"It's not just the medical aspects that are important": A qualitative exploration of first-time parents' experiences of antenatal imaging and their influence on parent-fetal bonding.

INTRODUCTION: Antenatal imaging provides clinical information regarding fetal growth and development. The additional benefit afforded by imaging for expectant parents in developing an emotional connection (bond) to the unborn baby is also acknowledged. However, the relationship between imaging and bonding is not fully understood, particularly where there are differing parental and pregnancy circumstances, for example use of advanced imaging techniques or the prenatal diagnosis of a congenital fetal condition. This study aimed to explore the role of antenatal imaging in enhancing the developing parent-fetal bond in first-time parents. METHODS: A descriptive, qualitative methodology was used. Semi-structured telephone interviews were conducted with first-time expectant parents attending a London hospital for clinical ultrasound (n = 20) or research MRI (n = 8) imaging during pregnancy. The sample included parents receiving specialist antenatal care for a diagnosed fetal cardiac condition (n = 8). Thematic analysis was conducted. RESULTS: The analysis generated three themes: 1) Our baby, our scan too; 2) Destination parenthood; and 3) Being in the dark, then finding the light. These themes highlight the important, but transient role of antenatal imaging in enhancing parent-fetal bonding, as well as the differing care needs of expectant parents. The integral role of healthcare professionals in providing a personalised, supportive, imaging experience to facilitate bonding is also reflected. CONCLUSION: Adopting parent-centred care approaches which involve expectant parents in fetal imaging influences bonding by helping parents to consider the reality of their impending parenthood. Knowledge acquired during scans is used to create an identity for the unborn baby, which parents can develop an emotional connection to. IMPLICATIONS FOR PRACTICE: To optimise the potential for enhanced parent-fetal bonding, care provision in fetal imaging should be tailored to the individual needs of expectant parents.

Dendritic Localization and Exocytosis of NAAG in the Rat Hippocampus.

While a lot is known about classical, anterograde neurotransmission, less is known about the mechanisms and molecules involved in retrograde neurotransmission. Our hypothesis is that N-acetylaspartylglutamate (NAAG), the most abundant dipeptide in the brain, may act as a retrograde transmitter in the brain. NAAG was predominantly localized in dendritic compartments of glutamatergic synapses in the intact hippocampus, where it was present in close proximity to synaptic-like vesicles. In acute hippocampal slices, NAAG was depleted from postsynaptic dendritic elements during neuronal stimulation induced by depolarizing concentrations of potassium or by exposure to glutamate receptor (GluR) agonists. The depletion was completely blocked by botulinum toxin B and strictly dependent on extracellular calcium, indicating exocytotic release. In contrast, there were low levels of NAAG and no effect by depolarization or GluR agonists in presynaptic glutamatergic terminals or GABAergic pre- and postsynaptic elements. Together these data suggest a possible role for NAAG as a retrograde signaling molecule at glutamatergic synapses via exocytotic release.

Corrigendum to "Is there a role for perfusion imaging in assessing treatment response following ablative therapy of small renal masses-A systematic review" [Eur. J. Radiol. Open 5 (2018) 102-107].

[This corrects the article DOI: 10.1016/j.ejro.2018.07.002.].

Creating high-quality radiology reports in foreign languages through multilingual structured reporting.

OBJECTIVES: Globalization and migration are increasing the demand for reports in different languages. We aimed to examine if structured reports created by non-German-speaking radiologists with multilingual templates show significant differences in quality to structured reports and free-text reports by German native speakers. METHODS: We used structured templates that allow radiologists to report in their mother tongue and then switch the report language to German or English automatically using proprietary software. German- and English-speaking radiology residents created structured reports in both German and English with these templates. Reports for three different exam types were created (intensive care chest x-ray, shoulder x-ray specifically for degenerative processes, and CT pulmonary angiogram for pulmonary embolism). The report quality of automatically translated German structured reports by English-speaking radiologists and German structured reports by German radiologists was then evaluated by German clinicians with a standardized questionnaire. The questionnaire was designed to assess attributes including content, comprehensibility, clinical consequences, and overall quality. RESULTS: Structured reports by English-speaking radiologists that were automatically translated into German and German structured reports by German radiologists both received very high or high overall quality ratings in the majority of cases, showing no significant differences in quality. Likewise, no significant differences were observed between the two report types regarding comprehensibility and clinical consequences. Structured reports by German radiologists received significantly better ratings for overall quality and comprehensibility compared to free-text reports by German radiologists. CONCLUSIONS: Multilingual structured reporting templates may serve as a feasible tool for creating high-quality radiology reports in foreign languages. KEY POINTS: • Multilingualism in structured reporting templates can be a useful tool for creating high-quality radiology reports in foreign languages. • German reports created with multilingual structured reporting templates by English-speaking radiologists and German structured reports by German radiologists exhibit no significant differences in overall report quality. • Multilingual structured reporting templates can help radiologists overcome communication barriers and facilitate teleradiology.

Is there a role for perfusion imaging in assessing treatment response following ablative therapy of small renal masses-A systematic review.

AIMS: Ablation therapies are an innovative nephron-sparing alternative to radical nephrectomy for early stage renal cancers, although determination of treatment success is challenging. We aimed to undertake a systematic review of the literature to determine whether assessment of tumour perfusion may improve response assessment or alter clinical management when compared to standard imaging. MATERIAL AND METHODS: Two radiologists performed independent primary literature searches for perfusion imaging in response assessment following ablative therapies (radiofrequency ablation and cryotherapy) focused on renal tumours. RESULTS: 5 of 795 articles were eligible, totaling 110 patients. The study designs were heterogeneous with different imaging techniques, perfusion calculations, reference standard and follow-up periods. All studies found lower perfusion following treatment, with a return of 'high grade' perfusion in the 7/110 patients with residual or recurrent tumour. One study found perfusion curves were different between successfully ablated regions and residual tumour. CONCLUSIONS: Studies were limited by small sample size and heterogeneous methodology. No studies have investigated the impact of perfusion imaging on management. This review highlights the current lack of evidence for perfusion imaging in response assessment following renal ablation, however it suggests that there may be a future role. Further prospective research is required to address this.

Pre- and postsynaptic localization of NMDA receptor subunits at hippocampal mossy fibre synapses.

The N-methyl-D-aspartate (NMDA) type of glutamate receptors is involved in synaptic plasticity in hippocampal mossy fibre-CA3 pyramidal neuron synapses. The ultrastructural localization of NMDA receptor subunits at this synapse type is not known. By postembedding electron microscopic immunogold cytochemistry we show that the NMDA receptor subunits GluN1, GluN2A, GluN2B, GluN2C and GluN2D are located in postsynaptic membranes of mossy fibre as well as CA3 recurrent associational commissural synapses. In the mossy fibres the GluN1, GluN2B and GluN2D labelling patterns suggested that these subunits were located also presynaptically in nerve terminal membranes and in mossy fibre axons. GluN3B was predominantly present in mossy fibre synapses as compared to recurrent associational commissural synapses, showing a presynaptic labelling pattern. In conclusion, while the postsynaptic localization of GluN1, GluN2A, GluN2B, and GluN2D is in good agreement with the recent finding of NMDA receptor-dependent long term potentiation (LTP) at CA3 mossy fibre synapses, we propose that presynaptic GluN1, GluN2B, GluN2D and GluN3B subunits could be involved in plastic phenomena such as certain types of LTP and recurrent mossy fibre growth.

Immunogold detection of L-glutamate and D-serine in small synaptic-like microvesicles in adult hippocampal astrocytes.

Glutamate and the N-methyl-D-aspartate receptor ligand D-serine are putative gliotransmitters. Here, we show by immunogold cytochemistry of the adult hippocampus that glutamate and D-serine accumulate in synaptic-like microvesicles (SLMVs) in the perisynaptic processes of astrocytes. The estimated concentration of fixed glutamate in the astrocytic SLMVs is comparable to that in synaptic vesicles of excitatory nerve terminals (≈ 45 and ≈ 55 mM, respectively), whereas the D-serine level is about 6 mM. The vesicles are organized in small spaced clusters located near the astrocytic plasma membrane. Endoplasmic reticulum is regularly found in close vicinity to SLMVs, suggesting that astrocytes contain functional nanodomains, where a local Ca(2+) increase can trigger release of glutamate and/or D-serine.

Expectations and experience of labial reduction: a qualitative study.

OBJECTIVE: To understand women's reasons for undergoing labial reduction surgery, their expectations and experiences. DESIGN: A retrospective qualitative study. SETTING: British National Health Service Hospital. SAMPLE: Six women who had experienced surgery for labial reduction. Method Qualitative study using semi-structured interviews. RESULTS: Results relating to 'Normality and defect', 'Sex lives' and 'The process of accessing surgery' are presented in this study. The women had seen their presurgery genital appearance as 'defective' and sought a 'normal' genital appearance. They thought that their presurgery genital appearance impacted on their sex lives, but their expectations of the effects of surgery on their sex lives were not all fulfilled. Information about labial surgery came from both the popular media and the health services. An emphasis on, for example, physical discomfort rather than appearance may have been used to legitimise a request for surgery. The process of accessing surgery had exposed them to potentially conflicting messages about their genital appearance. CONCLUSIONS: Women presenting for labial reduction may have unrealistic expectations of surgery, but their perceptions and expectations are long-standing and seem to be based on strong cultural norms. The gynaecologist is also meeting those women who have already negotiated the referral process. As demand for this surgery appears to be increasing, further research is needed. These findings may add to the case for the potential value of specialist staff to provide psychosocial interventions within gynaecology services.

A novel system for investigating the ability of smooth muscle cells and fibroblasts to regulate adhesion of flowing leukocytes to endothelial cells.

Stromal cells may contribute to the inflammatory processes which lead to the recruitment of circulating leukocytes. Here, we describe a multicellular model in which chosen cellular elements of tissue can be cocultured with endothelial cells (EC). Cocultures can be incorporated into a novel parallel plate flow chamber to determine if stromal cells influence the patterns of leukocyte adhesion to the EC. As an example relevant to the pathology of atherosclerosis, EC were cultured with arterial smooth muscle cells (SMC) of the 'secretory' phenotype. EC and secretory SMC were cultured on the opposite faces of commercially available porous polyethylene terepthalate (PET) culture inserts, which fitted into a parallel plate flow chamber. Binding of flowing purified lymphocytes, labelled with the fluorochrome calcein-AM, to cocultured EC was assessed by fluorescence microscopy. Lymphocyte adhesion was negligible on unstimulated EC cultured alone or cocultured with SMC. However, when tumour necrosis factor-alpha (TNF) was added to cocultures, the EC supported greatly increased levels of lymphocyte adhesion compared to TNF-treated EC cultured alone. Additionally, cocultured EC responded to TNF at concentrations far below those at which EC cultured alone responded. This priming was specific in that skin fibroblasts cocultured with EC did not modify lymphocyte adhesion induced by TNF. Thus, we have developed a coculture model to determine the ability of tissue stromal cells to modify leukocyte recruitment. This may have wide applications in the study of the cellular pathology of inflammation by allowing the contribution of the local microenvironment to be assessed.

Differential expression of chemokines and chemokine receptors shapes the inflammatory response in rejecting human liver transplants.

BACKGROUND: Graft rejection after liver transplantation is associated with a lymphocytic infiltrate, the nature of which will be determined by, among various factors, the local activity of chemokines that attract particular subsets of effector cells to the graft. METHODS: The expression of chemokines and receptors in human liver allografts was studied by immunohistochemistry of tissue and flow cytometry of blood and liver-derived lymphocytes. Receptor function was assessed with in vitro chemotaxis. RESULTS: We report increased expression of chemokine receptors CXCR3, CXCR4, and CCR5 on circulating and graft-infiltrating lymphocytes after liver transplantation. Liver-derived T cells responded to the ligands for these receptors in vitro, which suggests that the receptors are functionally active. The chemokine ligands for these receptors were detected in rejecting allografts. CXCR3 ligands interferon-inducible protein 10 and monokine-induced by gamma interferon were detected on sinusoidal endothelium and interferon-inducible T-cell alpha chemoattractant was detected on portal and hepatic vascular endothelium, whereas the CXCR4 ligand, stromal-derived factor (SDF), was restricted to biliary epithelium. CCR5 ligands have previously been shown on portal endothelium. An in vitro model of T-cell alloactivation demonstrated a similar pattern of expression of functional CXCR3, CXCR4, and CCR5 on T cells. Increased expression of chemokine receptors, especially CCR3 and CCR5, was associated with redistribution of activated Kupffer cells in rejecting grafts. CONCLUSIONS: The patterns of chemokine expression in liver allografts during rejection suggest that the recruitment and positioning of lymphocytes is mediated by specific chemokines. Although ligands for the receptors CXCR3 and CCR5 are important for recruitment, the restriction of SDF to bile ducts suggests that CXCR4 may be involved in the retention of alloactivated lymphocytes at sites of graft damage.

Migration of CD18-deficient neutrophils in vitro: evidence for a CD18-independent pathway induced by IL-8.

Neutrophils isolated from a child with severe leukocyte adhesion deficiency 1 (LAD1) had a complete absence of expression of the CD11/CD18 beta2 integrin family of adhesion molecules, and were shown to be deficient in the in vitro adhesion and migration properties. However, we found that interleukin-8 (IL8), a potent chemoattractant for neutrophils, and sputum sol phase induced these LAD1 neutrophils to migrate through an endothelial cell layer in vitro, and confirmed that this migration was CD18-independent. These findings add to evidence of CD18-independent mechanisms of neutrophil recruitment, in particular neutrophil infiltration into the lungs, where IL8 may be an important recruitment factor.

Chemokine and chemokine receptor interactions provide a mechanism for selective T cell recruitment to specific liver compartments within hepatitis C-infected liver.

The role played by chemokines in regulating the selective recruitment of lymphocytes to different tissue compartments in disease is poorly characterized. In hepatitis C infection, inflammation confined to portal areas is associated with a less aggressive course, whereas T cell infiltration of the liver parenchyma is associated with progressive liver injury and cirrhosis. We propose a mechanism to explain how lymphocytes are recruited to hepatic lobules during bursts of necroinflammatory activity in chronic hepatitis C infection. We report here that lymphocytes infiltrating hepatitis C-infected liver express high levels of the chemokine receptors CCR5 and CXCR3. However, whereas the CCR5 ligands macrophage inflammatory protein-1alpha and -1beta were largely confined to vessels within portal tracts, the CXCR3 ligands IFN-inducible protein-10 and monokine-induced by IFN-gamma were selectively up-regulated on sinusoidal endothelium. In vitro, human hepatic sinusoidal endothelial cells secreted IFN-inducible protein-10 and monokine-induced by IFN-gamma in response to stimulation with IFN-gamma in combination with either IL-1 or TNF-alpha. This suggests that intrahepatic Th1 cytokines drive the increased expression of IFN-inducible protein-10 and monokine-induced by IFN-gamma and thereby promote the continuing recruitment of CXCR3-expressing T cells into the hepatic lobule in chronic hepatitis C infection.

Promotion of leukocyte transendothelial cell migration by chemokines derived from human biliary epithelial cells in vitro.

Biliary epithelial cells are the focus of inflammatory damage in several liver diseases, including allograft rejection wherein intrahepatic bile ducts are infiltrated and damaged by T cells and neutrophils. Locally secreted chemotactic cytokines (chemokines) are important signals for leukocyte recruitment to an inflammatory site and include interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1), potent chemotactic agents for neutrophils and monocyte or T cells, respectively. In this study, we demonstrate that primary cultures of human biliary epithelial cells (BECs) express and secrete IL-8 and MCP-1, both of which are upregulated rapidly and markedly in response to the proinflammatory cytokines IL-1 and tumor necrosis factor-alpha. Interferon-gamma had a differential effect by reducing IL-8 secretion but stimulating MCP-1 secretion. BECs cocultured in transwell chambers below confluent monolayers of endothelial cells promoted the transendothelial migration of neutrophils, which was blocked by antibodies to CD18 or CD11b but only partially inhibited by blocking antibodies to IL-8. We conclude that human BECs produce and secrete potent, functional chemokines when stimulated by proinflammatory cytokines. The ability of BECs to secrete chemokines and thus to promote leukocyte infiltration into portal tracts seems likely to be an important cause of bile duct damage in such conditions as liver allograft rejection and may explain the involvement of intrahepatic bile ducts in a number of inflammatory liver diseases.

Calcium protects a mesophilic xylanase from proteinase inactivation and thermal unfolding.

Crystal structure analysis of Pseudomonas fluorescens subsp. cellulosa xylanase A (XYLA) indicated that the enzyme contained a single calcium binding site that did not exhibit structural features typical of the EF-hand motif. Isothermal titration calorimetry revealed that XYLA binds calcium with a Ka of 4.9 x 10(4) M-1 and a stoichiometry consistent with one calcium binding site per molecule of enzyme. Occupancy of the calcium binding domain with its ligand protected XYLA from proteinase and thermal inactivation and increased the melting temperature of the enzyme from 60.8 to 66.5 degrees C. However, the addition of calcium or EDTA did not influence the catalytic activity of the xylanase. Replacement of the calcium binding domain, which is located within loop 7 of XYLA, with the corresponding short loop from Cex (a Cellulomonas fimi xylanase/exoglucanase), did not significantly alter the biochemical properties of the enzyme. These data suggest that the primary function of the calcium binding domain is to increase the stability of the enzyme against thermal unfolding and proteolytic attack. To understand further the nature of the calcium binding domain of XYLA, four variants of the xylanase, D256A, N261A, D262A, and XYLA"', in which Asp-256, Asn-261, and Asp-262 had all been changed to alanine, were constructed. These mutated enzymes did not show any significant binding to Ca2+, indicating that Asp-256, Asn-261, and Asp-262 play a pivotal role in the affinity of XYLA for the divalent cation. In the presence or absence of calcium, XYLA"' exhibited thermal stability similar to that of the native enzyme bound to Ca2+ ions, although the variant was sensitive to proteinase inactivation. The role of the calcium binding domain in vivo and the possible mechanism by which the domain evolved are discussed.

Cell cultures from bronchial subepithelial myofibroblasts enhance eosinophil survival in vitro.

Mechanisms of eosinophil accumulation and activation in the bronchial mucosa are crucial for the pathogenesis of asthma. The location of specialized fibroblasts, myofibroblasts, beneath the bronchial basement membrane and their proximity to infiltrating eosinophils potentially enable the myofibroblasts to modulate eosinophil survival and function in asthma. The aim of this study was to investigate the effects of bronchial myofibroblasts on eosinophil survival in vitro. Eosinophils from human peripheral blood were exposed to cell cultures from bronchial myofibroblasts and to myofibroblast-conditioned media. Eosinophil viability was assessed and granulocyte/macrophage colony-stimulating factor (GM-CSF) production was examined in co-culture supernatants and as messenger ribonucleic acid (mRNA) in myofibroblasts. Eosinophil survival was significantly increased and eosinophil apoptosis was inhibited by co-culture with myofibroblasts. Conditioned medium from tumour necrosis factor-alpha (TNF-alpha)-stimulated myofibroblasts also prolonged eosinophil survival. This effect could be blocked by GM-CSF antibody. GM-CSF mRNA and secretion from myofibroblasts were increased in co-cultures and by eosinophil-conditioned medium. Addition of antibodies to TNF-alpha and interleukin-1 alpha (IL-1 alpha) to co-cultures resulted in significant reduction both in eosinophil survival and GM-CSF levels. Blocking of fibronectin in the co-cultures did not affect the eosinophil survival enhancing activity. Prednisolone inhibited the eosinophil survival enhancing activity of the co-cultures by suppression of GM-CSF production. Soluble eosinophil-derived cytokines are involved in the interaction of eosinophils with myofibroblasts, which results in a tumour necrosis factor-alpha/interleukin-1 alpha mediated release of granulocyte/macrophage colony-stimulating factor from myofibroblasts. Bronchial myofibroblasts can, thereby, contribute to allergic inflammation by granulocyte/macrophage colony-stimulating factor-mediated inhibition of eosinophil apoptosis.

Selective eosinophil leukocyte recruitment by transendothelial migration and not by leukocyte-endothelial cell adhesion.

Eosinophil infiltration is the hallmark of allergic inflammatory events. However, the mechanisms governing the influx of eosinophils into the tissue at a site of an allergic reaction remains unclear. We have examined the interactions of eosinophils and neutrophils isolated from the same atopic donor with cultured human umbilical vein endothelial cell (EC) monolayers in the search for a mechanism for this selective eosinophil recruitment. First, the adherence of eosinophils and neutrophils to ECs stimulated with lipopolysaccharide, interleukin (IL)-1 alpha, and tumor necrosis factor-alpha were compared. Each mediator induced a similar dose-dependent enhancement of eosinophil adhesiveness for both eosinophils and neutrophils. Thus, although cytokine activation of ECs in the vasculature adjacent to an inflammatory site probably serves as an important focusing mechanism for the extravasation of inflammatory cells at this site, there does not appear to be any selective EC-dependent mechanism for eosinophil recruitment. Little or no effect on eosinophil and neutrophil adherence was observed with IL-3, IL-5, granulocyte/macrophage colony-stimulating factor, platelet-activating factor (PAF), leukotriene B4, or histamine. Second, the migration of eosinophils and neutrophils through an EC monolayer in response to chemoattractants was examined. PAF was found to selectively enhance eosinophil transendothelial migration at doses of 10(-7) to 10(-10) M, with optimal effect at 10(-8) M. This effect was gradient dependent and could be inhibited by WEB 2086, a specific PAF inhibitor. These results suggest that localized production of PAF may be a prime factor in the events leading to eosinophil accumulation at allergic inflammatory sites, and that selectivity for eosinophil recruitment occurs at the stage of transendothelial cell migration under the influence of cell-specific chemoattractants.

Anti-idiotype and immunosuppressant treatment of murine lupus.

The effect of the administration of a xenogeneic anti-idiotype antibody (anti-Id33) to a cross-reactive idiotype (Id33) present on anti-dsDNA antibody was examined in 6-week-old (NZB/NZW) F1 (BWF1) female mice. The administration of anti-Id33 led to a transient reduction in immunoglobulins expressing Id33, followed by a rise at 30 and 34 weeks that was significantly higher than in untreated mice (P less than 0.05). Likewise, anti-dsDNA antibody levels were significantly higher at 10 and 18 weeks than in untreated mice (P less than 0.01). No differences were seen in survival to 40 weeks, proteinuria or the severity of glomerulonephritis. Concurrent administration of cyclosporin A (CyA) with anti-Id33 markedly ameliorated glomerular injury and proteinuria and improved survival. By contrast, glomerular injury, proteinuria and survival were worse in mice treated with cyclophosphamide plus anti-Id33, compared with untreated mice. Neither CyA nor cyclophosphamide treatment, when given with anti-Id33 altered serum levels of anti-dsDNA, anti-ssDNA or Id33+ immunoglobin, compared with untreated mice. The different effects of CyA and cyclophosphamide on T lymphocytes and their discrepant effects on glomerular injury when given with anti-Id33 in this model lead us to postulate a role for T lymphocytes in the glomerular injury of BWF1 lupus.

IgG subclasses of PEG precipitable IgG in systemic lupus erythematosus sera.

Polyethylene glycol (PEG, 4%)-precipitated macromolecular IgG isolated from the sera of 20 patients with systemic lupus erythematosus (SLE) and 15 control subjects was analyzed for its IgG isotype concentration by single radial immunodiffusion. PEG precipitates from SLE sera had higher mean levels of IgG1, IgG2 and IgG3 and lower IgG4 than PEG precipitates isolated from normal sera although only the IgG2 levels were significantly different. Using an anti-complementary assay there was a significant correlation between the ability of parent sera to fix complement and the absolute levels of PEG precipitable IgG1, IgG2 and IgG3. These data suggest that the ability of immune complexes in the sera of patients with SLE to fix complement is dependent on their IgG subclass composition.

Different types of segmental sclerosing glomerular lesions in six experimental models of proteinuria.

From 133 to 615 glomeruli were examined in sections of kidneys from each of 60 animals, representing six rodent models of proteinuria. Particular attention was paid to the position of segmental lesions. Lewis rats given sheep anti-rat glomerular basement membrane antibodies had lesions almost exclusively at the glomerulo-tubular junction. Wistar rats on a diet of 24 per cent casein or with subtotal nephrectomy and a diet of 24 per cent soya had lesions mainly at the hilum. Wistar rats given bovine serum albumin had global lesions but virtually no segmental lesions. Wistar rats given puromycin aminonucleoside had lesions at the glomerulo-tubular junction and global mesangial abnormalities shortly after the treatment but later developed segmental lesions at all parts of the glomerulus. Untreated BUF/Mna rats had lesions at the glomerulo-tubular junction early in life but later had lesions at all parts of the glomerulus. Untreated NZB/NZW hybrid mice had various types of glomerulonephritis and also had lesions at the glomerulo-tubular junction. These findings showed that (1) segmental lesions at the glomerulo-tubular junction, or glomerular tip, occur in experimental animals, a fact not previously reported, and these tip changes are a common feature in several different models of proteinuria; (2) hilar segmental lesions are seen in conditions with hyperfiltration of protein; and (3) segmental lesions at various parts of the glomerulus are seen in some models of proteinuria and probably indicate late effects of random toxic damage to the glomerulus. Thus, there are at least three different types of segmental glomerular lesions in experimental animals--tip, hilar, and random--with different morphology and pathogenesis. It is likely that these findings can be extended to human renal diseases with segmental glomerular lesions. This will help to clarify the controversial and unsatisfactory term focal segmental glomerulosclerosis.