactory agreement with the physiological experimental data: a dramatic pressure drop occurs in the arterioles and postcapillaries, a negative transmural pressure is shown in the postcapillary and small venous segments, a large reverse flow occurs in the main pulmonary artery during the diastolic period, and the reverse flow decreases gradually along the pulmonary tree. In the microgravity case where g = 180 cm s-2, the computation illustrated the effect of gravity force on the blood distribution in the different parts of the pulmonary circulation. The effect of gravity on the total output is not obvious. The effect of local factors which initiate the variations of the geometrical or pulmonary circulation can be stimulated quantitatively by this model. The proposal model can be very useful for clinical practice and for studying the extreme cases which are very difficult to investigate by experiments.

Vestibulo-ocular compensation following vestibular deafferentation was investigated in 26 acoustic neuroma patients following tumor removal and in 5 Menière's disease patients following vestibular nerve section by using sinusoidal harmonic acceleration testing. All three test parameters (phase lead, gain, and asymmetry), when averaged, shifted significantly on the first postoperative test (average 0.4 months after operation). A marked progression in central compensation with gain returning to the range of normal control values was seen in the tests performed 1 to 6 months (average 2.6 months) postoperatively. However, phase lead and asymmetry (especially at 0.01, 0.02, 0.04, and 0.08 Hz) remained outside the range of normal control values, and all three parameters failed to return to their preoperative level even when tested at more than 12 months (average 20.2 months) after operation. This finding indicates that the deficits of the vestibulo-ocular reflex to head acceleration are of long duration if not permanent.

Forty-one normal humans were tested with sinusoidal harmonic acceleration. Phase lag at 0.01, 0.02, and 0.04 Hz was the most stable parameter, with less test-retest variability than gain and asymmetry. There was no significant difference between men and women for phase lag, gain, or asymmetry at any of the five testing frequencies. Gain decreased as age increased. Age had no effect on phase lag at most test frequencies or on asymmetry at any frequency.

Twenty-seven patients with malignant lymphoma (14 Hodgkin's disease, 9 histiocytosarcoma, 2 plasmacytoma, 2 lympholeucosarcoma) were treated by Ailin-injection plus Chinese herbal medicine. The latter's composition and dose varied depending on the clinical manifestations. All the patients had stage III and IV lesions. The total remission rate was 70.37% (complete remission 13 patients, partial remission 6 patients, no remission 8 patients). In addition, we also studied the suppressive effect of Ailin on transplanted tumor in vivo (S-180). The suppression rates were 36.09%, 48.80%, 32.67% by three repetitions with an average of 39.18% (P less than 0.002). They were 37.25%, 35.29% on S37 with an average of 36.27% (P less than 0.005). They were 46.53%, 44.56%, 51.35%, 45.95% on Ehrlich ascites tumor cells with an average of 47.09% (P less than 0.001). The clinical and experimental studies suggest that Ailin-1 has no serious side effects and is well tolerated by patients with malignant lymphoma at moderate or advanced stages. No toxic reactions were observed at the clinical dose. In the above combination therapy, the Chinese herbal medicine has obvious supplementary effect in the treatment of the patients' cachexia and immuno-suppression.

Structure and development of hair cells in vestibular sensory organs of the larval bullfrog were examined with scanning electron microscopy. The larval vestibular sensory epithelia resembled those of the adult frog. Based on morphology of the ciliary tufts, seven hair cell types were identified. One of them, the type A hair cell, appears to be the morphogenetic precursor of other hair cell types. The size of the stereocilia of type A hair cells is comparable to the surrounding microvilli. The distribution of immature type A hair cells suggests that the periphery of the sensory epithelia is the principal growth zone and the site of formation of new hair cells. However, a far greater number of type A hair cells were found in high frequency sensitive sensory organs (sacculus, amphibian and basilar papillae) than low frequency sensitive vestibular sensory structures (canal cristae, utriculus and lagena). This phenomenon may suggest that the time period required for the maturation of type A hair cells to their ultimate hair cell types in the low frequency sensitive vestibular organs is shorter than in the high frequency sensory structures. It is also possible that the low frequency sensitive vestibular organs may have completed their morphogenetic development in the early larval stages, while morphogenesis of hair cells in the high frequency sensory structures continues throughout the lifetime of a bullfrog.

An experiment was undertaken to determine which sensory structures of the mouse embryo inner ear developed from what portion of the mouse otocyst. Otocysts of gestation days 10, 11, 12, and 13 were divided by surgical dissection into six anatomical groups: dorsal, ventral, anterior, posterior, medial and lateral halves. They were organ cultured separately. After a period of ten days, the explanted tissues were harvested and processed histologically for microscopic analysis. The surgical control specimens fixed at the time of explantation were composed of undifferentiated ectodermal cells for tissues of gestation days 10, 11, and 12. Otocysts of gestation days 11, and 12 showed, during the course of their subsequent growth, that the three semicircular ducts and their associated cristae developed from the dorsal and lateral halves. Only the anterior and posterior canals and cristae originated from the medial portion. The posterior half gave rise to the posterior crista and the anterior half provided for the development of the anterior and lateral cristae. The cochlear duct and its sensory epithelium developed in all the anatomical groups except the dorsal half. The utricle developed in the dorsal section of the middle third of the otocyst, while the utricular macula developed in the anterior half of the same section of the otocyst. The saccule and its macula differentiated from the ventral section of the middle third of the anterior half.

The growth and shape of the cochlea appears to be controlled by the formation of the cartilaginous capsule. Coiling of the cochlear duct is apparently the result of the physical barrier and support provided by the cartilage cells differentiating from mesenchyme surrounding the ventral portion of the otocyst. In addition, tissue interactions between this mesenchyme and the developing cochlear duct will influence the formation of the cartilaginous capsule and they may also be the origin of one of the controlling agents for the coiling mechanism.

The growth and shape of the membraneous labyrinth appears to be organized and restricted by the formation of the cartilaginous capsule. Coiling of the cochlear duct appears to be the result of the physical barrier and support provided by the cartilage cells differentiating from mesenchyme surrounding the otocyst. In addition, tissue interactions between this mesenchyme and the developing cochlear duct may be the source of a genetic message for the coiling mechanism.

Histologic development of the mammalian cochlea has been studied by many investigators. In 1978, Li reported on a preliminary scanning electron microscopic study of hair cell development in the embryonic mouse cochlea. The present study further examines the surface morphology of the embryonic cochlea.