scholarly journals The Specifics of the Stromal and Parenchymal Liver Components of 0–6-month-old Dead Children from HIV-monoinfected Mothers

2020 ◽  
Vol 8 (B) ◽  
pp. 495-500
Author(s):  
Sergiy O. Sherstiuk ◽  
Stanislav I. Panov ◽  
Igor V. Belozorov ◽  
Tetiana I. Liadova ◽  
Oleksij I. Tsivenko

OBJECTIVE: The objective of the study was to determine the specifics of the stromal and parenchymal liver components of 0–6-month-old children from HIV-monoinfected mothers. METHODS: The morphometric investigation included 84 liver tissue biopsies of 0–6-month-old dead children from HIV-monoinfected mothers. All morphometric parameters of the parenchymal and stromal liver components were calculated using the Avtandilov’s microscopic morphometric grid, which was consisted of 100 equidistant points. It was inserted into the microscope’s ocular tube with a total ×200 microscope magnification. The number of points that were found on the corresponding types of parenchymal and stromal liver components was calculated. In every case, it was selected 10 random microscopic areas and then all data were obtained, calculated, and presented as percentages. RESULTS: Morphometric parameters of hepatocytes: Mononuclear hepatocytes – 87.3 ± 6.2% (control – 93.5 ± 7.1), two-nuclear hepatocytes – 12.7 ± 1.3% (control – 6.5 ± 1.2), two-/mononuclear hepatocytes coefficient – 0.14 ± 0.01 (control – 0.06 ± 0.01), and hepatocytes with fat vacuoles – 15.6 ± 1.8% (control – 0.5 ± 0.2). Parenchymal and stromal liver components: Parenchyma – 64.3 ± 2.1% (control – 74.2 ± 1.3), stroma (including blood vessels and bile ducts) – 35.7 ± 1.9% (control – 25.8 ± 1.6), and stroma/parenchyma index – 0.55 ± 0.01 (control – 0.34 ± 0.01). Morphometric parameters of all of the liver components: Hepatocytes – 64.3 ± 3.1% (control – 74.2 ± 4.3), portal tracts – 14.9 ± 1.9% (control – 3.1 ± 0.6), central veins – 9.3 ± 1.3 % (control – 9.3 ± 1.4), sinusoids – 8.8 ± 1.1% (control – 10.5 ± 1.3), and bile ducts – 2.7 ± 0.2% (control – 2.9 ± 0.2). Expression level parameters: Fibronectin – 64.8 ± 4.1% (control – 17.3 ± 2.5), collagen Type I – 13.6 ± 1.7% (control – 9.7 ± 1.9), collagen Type III – 15.3 ± 1.4% (control – 10.1 ± 0.9), and collagen Type IV – 6.8 ± 0.2% (control – 5.9 ± 0.2). CONCLUSIONS: It was established that in the liver of 0–6-month-old dead children from HIV-monoinfected mothers, the parenchymal component of the liver showed the signs of its reduction, increase of regenerative activity of hepatocytes, and fatty degeneration of hepatocytes with a certain sign of reactive steatohepatitis. Furthermore, it was established that the stromal component of the liver of children from HIV-infected mothers showed the signs of its progressive proliferation and collagenization due to increased production and accumulation of fibronectin, Type I, Type III collagens in the stroma of portal tracts and newly formed septa, and the signs of hepatic sinusoid capillarization due to Type IV collagen accumulation in the space of Disse of the hepatic sinusoids.

To determine the morphological specifics of the stromal and parenchymal liver components of 6-12-months old children from HIV-mono-infected mothers. Materials and methods. The morphometric investigation included 87 liver tissue biopsies of 6-12-months old dead children from HIV-mono-infected mothers. All morphometric parameters of the parenchymal and stromal liver components were calculated using the Avtandilov`s microscopic morphometric grid, which was consisted of 100 equidistant points. It was inserted into the microscope`s ocular tube with a total × 200 microscope magnification. The number of points that were found on the corresponding types of parenchymal and stromal liver components was calculated. In every case, it was selected 10 random microscopic areas and then all data were obtained, calculated and presented as percentages. Results. Morphometric parameters of hepatocytes: mononuclear hepatocytes – 90.2±7.6 % [control – 93.5±7.1], two-nuclear hepatocytes – 9.8±1.2 % [control – 6.5±1.2], TMHC (two-/mononuclear hepatocytes coefficient) – 0.10±0.02 [control – 0.06±0.01], hepatocytes with fat vacuoles – 19.6±2.1 % [control – 0.5±0.2]. Parenchymal and stromal liver components: parenchyma – 56.1±3.3 % [control – 74.2±4.3], stroma (including blood vessels and bile ducts) – 43.9±3.7 % [control – 25.8±2.6], SPI (stroma/parenchyma index) – 0.78±0.02 [control – 0.34±0.01]. Morphometric parameters of all of the liver components: hepatocytes – 56.1±3.3 % [control – 74.2±4.3], portal tracts – 26.4±2.1 % [control – 3.1±0.6], central veins – 8.1±1.2 % [control – 9.3±1.4], sinusoids – 7.3±1.2 % [control – 10.5±1.3], bile ducts – 2.1±0.1 % [control – 2.9±0.2]. Expression level parameters: fibronectin – 73.2±4.2 % [control – 17.3±2.5], collagen type I – 15.9±1.2 % [control – 9.7±1.9], collagen type III – 20.1±2.6 % [control – 10.1±0.9], collagen type IV – 7.3±0.2 % [control – 5.9±0.2]. Conclusions. It was established, that in the liver of 6-12-months old children from HIV-mono-infected mothers, the parenchymal component of the liver showed the signs of its significant reduction, increase of regenerative activity of hepatocytes, and fatty degeneration of hepatocytes with a certain sign of reactive steatohepatitis. Also, it was established, that the stromal component of the liver of children from HIV-infected mothers showed the signs of its progressive proliferation and collagenization due to increased production and accumulation of fibronectin, type I, type III collagens in the stroma of portal tracts and newly formed septa, and the signs of hepatic sinusoid capillarization due to type IV collagen accumulation in the space of Disse of the hepatic sinusoids.


2020 ◽  
Vol 73 (9) ◽  
pp. 1895-1899
Author(s):  
Sergiy O. Sherstiuk ◽  
Stanislav I. Panov ◽  
Tetiana I. Liadova ◽  
Oleksij I. Tsivenko ◽  
Liudmila L. Sherstiuk

The aim: To determine the morphometric parameters of the parenchymal and stromal liver components of healthy newborns. Material and methods: The morphometric investigation included 45 liver tissue biopsies of healthy newborns. All morphometric parameters of the parenchymal and stromal liver components were calculated using the Avtandilov microscopic morphometric grid. It was inserted into the microscope ocular tube with a total × 200 microscope magnification. The number of points that were found on the corresponding types of parenchymal and stromal liver components was calculated. In every case, it was selected 10 random microscopic areas and then all data were obtained, calculated and presented as percentages. Results: Morphometric parameters of hepatocytes: mononuclear hepatocytes – 93.5±7.1 %, two-nuclear hepatocytes – 6.5±1.2 %, BMHC (bi-/mononuclear hepatocytes coefficient) – 0.06±0.01, hepatocytes with fat vacuoles – 0.5±0.2 %. Parenchymal and stromal liver components: parenchyma – 74.2±4.3 %, stroma (including blood vessels and bile ducts) – 25.8±2.6 %, SPI (stroma/parenchyma index) – 0.34±0.01. Morphometric parameters of all of the liver components: hepatocytes – 74.2±4.3 %, portal tracts – 3.1±0.6 %, central veins – 9.3±1.4 %, sinusoids – 10.5±1.3 %, bile ducts – 2.9±0.2 %. Expression level parameters: fibronectin – 17.3±2.5 %, collagen type I – 9.7±1.9 %, collagen type III – 10.1±0.9 %, collagen type IV – 5.9±0.2 %. Parameters of liver fibrosis biomarkers: APRI (index) – 0.19±0.01, а FIB-4 (index) – 0.022±0.001. Conclusions: The morphometric parameters of the parenchymal and stromal liver components of healthy newborns can be used as a control group in the study of any pathological conditions of the liver of newborns.


1992 ◽  
Vol 286 (1) ◽  
pp. 73-77 ◽  
Author(s):  
M Mörike ◽  
R E Brenner ◽  
G B Bushart ◽  
W M Teller ◽  
U Vetter

Collagen produced in vitro by bone cells isolated from 19 patients with different forms of osteogenesis imperfecta (OI) was analysed. Clinically, four patients were classified as OI type I, 10 patients as OI type III and five patients as OI type IV. Bone cells of 12 of the 19 OI patients produced structurally abnormal type I collagen. Electrophoretically uniformly slower migrating collagen type I alpha-chains were found in one case of OI type I, in seven cases of OI type III and in one case of OI type IV; two cultures of OI type III produced two different populations of collagen type I alpha-chains, and one culture of OI type IV showed reduction-sensitive dimer formation of alpha 1(I) chains, resulting from the inadequate incorporation of a cysteine residue into the triple helical domain of alpha 1(I). Quantitative analysis of collagen metabolism led to the distinction of two groups of cultured OI osteoblasts. In osteoblasts of OI type I, mainly production of collagen was decreased, whereas secretion, processing and pericellular accumulation of (pro)collagen type I was similar to that in control osteoblasts. In contrast, in osteoblasts of OI types III and IV, production as well as secretion, processing and pericellular accumulation of (pro)collagen type I were significantly decreased. Low levels of type I collagen were found irrespective of the presence or absence of structural abnormalities of collagen type I in all OI types.


Author(s):  
G. D. Gagne ◽  
M. F. Miller ◽  
D. A. Peterson

Experimental infection of chimpanzees with non-A, non-B hepatitis (NANB) or with delta agent hepatitis results in the appearance of characteristic cytoplasmic alterations in the hepatocytes. These alterations include spongelike inclusions (Type I), attached convoluted membranes (Type II), tubular structures (Type III), and microtubular aggregates (Type IV) (Fig. 1). Type I, II and III structures are, by association, believed to be derived from endoplasmic reticulum and may be morphogenetically related. Type IV structures are generally observed free in the cytoplasm but sometimes in the vicinity of type III structures. It is not known whether these structures are somehow involved in the replication and/or assembly of the putative NANB virus or whether they are simply nonspecific responses to cellular injury. When treated with uranyl acetate, type I, II and III structures stain intensely as if they might contain nucleic acids. If these structures do correspond to intermediates in the replication of a virus, one might expect them to contain DNA or RNA and the present study was undertaken to explore this possibility.


2020 ◽  
pp. 1-15
Author(s):  
Zhiwei Yuan ◽  
Wen Guo ◽  
Dan Lyu ◽  
Yuanlin Sun

Abstract The filter-feeding organ of some extinct brachiopods is supported by a skeletal apparatus called the brachidium. Although relatively well studied in Atrypida and Athyridida, the brachidial morphology is usually neglected in Spiriferida. To investigate the variations of brachidial morphology in Spiriferida, 65 species belonging to eight superfamilies were analyzed. Based on the presence/absence of the jugal processes and normal/modified primary lamellae of the spiralia, four types of brachidium are recognized. Type-I (with jugal processes) and Type-II (without jugal processes), both having normal primary lamellae, could give rise to each other by losing/re-evolving the jugal processes. Type-III, without jugal processes, originated from Type-II through evolution of the modified lateral-convex primary lamellae, and it subsequently gave rise to Type-IV by evolving the modified medial-convex primary lamellae. The evolution of brachidia within individual evolutionary lineages must be clarified because two or more types can be present within a single family. Type-III and Type-IV are closely associated with the prolongation of the crura, representing innovative modifications of the feeding apparatus in response to possible shift in the position of the mouth towards the anterior, allowing for more efficient feeding on particles entering the mantle cavity from the anterior gape. Meanwhile, the modified primary lamellae adjusted/regulated the feeding currents. The absence of spires in some taxa with Type-IV brachidium might suggest that they developed a similar lophophore to that in some extant brachiopods, which can extend out of the shell.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1094.1-1094
Author(s):  
A. S. Siebuhr ◽  
P. Juhl ◽  
M. Karsdal ◽  
A. C. Bay-Jensen

Background:Interleukin 6 (IL-6) is known to have both pro- and anti-inflammatory properties, depending on the receptor activation. The classical IL-6 signaling via the membrane bound receptor is mainly anti-inflammatory, whereas signaling through the soluble receptor (sIL-6R) is pro-inflammatory/pro-fibrotic. However, the direct fibrotic effect of IL-6 stimulation on dermal fibroblasts is unknown.Objectives:We investigated the fibrotic effect of IL-6 + sIL-6R in a dermal fibroblast model and assessed fibrosis by neo-epitope biomarkers of extracellular matrix proteins.Methods:Primary healthy human dermal fibroblasts were grown for up to 17 days in DMEM medium with 0.4% fetal calf serum, ficoll (to produce a crowded environment) and ascorbic acid. IL-6 [1-90 nM]+sIL-6R [0.1-9 nM] alone or in combination with TGFβ [1 nM] were tested in three different donors. TGFβ [1 nM], PDGF-AB [3 nM] and non-stimulated cells (w/o) were used as controls. Tocilizumab (TCZ) with TGFβ + IL-6 + sIL-6R stimulation was tested in one donor. Collagen type I, III and VI formation (PRO-C1, PRO-C3 and PRO-C6) and fibronectin (FBN-C) were evaluated by validated ELISAs (Nordic Bioscience). Western blot analysis investigated signal cascades. Gene expression of selected ECM proteins was analyzed. Statistical analyses included One-way and 2-way ANOVA and area under the curve analysis.Results:formation by the end of the culture period. The fibronectin and collagen type VI signal were consistent between the three tested donors, whereas the formation of type III collagen was only increased in one donor, but in several trials. Type I collagen formation was unchanged by IL-6 + sIL-6R stimulation. The gene expression of type I collagen was induced by IL-6 + sIL-6R. Western blot analysis validated trans-signaling by the IL-6+sIL-6R stimulation as expected.IL-6 + sIL-6R stimulation in combination with TGFβ decreased fibronectin levels compared to TGFβ alone but did not reach the level of unstimulated fibroblasts. The formation of collagen type IV was generally unchanged with IL-6 + sIL-6R + TGFβ compared to TGFβ alone. Collagen type I and III formation was more scattered in the signals when IL-6 + sIL-6R was in combination with TGFβ, as the biomarker level could be either decreased or increased compared to TGFβ alone. In two studies the type I collagen level was synergistic increased by IL-6 + sIL-6R + TGFβ, whereas another study found the level to be decreased compared to TGFβ alone. The gene expression of fibronectin and type I collagen was increased with TGFβ +IL-6+sIL-6R compared to TGFβ alone.Inhibition of IL-6R by TCZ in combination with IL-6 + sIL-6R did only decrease the fibronectin level with the lowest TCZ concentration (p=0.03). TCZ alone decreased the fibronectin level in a dose-dependent manner (One-way ANOVA p=0.0002).Conclusion:We investigated the fibrotic response of dermal fibroblasts to IL-6 + sIL-6R stimulation. IL-6 modulated the fibronectin level and modulated the collagen type III formation level in a somewhat dose-dependent manner. In combination with TGFβ, IL-6 decreased collagen type I and IV formation and fibronectin. However, in this study inhibition of IL-6R by TCZ did not change the fibrotic response of the dermal fibroblasts. This study indicated that IL-6 did not induce collagen formation in dermal fibroblasts, except type III collagen formation with high IL-6 concentration.Figure:Disclosure of Interests:Anne Sofie Siebuhr Employee of: Nordic Bioscience, Pernille Juhl Employee of: Nordic Bioscience, Morten Karsdal Shareholder of: Nordic Bioscience A/S., Employee of: Full time employee at Nordic Bioscience A/S., Anne-Christine Bay-Jensen Shareholder of: Nordic Bioscience A/S, Employee of: Full time employee at Nordic Bioscience A/S.


2007 ◽  
Vol 56 (8) ◽  
pp. 1005-1010 ◽  
Author(s):  
M. Sarkar-Tyson ◽  
J. E. Thwaite ◽  
S. V. Harding ◽  
S. J. Smither ◽  
P. C. F. Oyston ◽  
...  

Burkholderia pseudomallei is the causative agent of melioidosis, an infectious disease of humans and animals. Gene clusters which encode capsular polysaccharide (type I O-PS) and LPS (type II O-PS), both of which play roles in virulence, have previously been identified. Here, the identification of two further putative clusters, type III O-PS and type IV O-PS, is reported. Mice challenged with type III O-PS or type IV O-PS mutants showed increased mean times to death (7.8 and 11.6 days) compared to those challenged with wild-type B. pseudomallei (3 days). To investigate the possible roles of polysaccharides in protection, mice were immunized with killed cells of wild-type B. pseudomallei or killed cells of B. pseudomallei with mutations in the O antigen, capsular polysaccharide, type III O-PS or type IV O-PS gene clusters. Immunization with all polysaccharide mutant strains resulted in delayed time to death compared to the naïve controls, following challenge with wild-type B. pseudomallei strain K96243. However, immunization with killed polysaccharide mutant strains conferred different degrees of protection, demonstrating the immunological importance of the polysaccharide clusters on the surface of B. pseudomallei.


Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Masayuki Shimano ◽  
Rei Shibata ◽  
Yukiomi Tsuji ◽  
Noriyuki Ouchi ◽  
Yasuya Inden ◽  
...  

The occurrence and development of atrial fibrillation (AF) are associated with changes in electrical properties and cardiac structure, known as electrical and structural atrial remodeling. AF characterized by atrial remodeling also occurs with obesity-related conditions. Adiponectin, an adipose tissue-derived hormone, exerts beneficial effects on the heart in various pathological conditions. These observations led us to speculate that adiponectin levels affect the development and prevalence of AF. Here, we investigated a potential association between circulating adiponectin levels and atrial remodeling in patients with AF. We measured plasma adiponectin levels, serum carboxy-terminal telopeptide of collagen type I (CITP) levels, as a collagen type I degradation marker, and serum type III procollagen-N-peptide (PIIINP) levels, as a collagen type III synthesis marker in consecutive 414 patients; 225 paroxysmal AF, 81 persistent AF and 108 paroxysmal supra-ventricular tachycardia without AF history (control) patients, who admitted for scheduled radiofrequency catheter ablation. Plasma adiponectin levels were significantly higher in patients with persistent AF compared to paroxysmal AF and control patients (p<0.05). Serum CITP levels, but not serum PIIINP levels, were also higher in patients with persistent AF compared to paroxysmal AF and control patients (p<0.05). In addition, a positive correlation was observed between adiponectin levels and CITP levels (r=0.39, p<0.005) or the P wave duration (r=−0.31, p<0.05) in patients with persistent AF. High plasma adiponectin levels are associated with the presence of persistent AF, which is accompanied by increased CITP levels. Hyperadiponectinemia might also attenuate atrial conduction disturbance. Thus, measurement of plasma adiponectin could be useful for assessment of AF.


1996 ◽  
Vol 75 (4) ◽  
pp. 1411-1431 ◽  
Author(s):  
K. A. Davis ◽  
J. Ding ◽  
T. E. Benson ◽  
H. F. Voigt

1. The electrophysiological responses of single units in the dorsal cochlear nucleus of unanesthetized decerebrate Mongolian gerbil (Meriones unguiculatus) were recorded. Units were classified according to the response map scheme of Evans and Nelson as modified by Young and Brownell, Young and Voigt, and Shofner and Young. Type II units have a V-shaped excitatory response map similar to typical auditory nerve tuning curves but little or no spontaneous activity (SpAc < 2.5 spikes/s) and little or no response to noise. Type I/III units also have a V-shaped excitatory map and SpAc < 2.5 spikes/s, but have an excitatory response to noise. Type III units have a V-shaped excitatory map with inhibitory sidebands, SpAc > 2.5 spikes/s, and an excitatory response to noise. Type IV-T units typically also have a V-shaped excitatory map with inhibitory sidebands, but have a highly nonmonotonic rate versus level response to best frequency (BF) tones like type IV units, SpAc > 2.5 spikes/s, and an excitatory response to noise. Type IV units have a predominantly inhibitory response map above an island of excitation of BF, SpAc > 2.5 spikes/s, and an excitatory response to noise. We present results for 133 units recorded with glass micropipette electrodes. The purpose of this study was to establish a normative response map data base in this species for ongoing structure/function and correlation studies. 2. The major types of units (type II, type I/III, type III, type IV-T, and type IV) found in decerebrate cat are found in decerebrate gerbil. However, the percentage of type II (7.5%) and type IV (11.3%) units encountered are smaller and the percentage of type III (62.4%) units is larger in decerebrate gerbil than in decerebrate cat. In comparison, Shofner and Young found 18.5% type II units, 30.6% type IV units, and 23.1% type III units using metal electrodes. 3. Two new unit subtypes are described in gerbil: type III-i and type IV-i units. Type III-i units are similar to type III units except that type III-i units are inhibited by low levels of noise and excited by high levels of noise whereas type III units have strictly excitatory responses to noise. Type IV-i units are similar to type IV units except that type IV-i units are excited by low levels of noise and become inhibited by high levels of noise whereas type IV units have strictly excitatory responses to noise. Type III-i units are approximately 30% of the type III population and type IV-i units are approximately 50% of the type IV population. 4. On the basis of the paucity of classic type II units and the reciprocal responses to broadband noise of type III-i and type IV-i units, we postulate that some gerbil type III-i units are the same cell type and have similar synaptic connections as cat type II units. 5. Type II and type I/III units are distinguished from one another on the basis of both their relative noise response, rho, and the normalized slope of the BF tone rate versus level functions beyond the first maximum. Previously, type II units were defined to be those nonspontaneously active units with rho values < 0.3 where rho is defined as the ratio of the maximum noise response minus spontaneous rate to the maximum BF tone response minus spontaneous rate. In the gerbil, the average rho value for type II units is 0.25, although a few values are > 0.3, and the rate-level curves are consistently nonmonotonic with normalized slopes steeper than than -0.007/dB. The average rho value for type I/III units is 0.54, although a few values are < 0.3, and the rate-level curves tend to saturate with slopes shallower than -0.006/dB. In general, the response properties of type II units recorded in gerbil are similar to those recorded in decerebrate cat. 6. In comparison to decerebrate cat, the lower percentage of type IV units recorded in decerebrate gerbil may be due to a species difference (a reduced number of type II units in gerbil) or an electrode bias.


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