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Tissue factor is required for uterine hemostasis and maintenance of the placental labyrinth during gestation.

We employed a novel mouse line that expresses low levels of human tissue factor (TF) in the absence of murine TF to analyze the role of TF in gestation. Low-TF female mice had a 14-18% incidence of fatal postpartum uterine hemorrhage, suggesting that TF plays an important role in uterine hemostasis. Low-TF female mice mated with low-TF male mice had a 42% incidence of fatal midgestational hemorrhage (n = 41), whereas no fatal midgestational hemorrhages were observed in low-TF female mice mated with wild-type male mice (n = 43). Placentas of low-TF embryos from both low-TF and normal (+/-) TF females were abnormal and contained numerous maternal blood pools in the labyrinth. Placentas of TF null embryos surviving beyond embryonic day 10.5 exhibited similar defects. The mouse maternal-embryonic placental barrier consists of four cellular layers (layers I, II, and III and endothelial cells), where layer I lines the maternal lacunae. Comparison of TF-deficient placentas with control placentas by immunohistochemical and ultrastructural analyses revealed thinning of layer I and a reduction in the number of cellular contacts of layer I trophoblasts spanning the maternal blood space between adjacent trabeculae. These structural changes in low-TF and TF null placentas result in enlarged maternal lacunae, as determined by morphometric analysis, and placental hemorrhage, which leads to midgestational death of low-TF female mice. This study demonstrated that TF is required for uterine hemostasis and revealed an unexpected role of TF in the maintenance of the placental labyrinth.

Animals↗

Radiation streaming experiment through a labyrinth of the 12 GeV proton accelerator facility at KEK(2)--TLD REM-counter method.

The doses of radiation streaming through a labyrinth were measured using thermoluminescence dosemeters (TLDs) and neutron moderators for TLDs at the neutrino beam line of the 12 GeV proton accelerator facility of High Energy Accelerator Research Organization (KEK). The calculated doses using the Monte Carlo code, MCNPX basically agreed with the experimental results. However, unexpectedly, the calculated neutron doses were smaller than the measured ones along the upstream side of the labyrinth.

Computer-Aided Design↗

The incidence and distribution of cupular deposits in the pediatric vestibular labyrinth.

OBJECTIVES: Deposits of basophilic material on the cupulae of the semicircular ducts have been described in adult human temporal bones, and such deposits have been implicated in the clinical phenomenon of benign paroxysmal positional vertigo (BPPV). Although relatively rare, BPPV has been reported to occur in children. The goal of this study was to evaluate the occurrence of cupular deposits in pediatric material. STUDY DESIGN: Basic science, two-center histopathologic temporal bone study. METHODS: We examined 186 temporal bones from 121 individuals between the ages of newborn and 10 years. The average age was 14.7 months. All temporal bones were acquired at autopsy, embedded in celloidin, and sectioned for light microscopic study. The cupulae of the semicircular ducts were identified and any deposits found were graded according to their size and position on the cupula. RESULTS: A total of 276 cupulae were identified, and in 35 (12.7%) of these a basophilic deposit was found. In many cases the deposits contained recognizable otoconial crystals. Most deposits were small and they were almost equally distributed between the three semicircular ducts. However, the lateral and posterior cupulae were somewhat more involved than the superior cupula. Our data showed that cupular deposits are less frequently found in the pediatric labyrinth, compared with adults as reported in previous studies. CONCLUSIONS: The lower occurrence in children versus adults suggests that the deposits may be a phenomenon of the aging vestibular labyrinth.

Child↗

Rapid elevation of gentamicin levels in the human labyrinth following intravenous administration.

HYPOTHESIS: Adequate quantities of labyrinthine fluid can be sampled from the human labyrinth to perform quantitative analysis of medications. A rapid elevation of intralabyrinthine gentamicin levels after intravenous administration can be measured. A model for the sampling of human inner ear fluid in this manner is described. BACKGROUND: The risk of aminoglycoside ototoxicity has been a long-standing concern. The kinetics of gentamicin diffusion into the inner ear have been extrapolated to humans from various animal models. The validity of extrapolation to humans is unknown. We have developed a new model to measure the uptake of gentamicin in vivo. METHODS: A single intravenous dose of gentamicin (80 mg) was given perioperatively to 13 patients undergoing translabyrinthine acoustic neuroma surgery. The lateral semicircular canal and vestibule were opened and a microsyringe was used to obtain a sample of labyrinthine fluid concomitant with a serum sample. The gentamicin concentration of the labyrinthine fluid and serum was analyzed using a standard chemistry analyzer. RESULTS: After parenteral administration of gentamicin, fluid was obtained from the inner ear of 13 acoustic neuroma patients. Inner ear concentrations were between 1.0 and 3.8 mg/L. Serum gentamicin levels ranged from 1.2 to 10.5 mg/L. CONCLUSIONS: This method allows the sampling of intralabyrinthine fluid in humans. Gentamicin was noted immediately in the labyrinth after intravenous administration. This model may be expanded to measure other compounds given either by intravenous or transtympanic routes.

Adult↗

Identification of previously "undetectable" abnormalities of the bony labyrinth with computed tomography measurement.

BACKGROUND: In patients with congenital sensorineural hearing loss (SNHL), a computed tomography (CT) scan of the temporal bone identifies inner ear malformations in approximately 25%, whereas the inner ear is grossly normal to visual inspection in the remaining 75% of the patients. In the latter group, the hearing loss is often attributed to radiologically undetectable abnormalities of the membranous labyrinth. However, subtle bony malformations may be missed because visual inspection alone is insensitive for detection. OBJECTIVE: To test the hypothesis that there are subtle bony abnormalities of the inner ear in patients with SNHL who are radiologically deemed to have normal otic bone, using standardized measurements of the inner ear. STUDY DESIGN: Retrospective review. METHODS: Measurements of the cochlea, vestibule, and semicircular canals (SCCs) were made on axial and coronal temporal bone CT scans on 15 patients with normal hearing and 15 patients with congenital SNHL and grossly normal temporal bone CT scans. Student's t-test was performed to compare the measurements of the two groups. RESULTS All studies from the SNHL group were deemed normal by visual inspection and standardized measurements (+/-2 SD from normal). Surprisingly, there were significant differences in the measurements of the cochlea and of the SCCs between patients with and without SHNL (P <.05). CONCLUSIONS: As a group, patients with SNHL and a "normal CT scan" have significant differences in the dimensions of the inner ear. This suggests that these patients have disturbed morphogenesis of both membranous and bony labyrinth. This novel observation has important implications for understanding the etiology of SNHL.

Child↗

Spontaneous breaking of minimal surface condition: labyrinths in free standing smectic films.

We present a study of thin free standing films made of intercalated smectic-C liquid crystal in which, upon lowering the temperature, the minimal surface area condition is broken. A periodic modulation of the film thickness is obtained and a labyrinth structure of crests and valleys is formed. Thickness variation is coupled to the spatial variation of the molecular orientation. The transition to the labyrinth structure is explained to be driven by the mass density difference between the surface and the bulk layers.

Journal Article↗

The ultrastructure of a membranous structure, the labyrinth, present in bone marrow plasma cells.

The ultrastructure of a complex membranous structure, the labyrinth, is described. This structure was found in bone marrow plasma cells from patients with multiple myeloma as well as from other groups of patients. It is concluded that the labyrinth may represent a rare route of secretion by which plasma cells are able to excrete waste products and simultaneously secrete intracellularly synthesized material.

Bone Marrow↗

Benign paroxysmal positional vertigo predominantly affects the right labyrinth.

Benign paroxysmal positional vertigo (BPPV) occurs when there are freely moving particles in a semicircular canal and the head is turned in the plane of the affected canal. The aim of the present study was to clarify whether BPPV manifests equally in both labyrinths or whether there is a preponderance for one side. We conducted a PubMed literature search of BPPV case series which specified the affected side and a retrospective chart review of 80 consecutive patients with BPPV of the posterior canal who had presented at our dizziness clinic. Eighteen studies with a total of 3426 patients were identified. In our own series the right side was affected in 54 of 80 patients (right/left ratio 2.08). Altogether, in 3506 patients the right labyrinth was involved 1.41 times more often than the left (95% CI 1.37 to 1.45). We think that the reason for the predominant involvement of the right ear in BPPV is the habit-of most patients-of sleeping on the right side.

Ear, Inner↗

The ganoine membrane of the scales of Polypterus senegalus includes a labyrinth-like structure.

The ganoine membrane is a basement membrane-like structure appearing between the maturation stage inner ganoine epithelium (IGE) and mineralized ganoine of polypterids and lepisosteids. In the present study, further ultrastructural investigation of the ganoine membrane of Polypterus senegalus was made and it was confirmed that it possessed a specialized labyrinth-like structure. The complete ganoine membrane was composed of six distinct zones: (1) a filamentous zone facing the distal plasmalemma of IGE, (2) lamella zone I, (3) vertical striation zone, (4) lamella zone II, (5) electron-dense zone, (6) electron-lucent zone directly facing the maturing ganoine surface. The ganoine membrane sometimes partially lacked some of these zones, but the electron-dense zone was usually present. Oblique or horizontal sections of the membrane showed that the vertical striation zone was made up of a typical labyrinth-like structure. Certain sulfated glycoconjugates were localized at the filamentous zone, especially adjacent to the lamella zone I and over the electron-dense zones.

Animals↗

The interglobular spaces in the endochondral layer of the osseous labyrinth. Comparative anatomical study.

The endochondral layer of the osseous labyrinth in the rat, golden hamster, mouse, guinea pig, pig, rabbit, cat, dog and monkey was studied and compared with that of man. (1) With the exception of the mouse and golden hamster, interglobular spaces were found. (2) In all species but the rat, the interglobular spaces contain acid mucopolysaccharides. An analogy between these structures and the 'basophilic islands' (basophile Inseln) is discussed. (3) Extension, arrangement, direction, occurrence and frequency of interglobular spaces vary within each species so that no constant relations could be found, which are also lacking in man. Possible reasons for the persistence throughout life of interglobular spaces in the osseous labyrinth of man and some mammals are discussed.

Animals↗

Anemia induces 5'-nucleotidase in fibroblasts of cortical labyrinth of rat kidney.

We recently observed a strong increase of 5'-nucleotidase in renal fibroblasts of rats that were anemic due to an immunity against erythropoietin. In order to test if the change of 5'-nucleotidase was related with anemia, we studied the distribution of the enzyme in irradiated rats treated with phenylhydrazine. The hematocrit of these rats decreased to 15% within 4 days and erythropoietin levels were more than 200 times over controls. After 7 days a histochemical study showed that the enzymatic activity and the immunoreactivity for 5'-nucleotidase was markedly enhanced in the fibroblasts of the cortical labyrinth. There was no modification of 5'-nucleotidase in other cell types of the kidney. The 5'-nucleotidase activity of renal fibroblasts in cell culture increased by 72% upon addition of 160 microM 5'-AMP to the culture medium for 8 days. We propose that anemia provokes an energy deficit in some structure in the cortical labyrinth. This might increase the concentration of 5'-AMP which would induce 5'-nucleotidase. An interesting consequence of these events would be an increased production of adenosine in the direct vicinity of some of its putative targets, the glomerular arterioles and the erythropoietin-producing cells.

5'-Nucleotidase↗

Nature of blood-labyrinth barrier in experimental conditions.

The blood-labyrinth barrier is concept that has evolved based on marked difference in chemical composition between perilymph and blood. Studies reported here have been designed to manipulate physiologic, metabolic, and pharmacologic conditions in experimental animals in order to determine the characteristics of this regulatory mechanisms. Tracer studies of uptake of sodium, calcium, and albumin from blood into perilymph showed that these substances penetrate into inner ear fluids quite slowly. Injections of ototoxic substances (kanamycin, furosemide) show limited transport of these agents into perilymph. Administration of an osmotic agent (urea) resulted in a parallel but delayed elevation of perilymph concentration. The possible role of a alteration of blood-labyrinth barrier in inner ear disorders has been discussed.

Animals↗

Expression of intermediate filament proteins in the adult human vestibular labyrinth.

The immunohistochemical detection of intermediate filament proteins, cytoskeletal constituents that allow the characterization of tissues, was investigated in frozen sections of the chemically fixed, nondecalcified, adult human vestibular labyrinth. Cytokeratins (CKs) were detected in all epithelia (including the sensory epithelia), although substantial differences in the degree of staining between individual cells occurred. The expression of CKs 7, 8, 18, and 19 as detected with our subunit-specific monoclonal antibodies in the vestibular epithelia is typical of "simple" epithelia and is identical to the CK subtypes found in the human cochlea. Although immunostaining for CK 7 was very weak and was limited to certain vestibular wall cells, the other CKs demonstrated a pronounced and rather uniform distribution throughout the different epithelia. All epithelia (including the sensory epithelia) displayed expression of vimentin, thus demonstrating co-expression with CKs. Vimentin was also present in the subepithelial connective tissue fibroblasts and mesothelial lining of the vestibular labyrinth. Neurofilament proteins were detected in all neuronal structures. The intense staining for CKs in the maculae and cristae implies that these sensory organs are rigid structures, a finding that may possibly be of importance in the mechanoelectrical transduction process for the sense of equilibrium.

Aged↗

The Cdx4 mutation affects axial development and reveals an essential role of Cdx genes in the ontogenesis of the placental labyrinth in mice.

Caudal related homeobox (Cdx) genes have so far been shown to be important for embryonic axial elongation and patterning in several vertebrate species. We have generated a targeted mutation of mouse Cdx4, the third member of this family of transcription factor encoding genes and the last one to be inactivated genetically. Cdx4-null embryos were born healthy and appeared morphologically normal. A subtle contribution of Cdx4 to anteroposterior (AP) vertebral patterning was revealed in Cdx1/Cdx4 and Cdx2/Cdx4 compound mutants. Neither Cdx4-null nor Cdx1/Cdx4 double mutants are impaired in their axial elongation, but a redundant contribution of Cdx4 in this function was unveiled when combined with a Cdx2 mutant allele. In addition, inactivation of Cdx4 combined with heterozygous loss of Cdx2 results in embryonic death around E10.5 and reveals a novel function of Cdx genes in placental ontogenesis. In a subset of Cdx2/Cdx4 compound mutants, the fully grown allantois failed to fuse with the chorion. The remaining majority of these mutants undergo successful chorio-allantois fusion but fail to properly extend their allantoic vascular network into the chorionic ectoderm and do not develop a functional placental labyrinth. We present evidence that Cdx4 plays a crucial role in the ontogenesis of the allantoic component of the placental labyrinth when one Cdx2 allele is inactivated. The axial patterning role of Cdx transcription factors thus extends posteriorly to the epiblast-derived extra-embryonic mesoderm and, consequent upon the evolution of placental mammals, is centrally involved in placental morphogenesis. The relative contribution of Cdx family members in the stepwise ontogenesis of a functional placenta is discussed, with Cdx2 playing an obligatory part, assisted by Cdx4. The possible participation of Cdx1 was not documented but cannot be ruled out until allelic combinations further decreasing Cdx dose have been analyzed. Cdx genes thus operate in a redundant way during placentogenesis, as they do during embryonic axial elongation and patterning, and independently from the previously reported early Cdx2-specific role in the trophectoderm at implantation.

Allantois↗

Morphological study of blood-labyrinth barrier in the vestibular organs under normal and experimental acute hypertensive and acute hypotensive conditions.

In order to examine a blood-labyrinth barrier in the vestibular region, capillary permeability of the vestibular organs, i.e. the sacculus, the utriculus and the ampullae of semicircular canals, were studied light and electron microscopically by the horseradish peroxidase (HRP) tracer method. Intravenously infused HRP was not observed outside capillaries because of the tightness of endothelial tight junctions and the paucity of pinocytotic vesicles. Furthermore, the effect of drug-induced acute hypertension and acute hypotension on the capillaries of the vestibular organs was studied morphologically using the tracer technique. In each experiment, there was no extravasation of HRP from capillaries, thus agreeing with the results of the experiment made under normal conditions. These findings mean that capillaries of the vestibular region are of ordinary brain capillary type and contribute to the blood-labyrinth barrier to macromolecules such as HRP both under normal conditions and following abrupt changes in blood pressure.

Animals↗

Mechanical properties of membranous labyrinths measured with a microtension tester.

Mechanical properties of the semicircular canals of guinea pigs, frogs and water fishes, and of human membranous labyrinths were tested. Tensile strength of the semicircular canals of guinea pig, frog and water fish was greater in the order of guinea pig, frog and fish. In the human membranous labyrinth, the saccular membrane was the weakest, followed by Reissner's membrane, the utricular membrane and the semicircular canal. These values were converted from tensile strength to breakage pressure. The breakage pressure of the saccular membrane was 64.0 mmHg.

Animals↗

Positional nystagmus due to alteration of the specific gravity in the labyrinth.

Horizontal positional nystagmus having characteristics similar to ice water caloric nystagmus was induced by injecting heavy water into the rabbit middle ear cavity or facial nerve through the stylomastoid foramen. Furthermore, with general administration of glycerol to normal subjects, horizontal positional nystagmus as with general administration of heavy water to experimental animals was observed. It is possible that alteration of the specific gravity arising from infiltration of heavy water or glycerol into the labyrinth accounts for the manifestation of positional nystagmus. These studies on positional nystagmus may be one of the means to elucidate the mechanism of caloric nystagmus and to examine the function of the human blood-labyrinth-barrier.

Adolescent↗