Morphometric analysis of the glomerular capillary area--a comparison of minimal change nephrotic syndrome, focal glomerular sclerosis, and pre-eclampsia.

A morphometric analysis was performed to compare the capillary area in non-sclerotic glomeruli in focal glomerular sclerosis (FGS), pre-eclampsia with focal sclerotic change of the glomeruli, and minimal change nephrotic syndrome (MCNS). The mean and standard deviation of the capillary area was greater in FGS than in pre-eclampsia and MCNS. Tubulo-interstitial lesions, such as tubular atrophy, interstitial fibrosis, and lymphocytic infiltration, were more severe in FGS than in pre-eclampsia. The presence of tubulo-interstitial changes including tubular atrophy and interstitial fibrosis with lymphocytic infiltration is thought to be an important prognostic factor in pre-eclampsia as well as in FGS. Unequal dilatation of the glomerular capillaries in non-sclerotic glomeruli may be harmful to the glomeruli and may lead to the development of glomerular sclerosis.     

Cellular kinetics in the lungs of aging Fischer 344 rats after acute exposure to ozone.

Lung repair in aging Fischer 344 male rats was investigated after an acute inhalation exposure to ozone. Adult (9-month-old) and senescent (24-month-old) rats were exposed to 0.8 ppm ozone for a single period of 6 hours, and thereafter studied over 5 days of recovery in clean air. The animals were given intraperitoneal injections of colchicine and [3H]thymidine, 4 hours and 1.5 hours before termination, respectively. The lungs were inflated with glutaraldehyde, and tissue samples were embedded in epoxy resin for electron microscopy, or in glycol methacrylate for light-microscopic autoradiography. Exposure to ozone produced epithelial injury in alveolar ducts and terminal bronchioles, later reflected by the transient increase in mitotic activity of nonciliated bronchiolar cells and alveolar type 2 cells. The increase in metaphase-arrested cells and [3H]thymidine-labeled cells in bronchioles followed similar time courses, ie, maximal at days 1.5 to 2, and subsiding by day 3. In the alveoli, type 1 cell necrosis was observed early after exposure (6 hours recovery), without notable structural changes in the interstitial and endothelial compartments. The increased mitotic activity in the alveolar septa was mostly due to proliferation of epithelial type 2 cells, which was maximal at day 1.5, and of interstitial cells, maximal at day 2.5. The magnitude of the mitotic responses of nonciliated bronchiolar cells, alveolar type 2 cells and interstitial cells was highest (+50%) in the lungs of senescent rats. Although the cellular events during repair are essentially similar in both age groups, the results indicate that senescent rats have a significantly higher level of initial injury from inhalation of ozone than adult animals.     

A histopathologic and immunologic study of the course of syphilis in the experimentally infected rabbit. Demonstration of long-lasting cellular immunity.

Inoculation of the causative agent of syphilis, Treponema pallidum into the testes of rabbits initiated the following sequence of events: 1) a rapid proliferation of organisms in the interstitial tissues of the testes, reaching a maximum at about 10-11 days after infection; 2) systemic spread of organisms primarily in the lymphoid organs; 3) a prompt immune response manifested by hyperplasia of T cell domains in draining lymph nodes and spleen, blast transformation responses of lymphoid cells to sonicates of T pallidum, the appearance of serum antibody, and the marked infiltration of the infected areas of the testes by T cells; 4) essential clearing of organisms identified by immunofluorescence from the infected site 10-14 days after infection associated with evolution of the inflammatory response from primarily a T cell infiltrate to a larger mononuclear cell type, and the immunofluorescent identification of presumptive T pallidum antigen in macrophages; 5) interstitial fibrosis or resolution 17-21 days after infection so that examination of infected testes from 1 to 24 months later reveals foci of tubular atrophy and fibrosis of varying size, alternating with regenerated tubules, separated by interstitial areas with only minimal fibrosis. During the long period of latency there is no evidence of atrophy or hypoplasia of the lymphoid organs and long-lasting T cell memory with regard to T pallidum sonicates is demonstrable. Reinfection of previously inoculated rabbits indicates partial protection at 25 days after infection followed by essentially complete protection after 55 days. It is concluded that there is a prompt and long-lasting immune response to T pallidum in experimentally infected rabbits. The main mechanism for destruction of infecting organisms appears to be T-cell-initiated macrophage-mediated destruction, but a role for antibody dependent phagocytosis cannot be ruled out. The reason that some organisms may survive in various body organs remains unknown, but possible explanations are presented.     

The ultrastructure of human tubulo-interstitial fibrosis

Tubulo-interstitial fibrosis, comprising tubular atrophy, infiltration by inflammatory cells, accumulation of extracellular matrix, and proliferation of mesenchymal cells in the interstitium, is a major characteristic of most progressive chronic renal diseases leading to end-stage renal failure, regardless of cause. All of the ultrastructural characteristics of tubulo-interstitial fibrosis can correlate with clinically defined features of chronic renal dysfunction. The present review illustrates ultrastructural features, emphasising some novel findings, in tubulo-interstitial fibrosis, including widespread expression of actin filaments, fatty degeneration of tubular epithelial cells, presence of cilia, and infiltration of leukocytes into the tubular lumen. The hypothesised development of interstitial myofibroblasts from tubular epithelial cells, and the relationship between tubule injury and capillary abnormality are also discussed.     

Ozone-induced airway hyperresponsiveness in guinea pigs

We studied the time related changes of airway hyperresponsiveness induced by ozone inhalation (2.9 ppm, 30 min) in guinea pigs. In unanesthetized and spontaneously breathing guinea pigs, the respiratory resistance was measured by a forced oscillation technique. The respiratory resistance and respiratory frequency were unchanged until 24 hours after ozone inhalation. In mechanically ventilated guinea pigs, airway responsiveness to inhaled methacholine was determined using a modification of the Konzett-R?ssler technique, and after methacholine challenge bronchoalveolar lavage (BAL) was performed for cell yield. At 1 hour and 3 hours after ozone inhalation, airway responsiveness was increased significantly, but returned to the control level at 6 hours. In the BAL fluid, there was a significant increase in neutrophils at 3 hours after ozone inhalation and thereafter. In the separated groups, before air or ozone inhalation, human serum albumin (HSA) was administered intravenously, and BAL was performed 1 hour after inhalation. In the ozone inhalation group, the concentration of HSA in BALF was increased significantly compared to the air inhalation group. These results suggest that airway hyperresponsiveness induced by ozone inhalation may occur before the influx of neutrophils into the airways and may depend on some structural changes such as submucosal and mucosal edema induced by the enhancement of capillary permeability.     

Lymphocytic infiltration and destruction of parathyroid adenomas: a possible tumour-specific autoimmune reaction in two cases of primary hyperparathyroidism

Two cases of primary hyperparathyroidism with underlying parathyroid adenomas were found to be associated with lymphocytic infiltration and destruction of the neoplastic tissue. There was no inflammatory infiltrate in the adjacent rim of the remnant of parathyroid gland or in the other tumour-free glands. The lymphoid cell population within the tumours was composed of both infiltrating T-cells and compact nodule-forming B-cells. In one of the tumours there was considerable fibrosis and atrophy of the adenomatous tissue. The histological picture was consistent with an autoimmune process directed against the adenomas, indicating that this reaction had, in part, been successful in reducing the abnormal cell population.     

Fine structural capillary changes and basal lamina thickening in scleroderma (progressive systemic sclerosis) and Raynaud's disease

Capillary abnormalities were found by electron microscopy in labial salivary gland biopsies obtained from 20 patients with progressive systemic sclerosis (PSS). They consisted of marked thickening and multilayering of basal lamina, degenerative and adaptative endothelial cell changes, alterations of pericytes and perivascular mononuclear cell infiltration. There was no correlationship between the intensity of the capillary abnormalities and the duration of the disease. In 12 patients with Raynaud's disease (RD) such changes were not found. Thus capillaries displayed normal-looking ultrastructural appearances. Mean capillary basal lamina width was consistently thicker in the PSS group than in the RD group (p less than 0.001). These observations are consistent with the hypothesis that the primary event in PSS occurs in the microvessels. It is suggested that labial salivary gland biopsy may be helpful for early recognition of PSS among subjects with Raynaud's syndrome.     

Macrophages in the hamster parathyroid gland: immunohistochemical and ultrastructural investigations

The distribution and morphology of the parathyroid macrophages in golden hamsters from neonatal to senile periods were investigated using the monoclonal antibody to ED2 and electron microscopy. The results showed that definite ED2-positive cells were hardly detectable in the parathyroid gland of 1-day-old hamsters. A few ED2-positive cells could be identified in the parathyroid gland of 10-day-old hamsters. The ED2-positive cells were more densely and became conspicuous in 1-, 3-, and 12-month-old hamsters. The number of the cells seems to be increased with aging. Ultrastructurally, we did not find any macrophages in parathyroid glands of 1-day-old hamsters. In the 10-day-old hamster parathyroid gland, a few macrophages existed only in the interstitial tissues. In the parathyroid gland of 1-, 3-, and 12-month-old hamsters, many macrophages were found in the perivascular regions, some cells located among the parenchymal chief cells with no obvious vascular association. These cells showed some physical contacts with chief cells. These results suggest that the parathyroid macrophages exhibit dramatical changes in their distribution and morphology from neonatal to senile periods.     

严重急性呼吸综合征3例尸检病理分析

目的 探讨严重急性呼吸综合征(SARS)患者的病变的病理形态特点及与临床表现的相关性。方法 对3例SARS死亡病例进行尸体解剖,光镜观察各脏器的病理变化,并与临床表现进行联系。结果 肉眼突出的病理改变为双肺的弥漫性出血,镜下为肺泡的急性渗出性、出血性和纤维素性炎症,肺泡毛细血管充血,一些毛细血管内微血栓形成。肺泡壁增厚,单个核细胞浸润,肺泡上皮损伤脱落,肺泡腔内渗出物伴透明膜形成。部分肺泡腔内有纤维素样物质及红细胞,少数肺内支气管动脉内血栓栓塞。淋巴结及脾脏等出血坏死,淋巴细胞衰减。其他实质脏器如肝、心、肾、胰腺等呈非特异性改变,如水样变性,脂肪变性、间质细胞增生等以及3例老年患者此次人院前存在的基础病变。结论 SARS具有其病理形态特点,患者的肺部严重病变及免疫器官的损伤引起相应的临床表现并导致患者死亡。     

LYMPHOID FOLLICLES APPEARING IN GASTRIC MUCOSA, ESPECIALLY IN REACTIVE LYMPHOID HYPERPLASIA AND MALIGNANT LYMPHOMA

Histopathological analysis of reactive lymphoid hyperplasia (RLH) and malignant lymphoma (ML) of the stomach was made based on the observations of lymphoid follicles appearing in gastric mucosa. The materials used for study consisted of 28 stomachs without RLH or tumor obtained from either operation or autopsy, 18 stomachs with RLH, and 46 stomachs with ML. Lymphoid follicles appeared soon after birth, increased with mucosal atrophy, and decreased in mucosa with intestinal metaplasia. They possessed a sinusoidal structure and appeared in the muscularis mucosae intimately related to the lymphatic flow. Excepting for the significant proliferative nature, the structural evolution of lymphoid follicles in RLH was similar to that in atrophic mucosa. They showed, however, a wide spectrum of changes containing cases with simple reactive changes to those with prelymphomatous changes. As to ML, the large cell type demonstrated a destructive proliferation, while both small and medium-sized cell types showed proliferation and infiltration preserving their original structure. In the superficial type, ML was frequently accompanied by RLH and mucosal atrophy. The histological features of ML consisted of not only the characteristics of tumor cells but also the proper mucosal changes including lymphoid follicles.     

Lymphoid follicles appearing in gastric mucosa, especially in reactive lymphoid hyperplasia and malignant lymphoma

Histopathological analysis of reactive lymphoid hyperplasia (RLH) and malignant lymphoma (ML) of the stomach was made based on the observations of lymphoid follicles appearing in gastric mucosa. The materials used for study consisted of 28 stomachs without RLH or tumor obtained from either operation or autopsy, 18 stomachs with RLH, and 46 stomachs with ML. Lymphoid follicles appeared soon after birth, increased with mucosal atrophy, and decreased in mucosa with intestinal metaplasia. They possessed a sinusoidal structure and appeared in the muscularis mucosae intimately related to the lymphatic flow. Excepting for the significant proliferative nature, the structural evolution of lymphoid follicles in RLH was similar to that in atrophic mucosa. They showed, however, a wide spectrum of changes containing cases with simple reactive changes to those with prelymphomatous changes. As to ML, the large cell type demonstrated a destructive proliferation, while both small and medium-sized cell types showed proliferation and infiltration preserving their original structure. In the superficial type, ML was frequently accompanied by RLH and mucosal atrophy. The histological features of ML consisted of not only the characteristics of tumor cells but also the proper mucosal changes including lymphoid follicles.     

Myotonia dystrophica with heart involvement: an electron microscopic study of skeletal, cardiac, and smooth muscle.

The electron microscopic features of the striated skeletal muscle, the striated cardiac muscle, and the smooth muscle from a woman who had been suffering for many years from myotonia dystrophica with cardiac involvement are described. The skeletal muscle was studied at two different stages of the disease. In the first material the main changes consisted of centrally situated nuclei, disorganisation of the sarcomeres, and focal disruption of the Z-line. The satellite cells were well represented. Three years later atrophy and degenerative, necrotic changes of the skeletal muscle were evident. The satellite cells were absent. Few changes were seen in the striated cardiac muscle. These consisted of slight interstitial fibrosis and large accumulations of mitochondria with intramitochondrial dense granules. The smooth muscle cells of the oesophagus showed disorientated filaments and mild degenerative changes. It is concluded that the skeletal muscle was more severely affected than the other types of muscle.     

Ultrastructural pathology of ozone-induced experimental parathyroiditis. IV. Biphasic activity in the chief cells of regenerating parathyroid glands.

Sequential development of electron miscrosopic changes in the rabbit parathyroid gland was monitered during induction of parathyroiditis by 48 hours of ozone 0.75 ppm dosage regimen. By 4 to 7 days, electron microscopy revealed prominence of polyribosomes, rough endoplasmic reticulum, Golgi complex, secretory granules, microtubules, and frequent infoldings of the plasma membrane. Presumable this was the stage of parathyroid hormone synthesis. Between 14 to 18 days, ultrastructural observations showed dilatation of rough endoplasmic reticulum with continuity with annulate lamellae, disaggregation of polyribosome attached to the rough endoplasmic reticulum, and accumulation of numerous solitary free ribosomes in the cytoplasm. The dilated portion of endoplasmic reticulum contained medium electron-dense granular material, which also appeared between the intercellular spaces. The medium electron-dense material assumed to condensed appearance of basal lamina bordering the intercellular matrix. On the basis of the present observation it was concluded that the second set of ultrastructural changes signify the stage of basal lamina reconstruction. The significance of these changes as reparative responses to the inflammatory stimuli was discussed.     

Renal expression of intercellular adhesion molecule-1 in immunoglobulin A nephropathy: tubulointerstitial injury and prognosis

In immunoglobulin A nephropathy (IgAN), the abnormal expression of intercellular adhesion molecule-1 (ICAM-1) on proximal tubule epithelium is associated with the glomerular and interstitial infiltration of leucocytes, but its clinical significance remains uncertain. We analysed the relationship between the ICAM-1 (CD54) expression in tubular epithelial cells and interstitial leucocytes, macrophages (CD14) and T lymphocytes (CD3) with the histologic features, proteinuria and serum creatinine at the time of renal biopsy and after 2.42 years in 45 patients with IgAN and after 1.8+/-1.5 years in 29 patients with non-glomerulonephritis (non-GN). In IgAN, ICAM-1+ tubule epithelium was 0.1+/-0.18 (x+/-SD), and this was associated with extracapillary proliferation (up to 20% of Bowman's space), glomerular sclerosis involving less than 50% of glomerular area, interstitial cellular infiltration, tubular atrophy and proteinuria level. ICAM-1+ interstitial leucocytes were correlated with glomerular sclerosis involving less than 50% of glomerular area, glomerular sclerosis involving more than 50% of glomerular area, tubular atrophy, interstitial fibrosis and serum creatinine level. In patients with an increase of 50% in serum creatinine, ICAM-1+, CD14+ and CD3+, interstitial leucocytes were significantly outnumbered than in patients with stable serum creatinine. In non-GN, ICAM-1+ tubule epithelium was 0.02+/-0.04 (U=344, P<0.05, vs IgAN), and this was inversely correlated with the percentage of the normal glomeruli and associated with glomerular sclerosis covering more than 50% of glomerular area, tubular atrophy and serum creatinine level. The association between tubular ICAM-1 and proteinuria and the association between interstitial ICAM-1+, CD14+ and CD3+, leucocytes and renal failure at presentation and the deterioration in IgAN in contrast with non-GN suggest that tubular and interstitial expression of ICAM-1 may be a marker of tubulointerstitial disturbance in IgAN.     

Pathology of endocrine organs in chronic renal failure--an autopsy analysis of 66 patients

Gross and microscopic findings at autopsy are reported in 66 patients with end-stage renal disease (ESRD). Nineteen patients received renal transplant, and 47 were maintained on chronic dialysis. Thyromegaly was seen in over half of the dialysis patients and in a third of the transplant recipients. The mean weight of the thyroid gland in the two groups was similar (26.2 +/- 4.5 g in the transplant group and 27.2 +/- 6 g in the group on dialysis). The parathyroid glands were hyperplastic in 10/11 dialysis patients (91%), but of normal size in 78% of the transplant recipients. Adrenal gland atrophy was common in the transplant group, probably reflecting adrenal suppression by glucocorticoids. Seminiferous tubular atrophy was observed in 12/16 dialysis patients and small testes were noted on gross examination in 50% of the transplant recipients. Prominent autopsy findings were goiter, parathyroid gland hyperplasia, and testicular atrophy. Following transplantation parathyroid gland hyperplasia declined, whereas goiter and testicular atrophy appeared to persist.     

Pathological changes of the lungs after prolonged inhalation of high concentrations of oxygen

Summary The pathological changes in the lungs of six patients who were treated by an artificial ventilation with a Bird or Bennett type respirator for three days to six months with oxygen concentrations of 24–100% were examined by light microscopy, studies on thick-sections, reconstruction models and vascular casts, and morphometric methods. After prolonged inhalation of high concentrations of oxygen the lungs showed thickening of the alveolar wall, marked deposition of reticulin fibers and fibroblastic proliferation in the alveolar wall, reduction in the number of capillaries, an abnormal configuration of the capillary network and hyperplasia of alveolar lining cells. These lesions are not specific to this condition, and seemed to be less marked than similar lesions in cases of chronic forms of fibrosing alveolitis, chronic interstitial pneumonia, usual interstitial pneumonia and so-called pulmonary fibrosis. Morphometric results confirm these histological observations and show not only the concentrations of oxygen but also the duration of high and pure oxygen inhalation have important roles for these pulmonary lesions. The main reasons for these lesions seemed to be repeated damage to the capillaries and loss of the normal configuration of the capillary network, accompanied by rearrangement and reconstruction of the two types of reticulin fibers.     

Parathyroid morphology in rats after administration of active vitamin D3

The morphology of the parathyroid gland was examined in rats treated for one month with an active vitamin D3, 1 alpha-hydroxyvitamin D3. On continuous administration of 12.5 micrograms/kg/day of 1 alpha-hydroxyvitamin D3, the first histological change of the parathyroid gland, seen on day 10, was atrophy of the chief cells with marked accumulation of prosecretory granules. Replacement of the parenchyma by small or large cysts was evident on days 20 and 30. The remaining portion of the parathyroid parenchyma showed various histological changes: widened intercellular spaces intermingled with many cytoplasmic processes, shrinkage of the cytoplasm of the chief cells, and the presence of a few ghost cells in cysts. The appearance of cysts may be caused by suppression of parathyroid hormone secretion and is a characteristic lesion in hypervitaminosis in rats induced by treatment with active vitamin D3.     

Cell death and cell proliferation during atrophy of the rat parotid gland induced by duct obstruction

Rat parotid gland atrophy after unilateral duct ligation was studied by light and electron microscopy. Death of secretory acinar cells, which took the form of apoptosis, resulted in their complete disappearance within 5 days. The remnants of the dying cells were mostly phagocytosed and degraded by macrophages within the glandular epithelium; a few were taken up by adjoining epithelial cells. The acinar cell deletion was accompanied by increased mitosis of striated and intercalated duct epithelial cells. However, over many weeks, there was enhanced apoptosis of duct cells, which eventually led to marked shortening of intercalated ducts. Apoptosis of capillary endothelial cells was observed and may account for the reduction in the capillary bed known to accompany gland atrophy. The end-stage lesion comprised small numbers of ducts in a condensed stroma. Compensatory hyperplasia, involving proliferation of duct and acinar cells, was demonstrated in the contralateral glands.     

Immunohistochemical study of nodular hyperplastic parathyroid glands in patients with secondary hyperparathyroidism

Summary Thirty-seven nodular hyperplastic parathyroid glands obtained by subtotal parathyroidectomy from 11 haemodialysed patients with secondary hyperparathyroidism were examined both pathologically and immunohistochemically. Four consecutive sections of the largest section-surface of each gland were subject to 4 different stains (haematoxyline-eosin, Grimelius, and the immunohistochemical stains for parathyroid hormone and chromogranin A) for comparison of each nodule.It was found that the major part of each nodule consisted of a single cell type with a single pattern of cells. These reacted uniformly to each stain. The mechanism involved in the storage and secretion of the secretory granule appeared to be regulated at the nodule and not at the cell level. The results suggest that the nodules may come from a monoclonal proliferation of a single parathyroid cell.Our present light microscopic immunohistochemical study, failed to demonstrate completely identical immunoreactive positivity of each nodule or each parathyroid cell to PTH. Chromogranin A or secretory protein-I did not indicate the coexistence of PTH and SP-I in the same secretory granule, which was in good agreement with the electron microscopic immunocytochemical study of Arps using bovine parathyroid glands. Our present study, however, provides good evidence that chromogranin A positivity is demonstrable in the human parathyroid gland outside the adrenal medulla and sympathetic nerves.