Transplantation of central nervous tissue

Studies of post-lesional reorganization of central nervous connections have shown that central nerve fibers respond to nearby denervation by sprouting and formation of new terminals. The connections in the central nervous system (CNS) are accordingly much more plastic than was thought for a long time. This has revived the interest in transplantation of central nervous tissue. In this study we present some historical data on CNS transplantation supplemented by recent results obtained in our laboratory. Pieces of hippocampal tissue from embryonic or early postnatal rats were transplanted to different parts of the brain of littermates or adult rats. About two-thirds of the transplants were recovered after survival times ranging from 4 d to 2 years, and their cytological organization and intrinsic connections were monitored by cell and fiber stains and histochemical methods (AChE staining and Timm sulphide silver method). Comparison with both a normal and a lesioned control material revealed that in most transplants the tissue had developed as it does when left in situ in the donor brain, but deprived of its major afferent connections. In several instances we found evidence of a major exchange of connections between the transplants and host brains. The conditions needed for this to occur appeared to involve growth stimulation of host brain fibers by transection (host to transplant) and denervation of host neuropil (transplant to host). In cases where these conditions are met, the use of transplants may have future implications in attempts to repair lesions in the central nervous systems.     

Light microscopic morphometric analysis of castration effects in the different lobes of the rat prostate

The morphologic effects of androgen deprivation in the different lobes of the rat prostate were examined by light microscopic morphometry. The prostates of Wistar male rats (260-340 g) were fixed in situ by glutaraldehyde perfusion in castrated animals 1 week after gonadectomy and in intact animals. The ventral (VP), dorsal (DP), and lateral (LP) lobes as well as the coagulating gland (CG) were dissected out, weighed, and processed for light microscopy. Using stereologic methods the following parameters were estimated for each lobe: volume fraction of connective tissue, epithelium and glandular lumina, average epithelial height, average epithelial cell volume, and total number of epithelial cells. Castration leads to a 58-76% reduction of the wet weight of all prostatic lobes. The decrease of glandular tissue is greater in VP than in LP, DP, and CG. In VP and LP, there is a 39-45% reduction of the epithelial height, and this effect is less pronounced in DP and CG. For all lobes, the shrinkage of average epithelial cell volume is in the same range (25-30%). Moreover, in VP and LP, there is a 70% reduction of the total number of cells, whereas the reduction is less in DP and CG. It thus seems that the reduction of prostatic epithelial tissue mass upon castration is due to a reduction of the number of cells as well as a reduction of the volume of individual cells. VP and LP appear to be more androgen-dependent than DP and CG.     

Fluctuations in tumor blood perfusion assessed by dynamic contrast-enhanced MRI.

Temporal heterogeneity in blood perfusion is a common phenomenon in tumors, but data characterizing the nature of the blood flow fluctuations are sparse. This study investigated the occurrence of blood flow fluctuations in A-07 melanoma xenografts by using gadopentetate dimeglumine (Gd-DTPA)-based dynamic contrast-enhanced MRI (DCE-MRI). Each tumor was subjected to two DCE-MRI acquisitions separated by 1 hour. The data were processed by Kety analysis and resulted in two E.F images (E is the initial extraction fraction of Gd-DTPA and F is the perfusion) and two lambda images (lambda is the partition coefficient of Gd-DTPA) for each tumor. The E . F images were used to determine the changes in blood perfusion arising in the time between the two imaging sequences. The lambda images were used to control the reproducibility of the experimental procedure. The study showed that DCE-MRI with subsequent Kety analysis is a useful method for detection of blood flow fluctuations in A-07 tumors, and strongly suggested that the peripheral regions of A-07 tumors are more exposed to temporal changes in blood perfusion than are the central regions.     

The efficacy and efficiency of an in-vitro fertilization programme including embryo cryopreservation: a cohort study

A cohort of 485 couples starting their first in-vitro fertilization(IVF) attempt between January, 1989 and February, 1991 inclusive,were followed until June 1, 1992. A total of 1086 treatmentcycles were initiated (mean 2.2, range 1–6). Of these,235 (21.8%) cycles were cancelled, giving a total of 851 embryoreplacements (mean 1.7, range 1–5). After IVF treatment,189 women have either delivered or have an ongoing pregnancyin the second or third trimester. This gives a baby take-homerate of 17.4% per started cycle and 22.2% per embryo replacement.For 91 (18.6%) of the couples, the treatment was abandoned priorto completion of the three scheduled IVF attempts and 57 (11.7%)of these had no completed IVF cycles. In the group of coupleswith reduced sperm quality, the delivery rate was significantlylower than that of the other groups. A total of 193 women hadembryos cryopreserved in at least one IVF cycle; 124 of thesewomen started a frozen embryo replacement cycle and 88 had atleast one cycle with replacement of frozen/thawed embryos, resultingin 25 deliveries/ongoing pregnancies. Due to the Norwegian lawon assisted procreation 65 (33.7%) of the women have had theirfrozen embryos thawed and discarded after 12 months of storage.The cryopreservation programme, with the limitations of theNorwegian law, gives a 5.2% increase in the baby take-home ratefor women entering the IVF programme, an increase of 13.2% inthe number of ongoing pregnancies/deliveries and an 11.6% increasein number of children/viable fetuses. A total of 214 women havedelivered or have ongoing pregnancies in the second or thirdtrimester. This represents 44.1% of the 485 women accepted forIVF treatment, irrespective of whether they were treated ornot, and 50.0% of those couples who completed at least one IVFcycle.     

Regulation of tissue-degrading factors and in vitro invasiveness in progression of breast cancer cells

Hormone-independent growth and invasiveness represent phenotypic properties acquired during early progression of breast cancer. We compared human mammary adenocarcinoma cells, MCF-7, which are estrogen-dependent and poorly metastatic, with the estrogen-independent and highly metastatic subline, MCF7/LCC1, with regard to expression of tissue-degrading factors of the matrix metalloproteinase (MMP)-and urokinase (uPA)-dependent degradative pathways, as well as for their in vitro invasive properties. Both cell lines showed low constitutive mRNA expression of the MMP inhibitor TIMP-1. Baseline expression of TIMP-2 mRNA was also very low in MCF-7 cells, whereas the MCF7/LCC1 level was much higher (~10- fold). Furthermore, both cell lines revealed low constitutive capacity to migrate in an in vitro invasion assay. Treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA; 100 nM) induced the mRNAs for TIMP-1 as well as for MMP-1, MMP-9, the uPA receptor, and the uPA inhibitor PAI-1, am ongst which only the responses of MMP-9 and PAI-1 were cell-specific. The mRNA levels of MMP-9 and PAI-1 were ~10-fold and ~15-fold higher in MCF7/LCC1 cells compared to MCF-7 cells. The secretion of immuno-reactive PAI-1 was considerably elevated (. 20-fold) in TPA-treated MCF7/LCC1 cells, whereas the TPA-dependent level of 92-kDa MMP-9 was only ~2-fold higher in MCF7/LCC1 cells than in MCF-7 cells. In both cell lines treatment with TPA was associated with an increase (~10-fold) in in vitro migration, which in the MCF7/LCC1 cells was significantly attenuated by a reconstituted basement membrane extract (Matrigel). These data suggest that TPA-responsive in vitro invasive properties that are probably associ-ated with PAI-1 expression may co-vary with progression from hormone-dependent to -independent breast cancer. © Rapid Science 1998     

Contrasts in memory functions between adolescents with schizophrenia or ADHD

Previous research on memory and schizophrenia has relied on a limited number of global memory measures instead of a comprehensive assessment of various memory components. In addition, little effort has been directed at examining memory functioning in patients with early-onset schizophrenia. Published research often lacks a relevant neuropsychiatric comparison group to control for attention difficulties. Patients with Attention Deficit Hyperactivity Disorder (ADHD) were included in the present study for this purpose. To our knowledge, a direct comparison of the two patient groups on memory functions has never been made. In the present study, both adolescents with schizophrenia and adolescents with ADHD were compared on a comprehensive memory test battery. Nineteen adolescents with schizophrenia were compared to 20 ADHD adolescents and 30 normally functioning adolescents on measures of working memory and long-term episodic memory, including tests of verbal and visual memory, free recall and recognition memory. The performance of the adolescents with schizophrenia was impaired as compared to the normal group on most of the memory measures. They performed significantly more poorly than the adolescents with ADHD on the visual memory tests. The ADHD group scored more impaired than the schizophrenia group on working memory tests with focus on distractibility. The findings suggest a general memory deficit among adolescents with schizophrenia related to both verbal and visual material. Impairment on the measures of visual memory is specific to schizophrenia and does not characterise the ADHD subjects.     

Fatal and non-fatal injuries due to suspension trauma syndrome: A systematic review of definition,pathophysiology, and management controversies

BACKGROUND: Suspension trauma syndrome is a life-threatening event that occurs when a person is “trapped” in a prolonged passive suspension. It is most commonly seen in people who engage in occupational or sport activities that require harness suspension. The aim of this study is to identify the predisposing factors, pathophysiology, and management of suspension trauma. METHODS: A review and analysis of the literature published in English and Spanish from 1972 to 2020 on suspension trauma were performed. Search sources were PubMed, Medline, Cochrane Library, MeSH, UpToDate, and Google Scholar. Articles referring to suspension trauma associated with other injury mechanisms (traumatic impact injuries, drowning, asphyxiation, or bleeding), case reports, and pediatric population were excluded. RESULTS: Forty-one articles were identified. Of these, 29 articles related to mechanism, pathophysiology, and management of individuals who suffered prolonged suspension trauma without associated traumatic injuries were included in the study. We encountered several controversies describing the putative pathophysiology, ranging from blood sequestration in the lower extremities versus accumulation of metabolic waste and hyperkalemia to dorsal hook-type harness as a trigger cause of positional asphyxia; to vascular compression of femoral vessels exerted by the harness causing decreased venous return. Pstients suspended in a full-body harness with dorsal hook showed more hemodynamic alterations in response to the compressive effect on the rib cage, causing a reduction in perfusion by presenting a decrease in pulse pressure. Management strategies varied across studies. CONCLUSIONS: Progress has been made in individualizing the population at risk and in the management of suspension trauma. We recommend the formation of consensus definitions, larger cohort or registry studies to be conducted, and experimental animal models to better understand the mechanisms in order to develop management and life support guidelines from a trauma and emergency medicine perspective.     

Non-cholinergic afferents determine the distribution of the cholinergic septohippocampal projection: a study of the AChE staining pattern in the rat fascia dentata and hippocampus after lesions,X-irradiation,and intracerebral grafting

Summary The acetylcholinesterase (AChE) activity of the rat hippocampus and fascia dentata depends on an intact septohippocampal connection, and histochemical staining for AChE is commonly used to monitor the distribution of the cholinergic septohippocampal projection. It is also characteristic that the laminae of low or moderate to dense AChE staining in the hippocampus and fascia dentata coincide with the terminal fields of the major non-cholinergic, afferent pathways. While studying lesion-induced collateral sprouting and aberrant axonal growth of these pathways we observed that the AChE staining pattern changed in accordance with the reorganized distribution of the non-cholinergic pathways, and this occurred even without direct interfering with the septohippocampal projection itself. Widening and narrowing of the medial perforant path and mossy fiber terminal zones thus resulted in corresponding changes in the bands of AChE staining normally associated with these zones. Expansion of the commissural-associational hippocampodentate projections and the lateral perforant path was in a similar way paralleled by a widening of the AChE-poor zones which normally overlap with the termination of these projections. Observations of the same kind were made in intracerebral transplants of fascia dentata innervated by various host afferents, and in rats subjected to neonatal X-irradiation, where the mossy fiber projection is reduced and aberrant perforant pathways project into CA3 due to a reduced formation of granule cells. The observed sets of changes with linkage between the different noncholinergic projections and the activity of AChE in their respective terminal fields were accordingly reproduced under several different experimental conditions. It could not be explained alone by interaction between the septal afferents and their target cells. We therefore conclude that the density and laminar distribution of the AChE activities within the hippocampus and fascia dentata are determined at least in part by the major afferent, noncholinergic nerve connections. We suggest that the effect occurs through direct axonal interaction or through changes in the receptiveness of the common dentate and hippocampal target cells.     

Essential Role of Osteopontin in Smoking-Related Interstitial Lung Diseases

Smoking-related interstitial lung diseases are characterized by the accumulation of macrophages and Langerhans cells, and fibrotic remodeling, which are linked to osteopontin (OPN) expression. Therefore, OPN levels were investigated in bronchoalveolar lavage (BAL) cells in 11 patients with pulmonary Langerhans cell histiocytosis (PLCH), 15 patients with desquamative interstitial pneumonitis (DIP), 10 patients with idiopathic pulmonary fibrosis, 5 patients with sarcoidosis, 13 otherwise healthy smokers, and 19 non-smoking controls. Furthermore, OPN overexpression was examined in rat lungs using adenoviral gene transfer. We found that BAL cells from patients with either PLCH or DIP spontaneously produced abundant amounts of OPN. BAL cells from healthy smokers produced 15-fold less OPN, and those cells from non-smoking healthy volunteers produced no OPN. BAL cells from patients with either idiopathic pulmonary fibrosis or sarcoidosis produced significantly less OPN, as compared with patients with PLCH. These data were confirmed by immunochemistry. Nicotine stimulation increased production of both OPN and granulocyte-macrophage colony stimulating factor by alveolar macrophages from smokers. Nicotinic acetylcholine receptor expression resembled the pattern of spontaneous OPN production and was dramatically increased in both PLCH and DIP. OPN overexpression in rat lungs induced lesions similar to PLCH with marked alveolar and interstitial accumulation of Langerhans cells. Our findings suggest a pathogenetic role of increased OPN production in both PLCH and DIP by promoting the accumulation of macrophages and Langerhans cells.Cigarette smoke is linked to a variety of lung diseases including chronic obstructive pulmonary disease, lung cancer, and interstitial lung diseases. Respiratory bronchiolar interstitial lung disease, desquamative interstitial pneumonitis (DIP), and pulmonary Langerhans cell histiocytosis (PLCH) belong to the group of smoking-related interstitial lung diseases.^1,2,3 Cigarette smoke is a complex mixture of more than 4000 compounds and is known to cause systemic and pulmonary effects.⁴ However, the underlying mechanisms as to how cigarette smoking leads to the changes observed in smoking-related interstitial lung diseases are largely unknown.^1,2,3Cigarette smoke induces inflammation, oxidative stress, and tissue injury, and has an important effect on the number, distribution, and activation state of macrophages and Langerhans cells.^5,6 There is a strong epidemiological link between PLCH and smoking. PLCH is characterized by the accumulation of activated Langerhans cells originating from the distal bronchiole walls.^1,2,3,7 The accumulations of Langerhans cells are poorly demarcated and extend to the adjacent alveoli, which often contain an abundance of pigmented macrophages. These areas show morphological changes similar to DIP.^7,8 In DIP, the predominant feature is the accumulation of alveolar macrophages, densely filling the alveolar lumen, combined with moderate fibrotic interstitial remodeling.^1,2As measured by bronchoalveolar lavage (BAL) in healthy individuals, cigarette smoking induces a 5- to 10-fold increase in alveolar macrophages in a dose-response curve.^9,10,11 It was shown that concentrations of granulocyte-macrophage colony stimulating factor (GMCSF) in patients with PLCH are increased,¹² but the mechanisms that lead to the expansion of the pulmonary macrophage pool and fibrosis in smokers are poorly understood.^1,2,3 Based on the findings of a microarray study, Woodruff et al¹³ have recently proposed that alveolar macrophages from smokers exhibit a distinctive macrophage activation state that is accompanied by increased OPN expression. Osteopontin is a glycoprotein found in the extracellular matrix of bone.¹⁴ However, multiple studies have reported cytokine properties of OPN in cell-mediated immunity.¹⁴ Further, OPN exhibits a strong chemotactic activity for macrophages, monocytes, Langerhans cells, and dendritic cells.^15,16,17In the context of these findings we speculated that OPN might be involved in the pathogenesis of smoking-related lung interstitial diseases. We found abundant OPN production by alveolar macrophages from patients with PLCH and DIP. Alveolar macrophages from both healthy smokers and patients with DIP and PLCH show up-regulated nicotine receptor expression as a sign of chronic nicotine stimulation. Further, nicotine directly induced OPN and GMCSF in alveolar macrophages. Our data provides evidence for a role of osteopontin in the pathogenesis of smoking- related interstitial lung diseases.