Maturation of pyramidal cell form in relation to developing afferent and efferent connections of rat somatic sensory cortex.

Golgi and axonal labeling methods were used to examine the maturation of pyramidal cells in layers III and V of the rat somatic sensory cortex. The material came from animals late in the gestation period, postnatal, ranging from 0 to 43 days of age and at maturity. Special attention was paid to the period (0–7 days of age) during which it is known that thalamic and callosal fibers grow into the cortex. It is shown that the basic features of the pyramidal cell form are established before the long afferent fibers arrive in layers III and V and before the large number of synapses are established in these layers. Nevertheless, considerable dendritic growth and spine formation occurs after the afferent fibers establish an adult-like pattern of distribution. It is also shown that even at 1 day of age, the axons of pyramidal cells in all layers have reached the vicinity of targets such as the striatum, thalamus, brainstem, spinal cord and contralateral cortex.At 0–1 day the immature pyramidal cells are essentially bipolar in the upper cortical plate, but in the developing infragranular layers they have a few short, almost spine-free, basal dendrites and, rarely, a few oblique branches of the apical dendrite. The apical dendrite extends to the pial surface and the dendritic branches end in growth cones. The dendrites of cells in all layers increase in size and complexity of branching over the first postnatal week; the maturation of dendrites in layer V leads that of dendrites in the supragranular layers by about 2–3 days. As maturation proceeds, basal dendrites acquire secondary and tertiary branches and more oblique branches appear on the apical dendrite. Dendritic spines appear after 4 days of age but remain sparse up to 7–8 days. At 14 days of age, the spine density is much higher than in 7-day-old animals but remains at a much lower density than in 4-week-old, 6-week-old, or adult animals. By 7–14 days, the difference in maturity between superficial (layer III) and deep (layer V) pyramidal cells is difficult to discern qualitatively. All the pyramidal cells now have relatively complex, highly branched dendritic trees when compared to younger cells, but the dendritic tree is still immature in terms of the number, length and complexity of branching of the apical and basal dendritic systems.It can be concluded that the growth of the long axon of cortical pyramidal neurons precedes the acquisition of afferent connections and when these afferent fibers arrive in the cortex the dendritic tree of the pyramidal cell is still highly immature. Thus it remains possible that the finer modeling of the dendritic tree and the formation of spines may be affected by extrinsic influences such as the afferent fibers.     

Histopathology of tumour associated sarcoid-like stromal reaction in breast cancer

Summary In 5 cases of invasive ductal and lobular carcinoma of the breast multiple epithelioid and giant cell containing granulomas were detected, localized mainly in circumferential regions, but also in the center of the carcinomas. These granulomas were interpreted as sarcoid-like stromal reactions, occurring as sarcoid-like lesions in uni- and bilateral primaries, in a recurrent tumour, and also in axillary lymph nodes. Histopathologically, these granulomas were not quite uniform, some of them corresponding to typical sarcoidosis, others showing marked proliferations of epithelioid or giant cells or containing fibrinoid exudate or necroses. The granulomas were surrounded by dense infiltrates of mononuclear cells. Tuberculosis and mycosis was excluded. There were no hints of generalized sarcoidosis. Pathogenetically, these are reactions in the tumour stroma of varying intensity, and are not caused by necroses of the tumour tissue nor by microbial infections. Such tumour-associated sarcoid-like stroma reactions are interpreted as a T-cell mediated immune response to an antigen expression of the carcinoma acting as the local trigger; in 2 cases they were connected with sarcoid-like lesions of the axillary lymph nodes. Their occurrence in bilateral carcinoma of the breast points to an immunological disposition for this special kind of host-versus-tumour response. The intensity of these changes in a recurrent tumour reflects an immunological hypersensitivity reaction.The pathogenetic and differential diagnostic aspects of epithelioid granulomas of the female breast in chronic granulomatous mastitis, panniculitis, foreign body reaction, rare infections, and in therapeutically induced sarcoidosis are described and discussed.Dedicated to Prof. Dr. K. Lennert, Kiel, in Honour of his 65th Birthday     

Principal cells of the rat medial nucleus of the trapezoid body: an intracellular in vivo study of their physiology and morphology

The medial nucleus of the trapezoid body (MNTB) is one of several principal nuclei in the superior olivary complex (SOC) of mammals. It is classically thought to function as a relay station between the contralateral ventral cochlear nucleus and the lateral superior olive (LSO), playing a role among those brainstem nuclei that are involved in binaural hearing. In order to characterise the physiology and morphology at the cellular level of the major neuronal component of the MNTB, the principal cells, we have analysed these neurons in rats in vivo using intracellular recordings and horseradish peroxidase-labelling. Our data demonstrate that MNTB principal cells, when being stimulated acoustically via the contralateral ear, show a phasic-tonic response with an onset latency of 3.5 ms and a suppression of their spontaneous activity following stimulus offset. These neurons have an axonal morphology whose complexity has not yet been described. All cells (n=10) projected exclusively ipsilaterally and had terminal axonal arbors in a variety of auditory brainstem nuclei. At least two and maximally seven auditory targets were innervated by an individual cell. Each cell projected into the LSO and the superior paraolivary nucleus (SPN). Additional projections that were intrinsic to the SOC were often observed in the lateral nucleus of the trapezoid body and in periolivary regions, with only one cell projecting into the medial superior olive. Most, if not all, MNTB principal cells also had projections that were extrinsic to the SOC, as their axons ascended into the lateral lemniscus. In two neurons the ascending axon formed terminal arbors in the ventral nucleus of the lateral lemniscus, and the dorsal nucleus of the lateral lemniscus could be identified as a target of one neuron. The location of the cell bodies of the MNTB principal cells correlated with the neurons' best frequencies, thereby demonstrating a tonotopic organisation of the MNTB, with high frequencies being represented medially and low frequencies laterally. The axonal projections into the LSO and the SPN were also tonotopically organised and the alignment of the tonotopic axes was similar to that in the MNTB. Our results confirm previous data from other species and suggest that MNTB principal cells have a great amount of physiological and morphological similarities across mammalian species. Furthermore, the complexity of the axonal projections indicates that these neurons play a role in auditory information processing which goes far beyond their previously described classical role.     

Ecotropic and dualtropic mink cell focus-inducing murine leukemia viruses can induce a wide spectrum of H-2 controlled lymphoma types

Neonatal infection of C57BL and BALB/c mice by cloned ecotropic and dualtropic mink cell focus-inducing (MCF) murine leukemia viruses (MuLV) induces a wide spectrum of different lymphomas of T, B, and non-T/non-B cell types. Oncogenic dualtropic MCF viruses and poorly oncogenic ecotropic MuLV act synergistically in lymphomagenesis. Within one mouse strain virus-induced T-cell lymphomas arise earlier than B-cell lymphomas after neonatal inoculation of a single-cloned MuLV. The host genetic constitution, notably the H-2 complex has a marked influence on lymphoma type. This H-2 influence can be explained by an H-2-linked difference in penetration of the thymus early in life by oncogenic thymotropic MuLV, which in turn is correlated with, but not necessarily due to the magnitude of the anti-MuLV antibody response.     

Mechanism of disturbances of energy formation in acute ischemia of the liver

Respiration of rat liver mitochondria after the addition of ischemic toxin to the incubation medium was compared with respiration of mitochondria isolated from ischemic rat liver. The changes in respiration in both cases could be prevented by preliminary addition of dithiothreitol and reduced by subsequent addition of cytochrome c or dithiothreitol to the incubation medium. The similarity between the mechanisms of disturbance of energy formation is postulated.Laboratory of Transplantation of Organs and Tissues, Academy of Medical Sciences of the USSR, Moscow. Institute of Clinical and Experimental Medicine, Academy of Medical Sciences of the USSR, Siberian Branch, Novosibirsk. (Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Kovanov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 84, No. 9, pp. 301–303, September, 1977.     

Expression of alpha-methylacyl-CoA racemase (P504s) in various malignant neoplasms and normal tissues: astudy of 761 cases

Alpha-methylacyl CoA racemase (AMACR), also known as P504S, plays an important role in peroxisomal beta-oxidation of branched-chain fatty acids. It has recently been shown that AMACR is highly expressed in prostate cancer and that it may be an important diagnostic marker for prostate carcinoma. However, little is known about expression of AMACR in normal tissues and other malignant tumors. In this study, we investigated expression of AMACR in 539 malignant tumors and 222 normal human tissues of various types by immunohistochemical analysis. mRNA levels of AMACR in normal organs and in selected tumors were assessed by real time PCR. In normal tissue, high expression of AMACR mRNA was identified in liver, kidney and salivary gland, while AMACR protein was detected in liver (hepatocytes), kidney (tubular epithelial cells), lung (only bronchial epithelial cells), and gallbladder (only mucosal epithelial cells). High expression of AMACR mRNA was found in prostate, liver, and kidney cancers but rarely in stomach and bladder cancers. A high percent of adenocarcinomas arising from these organs express AMACR, including 17 of 21 (81%) of hepatocellular carcinomas and 18 of 24 (75%) of renal cell carcinomas. In addition, carcinomas arising from tissues normally not expressing AMACR were also positive for the antigen, including 17 of 18 (94%) prostate carcinomas, 9 of 29 (31%) of urothelial carcinomas, and 4 of 15 (27%) of gastric adenocarcinomas. Two hundred and fifty cases of adenocarcinomas from lung, breast, pancreas, bile duct, adrenal gland, salivary gland, ovary, thyroid and endometrium were negative or rarely positive for AMACR. Neuroendocrine carcinomas rarely expressed AMACR. Melanomas, squamous cell carcinomas, basal cell carcinomas, soft tissue tumors (including epithelioid sarcomas and synovial sarcoma), thymomas, and germ cell tumors were negative for AMACR. Our data provide important baseline information for using AMACR in clinical practice and also are valuable in furthering understanding of the pathogenic role of AMACR in malignant neoplasms.     

Laminar distribution and morphology of NADPH-diaphorase containing neurons in the superior colliculus and underlying periaqueductal gray of the rat

Summary We have studied the laminar distribution of reduced nicotinamide dinucleotide phosphate diaphorase (NADPH-d) activity and the morphology of positive neurons in the superior colliculus (SC) and the underlying periaqueductal gray (PAG) of the rat. The morphology of NADPH-d-positive neurons has been compared to that of Golgi-impregnated cells. The highest activity occurs in the stratum zonale and stratum griseum superficiale, contrasting with the pale neuropil in the stratum opticum, where only a few positive neurons are found. In the stratum griseum intermedium positive neurons are grouped in patches separated by narrow, NADPH-d-negative bands. In the deeper layers, the neuropil is NADPH-d-negative, and few neurons show enzymatic activity. In contrast, numerous neurons in the dorsolateral part of the PAG are intensely positive. They are continuous with the positive neurons in the stratum album profundum, with no clear border between the two centers. In both SC and PAG, only small and medium sized neurons are NADPH-d-positive. In comparison with Golgi material, all types of small neurons in the superficial layers show NADPH-d activity; NADPH-d histochemistry, however, does not visualize the characteristic dendritic appendages of these neurons. The large neurons of the SC and PAG, probably representing the long-projecting neurons of these centers, do not contain the enzyme.     

Evaluation of quantitative aerosol techniques for use in bronchoprovocation studies

To investigate airway physiology by use of inhaled aerosols, it is frequently necessary to measure the actual amount of material deposited on the airway wall as well as the site of particle deposition. To satisfy these needs, radiolabeled aerosols and gamma camera techniques have been used to measure regional deposition of inhaled particles. To make quantitative measurements of the amount deposited, previous investigators have used a "phantom" technique to indirectly calibrate the gamma camera for the attenuation of gamma rays through the lungs and chest wall. For this calibration, the phantom is a simulated lung containing a known amount of radioactivity. Radioactive counts emitted from the phantom are assumed to be attenuated in the same manner as the intact human lung. The present article describes a technique to determine directly the amount of inhaled aerosol deposited in the lung and simultaneously to calibrate the gamma camera for each individual subject. We used right angle light scattering and a gamma camera to measure individual values of the deposition fraction (DF) of inhaled aerosol deposited in the lung and the coefficient of attenuation (AC) of gamma rays in normal and obstructed lungs of human subjects. Radiolabeled monodisperse aerosols 1 and 2 microns in diameter were used. Knowledge of the activity of the inhaled aerosol (microcurie per liter), the volume inhaled, and the measured DF determined each subject's AC (counts per minute per microcurie). DF varied by an order of magnitude in normal (0.04 to 0.48) and obstructed (0.16 to 0.75) of subjects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Immune aspects of intestinal metaplasia of the stomach: An immunohistochemical study

Summary Immune characteristics of intestinal metaplasia of the stomach were analyzed by the immunoperoxidase technique in frozen and paraffin-embedded specimens. In fetal and minimally inflamed adult gastric mucosa, secretory component (SC) was absent from epithelial cells. Non-intestinalized gastric mucosa with evident inflammatory changes showed weak SC immunoreactivity at the generative cell zone. Enhanced immunoreactivity of SC with evidence of transepithelial transport of IgA and IgM, but not of IgG, was demonstrated in intestinalized glands of either the complete or incomplete type. The number of inflammatory cells and lymphoid follicles was decreased in intestinalized mucosa when compared with that in non-intestinalized gastritic mucosa; J chain-negative IgG plasma cells and T cells, both of which were fairly abundant in the latter mucosa, were remarkably decreased in the former mucosa, whereas the decrease of J chain-positive IgA or IgM plasma cells was slight or equivocal. In either mucosa, IgA was the most popular immunoglobulin class in plasma cells. IgD plasma cells were very rare. In the germinal centers of lymphoid follicles which were preferentially distributed in non-intestinalized gastritic mucosa, IgM or IgG germinocytes predominated over IgA germinocytes, and a few T cells and NK cells also were present. Intraepithelial lymphoid cells with a T-suppressor phenotype were detected in intestinalized glands. The possibility that intestinal metaplasia is an adaptation to long-standing chronic gastritis is discussed.     

Mixed epithelial and stromal tumors of the kidney. A report of 22 cases

Mixed epithelial and stromal tumor of the kidney (MESTK) is a recently described subset of renal neoplasm that tends to occur in middle-aged and older women and is characterized by a distinctive histological appearance. To further characterize this lesion, we report the clinicopathological and immunohistochemical features of 22 additional cases from our institutional files. Grossly, the tumors ranged in size from 1 cm to 14 cm (mean 6.7 cm), were well circumscribed but unencapsulated, and showed a cystic cut surface. The tumors were composed of a spindle cell proliferation that resembled ovarian stroma, as well as an epithelial component lining the cystic structures, which usually consisted of flat to hobnailed cells typical of collecting-duct epithelium. Areas displaying features of Müllerian differentiation were also documented in 6 cases, including epithelium of endometrioid, tubal, clear cell and squamous cell type as well as one case showing an architecture that closely resembled Müllerian adenofibroma and adenosarcoma. Follow-up in 14 patients (average 4.4 years) showed no evidence of recurrence or metastasis. We believe these tumors represent the renal counterpart of similar mixed epithelial and stromal neoplasms occurring in the biliary tract and pancreas, which is also characterized by cystic structures lined by epithelium, admixed with ovarian-type stroma. The differential diagnosis for these tumors includes cystic nephroma and cystic partially differentiated nephroblastoma, which we believe to represent clinically and morphologically distinct entities from MESTK. In particular, the distinction from cystic nephroma in adult male patients is emphasized, and two cases of this entity are included in the study for comparison.