Showing papers by "Karolinska Institutet published in 1985"
TL;DR: 7 years after the start of the study the excess of stage I cancers in the study group largely outweighs the deficit of advanced cancers, and the results to the end of 1984 show a 31% reduction in mortality from breast cancer and a 25% reduced in the rate of stage II or more advanced breast cancers.
1,696 citations
TL;DR: The hypothesis that different parts of the network controlling locomotion can be used in a variety of other motor acts, including learned ones, is reviewed.
Abstract: The general principles governing the nervous control of innate motor acts in vertebrates are discussed. Particular consideration is given to the control of locomotion in both mammals and lower vertebrates. One in vitro model of the lamprey central nervous system has been developed. It can be maintained in vitro for several days and the motor pattern underlying locomotion can be elicited in isolated sections of the spinal cord. These findings now allow a detailed analysis of the underlying neural mechanisms. The hypothesis that different parts of the network controlling locomotion can be used in a variety of other motor acts, including learned ones, is reviewed.
1,059 citations
TL;DR: Advances in molecular biology have made it possible to define some of these changes in molecular terms and to trace the steps by which certain tumours evolve.
Abstract: It is generally accepted that tumours arise through the accumulation of several changes affecting the control of cell growth. Recent advances in molecular biology have made it possible to define some of these changes in molecular terms and to trace the steps by which certain tumours evolve.
645 citations
TL;DR: The functional analysis revealed that CGRP caused cardiac stimulation and had, together with SP and neurokinin A, potent hypotensive effects, and the bronchial smooth muscle was particularly sensitive to neurokinIn A.
591 citations
TL;DR: It is suggested that the hypothalamic GR may be involved in the regulation of especially CRF secretion but also in the secretion of other anterior pituitary hormones such as TRH and somatostatin.
Abstract: By means of a monoclonal antibody against the rat liver glucocorticoid receptor (GR) in combination with the indirect immunoperoxidase technique it has been possible to demonstrate GR-immunoreactive nerve and glial cell nuclei all over the tel– and diencephalon of the male rat. Strongly GRimmunoreactive nerve cell nuclei were only present in the parvocellular part of the paraventricular hypothalamic nucleus, in the anterior periventricular hypothalamic nucleus, in the ventral part of the mediobasal hypothalamus, and in the CAl and CA2 subregion of the hippocampal formation. Within the paraventricular hypothalamic nucleus a substantial overlap exists between the GR–immunoreactive area and the CRF–immunoreactive area. Medium to high densities of moderately GR–immunoreactive nerve cell nuclei were present all over the cortical hemispheres. Medium densities of moderately GR–immunoreactive nerve cells were demonstrated in many thalamic nuclei and in the central amygdaloid nucleus. After adrenalectomy the GR im...
532 citations
TL;DR: It is suggested that innate pattern generators in the spinal cord produce the infant stepping and also generate the basic locomotor rhythm in adults, but that neural circuits specific for humans develop late in ontogeny and transform the original, non-plantigrade motor activity to a plantigrade locomotor pattern.
Abstract: Locomotor patterns of human infants were studied during stepping in the newborn period (first two months of life), during supported locomotion (6–12 months of age) and during independent locomotion in children who just were able to walk by themselves without external support (10–18 months of age). Leg movements, pattern of muscular activity and reaction forces were studied by a computerized system. The locomotor pattern during the newborn period lacked the specific functions that are unique for human plantigrade locomotion. There was no heel strike in front of the body; the foot was placed instead on its forepart straight under the body. Hip and knee joints were hyperflexed during the whole step cycle and flexed synchronously during swing. The specific knee-ankle coordination of human adults was missing. The ankle extensors were activated prior to touch down together with other extensor muscles. There was no propulsive force. A similar immature non-plantigrade pattern recurred after an inactive period. During the subsequent period of supported locomotion there was a gradual transformation of the infantile pattern towards the plantigrade pattern continuing after establishment of independent locomotion. It is suggested that innate pattern generators in the spinal cord produce the infant stepping and also generate the basic locomotor rhythm in adults, but that neural circuits specific for humans develop late in ontogeny and transform the original, non-plantigrade motor activity to a plantigrade locomotor pattern.
506 citations
445 citations
TL;DR: The decrease of galanin-like immunoreactivity in the dorsal horn of the spinal cord, following dorsal rhizotomy and pre-treatment of rats with capsaicin, indicates that many of the fibres, which are of small diameter, may well be derived from spinal sensory neurones.
427 citations
TL;DR: The same basic structure of the stride cycle as in other animals suggests similarities in the underlying neural control in human locomotion.
Abstract: Knowledge of adaptations to changes in speed and mode of progression (walking-running) in human locomotion is important for an understanding of underlying neural control mechanisms and allows a comparison with more detailed animal studies. Leg movements and muscle activity patterns were studied in ten healthy males (19-29 yr) during level walking (0.4-3.0 m X s-1) and running (1.0-9.0 m X s-1) on a motor-driven treadmill. Movements were recorded in the sagittal plane with a Selspot optoelectronic system. Recordings of EMG were made from seven different muscles of one leg by means of surface electrodes. Durations, amplitudes and relative phase relationships of angular displacements and EMG activity were analysed in relation to different phases of the stride cycle (defined by the leg movements). The durations of the entire stride cycle and of the support phase were found to decrease curvilinearly with velocity. Swing and support phase durations were linearly related to cycle duration in walking, and curvilinearly related in running. The characteristic occurrence of double support phases in walking was also seen in very slow running. Support length increased with speed up to about 1.2 m both in walking and running, but was longer in walking at the same velocity. Increases in net angular displacements were largest for hip movements and for knee flexion-extension during the swing phase in running. With increasing velocity a clear shift in relative rectus femoris activity occurred from knee extension to hip flexion. Gastrocnemius lateralis (LG) was co-activated with the other leg extensors prior to foot contact in running, whereas in walking LG was not turned on until later in the support phase. The ankle flexor tibialis anterior had its main peak of activity after touch-down in walking and before touch-down in running. The same basic structure of the stride cycle as in other animals suggests similarities in the underlying neural control. Human speed adaptation is distinguished primarily by an increase in both frequency and amplitude of leg movements and by a possibility of changing between a walking and a running type of movement pattern.
385 citations
TL;DR: The immunoperoxidase method of Sternberger ('79) was used to demonstrate the location of immunoreactive neurons, nerve fibers, and presumptive terminal processes in the caudal medulla oblongata of the rat.
Abstract: The aim of this study was to determine the anatomical relationships between catecholaminergic neurons and cytoarchitectonically defined nuclei in the caudal medulla oblongata. Previous studies have demonstrated the existence of noradrenergic cell bodies (designated as the A1 and A2 cell groups) in the caudal medulla oblongata of the rat (Dahlstrom and Fuxe, '64), including the nTS. There is no information currently available with regard to details of the distribution of these noradrenergic neurons in the functionally distinct subnuclei of the medulla oblongata. In this study the location of catecholamine-synthesizing enzymes was examined in the serial sections of the caudal medulla oblongata of the rat: tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH), and phenylethanolamine N-methyl transferase (PNMT). The immunoperoxidase method of Sternberger ('79) was used to demonstrate the location of immunoreactive neurons, nerve fibers, and presumptive terminal processes. This was followed by Nissl staining of the same sections to localize accurately the immunoreactivity. Noradrenergic neurons (TH- and DBH-positive and PNMT-negative) were localized in a number of subnuclei of the nucleus of the tractus solitarius (nTS), the area postrema (ap), and in the dorsal motor nucleus of the vagus (dmnX). The distribution of these noradrenergic cells was different at different rostrocaudal levels. In addition, adrenergic neurons (TH-, DBH-, and PMNT-positive) were identified dorsal to the tractus solitarius (TS), in the dorsal strip region (ds), the periventricular region (PVR), the dorsal parasolitarius region (dPSR), and the dmnX (rostral to obex). In addition, dopaminergic neurons (TH-positive and DBH- and PNMT-negative) were found in the ap and dmnX. The A1 cell group in the ventrolateral medulla consisted almost exclusively of noradrenergic neurons (TH- and DBH-positive and PNMT-negative). These results indicate that in the rat the A2 cell group is a mixed population of catecholaminergic neurons that are localized in well-defined regions of the dorsal medulla oblongata. The distribution of these neurons is very specific both in terms of rostrocaudal levels and cytoarchitectonic subdivisions of regions of the medulla known to be involved in central autonomic control. This supports the hypothesis that monoaminergic neurons in the dorsal medulla play important roles in the central regulation of visceral function.
368 citations
TL;DR: Findings indicate that a number of different pathways operate to produce enterolactone and enterodiol depending on the ingested dietary precursor.
Abstract: Lignans have, until recently, been found only in plants. Enterolactone and enterodiol are the major lignans present in the urine of humans and have a potential physiological protective role against cancer. It has been shown that these compounds can be formed in vitro by human faecal flora and that enterodiol is oxidized to enterolactone by bacteria that are present in stools at a concentration of up to 103/g. It was also possible to produce both of these lignans in vitro from linseeds and from secoisolariciresinol, a precursor present in linseed, by bacteria present in stools, at a concentration of between 103 and 104/g. Enterolactone was produced from matairesinol, a more abundant plant lignan than secoisolariciresinol, after incubation with a mixed faecal flora under both aerobic and anaerobic conditions. In each case conversion was dependent on the presence of viable bacteria. These findings indicate that a number of different pathways operate to produce enterolactone and enterodiol depending on the ingested dietary precursor.
TL;DR: Evidence is presented that these peptides have different modes of relaxing cerebral blood vessels in the cat, and the responses to SP and acetylcholine were absent in arteries where the endothelium had been removed, whereas the relaxations induced by CGRP and VIP persisted.
TL;DR: A new approach for identifying recessive mutant genes that lead to cancer and a conceptual basis for accurate prenatal predictions of cancer predisposition are suggested.
Abstract: Retinoblastoma is one of several human tumors to which predisposition can be inherited. Molecular genetic analysis of several nonheritable cases has led to the hypothesis that this tumor develops after the occurrence of specific mitotic events involving human chromosome 13. These events reveal initial predisposing recessive mutations. Evidence is presented that similar chromosomal events occur in tumors from heritable cases. The chromosome 13 found in the tumors was the one carrying the predisposing germline mutation and not the homolog containing the wild-type allele at the Rb-1 locus. These results suggest a new approach for identifying recessive mutant genes that lead to cancer and a conceptual basis for accurate prenatal predictions of cancer predisposition.
TL;DR: La formule de Bazett represente assez bien la relation entre l'intervalle QT et la frequence cardiaque andre applicable lorsque ces malades sont traites par les digitaliques, the quinidine ou le metoprolol.
TL;DR: Calcitonin gene-related peptide was found to potently inhibit a substance P endopeptidase isolated from human CSF, suggesting a possible mechanism is interaction for a common metabolic step.
TL;DR: The observations suggest that microtubules are partly responsible for the maintenance and functioning of the Golgi complex, possibly by arranging its stacks of cisternae three-dimensionally within the cell and in relation to other organelles and ensuring a normal flow of material into and away from them.
TL;DR: Double staining techniques using antibodies raised against choline acetyltransferase (ChAT) revealed that GAL- and ChAT-like immunoreactivities are colocalized within a subpopulation of the cholinergic neurons within the medial septum and diagonal band.
Journal Article•
TL;DR: The toxicity of NAPQI to isolated hepatocytes may result primarily from its oxidative effects on cellular proteins, especially in cells pretreated with BCNU or diethylmaleate.
Abstract: N-Acetyl-p-benzoquinone imine (NAPQI), a reactive metabolite of acetaminophen, rapidly reacts at physiological pH with glutathione (GSH) forming an acetaminophen-glutathione conjugate and stoichiometric amounts of acetaminophen and glutathione disulfide (GSSG). The same reaction products are formed in isolated hepatocytes incubated with NAPQI. In hepatocytes which have been treated with 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU) in order to inhibit glutathione reductase, the initial rise in GSSG concentration in the presence of NAPQI is maintained, whereas GSSG is rapidly reduced back to GSH in untreated hepatocytes. Oxidation by NAPQI of GSH to GSSG and the reduction of GSSG back to GSH by the NADPH-dependent glutathione reductase appear to be responsible for the rapid oxidation of NADPH that occurs in hepatocytes incubated with NAPQI in that the effect is blocked by pretreatment of cells with BCNU. When added to hepatocytes, NAPQI not only reacts with GSH but also causes a loss in protein thiol groups. The loss in protein thiols occurs more rapidly in cells pretreated with BCNU or diethylmaleate. Whereas both of these treatments enhance cytotoxicity caused by NAPQI, BCNU pretreatment has no effect on the covalent binding of [14C-ring]NAPQI to cellular proteins. Furthermore, dithiothreitol added to isolated hepatocytes after maximal covalent binding of [14C-ring]NAPQI but preceding cell death protects cells from cytotoxicity and regenerates protein thiols. Thus, the toxicity of NAPQI to isolated hepatocytes may result primarily from its oxidative effects on cellular proteins.
TL;DR: Present indications are that marathon runners, compared with normal individuals, have a higher turnover rate in fat metabolism at given high exercise intensities expressed both in absolute (m/sec) and relative %V̇O2 max terms.
Abstract: Performance in marathon running is influenced by a variety of factors, most of which are of a physiological nature. Accordingly, the marathon runner must rely to a large extent on a high aerobic capacity. But great variations in maximal oxygen uptake VO2 max have been observed among runners with a similar performance capacity, indicating complementary factors are of importance for performance. The oxygen cost of running or the running economy (expressed, e.g. as VO2 15 at 15 km/h) as well as the fractional utilisation of VO2 max max at marathon race pace %VO2 ma × VO2 ma
−1) [where Ma = mean marathon velocity] are additional factors which are known to affect the performance capacity. Together VO2 max, VO2 15 and %VO2 ma × VO2 ma
−1 can almost entirely explain the variation in marathon performance. To a similar degree, these variables have also been found to explain the variations in the ‘anaerobic threshold’. This factor, which is closely related to the metabolic response to increasing exercise intensities, is the single variable that has the highest predictive power for marathon performance. But a major limiting factor to marathon performance is probably the choice of fuels for the exercising muscles, which factor is related to the %VO2 ma × VO2 ma
−1. Present indications are that marathon runners, compared with normal individuals, have a higher turnover rate in fat metabolism at given high exercise intensities expressed both in absolute (m/sec) and relative %VO2 max terms. The selection of fat for oxidation by the muscles is important since the stores of the most efficient fuel, the carbohydrates, are limited. The large amount of endurance training done by marathon runners is probably responsible for similar metabolic adaptations, which contribute to a delayed onset of fatigue and raise the %VO2 ma × VO2 ma
−1. There is probably an upper limit in training kilometrage above which there are no improvements in the fractional utilisation of VO2 max at the marathon race pace. The influence of training on VO2 max and, to some extent, on the running economy appears, however, to be limited by genetic factors.
TL;DR: Systemic administration of 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine caused a rapid and long‐lasting reduction of both 3‐dihydroxyphenylalanine (dopamine, DA) and noradrenaline (NA) in mouse brain, as observed histo‐ and neurochemically.
Abstract: Systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) caused a rapid and long-lasting reduction of both 3,4-dihydroxyphenylalanine (dopamine, DA) and noradrenaline (NA) in mouse brain, as observed histo- and neurochemically. The depleting effects were more pronounced after repeated MPTP administration and the most marked reductions were observed after 2 X 50 mg MPTP/kg s.c., when DA in striatum and NA in frontal cortex were reduced by greater than 90% 1 week after MPTP. Mice with such catecholamine depletions were markedly sedated and almost completely immobilized. The behavioural syndrome after MPTP resembled that seen after reserpine, a monoamine-depleting drug. MPTP also caused a long-lasting reduction of catecholamine uptake in striatal DA and cortical NA nerve terminals and reduced tyrosine hydroxylase activity in these regions. There was no evidence that MPTP caused any marked DA and NA cell body death. MPTP given acutely transiently elevated serotonin levels. The results are compatible with a neurotoxic action of MPTP on both DA and NA nerve terminals. The nigro-striatal DA and the locus coeruleus NA neurone systems appeared to be most susceptible. Synthesis and utilization of residual striatal DA and cortical NA were increased, as often observed in partially denervated monoamine-innervated brain regions. Both DA and NA showed a gradual recovery, which took months to become complete and may have been related to a regrowth of catecholamine nerve terminals.
TL;DR: A 36 amino acid residue peptide, which contains a substance K sequence at its C-terminus has been isolated from porcine brain extracts and is highly biologically active with regard to gallbladder contraction, protein extravasation, hypotension and bronchial smooth muscle spasm.
TL;DR: It is concluded that multiple tachykinins, including SP, NKA, NPK and an ELE-like peptide, are present in capsaicin-sensitive sensory nerves in the guinea-pig.
TL;DR: It is suggested that low levels of 5‐HIAA in spinal fluid reflect a disorder of serotonin turnover, which makes the individual more prone to acts of violence in states of emotional turmoil.
Abstract: Concentrations of 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and 4-hydroxy-3-methoxyphenyl glycol (HMPG) in lumbar spinal fluid were measured by mass fragmentography in 16 men convicted for criminal homicide, 22 men who had attempted suicide, and 39 healthy male control subjects. Those men who had killed a sexual partner, and those who had attempted suicide, had lower levels of the serotonin metabolite, 5-HIAA in spinal fluid than the controls. It is suggested that low levels of 5-HIAA in spinal fluid reflect a disorder of serotonin turnover, which makes the individual more prone to acts of violence in states of emotional turmoil.
TL;DR: A sensitive method for the analysis of inorganic pyrophosphate (PPi) which utilizes the enzymes ATP sulfurylase and firefly luciferase is described, which has been used for continuous monitoring of formation of PPi in Rhodospirillum rubrum chromatophores.
TL;DR: To quantify muscle activity, sagittal knee joint moments and forces, enabling assessments to be made of different work postures, training exercises and joint derangements, a local biomechanical model of the knee was developed and correlated well with experimentally forces measured by others.
Abstract: The load moment of force about the knee joint during machine milking and when lifting a 12.8 kg box was quantified using a computerized static sagittal plane body model. Surface electromyography of quadriceps and hamstrings muscles was normalized and expressed as a percentage of an isometric maximum voluntary test contraction. Working with straight knees and the trunk flexed forwards induced extending knee load moments of maximum 55 Nm. Lifting the box with flexed knees gave flexing moments of 50 Nm at the beginning of the lift, irrespective of whether the burden was between or in front of the feet. During machine milking, a level difference between operator and cow of 0.70 m - 1.0 m significantly lowered the knee extending moments. To quantify the force magnitudes acting in the tibio-femoral and patello-femoral joints, a local biomechanical model of the knee was developed using a combination of cadaver knee dissections and lateral knee radiographs of healthy subjects. The moment arm of the knee extensor was significantly shorter for women than for men, which resulted in higher knee joint forces in women if the same moment was produced. A diagram for quantifying patellar forces was worked out. The force magnitudes given by the knee joint biomechanical model correlated well with experimentally forces measured by others. During the parallel squat in powerlifting, the maximum flexing knee load moment was estimated to 335-550 Nm when carrying a 382.5 kg burden and the in vivo force of a complete quadriceps tendon-muscle rupture to between 10,900 and 18,300 N. During isokinetic knee extension, the tibio-femoral compressive force reached peak magnitudes of 9 times body weight and the anteroposterior shear force was close to 1 body weight at knee angles straighter than 60 degrees, indicating that high forces stress the anterior cruciate ligament. A proximal resistance pad position decreased the shear force considerably, and this position is recommended in early rehabilitation after anterior cruciate ligament repairs or reconstructions. The methods presented quantify muscle activity, sagittal knee joint moments and forces, enabling assessments to be made of different work postures, training exercises and joint derangements.
TL;DR: A sensitive and specific radioimmunoassay was developed to determine the occurrence and concentration of neuropeptide Y ( NPY) in plasma and tissue extracts and NPY-like immunoreactivity (NPY-Li) was characterized by means of three different chromatographic systems.
Abstract: A sensitive and specific radioimmunoassay was developed to determine the occurrence and concentration of neuropeptide Y (NPY) in plasma and tissue extracts. Furthermore, NPY-like immunoreactivity (NPY-Li) was characterized by means of three different chromatographic systems. The NPY antiserum used (NI) did not cross-react with related peptides of the pancreatic polypeptide family except avian pancreatic polypeptide (1% cross-reactivity). Unextracted plasma contained high molecular weight proteins which interfered in the assay. Acid ethanol extraction removed this protein interference allowing a 90% recovery of NPY-Li. The content of NPY-Li in human plasma from healthy subjects was close to or below the detection limit (less than 22 pmol/l). Sympathetic nerve stimulation in the cat increased the output of NPY-Li from the splenic vein suggesting the release of this peptide upon sympathetic activation. The major peak of NPY-Li in spleen extracts and splenic vein plasma co-eluted with synthetic porcine NPY and a minor peak with larger Stokes radius was also present. The present radioimmunoassay enables further studies on the physiological and pathophysiological role of NPY.
TL;DR: The present findings indicate the presence of yet another neuropeptide or peptide family in the gastro-intestinal tract of several rodents and the pig.
Abstract: The distribution of galanin-immunoreactive (GAL-IR) neurons was mapped in detail in the gastro-intestinal tract of the rat, mouse, guinea-pig and pig by use of the indirect immunofluorescence technique. GAL-IR cell bodies were found in both the submucous and the myenteric plexus, with considerably higher numbers in the former ganglia. The largest number of GAL-IR perikarya was seen in the duodenal submucous plexus of the pig. With some (single) exceptions, GAL-IR cell somata were not observed in the myenteric plexus of the pig and guinea-pig, and in the submucous plexus of the esophagus and the stomach of the guinea-pig. GAL-IR fibers occurred in most parts of the gastro-intestinal tract. In the lamina propria a few non-varicose, weakly fluorescent fibers were noted in the mouse and rat, whereas in the pig and guinea-pig were large numbers of GAL-IR fibers with a varicose appearance was observed. These fibers were in all species most numerous in the distal portion of the intestinal tract. In the submucosa GAL-IR fibers were detected in all four species, and in the pig and guinea-pig some fibers surrounded blood vessels. A large number of GAL-IR fibers was generally seen in the circular smooth muscle layer, except in the guinea-pig, which only seemed to contain a few fibers. In the longitudinal muscle layer only single fibers could be detected. However, the gastric fundus region of the pig contained a moderate number of fibers in the longitudinally and obliquely oriented layers. In general, in the rat, mouse and pig, the submucous and myenteric plexus contained moderate or large numbers of GAL-IR fibers. In the guinea-pig, no or only single fibers were observed in the plexus of the upper gastro-intestinal tract and the rectum, while moderate numbers were seen in the ileum and colon. Thin adjacent sections stained for vasoactive intestinal polypeptide (VIP) and GAL revealed the coexistence of these two peptides in cell bodies of the myenteric plexus in the pig duodenum and guinea-pig colon. In these two species the GAL- and VIP-nerve fiber networks also exhibited marked similarities. However, in the rat and mouse VIP- and GAL-distribution patterns were in general different. The present findings indicate the presence of yet another neuropeptide or peptide family in the gastro-intestinal tract of several rodents and the pig.
TL;DR: Bleier et al. as mentioned in this paper examined the normal morphology, efferent projections and possible neurotransmitter content of neurons in the tuberomammillary nucleus (caudal magnocellular nuclei) of the adult male rat.
TL;DR: It is shown that wheat germ agglutinin-and choleragenoid-horseradish peroxidase give rise to markedly different labelling patterns, with different concentrations of labelled primary afferents in the marginal zone and substantia gelatinosa and less pronounced in the deep parts of the dorsal horn.
TL;DR: The developing inner ears of mice (CBA/CBA), ages ranging from gestational day 12 through postnatal day 21, were examined using scanning electron microscopy following the epoxy-embedding/freeze-fracture technique, allowing excellent preservation of the relationships between the developing sensory epithelium and the overlying membranes during their development.
Abstract: The developing inner ears of mice (CBA/CBA), ages ranging from gestational day 12 through postnatal day 21, were examined using scanning electron microscopy following the epoxy-embedding/freeze-fracture technique. This technique provides unique three-dimensional views of surface and fractured structures of the developing inner ear, thus allowing excellent preservation of the relationships between the developing sensory epithelium and the overlying membranes (i.e. the tectorial membrane and cupula) during their development. The tectorial membrane is formed of two distinct parts: the major (medial) and the minor (distal). The major portion is produced by the cells of the greater epithelial ridge prior to the formation of the minor part, which is produced largely by the primordial supporting cells of the lesser epithelial ridge. The developing tectorial membrane has two types of fibers: radial (found mainly in the major part) and slanted (found mainly in the minor part). The slanted fibers become the cover net, which fuses with the marginal band. The marginal zone of the developing tectorial membrane is completely sealed during development by the third row of Deiters' cells. The surfaces of cells that produce the tectorial membrane are characterized by numerous long microvilli which are largely lost when the tectorial membrane completely forms and separates from the supporting cells. The surface of developing auditory sensory cells is initially covered with numerous microvilli, some of which become future stereocilia. Stereocilia form stepped rows in the shape of a "W", with the tallest row located at the periphery of the cell. As the sensory cell matures, the short transitional stereocilia gradually disappear. Kinocilia on hair cells are still seen in the 14-day-old mouse (even though the organ of Corti is morphologically mature) but not in the 21-day-old mouse, indicating that complete maturation of the sensory cells in all turns is attained by 21 days of age. The mouse has upper radial tunnel fibers and basal tunnel fibers. Neural contacts of the upper radial tunnel fibers with the outer hair cells at the apical portions are frequent in the developing organ of Corti. The external sulcus cells undergo drastic changes during development, forming numerous pits that are often covered with mucus-like droplets or grape-like spherical structures of varying sizes. This phenomenon was observed only during postnatal days 6 and 14. The developing cupula starts as a thin amorphous membrane, which later becomes compact and fibrotic-like as the mass increases. By the 6th postnatal day well-developed cupular canals occur.(ABSTRACT TRUNCATED AT 400 WORDS)