Bio-morphological events in the development of the human female mammary gland from fetal age to puberty

Bio-morphological understanding of the developing human mammary glands may clarify some aspects of breast pathology, including cancer. In particular, some epidemiological data suggests that during fetal growth an altered intrauterine hormonal status, especially a change in estrogen status, could predispose to carcinogenesis. In an attempt to achieve new information on early breast growth, a series of developing human breasts have been analyzed, namely: 4 fetal breasts (28–32 weeks of gestational age), 7 infant breasts (7 h to 2 years) and 1 puberal breast (12 years). In addition to the morphological features, we studied the immunohistochemical expression of some markers involved in morphogenesis, such as MIB-1 for cell proliferation, bcl-2 for apoptosis control, CD34 for vasculogenesis, estrogen (ER) and progesterone (PR) receptors for hormonal profile, and smooth-muscle actin for myoepithelial differentiation. The results were as follows: (a) lobules, absent between 28 weeks and 2 days, were well evident at 2 years of age and at puberty; (b) myoepithelial cells appeared from 28 weeks onward and persisted later with no modification in quantity and distribution; (c) epithelial cell proliferation was constantly low; (d) in all breasts inner epithelial cells showed diffuse bcl-2 positivity, while basal myoepithelial-like cells were generally negative; (e) all breasts were well vascularized with two different patterns: periductal vascularization (PDV) and interductal vascularization (IDV), IDV being always present, whereas PDV was found only in infant breasts; (f) ER and PR were almost absent in fetal and infant breasts, while their expression was high in the epithelial cells of the puberal breast; (g) stromal cells had no hormonal receptors and were heterogeneous for proliferation and bcl-2 expression. Interestingly, two fetal breasts showed high proliferation and high ER expression, respectively, in their epithelial compartment. This could be the expression of an altered hormonal environment in utero, representing a basis for possible subsequent cancer initiation. Received: 14 July 1999 / Accepted: 3 November 1999     

The development of stomach during the fetal period

The objective of this study was to explore the fetal development of the stomach, its morphology and relationship with neighboring structures. The study is carried out in 2003 using 160 human embryos and fetuses (81 males and 79 females) aged between 9 and 40 weeks of gestation. None of the cases had any external pathology or anomaly. Its topographical localization and relationship with surrounding structures were revealed with anatomical dissections. Width and height of the stomach, lengths of the greater and lesser curvatures, the angle between horizontal and vertical axes of the stomach and types of stomach were established. During the fetal life stomach was most commonly located above the transverse axis passing through the umbilicus, in left and right hypochondrium (81%). There were significant differences among trimester groups with respect to the localization of the stomach in the quadrants (P < 0.001). There were no significant sex differences in parameters. After the second trimester, the height of the stomach increased more than the width of the stomach and anterior abdominal height. The angle of stomach decreased from 100° to 50° throughout the fetal period. During the fetal period, wide angles stomach was more common in the first^f and second trimesters while acute-angled stomach was more common in the third trimester and term fetuses. Diagnosis and treatment of fetal anomalies and pathologies of the stomach requires knowledge of fetal anatomy of the stomach. Data acquired in this study are believed to contribute to the studies of obstetrics, perinatology, forensic medicine and fetal pathology on fetal development of the stomach, and diagnosis and treatment of its anomalies, pathologies, and variations.     

人早期胚肝中前B细胞的发生

采用抗人μ重链单抗结合 APAAP 酶标记法对6～11周人早期胚肝的研究结果表明:6～6.5周的胚肝中未发现有μ~ 细胞;1例47天的胚肝中最早观察到胞浆μ~ 的前 B 细胞,7～11周的所有样本中都存在有前 B 细胞,因此胚肝中最早出现前 B 细胞的时期是在7周(49天)前后,最早出现的前 B 细胞为椭圆形大淋巴样细胞;在6～11周的胚肝中前 B 细胞呈散在分布,可能都是独立发生且处于分裂不活跃的状态。     

Characterization of angiotensin receptors on human skin fibroblasts

 Angiotensin II is involved in blood pressure regulation, cell growth and angioneogenesis. The angiotensin receptors which mediate the intracellular effects of angiotensin II are expressed in numerous tissues and cell types. We studied the expression of angiotensin II receptors in cultured human skin fibroblasts derived from a skin biopsy. Angiotensin II binding characteristics were analyzed by radioligand binding assays. The DNA synthesis was assessed by [H]thymidine incorporation assays. Intracellular calcium concentrations were measured by fura-2 spectrofluorometry, and mRNA expression levels were analyzed by northern blot technology. Two distinct angiotensin receptors were detectable on human skin fibroblasts: the AT1 receptor with K _d=1.0± 0.7 nmol/l and B _max=17.9±0.9 fmol/mg protein, and an angiotensin_(1–7) binding site with K _d=26±6.6 nmol/l and B _max=80.4±3.5 fmol/mg protein, as shown by competition binding assays using selective angiotensin II receptor antagonists and the heptapeptide angiotensin_(1–7). The angiotensin AT1 receptor mRNA was substantially expressed in human skin fibroblasts and was subjected to homologous downregulation. In human skin fibroblasts angiotensin II caused a profound increase in intracellular calcium which was blocked by angiotensin AT1 receptor antagonists such as Exp-3174. Furthermore, both angiotensin II and angiotensin_(1–7) led to increased DNA synthesis in human skin fibroblasts. In conclusion, cultured human skin fibroblasts express angiotensin AT1 receptors and a putatively new angiotensin receptor activated by angiotensin_(1–7), both coupled to signaling pathways involved in DNA synthesis. Received: 5 July 1996 / Accepted: 29 November 1996     

Myoepitheliomas of the skin and soft tissues

 We describe 12 cutaneous and soft tissue myoepitheliomas, most of them in elderly patients. Morphologically the cutaneous and soft tissue myoepitheliomas revealed the same spectrum as their salivary gland counterparts. They were composed of a mixture of spindle, epithelioid and clear myoepithelial cells. Immunohistochemically they were positive to keratins and S-100 protein and reacted inconsistently with antibodies to smooth muscle actin. Morphologically they lacked any folliculo-sebaceous or apocrine differentiation. We believe that they are related to the eccrine type of cutaneous mixed tumours. Most cases had a benign behaviour, but 1 tumour metastasized, and the patient died of the tumour. Myoepitheliomas of soft tissues should be distinguished from other neoplasms with epithelial differentiation and from ossifying fibromyxoid tumour of soft parts, parachordoma and extraskeletal myxoid chondrosarcoma. Received: 6 July 1998 / Accepted: 5 December 1998     

Recordings of polymodal single C-fiber nociceptive afferents following mechanical and argon-laser heat stimulation of human skin

Recordings were made in the peroneal nerve of healthy volunteer subjects from C-mechano-heat (CMH) nociceptors (n=25) with their receptive fields in the skin on the dorsum of the foot. The investigation focused on afferent single C-fiber activity induced by short (200 ms) high-intensity argon-laser light pulses projected to localized spots of the skin. Cutaneous heat stimulation with the argon laser, 2–3 times the activation threshold, induced inter-burst spike frequencies in the nerve, reaching 50 Hz, while mechanical stimulation 10–20 times threshold only evoked frequencies reaching 10 Hz. The decrease in conduction velocity of action potentials in the C-fiber afferents following mechanical and heat stimulation was closely related to the degree of activation. Following a laser pulse of 200 ms, a spike pattern with highly reproducible inter-spike intervals was evoked with a fast saturation. On the contrary, a high variability in the number of action potentials evoked by both heat and mechanical stimuli was found, depending on the location of stimuli within the receptive field. A relation between the conduction velocity and the peak firing within the spike train following laser stimulation was detected. Heat and mechanical stimulation activated single C-fibers in matching spots within the same skin areas, in line with the assumption that the two modalities in the CMH-fibers share matching morphological cutaneous substrates. No correlation was found in thresholds or excitability to mechanical and heat stimulation, respectively. This suggests that subsets of receptors exist within nerve endings of the cutaneous receptive fields, with the ability to generate action potentials independent of heat and mechanical stimuli. Unexpectedly, no signs of sensitization or other inflammatory responses were observed after repeated laser pulses; on the contrary, a rapidly developing fatigue was observed when single spots were repeatedly stimulated. However, no fatigue was observed if neighboring spots were stimulated, indicating a localized generator of the fatigue. In each subject, a good correlation was observed between the reported pain sensation and the activity evoked in the afferent C-fibers by the laser. However, the magnitude of the reported pain sensation to comparable degrees of C-fiber activation showed a high variability between different subjects. A fairly good subjective estimate of the afferent-fiber activation was observed when skin spots from 3- down to 1-mm diameter were stimulated. In a few individuals, no painful sensation was reported when the stimulated spots were reduced to 1-mm diameter, despite the occurrence of multiple spikes in single C-fiber afferents, amplifying the importance of spatial summation in the perception of pain. Received: 14 December 1997 / Accepted: 24 March 1998     

The transient disappearance of cytokeratin in human fetal and adult ovaries

Cells from the inner and outer granulosa cell layers of the ovarian follicles differ in function, probably because of their different origins from the surface epithelium and from the rete. This suggestion has not so far been thoroughly investigated in the human ovary. We examined fetal ovaries from the early, middle and late gestational periods, ovaries from fertile women, and preovulatory follicular cells obtained from patients under in vitro fertilization therapy (IVF). Indirect immunohistology and immunocytology were used to detect the presence of cytokeratin (CK)-positive epithelial cells. In fetal ovaries from the early gestational period, prominent rete tubules (sometimes with oocytes) appeared to be fused with the sex cords and primordial follicles. Both showed CK-positively, detected with the pan-CK antibody Lu-5. Cytokeratin 19 was clearly expressed in the fusion area. In the fetal and adult ovaries, CK-positive follicular or granulosa cells were noted in the primordial and primary follicles as well as the preovulatory follicles. Cytokeratin was not detected in the granulosa cells of growing follicles, CK-positive and -negative luteal cells were identified in the developing corpus luteum. We conclude for the human ovary: (1) the heterogeneous morphology of granulosa cells may be explained by their twofold origin from the surface epithelium and the rete, (2) the rete tubules appear to be involved in folliculogenesis, (3) the transient absence of CK expression in growing follicles compared to resting and mature follicles or to the developing corpus luteum indicates a particular role of CK-positive cells at the periovulatory period. Accepted: 20 September 1999     

The development of fetal pylorus during the fetal period

Objective  The objective of this study was to explore the localization of the pylorus, its macroscopic and microscopic development and relationship with neighboring structures. Materials and methods  The study is carried out on 160 human fetuses aged between 9 and 40 weeks of gestation. Abdomen was divided into four quadrants by horizontal and vertical planes passing through the umbilicus. Topographical localization of the pylorus in reference to these quadrants and its distance were determined. Pylorus was divided into pre-pyloric, pyloric, and post-pyloric regions. Starting from the pre-pyloric end, serial sections spanning whole pyloric part were obtained. Wall thickness, the thickness of the muscular coat were measured under light microscope using sections stained with hematoxylin eosin. Sections with the thickest muscular coat were considered as the region where pyloric sphincter was. Findings  Pylorus was located in the right upper quadrant, on the median plane and in the left upper quadrant. There was a significant relation between the thickness of the muscular coat in the stomach, duodenum and the pyloric region and gestational age. In the region of the pyloric sphincter, the rate of increase in the thickness of the muscular coat was higher in the first and the first half of the second trimesters than term fetuses. Conclusion  We believe that data obtained in the present study will contribute to the assessment of development of the pyloric region in intra-uterine cases.     

Intermediate filament proteins in developing human arteries

 The distribution of intermediate filament proteins in adult human blood vessels and in human fetal elastic arteries is relatively well-known. However, the distribution of these proteins in the course from neonate to adult has not been established. In this investigation, human postnatal arteries were studied with immunohistochemistry, using antibodies targeted on the intermediate filament proteins desmin, vimentin and cytokeratins 8, 18 and 19. Vimentin was present in most smooth muscle cells in all vessels and at all ages. The proportions of desmin-expressing cells increased in the elastic arteries during the first year of life and was higher in the pulmonary trunk than in the aorta. In the muscular arteries, the proportion of desmin-labelled cells increased in the coronary and the deep femoral arteries, but remained constant in the renal and the cerebral arteries. Cytokeratins were detected in the pulmonary trunk earlier than in the aorta. Cytokeratins were present throughout the wall of the ductus arteriosus, but desmin was present only in some cells. Thus, there are postnatal changes in the distribution of intermediate filament proteins in the elastic arteries and in some muscular arteries, whereas the intermediate filament pattern remains unchanged in other muscular arteries. Accepted: 31 July 1998     

Brain temperature and metabolic responses during umbilical cord occlusion in fetal sheep

 The purpose of this study was to compare core body and brain temperatures after complete but intermittent occlusions of the umbilical cord. Thermocouple probes were placed in the parasagittal parietal cortex, ascending aorta, and jugular vein of eight near-term fetal sheep and in the maternal descending aorta. Three days later, after an initial control period, the umbilical cord was occluded for 5 min, followed by a 30-min recovery period, and this cycle was repeated 4 times. Temperature changes, blood gases, and plasma glucose, lactate and adenosine were measured. In the first occlusion period, body core temperature increased 0.12°C over control, and then declined to baseline after cord release, and this pattern was repeated with subsequent occlusions. Brain temperature, however, did not increase in response to any of the cord occlusions. Plasma adenosine increased 2.4-fold during the first occlusion, but not during subsequent occlusions, despite a continuing pattern of constant brain temperature, a result which minimizes adenosine’s importance as a continuing regulator of cerebral metabolism. We conclude that brain temperature fails to increase because of diminished heat production by the brain and increases in cerebral blood flow, responses which delay complete depletion of adenosine 5′-triphosphate stores in brain tissue. Received: 18 March 1998 / Received after revision: 18 May 1998 / Accepted: 30 May 1998     

Immunohistochemistry and in situ hybridization of the androgen receptor in the developing human prostate

 As it is suggested that the androgen receptor mechanism is required for prostatic development, we attempted to determine the appearance, expression and distribution of the androgen receptor in embryonic, infantile and pubertal human prostate. Using mono- and polyclonal antibodies and a digoxigenin-labeled 713 bp riboprobe, the androgen receptor expression in paraffin sections of fetal, infantile, and pubertal prostates was studied at the protein and RNA level. Under highly standardized conditions, application of the polyclonal antibodies resulted in a weak cytoplasmic and nuclear labeling of the epithelium of fetal glands. No immunoreaction was obtained with monoclonal antibodies. Applying the polyclonal antibody to pubertal and adult specimens, immunoreactivity of the androgen receptor was positive in nuclei of adluminal and basal epithelial cells, in interstitial and vascular smooth muscle cells and vascular endothelium, whereas ganglionic cells and enteroendocrine cells were negative. In situ hybridization with the digoxigenin-labeled riboprobe gave clear positive results already in epithelium of very young fetal specimens. A semiquantitative visual evaluation of in situ hybridizations showed that intermediate intensity of expression was increased in pubertal and adult specimens, whereas strong expression was reduced in prostatic epithelium. Conclusions: The essential findings are: (1) an early expression of androgen receptor mRNA in the fetal prostate; (2) no immunoreaction of monoclonal antibodies against the androgen receptor in the same specimens, (3) a decrease of androgen receptor mRNA expression, but increase in immunoreactivity of the androgen receptor protein with the onset of glandular maturation during puberty. Accepted: 29 September 1997     

Cytomegalovirus genome and the immediate-early antigen in cells of different layers of human aorta

A number of data suggest that reactivation of cytomegalovirus (CMV) latent in arterial wall cells may contribute to atherogenesis; however, there is no direct evidence available. To address this issue, we have examined, using in situ hybridization or immunohistochemical staining, the frequency of occurrence of cells containing viral genome and of those expressing the IE 70 viral antigen in the endothelial layer and in deeper layers of human aortas with or without visible atherosclerotic lesions. Using endothelial cell cultures or tissue endothelial preparations, we found CMV-hybridizing endothelial cells in 6 of 8 grossly normal aortas and in 16 of 18 lesioned aortas. Antigen-positive endothelial cells were detected in 1 of 5 grossly normal vessels and in 6 of 7 lesioned vessels. Infected endothelial cells were abundant in areas adjacent to orifices of intercostal arteries of grossly normal aortas and in fatty spots of lesioned aortas, but no infected endothelial cells were observed in most plaques examined. In paraffin sections of grossly normal vessels, we detected CMV genome in cells adjacent to lumen and in cells randomly scattered through subendothelial intima and the media; however, no immunoreactive viral protein was found in the same tissue samples. In sections of lesioned vessels, clusters of CMV-hybridizing cells were found in the media in addition to infected cells randomly scattered through the intima and the media. In these samples of lesioned vessels, viral antigen was detected in cells adjacent to lumen and in cells clustered at the intima/media border. We found antigen-positive cells in grossly normal areas of lesioned aortas and in fatty lesions, but not in plaques of the same vessels. The data suggest that accumulation of the immediate-early CMV antigen in cells of endothelial layer and development of antigen-positive cell clusters in deeper layers of vascular wall accompany early atherogenic events in human aorta. Received: 10 June 1999 / Accepted: 16 November 1999     

Postnatal development of interhemispheric asymmetry in the cytoarchitecture of human area 4

 The postnatal development of interhemispheric asymmetry was analyzed in the primary motor cortex (area 4) of 20 human brains with quantitative cytoarchitectonic techniques. The volume fraction of cortical tissue occupied by cell bodies (grey level index) was determined by automated image analysis. In children as well as in adults, the volume fraction of cell bodies averaged over all cortical layers was greater on the right than on the left. Thus, the space between cell bodies, i.e. the volume fraction of neuropil containing axons, dendrites and synapses, was greater in the left than in the right primary motor cortex. At the level of single layers, however, interhemispheric asymmetry of the neuropil volume fraction differed between age groups. The supragranular layers were significantly less asymmetrical in children than in adults, whereas the infragranular layers showed a similar degree of asymmetry in both age groups. Thus, the postnatal development of the architectonic asymmetry in the supra- and infragranular layers of area 4 follows the same sequence of maturation as found during neuronal migration, i.e. an inside-to-outside gradient. Comparing the layer-specific developmental pattern with available functional data, it was found that the structural maturation of interhemispheric asymmetry in the supragranular layers correlates with the development of hand preference. Accepted: 25 June 1997     

Proximodistal structure of early reaching in human infants

Nine infants were tested, at the age of onset of reaching, seated on their parent’s lap and reaching for a small plastic toy. Kinematic analysis revealed that infants largely used shoulder and torso rotation to move their hands to the toy. Many changes in hand direction were observed during reaching, with later direction changes correcting for earlier directional errors. Approximately half of the infants started many reaches by bringing their hands backward or upward to a starting location that was similar across reaches. Individual infants often achieved highly similar peak speeds across their reaches. These results support the hypothesis that infants reduce the complexity of movement by using a limited number of degrees-of-freedom, which could simplify and accelerate the learning process. The proximodistal direction of maturation of the neural and muscular systems appears to restrict arm and hand movement in a way that simplifies learning to reach. Received: 27 July 1998 / Accepted: 26 March 1999     

Overexpression of cyclin D1 in nonmelanocytic skin cancer

Although the overexpression of cyclin D1 has been believed to play important roles in neoplastic transformation of some tumors, little is known about the function of cyclin D1 protein in carcinogenesis in human skin. A total of 307 patients with nonmelanocytic skin cancer, being 46 with Bowen’s disease (BOD), 134 with squamous cell carcinoma (SCC) and 127 with basal cell carcinoma (BCC), were investigated immunohistochemically using monoclonal antibody to cyclin D1 by the LSAB method, to assess the expression of cyclin D1 in skin cancer including its precursors. The positive rates of cyclin D1 immunostaining in BOD, SCC and BCC were 63.0%, 69.4% and 54.3%, respectively. The positive rates in dysplasia adjoining BOD, SCC and BCC were 43.6%, 67.9% and 59.8%, respectively. In morphologically normal skin, however, only 2 cases, 1 of SCC and 1 of BCC, exhibited positive staining. These findings suggested that overexpression of cyclin D1 is an early event in dysplastic lesions of skin. Overexpression of cyclin D1 was related to sun exposure, especially in dysplasia of SCC. The score for cyclin D1 expression in dysplasia of BCC was correlated with age. Expression of cyclin D1 markedly increased from normal skin through dysplasia to BOD, but was not significantly related to the degree of SCC differentiation. These findings demonstrate that the effect of cyclin D1 overexpression is restricted to proliferation of cells, so that they gain a growth advantage, but their differentiation is not increased. Comparison with the results for p53 protein expression in these tumors, a significant correlation with cyclin D1 expression was found in dysplasia in BOD and SCC, and in patients with BCC who were less than 74 years old. These findings suggested the hypothesis that prior aberrant p53 expression may affect or regulate the overexpression of cyclin D1. Received: 6 September 1999 / Accepted: 10 November 1999     

Practice modifies the developing automatic postural response

 The purpose of this study was to examine effects of experience with a postural task on components of the automatic postural response including: (1) probability of activation of functionally appropriate postural muscles; (2) number of functionally appropriate postural muscles activated; and (3) onset latencies of functionally appropriate postural muscles in infants. Infants (n=15; age 36–48 weeks old) able to pull themselves into a standing position but not able to walk independently were tested using a postural task requiring the infant to stand and balance, with support, following a forward or backward movement of the support surface (platform perturbation). Infants were tested twice at 5-day intervals. One-half of the infants, the training group, were given intense platform perturbation training on the days between test sessions. Infants in the second group were also brought into the laboratory on the days between test sessions but were not exposed to platform perturbations during those days. Electromyograms of six leg and trunk muscles were recorded during test sessions to provide muscle onset latencies, probability of muscle activation data, and the number of postural muscles activated following a perturbation. Training infants demonstrated significant increases in probability of activating functionally appropriate muscles with tibialis anterior, quadriceps, and abdominal muscles activated in response to backward sway and gastrocnemius muscle in response to forward sway. The number of functionally appropriate postural muscles activated in a single trial also increased in the training group. There were no significant changes in mean postural muscle onset latencies or number of trials with antagonist muscle coactivation for either training or control groups. These findings suggest that during development selective parameters of the automatic postural response are affected by experience with the postural task. Received: 30 November 1996 / Accepted: 12 September 1996     

Development of the vermiform appendix during the fetal period

This study aimed to determine the location and development of the vermiform appendix (VA) in terms of morphometry. It was carried out on 80 human fetuses that exhibited neither external pathology nor anomaly and whose gestational ages were between 10 and 40 weeks. The location of the VA and cecum was established. Total VA diameter, lumen diameter, wall thickness, serosa, muscularis and mucosa thickness were measured on microscope slides. The VA was almost always observed in the subcecal region during the fetal period. The length of the VA and the attachment length of the meso-appendix to the VA increased with the gestational age. Lymphocyte aggregation was first seen at the 17th week of the fetal period. Positive and meaningful correlation was found between gestational age and morphometric parameters of the VA. A significant difference was found between the genders in the thickness of mucosa, which was larger in girls (p<0.05). When the proximal, median and distal parts were compared, the thickness of serosa between the proximal and distal parts was also significantly different (p<0.05). The present study has revealed that the VA matures in the second trimester during the fetal period. Furthermore, the morphologic development of the VA is almost uniform from the proximal to distal part.This study was presented as an oral presentation at the Meeting of the Anatomical Society of Turkey, 25–30 October 1999, Antalya, Turkey     

Movement detection at the distal joint of the human thumb and fingers

To determine whether proprioceptive acuity is the same at all digits, particularly when postured as in a ’grasp’, we imposed 10° movements at the distal joint of the thumb, index and ring finger, at three velocities; 1.25°/s, 2.5°/s and 5°/s. The test joint was initially flexed by 25° and the joints proximal to the test joint were maintained in a standard posture for each study. When in a grasp posture that disengaged the extensor muscles at the distal joint of the finger, movement detection at the thumb was superior to that at the fingers for all velocities. However, when the fingers were positioned so that all proprioceptive inputs were able to contribute (i.e. cutaneous, joint and both flexor and extensor muscle afferents), proprioceptive acuity was similar for the three digits. Loss of local cutaneous (and joint) inputs by digital anaesthesia significantly impaired performance at all digits, suggesting a critical role for cutaneous input in normal proprioceptive sensibility at all distal joints of the digits. Anaesthesia of the extensor muscle afferents innervating the thumb did not affect its proprioceptive acuity. Thus, for the thumb, the extensor muscle afferents do not provide critical information. The greater change in muscle fascicle length for the thumb’s long flexor muscle (3% per 10°) compared with that in the finger flexor muscles (e.g. 0.1% per 10°) could contribute to the thumb’s performance. There appears to be less redundancy of muscle and non-muscle signals for the fingers than for the thumb, because a reduction in either cutaneous or muscle input significantly impaired acuity at the fingers. Overall, when the hand is in a grasping posture, irrespective of the contribution of local cutaneous inputs, the long flexor acting on the thumb may contribute more to its proprioceptive acuity than the long finger flexors contribute to acuity at the fingers. Received: 20 January 1998 / Accepted:25 March 1998