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Histological changes associated with enlargement and regression of the thymus glands of the red-billed quelea Quelea quelea L. (Ploceidae: weaver-birds).

Thymic lobes form over 200 red-billed queleas, Quelea quelea L., were examined histologically. Samples were taken from embryos about to hatch, juveniles and adults. The lobes varied in size from very small to very enlarged (1- greater than 5 mm long). The constituent cell types are described in detail and the occurrence of these cells in different sized lobes is discussed. A cycle of events is proposed which accounts for the observations presented here. It is suggested that the large numbers of erythroid cells found in the cortex of some individuals were developing in situ. The significance of erythropoiesis within the thymus is discussed.

Age Factors

[Morphologic changes in cryptorchism (author's transl)].

Histologic changes caused by malposition occur in the undescended testicle after the second year of life. Histologic changes like those seen in the human are found in experimental cryptorchism in dogs. The same pathologic changes also occur in the unilaterally descended testicle. The results of preliminary experiments in dogs allow the statement that in unilateral cryptorchism the damage to the contralateral, descended, testicle is produced by an autoimmunologic mechanism.

Animals

Experimental cryptorchidism in adult male rats: histological and hormonal sequelae.

Mature male rats were rendered cryptorchid and followed for up to nine weeks during which serial blood specimens were obtained for multiple hormonal analyses; serial testicular samples were obtained as well. In contrast with control animals, cryptorchid rats showed transient rises in FSH which returned to normal at the end of the study; estrogen levels were high in the final weeks. Plasma testosterone levels were unchanged and LH levels changed little. Light and electron microscopic studies of testicular biopsy specimens showed prompt disruption of spermatogenesis which became more extensive with time. Sertoli cells underwent multiple changes including increased lipid storage and phagocytosis of spermatozoa. Comparisons are made between the sequence of hormonal changes and that of histological changes. In addition, questions are raised concerning the ways in which Sertoli cells are affected by experimental cryptorchidism.

Animals

The growth of respiratory syncytial virus in organ cultures of bovine foetal trachea.

Respiratory syncytial (RS) virus grown in organ cultures of bovine foetal trachea at 37 degrees C and pH 7.2 reached maximum titres of up to 1 X 10(5) PFU/ml between 11 and 21 days after inoculation. Virus yield was increased three fold by incubation at 33 degrees C, but depressed by the addition of RS virus antiserum, with or without bovine complement, or by the addition of alveolar macrophages. Variation in pH or the concentration of foetal calf serum and magnesium chloride did not affect the virus yield. Virus growth did not affect ciliary activity of the cultures. Histological changes involved slight flattening of the epithelium and the appearance of phloxinophilic inclusion bodies. Fluorescent antibody staining showed more virus antigen in the peri-tracheal connective tissue than in the ciliated epithelium. The presence of non-cytopathic mucosal disease (MD) virus in RS virus infected organ cultures slightly depressed RS virus growth but did not influence ciliary activity. These in vitro experiments suggest that the tracheal epithelium may not be an important target in the pathogenesis of RS virus infection in vivo.

Animals

Organotoxic effects of excessive doses of sodium nitroprusside in the rabbit.

The simultaneous iv. infusion in conscious rabbits of 7.5 mg/kg.h sodium nitroprusside (SNP) plus sodium thiosulfate in the molar ratios 1:5 or 1:10, respectively, for 4 h produced perilobular necroses of liver cells. 21 days after the infusion, regeneration of the damaged cells was complete. No histological changes were found in various other organs after this high dose of SNP. No signs of liver toxicity were found in rabbits that had received 0.75 mg/kg.h SNP for 8 h daily during a period of 5 consecutive days. This dose was in the range of SNP doses recommended for clinical use in human patients. Nevertheless we suggest that apart from the thiocyanate plasma levels, also the GOT, GPT, and gamma-GT concentrations in blood be controlled, especially when high doses of SNP are to be given for prolonged periods in order to exclude possible hepatotoxic effects of SNP.

Alanine Transaminase

Clinical significance of hyperparathyroidism in familial multiple endocrine adenomatosis type I (MEA I).

In order to investigate the suggestion that hyperparathyroidism in patients with familial MEA I has a mild and nonprogressive clinical course, we have compared clinical, biochemical, roentgenologic and histologic features of 29 patients with hyperparathyrodism originating from six families with the MEA I syndrome with those of 28 unselected patients with isolated nonfamilial hyperparathyroidism. The patients from the families with MEA I were significantly younger, had lower serum calcium and inorganic phosphate concentrations and a lower incidence of elevated alkaline phosphatase levels. Furthermore, they had multiple enlarged parathyroid glands and recurrence of the disease significantly more often. There was, however, no significant difference in the incidence of renal impairment, urolithiasis, subperiosteal resorption or large bone cysts on roentgenograms, histologic changes in bone biopsy specimens or mortality due to hyperparathyroidism. Therefore, the suggestion that this type of hyperparathyroidism has a milder clinical course is not confirmed in the present study.

Adolescent

Cryptorchidism in the subfertile male.

Certain conclusions may be drawn from the present review and presentation of new data concerning the unilaterally cryptorchid patient and possible subfertility: 1. The truly undescended testis--not the retractile testis of infancy--will not descend spontaneously after 1 year of age. 2. The seminal quality of the unilaterally cryptorchid patient is definitely impaired, although not rendered infertile, in a great majority of patients irrespective of the time of surgery. 3. The dystopic position of the maldescended testis appears to superimpose a second insult on what very likely may be an inherent abnormality in the cryptorchid testis, the latter accounting, perhaps, for its abnormal extrascrotal position. 4. Orchiopexy before the age of 5 seems advisable to ensure minimal histologic changes that may be secondary to the testis' increased exposure to elevated extrascrotal temperature. 5. The cryptorchid testis will be smaller in size irrespective of surgery, and usually correlates with significant testicular pathology. 6. Basal levels of gonadotropins, especially follicle-stimulating hormone, are likely to be elevated, but this does not necessarily imply overwhelming testicular damage. Androgen production should not be affected. 7. Surgical correction is advised when human chorionic gonadotropin stimulation fails to produce teticular descent, thereby defining the maldescended testis as not merely retractile but truly "crytorchid."

Androgens

Thick Ascending Limb Specific Inactivation of Myh9 and Myh10 Myosin Motors Results in Progressive Kidney Disease and Drives Sex-specific Cellular Adaptation in the Distal Nephron and Collecting Duct.

Our previous work established a role for myosin motor proteins MYH9 and MYH10 in trafficking of thick ascending limb (TAL) cargoes uromodulin and Na+-K+-2Cl- cotransporter NKCC2. We have generated a TAL-specific Myh9&10 conditional knockout (Myh9&10 TAL-cKO) mouse model to determine the cell autonomous roles for MYH9&10 in TAL cargo trafficking and to understand the consequence of TAL dysfunction in adult kidney. Myh9&10 TAL-cKO mice develop progressive kidney disease with pathological tubular injury confirmed by histological changes, tubular injury markers, upregulated endoplasmic reticulum (ER) stress/unfolded protein response, and higher blood urea nitrogen and serum creatinine. However, male mice survive twice as long as female mice. We have determined this sexual dimorphism in morbidity is due to adaptation of the distal nephron and collecting duct in response to TAL dysfunction and lower NKCC2 expression. We demonstrate that this triggers a compensatory mechanism involving sex-specific cellular adaptation within the distal nephron and collecting duct to boost sodium reabsorption. While both sexes overcompensate by activating epithelial sodium channel (ENaC) expression in medullary collecting ducts resulting in hypernatremia, this is initially subdued in male Myh9&10 TAL-cKO mice through higher sodium chloride cotransporter (NCC) expression within the distal nephron. Our results indicate that compromised TAL function ultimately results in maladaptation of medullary collecting duct cells which acquire cortical-like properties including ENaC expression. This work further confirms a cell autonomous role for MYH9&10 in maintenance of NKCC2 expression in the TAL and uncover distal nephron and collecting duct adaptive mechanisms which respond to TAL dysfunction.

Animals

Single-cell transcriptomic atlas of Alzheimer's disease middle temporal gyrus reveals region, cell type and sex specificity of gene expression with novel genetic risk for MERTK in female.

Alzheimer's disease, the most common age-related neurodegenerative disease, is closely associated with both amyloid-ß plaque and neuroinflammation. Two thirds of Alzheimer's disease patients are females and they have a higher disease risk. Moreover, women with Alzheimer's disease have more extensive brain histological changes than men along with more severe cognitive symptoms and neurodegeneration. To identify how sex difference induces structural brain changes, we performed unbiased massively parallel single nucleus RNA sequencing on Alzheimer's disease and control brains focusing on the middle temporal gyrus, a brain region strongly affected by the disease but not previously studied with these methods. We identified a subpopulation of selectively vulnerable layer 2/3 excitatory neurons that that were RORB-negative and CDH9-expressing. This vulnerability differs from that reported for other brain regions, but there was no detectable difference between male and female patterns in middle temporal gyrus samples. Disease-associated, but sex-independent, reactive astrocyte signatures were also present. In clear contrast, the microglia signatures of diseased brains differed between males and females. Combining single cell transcriptomic data with results from genome-wide association studies (GWAS), we identified MERTK genetic variation as a risk factor for Alzheimer's disease selectively in females. Taken together, our single cell dataset revealed a unique cellular-level view of sex-specific transcriptional changes in Alzheimer's disease, illuminating GWAS identification of sex-specific Alzheimer's risk genes. These data serve as a rich resource for interrogation of the molecular and cellular basis of Alzheimer's disease.

Journal Article

GPER stimulation attenuates mitochondrial dysfunction and cardiac dysfunction in ovariectomized mice with heart failure with preserved ejection fraction (HFpEF).

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is prevalent among postmenopausal women and is strongly linked to estrogen deficiency. G-protein coupled estrogen receptor (GPER) mediates non-genomic estrogen signalling and exerts cardiovascular protective effects. Its role in the pathogenesis of HFpEF remains unclear. This study aimed to explore whether GPER activation could attenuate mitochondrial dysfunction and cardiac damage in ovariectomized (OVX) mice with HFpEF. METHODS: Circulating GPER levels were measured in postmenopausal women with HFpEF and healthy controls. A correlation analysis was performed to assess the associations between GPER and cardiac function. Female C57BL/6J mice underwent ovariectomy and were fed with high-fat diet and l-NAME to induce HFpEF. Mice were treated with the GPER agonist G-1 for 4 weeks. Cardiac function, histological changes, oxidative stress, mitochondrial function and mitophagy were evaluated in vivo and in vitro. RESULTS: Serum GPER levels were significantly higher in postmenopausal women with HFpEF and correlated with NT-proBNP and E/e'. In OVX mice with HFpEF, GPER expression was up-regulated, and G-1 improved diastolic function, reduced myocardial hypertrophy and oxidative stress. Importantly, G-1 restored mitochondrial ATP production, normalized mitochondrial dynamics and promoted mitophagy in vivo and in vitro. These effects were associated with activation of the AMPK/ULK1 pathway. Inhibition of AMPK diminished the protective effects of G-1 in cardiomyocytes. CONCLUSIONS: GPER agonist G-1 ameliorated mitochondrial dysfunction, promoted mitophagy and alleviated cardiac diastolic dysfunction in OVX mice with HFpEF, partially through the AMPK/ULK1 pathway, indicating GPER as a therapeutic target for postmenopausal women with HFpEF.

AMPK/ULK1 signalling pathway

Nephrotic syndrome in indian children.

A clinicopathological study of 206 Indian children with nephrotic syndrome showed a primary renal cause in 195 (96%), of which 77% were boys. In 126 children (96 boys, 30 girls) onset of the disorder occurred before the age of 5 years. Renal biopsy showed minimal lesions in 150 patients (77%); in 85 of these biopsy was done 3 months to 16 years after onset of the nephrotic syndrome. Significant renal histological abnormalities in 45 cases were labelled as mesangiocapillary 8, mesangioproliferative 4, proliferative with extensive crescents 2, membranous 3, focal segmental glomerulosclerosis 9, focal global glomerulosclerosis 2, advanced nonspecific 8, and mild proliferative 9. Nephritic manifestations were mainly associated with significant renal lesions, which were more frequently encountered when the onset of disease was after the age of 5 years. Clearance of proteinuria with corticosteroid therapy was practically confined to patients with minimal or mild renal histological changes. Our findings suggest that the pattern of idiopathic nephrotic syndrome in Indian children is similar to that reported from Western countries.

Adolescent

Some effects of ammonium salts on renal histology and function in the dog.

NH4Cl was infused into the left renal artery of anesthetized dogs at 50-125 mum/kg/min for up to 110 min. Renal blood flow declined early then increased to supra-control levels during infusion. Kidneys perfused at 125 mum/kg/min for 90 min showed patchy to confluent mixtures of cortical necrosis and tubular necrosis. Experimental kidneys invariably showed lower urine osmolality than contralateral controls 48 h after perfusion. Kidneys with necrosis showed depressed creatinine clearance as well. Renal artery infusion of NH4 acetate or intravenous infusion of NaHCO3 during arterial infusion of NH4Cl prevented significant acidosis and caused minimal histological changes, but depression of urine osmolality was not prevented. It is concluded that renal ammonium concentrations up to 40 mum/liter for 90 min does not cause tubular necrosis but does impair urine concentration. Severe tissue damage followed renal exposure to high ammonium concentrations in the presence of metabolic or renal acidosis.

Ammonia

Single-cell transcriptomic atlas of Alzheimer's disease middle temporal gyrus reveals region, cell type, and sex specificity of gene expression with novel genetic risk for MERTK in female.

BackgroundAlzheimer's disease (AD), the most common age-related neurodegenerative disease, is closely associated with both amyloid-β plaque and neuroinflammation. Two thirds of AD patients are female, and they have a higher disease risk; women with AD have more extensive brain histological changes than men along with more severe cognitive symptoms and neurodegeneration.ObjectiveThis study aimed to determine how sex difference induces structural brain changes and molecular cell vulnerabilities in AD, with a focus on identifying sex-specific transcriptional alterations and genetic risk factors.MethodsWe performed single nucleus RNA sequencing on postmortem brains from individuals with AD and age- and sex-matched controls, focusing on the middle temporal gyrus, a cortical brain region strongly affected by the disease, and integrated single nucleus RNA sequencing results with genome-wide association study (GWAS) data using cell type-specific enrichment and generalized gene-set analysis approaches. The analysis pipeline is provided with threshold information.ResultsWe identified a selectively vulnerable subpopulation of layer 2/3 excitatory neurons that were RORB-negative and CDH9-expressing in both males and females. Disease-associated, but sex-independent, reactive astrocyte signatures were also present. In clear contrast, the microglia signatures of AD brains differed between males and females. Integrating single cell transcriptomic data with results from GWAS, we identified MERTK genetic variation as a candidate novel risk factor for AD selectively in females.ConclusionsTaken together, our single cell atlas of middle temporal gyrus revealed a unique cellular-level view of sex-specific transcriptional changes in AD, illuminating GWAS identification of sex-specific AD genes. These data serve as a rich resource for interrogation of the molecular and cellular basis of AD.

Alzheimer's disease

Estradiol binding capacity in the cryptorchid rat testis.

Mature male Sprague-Dawley rats were made surgically cryptorchid at 47--50 days of age. Animals were sacrificed as controls and at 7, 14, and 21 days post-surgery. The testes were removed and utilized to determine the effects of cryptorchidism on tissue weight loss, histological changes, and cytoplasmic estradiol binding capacity. Testis weight decreased from a mean +/- SE of 1.1 +/- 0.09 to .41 +/- 0.02 g during the 21 day period, a 66% decrease in weight. Light microscopy revealed that the process of spermatogenesis was inhibited, the germinal epithelium had degenerated, and the tubules had become smaller in diameter. The interstitial tissue volume progressively increased through day 21 post-surgery. The cytoplasmic estradiol binding capacity, expressed as fmoles [3H]-estradiol/mg cytosol protein, increased markedly from a control of 16 +/- 1.1 to 36 +/- 8.0 at day 7 after surgery; this represented a 126% increase in binding capacity in one week. Binding capacity was equivalent to 54 +/- 7.4 and 58 +/- 10.5 fmol/mg on days 14 and 21 post-surgery, respectively. Testicular content of cytoplasmic estrogen receptors was shown to increase from 349 to a maximum of 575 fmoles/testis at day 7. Receptor content then declined slowly to a value of 481 at day 21. Testicular content of receptor is presumed to reflect an alteration in the Leydig cells induced by cryptorchidism.

Animals

Response to cryptorchidism of the testis and epididymis of the opossum (Didelphis virginiana).

Adult male opossums, Didelphis virginiana, were rendered hemicryptorchid for 35 days. The cyrptorchid testis exhibited a significant reduction in weight, while the contralateral testis had a compensatory weight gain compared with testes of untreated animals. Histological changes in the cryptorchid testis included fibrosis of the tunica propria, involution of the seminiferous tubules and an apparent increase in the interstitial tissue. Many seminiferous tubules were empty and germinal cells were absent. Some Sertoli cells persisted, but the cytoplasm was vacuolated. Cryptorchid testes were characterized by mononuclear leucocytic invasion around the tubules, and some eosinophils were observed. Cryptorchidism in the opossum may induce a reaction similar to experimental orchitis.

Animals

Chimeric vaccine based on Iraqi HLA alleles against a predominant local Escherichia coli phylogroup.

INTRODUCTION: Escherichia coli remains amongst the most globally important pathogens implicated in severe clinical manifestations. The progressive rise in multidrug-resistant strains highlights the urgent need for new vaccines. Therefore, this study was designed to develop a new multi-epitope vaccine containing the most conserved epitopes across E. coli pathotypes. Consequently, the study aimed to investigate the immunoadjuvant role of faecal microbiota transplantation in enhancing vaccine efficacy. METHODS: Eighteen of the most conserved B-cell and T-cell epitopes of FimH, LptD, and BamA proteins were selected and included in a single construct. During the epitope selection process, HLA alleles predominant in the Iraqi population, as reported in previous studies, were used as criteria for selecting T-cell epitopes. The chimeric protein was expressed in BL21 E. coli and purified using affinity chromatography. Vaccine cross-protective immunity and protection were tested in in vivo experiments. Different formulations were used in the experimental evaluation: three doses of 100 μg of purified chimeric protein, injected intraperitoneally alone or encapsulated in PLGA nanoparticles, after faecal microbiota transplantation with and without gut microbiota modulation mediated by a cocktail of antibiotics. IgG1, IL-4, INF-γ, and NLRP3 levels were measured at 30 and 75 days after the first immunisation dose. Immunised mice were challenged with the local B2 UPEC phylogroup, and protection efficacy was considered 48 h later. Finally, the histological effects of the different chimeric protein formulations on the liver were assessed. RESULTS: All vaccine formulations except those after faecal microbiota transplantation without gut microbiota modulation induce significant increases in IgG1, IL-4, and INF-γ levels at different times. Only vaccination after faecal microbiota transplantation with gut microbiota modulation elicited robust NLRP3 levels at 30 and 75 days after, and this was linked to the highest reduction in bladder bacterial load by 813-fold compared to the other formulations, as well as the mildest effect on liver histological changes. DISCUSSION: These results demonstrated that the chimeric vaccine provides preliminary protection against a local B2 UPEC isolate. Furthermore, modulating gut microbiota via faecal transplantation markedly enhances the immunogenicity and protective efficacy of vaccination, suggesting its adjuvanticity.

Animals

Histological response of various endocrine glands after administration of certain neurohumors in chicks.

Histological response of various endocrine glands like pituitary, adrenal, testes and pancreas after administration of certain neurohumors like acetylcholine, adrenaline and histamine in a particular dose and sequence, has been carried out in white leghorn chicks. Result of this study revealed that administration of these neurohumors produced definite changes in various endocrines. Histological changes are more prominent in pituitary and adrenal glands, whereas, pancreas and testes did not reveal much influence of these neurohumors.

Acetylcholine