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The management of schizophrenia necessitates a comprehensive treatment paradigm that considers individual patient nuances and the efficacy of lurasidone in addressing schizophrenia symptoms, particularly at elevated dosages. Numerous randomized trials have affirmed the efficacy of lurasidone across various dimensions of schizophrenia, demonstrating marked enhancements in positive, negative and cognitive symptoms compared to a placebo. In addition, lurasidone exhibits potential in ameliorating agitation amongst acutely ill patients, showcasing greater efficacy at higher doses. However, despite the favourable outcomes observed with higher lurasidone doses, routine clinical practice often opts for lower doses, potentially limiting its maximal therapeutic impact. Furthermore, lurasidone also shows efficacy in reducing post-psychotic depression in dual psychosis. Moreover, practical insights into lurasidone usage encompass swift dose escalation within a 1-5-day span and recommended combination strategies with other medications such as benzodiazepines for insomnia or agitation, beta-blockers for akathisia, and antihistamines or antimuscarinic drugs for patients transitioning rapidly from antipsychotics with substantial antihistamine and/or anticholinergic effects. Finally, a series of clinical cases is presented, highlighting benefits of lurasidone in terms of cognitive function, functional recovery and other therapeutic aspects for the management of schizophrenia., Competing Interests: Disclosure and potential conflicts of interest: JLPO has received honoraria as a consultant and/or advisor to Angelini, Janssen/J&J and Lundbeck. AC is an employee of Angelini Pharma España SLU. All other authors declare that they have no conflicts of interest relevant to this manuscript. The International Committee of Medical Journal Editors (ICMJE) Potential Conflicts of Interests form for the authors is available for download at: https://www.drugsincontext.com/wp-content/uploads/2024/07/dic.2024-4-4-COI.pdf, (Copyright © 2024 Guarro Carreras MT, Jiménez Suárez L, Lago García L, Montes Reula L, Neyra del Rosario A, Rodríguez Batista FA, Velasco Santos M, Prados-Ojeda JL, Diaz-Marsà M, Martín-Carrasco M, Cardenas A.)

Background: The demand for urgent psychiatric care is increasing, but in Spain there are no clear recommendations for emergency departments (ED) on how to optimize care for patients with psychiatric emergencies. We aimed to provide expert consensus recommendations on the requirements for general hospitals´ emergency departments to treat patients with urgent psychiatric symptoms., Methods: We used a modified Delphi technique. A scientific committee compiled 36 statements based on literature search and clinical experience. The statements covered the organizational model, facilities, staffing, safety, patient interventions, and staff training. A panel of 38 psychiatry specialists with expertise in psychiatric emergencies evaluated the questionnaire in two rounds., Results: After two rounds of voting, 30 out of 36 proposed items (83%) were agreed upon. The panel agreed that psychiatric emergencies should be managed in a general hospital, with dedicated facilities for patient assessment, direct supervision of patients at risk, and an observation unit run by the psychiatric service. In addition to the psychiatrist, the ED should have specialist nurses and security staff available 24/7. Social workers should also be readily available. ED and consulting rooms should be designed to ensure patient and staff safety. A triage system should be established for patients with psychiatric symptoms, with medical evaluation preceding psychiatric evaluation. Guidance on supplies, equipment, and staff training is also provided., Conclusion: All ED in general hospitals should have adequate resources to handle any psychiatric emergency. This paper provides recommendations on the minimum requirements to achieve this goal., (© 2024. The Author(s).)

Background: There is a lack of standardised psychometric data in electronic health record (EHR)-based research. Proxy measures of symptom severity based on patients' clinical records may be useful surrogates in mental health EHR research., Aims: This study aimed to validate proxy tools for the short versions of the Positive and Negative Syndrome Scale (PANSS-6), Young Mania Rating Scale (YMRS-6) and Montgomery-Åsberg Depression Rating Scale (MADRS-6)., Method: A cross-sectional, multicentre study was conducted in a sample of 116 patients with first-episode psychosis from 12 public hospitals in Spain. Concordance between PANSS-6, YMRS-6 and MADRS-6 scores and their respective proxies was evaluated based on information from EHR clinical notes, using a variety of statistical procedures, including multivariate tests to adjust for potential confounders. Bootstrapping techniques were used for internal validation, and an independent cohort from the Treatment and Early Intervention in Psychosis Program (TIPP-Lausanne, Switzerland) for external validation., Results: The proxy versions correlated strongly with their respective standardised scales (partial correlations ranged from 0.75 to 0.84) and had good accuracy and discriminatory power in distinguishing between patients in and not in remission (percentage of patients correctly classified ranged from 83.9 to 91.4% and bootstrapped optimism-corrected area under the receiver operating characteristic curve ranged from 0.76 to 0.89), with high interrater reliability (intraclass correlation coefficient of 0.81). The findings remained robust in the external validation data-set., Conclusions: The proxy instruments proposed for assessing psychotic and affective symptoms by reviewing EHR provide a feasible and reliable alternative to traditional structured psychometric procedures, and a promising methodology for real-world practice settings.

(1) Background: About 50% of prescribed colonoscopies report no pathological findings. A secondary screening test after fecal immunochemical test positivity (FIT+) would be required. Considering thermal liquid biopsy (TLB) as a potential secondary test, the aim of this work was to study possible interferences of colonoscopy bowel preparation on TLB outcome on a retrospective study; (2) Methods: Three groups were studied: 1/514 FIT(+) patients enrolled in a colorectal screening program (CN and CP with normal and pathological colonoscopy, respectively), with blood samples obtained just before colonoscopy and after bowel preparation; 2/55 patients from the CN group with blood sample redrawn after only standard 8-10 h fasting and no bowel preparation (CNR); and 3/55 blood donors from the biobank considered as a healthy control group; (3) Results: The results showed that from the 514 patients undergoing colonoscopy, 247 had CN and 267 had CP. TLB parameters in these two groups were similar but different from those of the blood donors. The resampled patients (with normal colonoscopy and no bowel preparation) had similar TLB parameters to those of the blood donors. TLB parameters together with fluorescence spectra and other serum indicators (albumin and C-reactive protein) confirmed the statistically significant differences between normal colonoscopy patients with and without bowel preparation; (4) Conclusions: Bowel preparation seemed to alter serum protein levels and altered TLB parameters (different from a healthy subject). The diagnostic capability of other liquid-biopsy-based methods might also be compromised. Blood extraction after bowel preparation for colonoscopy should be avoided.

Schizophrenia is a common debilitating disorder characterized by significant impairments in how reality is perceived, combined with behavioural changes. In this review, we describe the lurasidone development programme for adult and paediatric patients. Both the pharmacokinetic and pharmacodynamic characteristics of lurasidone are revisited. In addition, pivotal clinical studies conducted on both adults and children are summarized. Several clinical cases, which demonstrate the role of lurasidone in real-world practice, are also presented. Current clinical guidelines recommend lurasidone as the first-line treatment in the acute and long-term management of schizophrenia in both adult and paediatric populations., Competing Interests: Disclosure and potential conflicts of interest: IG-I is an employee of Angelini Pharma España SLU. All other authors declare that they have no conflicts of interest relevant to this manuscript. The International Committee of Medical Journal Editors (ICMJE) Potential Conflicts of Interests form for the authors is available for download at: https://www.drugsincontext.com/wp-content/uploads/2023/01/dic.2022-10-1-COI.pdf, (Copyright © 2023 Guilera T, Chart Pascual JP, Blasco MDC, Calvo Estopiñán P, Piernas González RA, Ramírez Martínez I, Rodríguez Moyano C, Prieto Pérez R, Gabarda-Inat I, Prados-Ojeda JL, Diaz-Marsà M, Martín-Carrasco M.)

The impact of the COVID-19 pandemic and lockdown may affect suicide risk and behavior. We compared suicide-related presentations during the national quarantine with pre-COVID data. This observational incidence study compared all suicide-related presentations at the University Hospital Reina Sofia emergency department (ED) in Cordoba, Spain, for the lockdown period from 15 March to 15 May 2020, with the same period in 2019. Descriptive and inferential analyses of case characteristics between 2019 and 2020 periods were conducted, and a multivariable logistic regression model developed. Results: Despite a decrease in overall ED cases during the lockdown, the number of suicide-related presentations stayed the same and represented a significantly larger proportion of cases in comparison to the pre-COVID period (0.42 vs. 0.87%, in 2019 and 2020, respectively; p  < .001). The number presenting alone more than doubled during the COVID lockdown, increasing to 42.9% compared with 19.4% in 2019 ( p  = .002). An increase in presentations with a family history of suicide was also found. Conclusions: Suicide cases represented an increased proportion of ED cases during the lockdown. Presenting to ED alone, having a family history of suicide, habitual drug consumption, and hospital admission to ICU differentiated cases between pre and during COVID periods. These findings should be considered in light of the second wave and further implementation of lockdown measures.

This study aimed to characterize the clinical profile of patients with brief psychotic disorders (BPD) triggered by the psychosocial distress derived from the COVID-19 crisis. A multicenter study was conducted from March 14 to May 14, 2020 (the peak weeks of the pandemic in Europe). All consecutive patients presenting non-affective psychotic episodes with a duration of untreated psychosis of less than 1 month and whose onset was related to the COVID-19 crisis were recruited, but only those patients meeting Diagnostic Statistical Manual 5th edition (DSM-5) criteria for "BPD with marked stressors" (DSM-5 code: 298.8) during follow-up were finally included. Patients' sociodemographic and clinical characteristics were collected at baseline and summarized with descriptive statistics. During the study period, 57 individuals with short-lived psychotic episodes related to the emotional stress of the COVID-19 pandemic were identified, of whom 33 met DSM-5 criteria for "BPD with marked stressors". The mean age was 42.33 ± 14.04 years, the gender distribution was almost the same, and the majority were rated as having good premorbid adjustment. About a quarter of the patients exhibited suicidal symptoms and almost half presented first-rank schizophrenia symptoms. None of them were COVID-19 positive, but in more than half of the cases, the topic of their psychotic features was COVID-19-related. The coronavirus pandemic is triggering a significant number of BPD cases. Their risk of suicidal behavior, their high relapse rate, and their low temporal stability make it necessary to closely monitor these patients over time., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Inflammatory and autoimmune processes have been associated with the onset of depressive and psychotic symptoms. Rheumatoid arthritis (RA) and spondyloarthritis (SpA) are rheumatic diseases with an inflammatory etiology. A high prevalence of depressive and anxiety-related comorbidity has been reported for both diseases, with no evidence of a greater prevalence of psychosis. The objective of the present study was to evaluate for the first time subclinical psychotic symptoms in patients with RA and SpA. This is a cross-sectional, single-center study including RA and SpA patients, as well as healthy controls. Abnormal psychotic experiences (positive, negative, and depressive symptoms) were evaluated using the Community Assessment of Psychic Experiences (CAPE-42). Functional capacity was evaluated using the Short-Form Health Survey SF-12. We compared the CAPE and SF-12 scores between the three groups. We recruited 385 individuals: 218 with RA, 100 with SpA, and 67 healthy controls. According to the CAPE scale, the frequency of subclinical psychotic symptoms was greater in patients than in healthy controls (RA, 1.90 vs. 1.63, p < 0.001; SpA, 1.88 vs. 1.63, p = 0.001). Distress was also greater in patients than in controls owing to the presence of symptoms. No differences were observed between the three groups for the mental dimension scores in the SF-12 Health Survey (43.75 in RA, 45.54 in SpA, and 43.19 in healthy controls). Our findings point to a greater prevalence of subclinical psychotic symptoms in patients with RA and patients with SpA than in the general population. The results suggest an association between inflammation and depression/subclinical psychotic symptoms.

(1) Background: Biophysical techniques applied to serum samples characterization could promote the development of new diagnostic tools. Fluorescence spectroscopy has been previously applied to biological samples from cancer patients and differences from healthy individuals were observed. Dendronized hyperbranched polymers (DHP) based on bis(hydroxymethyl)propionic acid (bis-MPA) were developed in our group and their potential biomedical applications explored. (2) Methods: A total of 94 serum samples from diagnosed cancer patients and healthy individuals were studied (20 pancreatic ductal adenocarcinoma, 25 blood donor, 24 ovarian cancer, and 25 benign ovarian cyst samples). (3) Results: Fluorescence spectra of serum samples (fluorescence liquid biopsy, FLB) in the presence and the absence of DHP-bMPA were recorded and two parameters from the signal curves obtained. A secondary parameter, the fluorescence spectrum score (FS score ), was calculated, and the diagnostic model assessed. For pancreatic ductal adenocarcinoma (PDAC) and ovarian cancer, the classification performance was improved when including DHP-bMPA, achieving high values of statistical sensitivity and specificity (over 85% for both pathologies). (4) Conclusions: We have applied FLB as a quick, simple, and minimally invasive promising technique in cancer diagnosis. The classification performance of the diagnostic method was further improved by using DHP-bMPA, which interacted differentially with serum samples from healthy and diseased subjects. These preliminary results set the basis for a larger study and move FLB closer to its clinical application, providing useful information for the oncologist during patient diagnosis.

Background: Current efforts in the identification of new biomarkers are directed towards an accurate differentiation between benign and premalignant cysts. Thermal Liquid Biopsy (TLB) has been previously applied to inflammatory and tumor diseases and could offer an interesting point of view in this type of pathology., Methods: In this work, twenty patients (12 males and 8 females, average ages 62) diagnosed with a pancreatic cyst benign (10) and premalignant (10) cyst lesions were recruited, and biological samples were obtained during the endoscopic ultrasonography procedure., Results: Proteomic content of cyst liquid samples was studied and several common proteins in the different groups were identified. TLB cyst liquid profiles reflected protein content. Also, TLB serum score was able to discriminate between healthy and cysts patients (71% sensitivity and 98% specificity) and between benign and premalignant cysts (75% sensitivity and 67% specificity)., Conclusions: TLB analysis of plasmatic serum sample, a quick, simple and non-invasive technique that can be easily implemented, reports valuable information on the observed pancreatic lesion. These preliminary results set the basis for a larger study to refine TLB serum score and move closer to the clinical application of TLB providing useful information to the gastroenterologist during patient diagnosis., Competing Interests: The authors declare no conflict of interest.

Risk population screening programs are instrumental for advancing cancer management and reducing economic costs of therapeutic interventions and the burden of the disease, as well as increasing the survival rate and improving the quality of life for cancer patients. Lung cancer, with high incidence and mortality rates, is not excluded from this situation. The success of screening programs relies on many factors, with some of them being the appropriate definition of the risk population and the implementation of detection techniques with an optimal discrimination power and strong patient adherence. Liquid biopsy based on serum or plasma detection of circulating tumor cells or DNA/RNA is increasingly employed nowadays, but certain limitations constrain its wide application. In this work, we present a new implementation of thermal liquid biopsy (TLB) for lung cancer patients. TLB provides a prediction score based on the ability to detect plasma/serum proteome alterations through calorimetric thermograms that strongly correlates with the presence of lung cancer disease (91% accuracy rate, 90% sensitivity, 92% specificity, diagnostic odds ratio 104). TLB is a quick, minimally-invasive, low-risk technique that can be applied in clinical practice for evidencing lung cancer, and it can be used in screening and monitoring actions.

Appendectomy is the most frequently performed emergent surgical procedure in western countries. There is still controversy about which alternative is clinically and economically superior: open or laparoscopic appendectomy (LA). Our aim was to determine clinical outcomes and cost of both procedures in our academic institution. A retrospective comparative study was performed including patients undergoing appendectomy from January to December 2011. Demographic data, operating room occupancy time, hospital length of stay, complications, and economic data were obtained. A total of 116 appendectomies were performed along the time of study, 23.27% laparoscopic and 76.72% open. Groups were similar in terms of demographics and intraoperative findings. Operating room occupancy time was longer in laparoscopic group and hospital stay was shorter. No significant differences were found respecting to postoperative complications rate. Cost minimization analysis showed that LA saved 1561.08&OV0556; per patient. In our teaching setting, LA may have clinical and economic advantages over open appendectomy.

This paper presents a body-fixed-sensor-based approach to assess potential sleep apnea patients. A trial involving 15 patients at a sleep unit was undertaken. Vibration sounds were acquired from an accelerometer sensor fixed with a noninvasive mounting on the suprasternal notch of subjects resting in supine position. Respiratory, cardiac, and snoring components were extracted by means of digital signal processing techniques. Mainly, the following biomedical parameters used in new sleep apnea diagnosis strategies were calculated: heart rate, heart rate variability, sympathetic and parasympathetic activity, respiratory rate, snoring rate, pitch associated with snores, and airflow indirect quantification. These parameters were compared to those obtained by means of polysomnography and an accurate microphone. Results demonstrated the feasibility of implementing an accelerometry-based portable device as a simple and cost-effective solution for contributing to the screening of sleep apnea-hypopnea syndrome and other breathing disorders.

Background: The electronic Schizophrenia Treatment Adherence Registry (e-STAR) is a prospective, observational study of patients with schizophrenia designed to evaluate long-term treatment outcomes in routine clinical practice., Methods: Parameters were assessed at baseline and at 3 month intervals for 2 years in patients initiated on risperidone long-acting injection (RLAI) (n=1345) or a new oral antipsychotic (AP) (n=277; 35.7% and 36.5% on risperidone and olanzapine, respectively) in Spain. Hospitalization prior to therapy was assessed by a retrospective chart review., Results: At 24 months, treatment retention (81.8% for RLAI versus 63.4% for oral APs, p<0.0001) and reduction in Clinical Global Impression Severity scores (-1.14 for RLAI versus -0.94 for APs, p=0.0165) were significantly higher with RLAI. Compared to the pre-switch period, RLAI patients had greater reductions in the number (reduction of 0.37 stays per patient versus 0.2, p<0.05) and days (18.74 versus 13.02, p<0.01) of hospitalizations at 24 months than oral AP patients., Conclusions: This 2 year, prospective, observational study showed that, compared to oral antipsychotics, RLAI was associated with better treatment retention, greater improvement in clinical symptoms and functioning, and greater reduction in hospital stays and days in hospital in patients with schizophrenia. Improved treatment adherence, increased efficacy and reduced hospitalization with RLAI offer the opportunity of substantial therapeutic improvement in schizophrenia.

This work studies the structural and lectin-binding modifications experienced by the renal corpuscle of the African lungfish Protopterus dolloi during aestivation. The kidney of the aestivating animals was studied by light- and electron-microscopy, and by immunofluorescence methods. Upon aestivation, the renal corpuscles (RCs) undergo a marked size reduction, and all the structural RC components are affected. The parietal cells of Bowman's capsule lose their flattened appearance and adopt the organization of a stratified epithelium. The glomerular capillaries collapse. The podocytes approach each other. Concomitantly, the major processes between contiguous cells are lost, the rest of the major processes adopting a lamina-like configuration. The foot processes lose their regular arrangement, the filtration slits are difficult to observe, and the subpodocyte space disappears. The glomerular basement membrane (GBM) thickens enormously, increases the amount of amorphous material and of collagen, and round inclusions formed by amorphous material and coiled fibrils appear. The mesangial cells compact and form a dense network embedded in the subendothelial lamina of the GBM. The endothelial cells show numerous irregularities, establishing abnormal interrelationships with the mesangial cells. These modifications are accompanied by changes in the expression of the carbohydrate moieties, as indicated by the modifications in lectin-binding patterns. On the whole, these modifications thicken and compact the filtration barrier, thus reducing the filtration coefficient and allowing the organism to cope with dehydration. All these modifications are partially reversed during the first days of returning the animals to freshwater. The renal corpuscle appears to be a highly dynamic structure capable of modifying its architecture in response to environmental changes.

This study considers the nonparametric estimation of a regression function when the response variable is the waiting time between two consecutive events of a stationary renewal process, and where this variable is not completely observed. In these circumstances, our data are the recurrence times from the occurrence of the last event up to a pre-established time, along with the corresponding values of a certain set of covariates. Estimation of the error density function and some of its characteristics are also considered. For the proposed estimators, we first analyze their asymptotic behavior and, thereafter, carry out a simulation study to highlight their behavior in finite samples. Finally, we apply this methodology to an illustrative example with biomedical data.

In this paper, an accelerometer is used to measure the vibration of the neck and thorax, in order to detect important signals that can be used in the diagnosis of sleep apnoea. Accelerations produced by the heart signals, the breathing movement and the snoring sounds are detected by an accelerometer attached to the skin. Mean power levels of the signal in different frequency bands are used to map the surface of the neck and thorax, where the accelerometer has been positioned in 15 different locations. A program in Matlab is used to fit this surface plot. Getting an adequate location for the accelerometer is a clear help to the diagnosis of sleep apnea.

In this paper we present a system based on a sensor of acceleration for acquisition and monitoring of diverse physiological signals, by extracting respiratory, cardiac and snoring components inside the main source. Digital signal processing techniques used frequently in Biomedical Engineering have been used. The acceleration produced by the cardiac signals, the respiratory movements and the vibrations generated by the snores are detected with help of an accelerometer placed on the skin of the subject in not invasive way. The presented device allows the monitoring of several biomedical parameters: heart rate (HR), heart rate variability (HRV), Sympathetic, parasympathetic and baroreflex activity, respiratory rhythms and their variations (bradypnea - tachypnea), snoring and abdominal-thoracic efforts. A simple and effective method and device [1] is provided for helping to the diagnosis of Sleep Apnea-Hypopnea Syndrome (SAHS) and other breathing disorders.

The Dipnoi (lungfishes) have developed true lungs, having the ability to take oxygen from both the gills and the lungs. During the tropical dry season, many lungfish estivate on land, breathing only air. The estivation period is accompanied by profound functional modifications, including the suppression of urine. Thus, the lungfish kidney must be designed to cope with these dramatic cyclic changes in renal function. We study here the microanatomy and the structure of the kidney of the African lungfish Protopterus dolloi, maintained under controlled freshwater conditions. Chemical microdissection, light microscopy, and scanning and transmission electron microscopy have been used. The nephrons of P. dolloi are composed of a renal corpuscle (RC) and of a renal tubule that appears divided into five morphologically distinct segments: neck segment (NS), proximal tubule (PT), intermediate segment (IS), distal tubule (DT), and collecting tubule (CT). Paired CTs abut into a collecting duct, the latter emptying into an archinephric duct. The RCs lie in the mid-zone of the kidney, between the PTs and the convoluted DTs. The spatial distribution of these elements allows recognition of a kidney zonation. The RCs group into clusters (3-4 RCs per cluster) that are supplied by a single arteriole surrounded by pericytes. Each cluster appears to represent a functional unit with a common hemodynamic regulatory mechanism. The major processes of the podocytes form flattened networks that appear to constitute an integrated system due to the presence of gap junctions. The existence of mesangial cells with large cell processes, and of mesangial cells with a dendritic appearance, suggests a complex functional role (contractile and phagocytic) for the mesangium. The NS and the IS are the narrowest nephron segments, formed only by multiciliated cells. The PT and the DT can be subdivided, based on the tubular morphology and on cell composition, into portions I and II: PTI is formed only by brush border (BB) cells, while PTII contains BB and multiciliated cells. The DTI is formed by segment-specific cells, while the DTII contains segment-specific and a small number of flask cells. The CT contains principal and flask cells in a 5:1 ratio. The flask cells adopt two different configurations (with a narrow canaliculus or with a large cavity). The main goal of this study was to disclose specific kidney features that could be related to function, phylogeny, and habitat. In addition, the present results constitute the basis for a study of the morphologic changes that should occur in the kidney of P. dolloi during estivation.

Objective: Mitral regurgitation due to prolapse of the mitral leaflets frequently compromises annuloplasty repair procedures. We present a new annuloplasty ring that overcomes this difficulty, preventing displacement of the leaflets into the atrium., Methods: The 'Valve Racket' is a prosthetic ring transformed into a racket by means of handmade mesh using expanded polytetrafluoroethylene (ePTFE Gore-Tex). After transection of the marginal chordae tendineae, five sheep had the new racket implanted in the mitral (n = 3) and in the tricuspid position (n = 2). The surviving sheep underwent postoperative evaluation., Results: After six months of operation, a standard transthoracic study showed competent valves without significant gradients and without residual valve regurgitation. The ring appeared encapsulated by a uniform fibrous tissue but the threads showed a completely denuded surface except in the zone proximal to the ring. Thrombi or calcification deposits in the ring, racket's mesh, or cardiac chamber were not observed., Conclusion: This initial experience confirmed the efficacy and simplicity of the technique.

Basement membranes (BMs) constitute a distinct compartment of the extracellular matrix (ECM). All BMs show a similar structural appearance but differ in molecular composition. These variations have critical functional implications. The aim of this study is to establish the pattern of the tomato lectin (Lycopersicon esculentum agglutinin--LEA) binding sites in the BMs of the developing chick embryo (stages 4-21, Hamburger and Hamilton, 1951) in order to achieve a better understanding of the molecular heterogeneity of BMs. The study was performed with transmission electron microscopy (TEM) histochemistry, and confocal laser microscopy. TEM showed that LEA bound to the lamina densa and to the lamina fibroreticularis of the BMs. Through the period studied, most of the LEA binding appeared in the ectodermal BM and its derivatives. In the limb bud, LEA binding to the ectoderm BM was more intense in the ventral half than in the dorsal half. Furthermore, LEA allowed the early (HH16) detection of the transverse fibrillar tracts. In the lens and in the inner ear primordium, the BMs were LEA positive through the placode and cup stages. The binding was progressively reduced through the vesicle stage. The BMs of the olfactory primordium, and of the Rathke's pouch were positive. In contrast, the BMs of the developing central nervous system were negative. The BMs of both the paraxial and the lateral plates of the mesoderm were negative, whereas the notochord and the BM of the Wolffian duct were positive. The endodermal BM and its derivatives were negative. The ECM located between the fusing endocardial tubes, and the BM of the fusion zone of the paired aortae, were positive. This suggested an active role of the LEA-positive glycoproteins in the fusion of endothelia. Our results show the heterogeneity of the chick embryo BMs during development. In addition, LEA constitutes an excellent marker for the primordial germ cells.

We report a morphologic study of the heart inflow tract of the African lungfish Protopterus dolloi. Attention was paid to the atrium, the sinus venosus, the pulmonary vein, and the atrioventricular (AV) plug, and to the relationships between all these structures. The atrium is divided caudally into two lobes, has a common part above the sinus venosus, and appears attached to the dorsal wall of the ventricle and outflow tract through connective tissue covered by the visceral pericardium. The pulmonary vein enters the sinus venosus and runs longitudinally toward the AV plug. Then it fuses with the pulmonalis fold and disappears as an anatomic entity. However, the oxygenated blood is directly conveyed into the left atrium by the formation of a pulmonary channel. This channel is formed cranially by the pulmonalis fold, ventrally by the AV plug, and caudally and dorsally by the atrial wall. The pulmonalis fold appears as a wide membranous fold which arises from the left side of the AV plug and extends dorsally to form the roof of the pulmonary channel. The pulmonalis fold also forms the right side of the pulmonary channel and sequesters the upper left corner of the sinus venosus from the main circulatory return. The AV plug is a large structure, firmly attached to the ventricular septum, which contains a hyaline cartilaginous core surrounded by connective tissue. The atrium is partially divided into two chambers by the presence of numerous pectinate muscles extended between the dorsal wall of the atrium and the roof of the pulmonary channel. Thus, partial atrial division is both internal and external, precluding the more complete division seen in amphibians. The present report, our own unpublished observations on other Protopterus, and a survey of the literature indicate that not only the Protopterus, but also other lungfish share many morphologic traits.

Intranuclear inclusions composed of tubular filaments constitute a pathological hallmark of oculopharyngeal muscular dystrophy (OPMD). Autosomal dominant OPMD is caused by (GCG) repeat expansions in the gene that encodes for poly(A) binding protein nuclear 1 (PABPN1). The mutation results in the expansion of a polyalanine stretch in the N-terminus of the protein. It has been proposed that mutated PABPN1 induces protein aggregation, which in turn causes the formation of the filamentous nuclear inclusions. Here we report the presence of intranuclear inclusions composed of tubular filaments in oxytocin-producing neurons from normal rat hypothalamus. Like OPMD inclusions, the filamentous structures in neurosecretory neurons accumulate PABPN1, poly(A) RNA, ubiquitin and proteasomes. These inclusions do not contain members of Hsp40 and HDJ-2/DNAJ families of chaperones. The proportion of oxytocin-producing neurons that contain inclusions decreases during parturition and lactation (when synthesis and release of oxytocin is maximal) and increases at 1 day post-weaning (when occurs a drastic reduction in the production of the hormone). Thus, PABPN1 filaments in normal neurons are dynamic structures, the appearance of which correlate with changes in cellular activity. These data provide the first physiological evidence that polyalanine expansions are not essential to induce polymerization of PABPN1 into filamentous nuclear inclusions.

Renal cysts in the cortex of a juvenile Belgian Malinois dog with acute renal failure were studied by means of light, scanning and transmission electron microscopy, immunohistochemistry for intermediate filaments, and binding for wheat germ agglutinin (WGA), peanut agglutinin (PNA), and Maclura pomifera agglutinin (MPA) lectins to determine the morphological and histochemical features of the epithelial cells of these cysts. The cysts were renal corpuscles with expanded urinary space. Glomerular tufts were small with poorly developed capillary loops and increased mesangial matrix. Continuity with the proximal tubule was evident in some cystic glomeruli. Two cell types lined Bowman's capsule. One was squamous with a central cilium and microvilli. The other had morphological and histochemical features of immature podocytes (parietal podocytes). These cells were round and protruded into the urinary space; they had thick cytoplasmic projections that resembled foot processes of podocytes, microvilli, and filtration slits. The parietal podocytes expressed vimentin and cytokeratins and had affinity for WGA as do normal immature podocytes. These features suggest that the parietal podocytes are derived by metaplasia of the parietal cells. The basement membrane of Bowman's capsule was irregularly thickened and showed multifocal glycosylation changes with lectin histochemistry (WGA, PNA, MPA) in areas adjacent to the parietal podocytes. Histologic and ultrastructural findings in this dog are consistent with glomerulocystic kidney disease. This is the second report of canine glomerulocystic kidney disease. Features are similar to those of the human counterpart, but it is unclear whether genetic defects cause the disease in the dog. The presence of parietal podocytes in all cysts suggests that abnormal differentiation may play an important role in the pathogenesis of this type of polycystic kidney disease.

The conus (bulbo-ventricular) valves of teleosts perform a key function in the control of blood backflow during ventricular diastole. However, the structural characteristics of these valves are almost unknown. This paper presents a systematic anatomical, histological and structural study of the conus valves of the adult gilthead seabream (Sparus auratus). S. auratus shows two major left and right valves consisting of the leaflet and the supporting sinus. Each valvar leaflet can be divided into a stout proximal body and a flap-like distal region. The proximal body is structured into three layers: a luminal fibrosa, a dense cellular core and a parietal fibrosa. The luminal fibrosa is a collagenous structure extending the entire length of the leaflet, while the parietal fibrosa is restricted to the most proximal area. The dense cellular core consists of fibroblastic cells and a matrix rich in glycoconjugates, collagen and elastin. The histochemical and structural data suggest that the luminal fibrosa bears most of the force associated with valvar closure, while the cellular core acts as a cushion dampening vibrations and absorbing the elastic recoil. The sinus wall is a fibrous layer which shows proximal-distal differences in thickness. It also shows compositional differences that can be related to mechanical function. We describe the presence of a fibrous cylinder formed by the sinus wall, the fibrous interleaflet triangles and the fibrous layer that covers the inner surface of the conus myocardium. This fibrous cylinder constitutes the structural nexus between the ventricle, the conus and the bulbus arteriosus, provides support for the conus valves and separates the valvar complex from the surrounding tissues. The structure of the conus valves in S. auratus is different from that found in other vertebrates. Anatomical similarities between the conus valves and the mammalian arterial valves are emphasized. Each phyletic group appears to have developed specific structures in order to perform similar functions.

The sturgeon is an ancient species of fish that thrives in a wide range of ecological environments, from freshwater to seawater. Basic in this process of adaptation is the ability of the kidney to control fluid filtration and urine formation. However, the morphological basis of this process is mostly unknown. The aim of the present study was to use microdissection techniques (scanning electron microscopy (SEM), transmission electron microscopy (TEM), and lectin-binding histochemistry) to examine the structure of the renal corpuscle of the sturgeon Acipenser nacarii in order to reveal morphologic features that could be related to function, phylogeny, and habitat. The renal corpuscles are aligned along the intrarrenal arteries. The urinary pole shows a siphon-like neck segment (NS) in 92% of the nephrons, whose structural characteristics are different from those of other fish. The podocytes have cuboidal cellular bodies, intercellular contacts, and poorly developed cell processes. The podocyte glycocalyx contains N-acetylglucosamine and lacks sialic acid. The structural and lectin-binding patterns are similar to those found in the immature mammalian kidney. The glomerular basement membrane (GBM) is very thick and consists of three layers: a lamina rara externa, a lamina densa, and a thick subendothelial lamina. The latter contains tubular microfibrils, collagen fibers, and long mesangial cell processes. Frequently, the podocyte bodies attach directly to the GBM, and the area occupied by the filtration slits is very small. Furthermore, the GBM shows a glycosylation pattern different from that observed in most vertebrates. Contrary to what would be expected in sturgeons living in freshwater, the A. nacarii renal corpuscle morphology suggests a low glomerular filtration rate., (Copyright 2003 Wiley-Liss, Inc.)

The cell nucleus is divided into chromosome territories and the extrachromosomal domain. The latter includes several structural and functional compartments involved in RNA processing and transport. Morphological and cytochemical analyses of the cell nucleus in sturgeon podocytes revealed the existence of a previously uncharacterised nuclear compartment. It appears as a cleared nucleoplasmic area of variable size within the extrachromosomal domain. Conventional light and electron microscopy revealed that this compartment, here referred to as cleared extrachromosomal domain (CED), appears free of chromatin and RNA-containing organelles and is closely surrounded by heterochromatin masses. Cytochemical and immunogold electron microscope studies indicated that CEDs lack DNA, RNA and glycoconjugates. The ultrastructural examination of Lowicryl-embedded sections showed that CEDs are formed by a fibrillar network. In resinless preparations, this network appears as a dense mesh of crosslinked nuclear matrix filaments. The density of nuclear matrix filaments within the CED is remarkably higher than that observed in the rest of the nucleus. Our results indicate that the CED is a single, distinct extrachromosomal domain of the nuclear matrix of sturgeon podocytes. The absence in the CED of detectable DNA and RNA, as well as the lack of chromatin and RNA-containing structures, suggests that transcription and RNA processing do not occur in this novel nuclear compartment. The volume occupied by the CED may preserve the volume-to-cytoplasm ratio in the podocyte and contribute to modulate the spatial organisation and the volume occupied by the chromosomal territories.

The three-dimensional (3D) microanatomy of the cornea is the major determinant of its optical and mechanical properties. Scanning electron microscopy (SEM) is the most commonly used method to obtain information on the overall 3D microanatomy of organs. However, SEM has not been successful in revealing the 3D microanatomy of the cornea, because the interior of the cornea is too compact to be explored by the electron beam. In this study, the 3D organisation of the cells and extracellular materials of human and rabbit corneas was examined after exposure by HCl and NaOH digestion, and by microdissection by the adhesive tape method. In the cornea of both species, all epithelial cells exhibited microplicae regardless of their location. This raises doubts about the tear film-holding role assigned to the microplicae of the superficial cells. Human and rabbit corneas differed in the collagen fibre patterns of the epithelial basement membranes. The 3D organisation of the stromal lamellae was similar in both species. In humans and rabbits, the keratocytes showed similar 3D features. However, the surface of human keratocytes located near Descemet's membrane exhibited small fenestrations that were not present in the rabbit keratocytes. The pattern of keratocyte innervation by the stromal neural plexus and 3D keratocyte microanatomy confirms that keratocytes form a large intercommunicating network within the corneal stroma. Two morphologically discrete subpopulations of keratocytes located at different stromal levels were identified in both human and rabbit corneas, suggesting that keratocytes are not functionally homogeneous. In addition, the density of the stromal neural plexus appeared to be greater in rabbits than in humans. Clear differences between human and rabbit corneas were observed in the collagen arrangement in Descemet's membrane, which may reflect their different biomechanical requirements.

Trigeminal ganglion neurons comprise three main cell body-size types. This cell size heterogeneity provides an excellent neuronal model to study the cell size-dependent organization and dynamics of the nucleoli, Cajal (coiled) bodies (CBs), and nuclear speckles of pre-mRNA splicing factors, nuclear structures that play a key role in the normal neuronal physiology. We have analyzed the number of nucleoli and CBs and the structural and molecular organization of CBs and nuclear speckles in the three neuronal types by using immunofluorescence with antibodies that recognize nucleoli (fibrillarin), CBs (coilin), and nuclear speckles (snRNPs), confocal microscopy, and electron microscopy. Whereas the mean number of nucleoli per neuron decreases as a function of cell size, the number of CBs per cell significantly increases in large neurons in comparison with the small ones. In addition, large neurons have a higher proportion of CBs associated with the nucleolus. In all neuronal types, CBs concentrate coilin, fibrillarin, snRNPs, and the survival motor neuron protein (SMN). Immunostaining for snRNPs shows small speckle domains and extensive areas of diffuse nucleoplasmic signal in large neurons, in contrast with the large nuclear speckles found in small neurons. Furthermore, flow cytometric analysis shows that all neurons are in the range of diploid cells. These findings indicate that the fusion behavior of nucleoli, the formation of CBs and their relationships with the nucleolus, as well as the compartmentalization of the pre-mRNA splicing machinery, is related to cell body size in the trigeminal ganglion neurons. Because transcriptional activity is a basic determinant mechanism of cell size in diploid cells, we suggest that our findings reflect a distinct transcription-dependent organization of the nucleolus and splicing machinery in the three cell types of trigeminal ganglion neurons., (Copyright 2001 Wiley-Liss, Inc.)

The first rudiment of the central nervous system is a simple tube, the neural tube, and its cavities become the cerebro-ventricular system. The elements located within this system, their composition and precise morphogenetic role are poorly understood. This study used transmission (TEM) and scanning (SEM) electron microscopy, and immunoelectron microscopy, and describes in the chick the development, ultrastructure, composition, and regression of a previously undescribed extracellular structure located in close relationship with the luminal pole of the developing rhombencephalic tectoria lamina. We have called it the rhombencephalic roof network (RRN). The RRN was first observed in stage 12, closely related to a cluster of apoptotic cells. Between stages 15 and 18, the RRN attained its greatest development; it was rhomboid in shape and SEM revealed a network of fibers. Between stages 19 and 22, the RRN underwent a process of fragmentation and regression, and was not observed after stage 23. With TEM, the RRN appeared formed by amorphous ruthenium-red-positive material and sets of tubes between 4 and 25 nm in diameter. Each tube was formed by the superposition of annular units. Immunolabelling showed the presence of laminin and heparan sulfate proteoglycan in both the amorphous material and fibers; the former also contained tenascin. In terms of ultrastructure and composition, the fibers were similar to one the basic components of the lamina densa of basement membranes. The developing tectoria lamina exhibited openings as early as stage 12+, showing that the neural cavity is not a closed system and that the neural tube fluid (NTF) could be a circulating liquid. The presence in the RRN of three molecules of the extracellular materials actively involved in several developmental processes and the very early appearance of the RRN suggest that this structure plays a developmental role in rhombencephalic morphogenesis.

Extracellular material molecules play a key role in the regulation of morphogenesis and differentiation of a large number of organs including the central nervous system. However, the role of the neural basement membrane in the growth of different parts of the neural tube has yet to been delineated. Here, the structural and compositional modifications of the basement membrane (BM) of rhombencephalic tectoria lamina anlage (RTLA) have been examined during the process of RTLA epithelial attenuation. Between stages 10 to 11-the presumptive RTLA epithelium showed a structure, thickness and cell-proliferating capacity similar to those observed in other zones of the rhombencephalic walls. Moreover, the rhombencephalic vesicles were surrounded by a continuous BM that was heterogeneous both ultrastructurally and with regard to ruthenium red, laminin and tenascin distribution. After stage 11, the RTLA epithelium underwent a rapid process of attenuation and change to a stratified flattened epithelium. During this remodelling process, apoptosis and inhibition of both PCNA expression and 3H-thymidine uptake occurred in the RTLA epithelium. The BM of the RTLA underwent a process of degration at the beginning of the remodelling, and apoptosis and cell proliferation inhibition of RTLA epithelium were also observed. The loss of the biochemical signals encoded within the BM could lead to cell shape changes, cell proliferation inhibition and to the anoikis type of cell death. Our findings support the idea that the BM surrounding the neural tube plays a key role in controlling both the structure and growth of the CNS during the early developmental stages.

The mechanisms responsible for renal cyst formation in congenital polycystic kidney disease (PKD) remain unknown. Changes in extracellular matrix (ECM) are regarded as an important pathogenic factor in PKD. Tenascin, an ECM glycoprotein implicated in abnormal growth in adult organs, has not been systematically evaluated in PKD. In this study, tenascin expression was studied by immunohistochemistry in the autosomal recessive polycystic kidneys of C57BL/6J (cpk/cpk) mice. Scanning electron microscopy was performed to determine the cyst types and their temporal evolution, and to establish correlations with the immunohistochemistry observations. Cystic lesions evolved in three main stages. Initially, the cysts appeared as segmental dilatations of both proximal and collecting ducts. In the second stage, the collecting duct cysts (CDCs) underwent rapid growth that led to the destruction of all other kidney elements. In the final stage, the CDCs reached their maximum size and the PKD mice died. Normal differentiated principal cells and three types of intercalated cells were present in the CDC epithelium. In all three stages an intense tenascin expression was detected selectively in the basement membranes of the cysts. In the last stage, an intense tenascin immunoreactivity was also observed in the interstitial fibrotic tissue. The abnormal presence of tenascin in the basement membranes of the cysts suggests that this glycoprotein is implicated in the pathogenesis of the cysts, possibly by stimulating cell proliferation.

Supraependymal cellular elements are a constant feature in the adult cerebroventricular system. However, there has been no analysis of their distribution and morphology during the embryonic stages of the chick brain. The ultrastructural features of the rhombencephalic luminal surface of chick embryos ranging from stage 10 to 22 were studied with both scanning and transmission electron microscopy. In addition, immunocytochemistry and confocal laser microscopy were used to examine the presence of 68 kD neurofilaments in supraependymal elements. The ultrastructural observations revealed significant morphological differences in the apical cell surface between the cells at rhombomere boundaries and those in the rhombomere bodies. These differences support the idea that the boundary and the body of rhombomeres contain two morphologically distinct cell types. Supraependymal (SE) cells and SE fibers were present in the rhombencephalon of all embryos studied from stage 12 to 22. The cells were bipolar spindle-shaped. The SE fibers showed a characteristic spatial pattern within the rhombencephalon, following a straight course parallel to the rhombomere boundaries. The SE fibers showed varicosities and their endings contained small vesicles. Both SE cells and SE fibers were positive for 68 kD neurofilaments. Their morphology and reactivity for neurofilaments indicate a neuronal function. The constant presence of SE cells and SE fibers on the surface of the developing rhombencephalon, their special pattern and close relationship with the neural tube fluid (NTF) suggest that these supraependymal elements may be involved in a neuronal signalling pathway between different parts of the same rhombomere and also in chemical communication and integration within the ventricular system, linking distant parts of the developing central nervous system by means of NTF.

Background: Insulin-like growth factor-I (IGF-I) is a peptide growth factor whose biological effects are mediated through a specific receptor (IGF-IR). IGF-I and IGF-IR are detected in both fetal and adult kidneys and have both metabolic and growth effects. IGF-IR expression during postnatal kidney development is not well defined and the biological role of this receptor during the postnatal stage is not clearly established. The purpose of the present study was to analyze IGF-IR gene expression during the postnatal development of rabbit kidney to achieve a better understanding of the correlation between growth and differentiation of kidney tissues and IGF-IR expression., Methods: Using in situ hybridization, we studied changes in IGF-IR expression in the kidneys of newborn rabbits and those up to 35 days old. Evaluation of the stage of kidney development and morphological maturation was made on histological sections stained with hematoxylin-eosin., Results: High levels of IGF-IR gene expression in the rabbit kidney occurred in the last stages of postnatal development and in the adult stages; during the development of the subcapsular metanephrogenic zone, IGF-IR gene expression was not observed. IGF-IR mRNA was expressed by proximal and distal tubules and by collecting ducts after these tissues attained morphological maturation. The appearance of IGF-IR mRNA in these kidney structures followed a precise temporo-spatial sequence. IGF-IR was not expressed by renal corpuscles, Henle's loops, inner medullary collecting ducts, vessels, or interstitial cells at any study stage., Conclusions: The temporal and spatial patterns of IGF-IR gene expression during postnatal development of the rabbit kidney suggest that IGF-IR and its ligands are relevant for the acquisition of the function, and not for development events, by proximal and distal tubules and collecting ducts. This study also suggests that IGF-IR mRNA localization constitutes a useful marker to determine the functional maturation of these renal structures.

Fluorochrome-labelled lectins and the Jones method of silver impregnation preceded by different oxidation and enzymatic digestion procedures were used to study the patterns of glycosylation and silver affinity of the macula densa (MD) and thick ascending limb (TAL) basement membranes of the rabbit kidney. The goal of this study was to analyse the morphological basis of MD basement membrane permeability and its possible role in modulation of the signal involved in tubuloglomerular feedback control of the juxtaglomerular apparatus. The lectin-binding pattern and silver affinity of basement membrane differed clearly from those of the TAL basement membrane. The former had greater WGA and Con A affinity than the latter. Furthermore, the MD basement membrane lost argyrophilia in permanganate oxidized sections whereas that of the TAL did not. The cell coat of MD cells differed from that of the TAL cells in that it had N-acetyl neuraminic acid and Con A binding sites. Our results suggest that the MD basement membrane has a distinctive macromolecular composition which may be related to its permeability to high molecular weight molecules.

Fluorochrome-labeled lectins were used to study the expression of glycoconjugates during the postnatal differentiation of normal and cystic rabbit renal corpuscles. Glomerular cysts (GC) are induced in the rabbit by a single injection of corticoids. The Bowman's capsule of these cysts is exclusively formed of podocytes (parietal podocytes). During normal development, the cell coat of the podocytes is intensely positive for wheat germ agglutinin (WGA) and Maclura pomifera agglutinin (MPA). This reaction decreases considerably during maturation, in parallel with an increase in the number of binding sites masked by terminal sialylation. Throughout the stages studied, the podocyte coat is peanut agglutinin (PNA)-negative, but it becomes intensely positive after neuraminidase treatment. Visceral and parietal podocytes in the glomerular cysts show the same pattern of glycosylation as the normal podocytes. In contrast, normal parietal cells only transiently expressed a weak reactivity to WGA and MPA during the first stages of differentiation, and did not express cryptic binding sites at any stage. The glomerular basement membrane (GBM) is positive to WGA, to succinylated WGA, and to MPA, in all the stages studied. Maturation of the GBM is characterized by expression of cryptic MPA-binding sites, and by a considerable increase in the number of cryptic PNA-binding sites. The basement membrane of the parietal layer of the cystic Bowman's capsule shows the same pattern of glycosylation, despite the fact that this epithelial layer is solely formed of podocytes and lacks endothelial cells. In contrast, the normal parietal basement membrane does not express PNA or MPA cryptic sites at any stage.(ABSTRACT TRUNCATED AT 250 WORDS)

Anomalous origin of right coronary artery from the left sinus of Valsalva is a uncommon congenital anomaly which is difficult to demonstrate angiographically. For many years pathologists classified it as a minor anomaly of no clinical significance. It has only recently been associated with significant manifestations of myocardial ischemia. These manifestations have included acute myocardial infarction, angina pectoris, syncope, ventricular tachycardia and fibrillation, and sudden death. Two patients with this anomaly are reported. One patient had angina pectoris in the absence of significant atheromatous coronary lesions. In the second patient the aberrant origin of the right coronary artery was associated to aortic valve disease. The possible physiopathology mechanisms responsible for manifestations of myocardial ischemia in patients with this anomaly are analyzed.

The three-dimensional structure of the neck segment (NS) of the rabbit nephrons was studied by scanning electron microscopy (after fracture, micro-dissection, or after corrosion nephron casts), and by the air-cast method. The NS was observed at the glomerulotubular junction in 68.5% of all nephrons. In every case the NS appeared as a straight tube with its long axis oriented radially in relation to the glomerulus. Although the external diameter of the NS was smaller than that of the proximal tubule, its luminal diameter was greater. No valve-like structures were observed. Three cell types were observed in the NS: parietal-like, tubule-like, and intermediate. Parietal-like cells showed the same morphology as the parietal cells of the Bowman's capsule. Parietal-like cells constituted the only cell type in 25% of the NS. Tubule-like cells showed morphologic characteristics similar to proximal tubule cells; however, their microvilli were less numerous and exhibited an irregular pattern. Intermediate cells presented an intermediate morphology between tubule-like and parietal cells. In 75% of all NS, the three cellular types were present at the same time. The presence of tubule-like and intermediate cells is interpreted as the result of metaplasic transformation of the parietal cells. Our observations suggest that, in rabbits, the presence of the NS can be explained on the basis of phenotypical lability of the cells located at the glomerulo-tubular junction.

Tubular cysts consisting of dilatation of the collecting ducts at the level of the subcapsular zone of the kidney were induced in newborn rabbits by a single injection of methylprednisolone acetate. We describe here the structural and compositional modifications of the tubular basement membrane (BM) during the formation, growth, and regression of the tubular cysts. During development of the tubular cysts the cystic BM appeared thickened and multilayered, with numerous matrix vesicles. Alcian blue- (AB) and ruthenium red- (RR) positive material distributed differently along the BM of control and cystic tubuli. While the amount of RR-positive material appeared increased in the cystic BM, no differences in the intensity of the AB staining could be discerned between normal and cystic tubuli. Immunofluorescent staining for laminin and type IV collagen appeared to be slightly decreased in the cystic tubuli. However, the amount of fibronectin appeared clearly increased. These changes in the cystic BM appear at the beginning of the tubular dilatation and are not observed in other renal BM. We suggest that there is a causal relationship between the modifications of the BM and the development of the tubular cysts. Glucocorticoids appear to modify the synthesis and/or secretion of the BM components. An abnormal BM should modify the spatial and chemical signals encoded within the BM that, in turn, could lead to abnormal behavior of the tubular cells. This may result in a loss of the normal developmental constraints imposed upon the tubular epithelium, which then undergoes cystic dilatation. During the regression of the cysts, the abnormalities of the BM progressively disappear. The sharp increase in the number of interstitial cells, which show close relationships with the components of the BM, suggests that these cells may be involved in the removal of the cyst BM.

This paper presents a quantitative study of the position of the Golgi apparatus in the developing chick myocardium between stages 8+ and 13+. In addition we have studied the effects of colchicine on the position and structure of the Golgi apparatus. During the formation of the heart tube and loop the position of the Golgi apparatus in the myocytes situated in the vicinity of the dorsal mesocardium is related to that found in the cells of the precardiac mesoderm, but it is completely different from that found in the bulk of myocytes of the heart tube and loop. The position of the Golgi apparatus in both pre- and myocardial cells shows clear significative patterns of polarity. The possible significance of the Golgi apparatus polarity is discussed. After colchicine treatment microtubules disappear, the Golgi apparatus loses its polarization and vacuoles filled with amorphous material and/or collagen fibrils are observed. A possible role of the microtubular system in the maintenance of the structure and polarity of the Golgi apparatus and in the intracytoplasmic transport of the cardiac jelly materials is proposed.

To evaluate the benefits of intravenous streptokinase (SQIV) in acute myocardial infarction (AMI), we joined a group of ten Mexican university hospitals, that were coordinated by the National Institute of Cardiology of Mexico. We included patients less than 70 years of age admitted to the hospital with less than 6 hours from the onset of chest pain during their first myocardial infarction. All patients had ST segment elevation of 1.5 mm or more, and none had contraindication for SQIV. They received 1.5 millions of SQIV in one hour. Reperfusion criteria included absence of pain, ST segment reduction and a rapid rise and fall of enzyme levels. Angiographic criterion for reperfusion was the permeability of the affected coronary vessel. Of 66 patients studied, 57 (86%) had clinical reperfusion; of the 24 available angiographic studies, 92% demonstrated reperfusion. Eight (12%) of the patients had minor complications and 7 (10%) had serious complications. There were 0 deaths. We concluded that SQIV is a useful therapeutic procedure, easy to perform in general hospitals.

We describe here a procedure to improve contrast and resolution in fluorescence microscopy of sectioned tissues. Tissue fragments were fixed in ethanol-glacial acetic acid, embedded in diethylene glycol distearate, and semithin sectioned. This method maintains tissue antigenicity while preserving the structure of cells and tissues. The thinness of the sections eliminates scattered and emitted light from tissue structures outside the plane of focus. The procedure is simple and quick, and works excellently with fluorescein-conjugated lectins and antibodies.

A simple procedure for studying the microanatomy of the kidney by light microscopy is described. Specimens are dried by the critical-point method and later impregnated with a mounting medium. The retention of air within the lumen of nephrons and collecting tubules permits their visualization. The method allows the observation of renal microanatomy without the distortions produced by microdissection or the loss of structural relationships among different kidney components. It also permits observation of the same specimen by both light and scanning electron microscopy.

The sequential changes of cell morphology and the ratio distribution of the different types of cells which exist in tubular cysts induced by methylprednisolone acetate have been studied by light, transmission and scanning electron microscopy. We have also studied the blood levels of sodium and potassium by flame photometry. In both control and cystic ducts, at the level of the outer cortex, the first intercalated cells (IC) were not observed until the 4th postnatal day. Some intermediate cell configurations were observed during the 3rd postnatal day, suggesting that some primitive principal cells (PC) are transformed into IC. Development of IC seems to be independent of both the effects of corticoids and the blood levels of potassium. The ratio distribution and the types of IC observed throughout the period studied was similar in both normal and cystic ducts. The type of IC characterized by the presence of a huge apical process, which has gone previously undescribed with either TEM or SEM, was observed in both control and cystic ducts. We propose to name these cells as cells with surface pattern type V. During the period of regression of the tubular cysts dead and migrating cells were observed closely associated with cilia of the PC. Both types of cells do not seem to represent, based in their localization and frequency, abnormal cell types of the cyst wall. Our results support the hypothesis that renal cysts are giant collecting ducts which conserve both the morphology and the function of the epithelium.

This paper reports an anatomical study of the vascular supply in 60 human cerebelli from subjects of both sexes, aged between 20 and 60 years, who had died of various accidental causes. The origin, branching pattern and cortical and central distributions of the cerebellar arteries have been studied by gross dissection, vascular injection and corrosion procedures. Variations of the normal pattern of the cerebellar arteries in both origin and cortical distribution are frequently found, the anterior inferior and the posterior inferior cerebellar arteries being the arteries showing the highest number of variations. The anomalies most frequently found are duplication in the origin, abnormal origin, and the presence of hypoplastic vessels. The cerebellar nuclei were supplied by the rhomboidal artery, a collateral branch of the superior cerebellar artery. The formation of a precise segmentary vascular pattern into the dentate nucleus by branches arising from the rhomboidal artery is described. The results are discussed in the light of other anatomical studies.

The role of microtubules in the early development of the chick embryo heart was studied. The microtubules were disrupted by treatment of the embryos with colchicine. The embryos were divided for study into three groups: (I) before the fusion of the paired cardiac primordia; (II) before the starting of the cardiac loop, and (III) during the formation of the looping process. Colchicine did not impair the fusion of the paired heart primordia nor the acquisition of an asymmetric C-shaped form. However, the normal counterclockwise movement of the heart loop was prevented. From these results we conclude that the formation of the tubular heart and its looping are independent of the integrity of the microtubular system. Under the effects of colchicine the developing myocytes rounded up bulging into the pericardial cavity. The cell contours became scarcely discernible and the individual cell surfaces gave rise to blebs and ruffles of different sizes. In older embryos, clefts of different sizes appeared between the myocardial cells. The effects of colchicine on the pulsatile activity of the heart were recorded. These effects, as well as those on the cell surface characteristics, were found to be age dependent. The more mature the hearts were, the more resistant to colchicine they became. The developmental significance of the results reported here is discussed.