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Clinical aspects, cytogenetics and disease evolution in myelodysplastic syndromes.

Myelodysplastic syndrome (MDS) is a morphologically characterized hematologic entity that is one of the clonal myeloproliferative disorders. Approximately 50 approximately 70% of MDS patients have cytogenetic abnormalities; these are usually chromosomal deletions, but some involve translocations such as t(1;7) (q10;p10). Translocations involving chromosomal regions 3q26 or 22q11 are often therapy-related. Recent studies have demonstrated that cytogenetic changes in MDS patients have clinical relevance. Accordingly, there are now scoring systems for predicting the prognoses of MDS patients. In this review, we describe the clinical significance of cytogenetic changes in MDS. We include MDS with some atypical forms, such as MDS with hypocellular bone marrow, MDS with minimal dysplasia, and MDS with myelofibrosis.

Chromosomes, Human↗

Prolonged biochemical and morphological stability of encapsulated liver cells--a new method.

In this work a new type of polyelectrolyte complex capsules is introduced as an artificial housing for liver cells. Male Wistar rat hepatocytes were encapsulated using cellulose sulphate and polydimethyldialyllammonium chloride as polyelectrolytes. Amino acid metabolism rate and urea synthesis of the cells increased over the investigation period in contrast to the decrease observed in control monolayer cultures. The encapsulated cells were morphologically characterized. The described procedure represents a sufficient method for the cultivation of living cells in mechanically stable semipermeable microcapsules.

Amino Acids↗

[Studies On Intestinal Trematodes In Korea Xiv. Infection Status Of Loaches With Metacercariae Of Echinostoma Cinetorchis And Their Development In Albino Rats]

The metacercariae of Echinostoma cinetorchis (Trematoda: Echinostomatidae) were found infected in the loaches (Misgurnus anguillicaudatus) purchased from two local markets in Korea. Identification of the metacercariae was done after obtaining adult worms from experimentally infected albino rats. Brief course of worm development in rats was also observed up to 28th post-infection day. The results are as follows: The metacercariae of E. cinetorchis were detected from 5 (10.9 %) out of 46 loaches examined and the average metacercarial burden per infected loach was 34.4. They were always found from the posterior abdominal wall. The worm recovery rate from 8 rats was 24.6 % in average. It was observed that the rate decreased according to age of infection; from 40.7 % after 6 days to 15.0 % after 28 days. The adult worms were morphologically characterized by the presence of head crown with dorsally uninterrupted collar spines, 37-38 in number, and the tendency of migration or disappearance of testes. So that they were identified as Echinostoma cinetorchis Ando et Ozaki, 1923. The development of worm was very rapid during 6-10 days after infection and became much slower thereafter. During the rapid worm growth the development of genital organs was more prominent than that of non-genital organs. From the results it is concluded that the loach is involved in the life cycle of E. cinetorchis in this country and may take a role for infection source to animals and man. It is also confirmed that migration or loss of testes is the distinct specific character of this echinostomatid fluke.

Journal Article↗

Stictodora sp. (Trematoda: Heterophyidae) recovered from a man in Korea.

Two adult specimens of heterophyid fluke, which belong to the genus Stictodora, were collected from the stool of a 24-year old man after chemotherapy. The flukes were morphologically characterized by their small body size (0.90~0.98 mm long and 0.38 mm wide) and peculiar structure of ventrogenital sac with armed gonotyl (with about 12~15 spines) not enveloping genital pore. Species identification is deferred until more worms are obtained, although they closely resemble Stictodora fuscatum (Onji and Nishio, 1916). The patient used to eat raw flesh of mullets and gobies, which are regarded as the infection source of Stictodora sp., together with 3 other kinds of heterophyids described elsewhere. This is the first record of human Stictodora infection in the literature.

Journal Article↗

Parvatrema timondavidi (Digenea; Gymnophallidae) transmitted by a clam, Tapes philippinarum, in Korea.

Metacercariae of Parvatrema timondavidi (Digenea; Gymnophallidae) were found from Tapes philippinarum, one of the most common marine clams in Korea. T. philippinarum was collected from a fishery market in Seoul, and all of the clams examined were found to contain many gymnophallid metacercariae. To get adult worms, 10 ICR mice were fed with 100 metacercariae each and sacrificed by cervical dislocation at 7, 10 and 14 days after the infection. The adult worms harvested from the intestinal contents of the mice were morphologically characterized by oval body shape, large oral sucker with lateral projections on the lip, absence of the ventral pit, single cluster of vitellaria, and separately located genital pore from the ventral sucker. Based on these characters they identified as P. timondavidi Bartoli, 1964. This study first confirms the presence of P. timondavidi metacercariae in T. philippinarum in Korea.

Animals↗

Neoplagioporus zacconis (Trematoda: Opecoelidae) from the intestine of the pale chub, Zacco platypus, in Korea.

Neoplagioporus zacconis (Yamaguti, 1934) (Trematoda: Opecoelidae) was found from the intestine of the pale chub, Zacco platypus, for the first time in Korea. The worms were characterized morphologically by oval body shape, bipartited seminal vesicle, sinistrally located genital pore, and lobed ovary, and distinguished from the two other species of Neoplagioporous by body shape and distribution of vitelline follicles. The morphological characteristics, except the ovary, well corresponded to those of the previous descriptions. The morphological difference of the ovary was considered as a character of geographical phenotypic variation.

Animals↗

Identification of Acanthotrema felis (Digenea: Heterophyidae) metacercariae encysted in the brackish water fish Acanthogobius flavimanus.

The metacercariae of Acanthotrema felis Sohn et al., 2003 (Digenea: Heterophyidae) were discovered in a species of the brackish water fish, Acanthogobius flavimanus, in the Republic of Korea. They were experimentally fed to kittens, and adult flukes were harvested 7 days later. The adults were morphologically characterized by the presence of a bipartite seminal vesicle, the ventral sucker associated with a ventrogenital sac enclosing 3 sclerites (2 long and pointed, and 1 short and thumb-like), and an unarmed gonotyl. The adult flukes were identified as A. felis Sohn et al., 2003, and the brackish water fish A. flavimanus has been verified as one of its second intermediate hosts.

Animals↗

Genome-wide association studies reveal genetic variants associated with antineoplastic monoterpenoid indole alkaloid accumulation in Catharanthus roseus.

Catharanthus roseus produces pharmacologically important monoterpenoid indole alkaloids (MIAs), yet their natural accumulation is low, limiting therapeutic exploitation. To dissect the genetic basis of natural variation in MIA accumulation, we integrated phenotypic, chemotypic, and genomic analyses of 93 C. roseus accessions sampled from six locations across India, including New Delhi, Lucknow, Jodhpur, Bangalore, and two locations in Gujarat: Navsari and Bardoli. Morphological characterization showed limited differentiation among locations, whereas accessions from Gujarat tended to be taller compared to other locations and more frequently white-flowered. Quantitative HPLC profiling revealed substantial accession- and location-dependent variation in total indole alkaloid levels, with Gujarat accessions showing the highest accumulation, largely driven by vindoline and catharanthine. Genotyping-by-sequencing generated 10,801 high-quality variants comprising 10,087 SNPs and 714 InDels corresponding to an average density of 19.34 variants per Mbp of the genome, revealing three genetic subgroups with overall admixed ancestry and weak geographic stratification. Genome-wide association study (GWAS) using five benchmark models identified 47 variants potentially associated with catharanthine, vindoline, and vinblastine content. These putative candidate loci were located near genes implicated in hormone signaling, mitochondrial function, nitrogen metabolism, and RNA processing, suggesting complex regulatory control of MIA biosynthesis. Notably, two missense variants in a carboxylesterase-like gene were associated with vindoline accumulation, and highly significant intergenic SNP clusters suggested putative regulatory hotspots for vinblastine biosynthesis. These results provide GWAS-based insights into the genetic architecture of MIA metabolism in C. roseus and nominate candidate variants for precision breeding and metabolic engineering to enhance pharmaceutical alkaloid production.

Catharanthus roseus↗

Fungal spore diversity of arbuscular mycorrhizal fungi associated with spring wheat: effects of tillage.

We investigated the influence of tilling, N fertilization and crop stage on arbuscular mycorrhizae (AM) fungal species diversity in a wheat monoculture in the Pampa region of Argentina. Glomalean spores were isolated by wet sieving and decanting from conventionally tilled and nontilled soils cropped with wheat with or without N fertilization, at three phenological stages of the crop (tilling, flowering and grain filling) and fallow. Morphological characterization yielded at least 24 AM fungi taxa in the field samples, belonging to six genera of AMF: Acaulospora Archaeospora, Entrophospora, Gigaspora, Glomus and Scutellospora. Tilling and fertilization treatments did not result in decreased spore biodiversity. Wheat phenology influenced AM communities, with highest spore biodiversity during grain filling.

Agriculture↗

[Study on proliferation and function of periodontal ligament fibroblasts and osteoblastic cells under hypoxia].

There have been many reports recognizing vascular changes on pressure side of periodontal tissues during orthodontic tooth movement. The vascular changes cause local hypoxia which seems to affect the phenotypes of periodontal tissue cells. In order to clarify the effect of hypoxia on proliferation and function of periodontal tissue cells, DNA content, alkaline phosphatase (ALP) activity and prostaglandin E2 (PGE2) production under a hypoxic condition in both periodontal ligament fibroblasts (PLF) and osteoblastic cells (MC3T3-E1 cells) were examined in vitro. PLF were cultured from human periodontium and identified by both morphologic characterization and presence of ALP. The results obtained were as follows: 1. Under 10% O2 condition, the activity of proliferation in PLF did not change but that of osteoblasts was inhibited. 2. ALP activity in PLF was stimulated but that of osteoblasts was inhibited under the hypoxic condition. 3. Production of PGE2 in osteoblasts increased after 7 days of hypoxia though that in PLF decreased. In addition, the enhancement of PGE2 production in osteoblasts was due to activation of both phospholipase A2 and PGE2-synthesizing enzymes. 4. From the orthodontic point of view, hypoxia on the pressure side may induce bone resorption by inhibiting mineralization activity of osteoblasts and enhancing production of PGE2 in osteoblasts.

Alkaline Phosphatase↗

Characterization and plasticity of the double synapse spines in the barrel cortex of the mouse.

The somatosensory barrel cortex of rodents and its afferent pathway from the facial vibrissae is a very useful model for studying neuronal plasticity. Dendritic spines are the most labile elements of synaptic circuitry and the most likely substrate of experience-dependent alterations in neuronal circuits in cerebral cortex. We characterized morphologically and numerically a specific population of spines, i.e. double synapse spines, which have two different inputs--one excitatory and the other inhibitory, in the B2 barrel of mouse somatosensory cortex. We also described changes in morphology of double synapse spines induced by classical conditioning in which stimulation of vibrissae was paired with a tail shock. The analysis was carried out by means of serial EM micrograph reconstruction. We showed that double spines account for about 10% of all analyzed spines. The morphology of a typical double synapse spine is similar to the morphology of single synapse spine and both consist of two parts--a large head and a narrow, long neck. Excitatory synapses are preferentially located on the head of double synapse spines and inhibitory synapses are usually located on the neck of these spines. The length of the double synapse spine neck decreases and the cross-section area of the spine neck increases significantly as a result of sensory conditioning.

Animals↗

Lipid-laden macrophages in bone marrow of leprosy patients.

While conducting a study to observe bone marrow cytomorphological changes in multibacillary leprosy, lipid laden macrophages as seen in sphingolipidoses were noted. The present study was planned to observe the occurrence and morphological characterization of these macrophages in various types of leprosy. Bone marrow records from 48 cases of paucibacillary and 72 cases of multibacillary leprosy were analysed. The macrophages accounting at the most for 3.5% of marrow cells were observed in 5 cases of paucibacillary and 43 cases of multibacillary leprosy with a maximum incidence being observed in patients with ENL (16/17). The lipid present in the cytoplasm of these cells could be derived from the lipid of the cell wall of Mycobacterium leprae. To the best of our knowledge, these cells have not been reported in leprosy so far.

Bone Marrow↗

Development of B-cell lymphoma in homosexual men. Clinical and immunologic findings.

Serious infections, neoplasms, and immunologic abnormalities have been found in homosexual men. We describe the development of malignant lymphoma in six such patients, three of whom had persistent, generalized lymphadenopathy. In biopsies done before the lymphoma developed, the lymphadenopathy was characterized morphologically by a distinctive pattern of B-cell follicular hyperplasia. All lymphomas were of B-lymphocytic origin, including B-cell immunoblastic sarcoma; small noncleaved, Burkitt-like lymphoma; and plasmacytoid lymphocytic lymphoma. Extranodal presentation with B symptoms occurred in five patients. Median age of our patients was 33 years. Three patients had histories of repeated systemic infections. The peripheral blood lymphocyte count was depressed in four, with depression of OKT 4+ (helper phenotype) cell levels and reversal of the T-helper: T-suppressor ratio in all. We conclude that these patients are at risk for the development of abnormalities of the B-lymphocytic system, manifested by abnormal hyper-B-cell response in enlarged reactive lymph nodes and aggressive, extranodal B-cell lymphomas.

Adult↗

Angiogenesis: characterization of a cellular model.

Endothelial cell proliferation and differentiation into blood capillaries (i.e., angiogenesis) are essential for growth and development, wound healing, osetogenesis, etc. But abnormal angiogenesis during tumor progression could lead to serious consequences. Angiogenesis is a complex biochemical process, and is often difficult to study the molecular mechanism in vivo due to interference by multitude of factors. Here, I present a non-transformed capillary endothelial cell line as a model which has been extensively characterized morphologically and biochemically to study the fundamentals of the angiogenic process. Studies completed in our laboratory also evidenced that expression of Glc3Man9GlcNAc2-PP-Dol is intricately connected with the balance between the cellular proliferation and apoptosis during angiogenesis.

Adult↗

Müller cell swelling, glutamate uptake, and excitotoxic neurodegeneration in the isolated rat retina.

We characterized morphological effects of the endogenous excitotoxin, glutamate in ex vivo retinal segments prepared from 30-day-old rats. Initial changes induced by glutamate consisted of reversible, sodium-dependent Müller cell swelling. This glial swelling was mimicked by glutamate transport substrates but not by ionotropic glutamate receptor agonists. Only very high concentrations of exogenous glutamate (3,000 microM) produced excitotoxic neuronal damage. The neuronal damage was accompanied by severe glial swelling and was blocked by an antagonist of non-N-methyl-D-aspartate (NMDA) receptors but not by an NMDA receptor antagonist. Because glutamate uptake can be influenced by changes in cellular energy levels, we studied the effects of oxidative and glycolytic energy depletion on glutamate-mediated Müller cell swelling. Oxygen deprivation produced little morphological change and did not alter either glutamate-mediated Müller cell swelling or glutamate-induced excitotoxicity. In contrast, inhibition of glycolysis by iodoacetate produced severe neuronal damage without Müller cell swelling. In the presence of iodoacetate, exogenous glutamate failed to cause glial swelling. The neuronal damage produced by iodoacetate was inhibited by pyruvate, a substrate that sustains oxidative energy pathways. In the presence of iodoacetate plus pyruvate, glutamate failed to cause Müller cell swelling but became neurotoxic at low concentrations through activation of non-NMDA receptors. These results indicate that glycolytic energy metabolism plays a critical role in sustaining ionic balances required for Müller cell glutamate uptake and glial uptake helps to prevent glutamate-mediated excitotoxicity.

Animals↗

Preeclampsia: the endothelium, circulating factor(s) and vascular endothelial growth factor.

It has been proposed that endothelial cell activation is the primary event in the multisystem disorder of preeclampsia. Evidence for endothelial involvement in this condition abounds. The best-characterized morphologic abnormality of this syndrome, glomerular endotheliosis, involves endothelial cells. Also associated with preeclampsia is a loss of endothelial cell integrity, with the consequent increase in vascular permeability, and an increase in the circulating levels of the endothelial cell markers, fibronectin, von Willebrand factor, tissue plasminogen activator, and plasminogen activator inhibitor-1. It is now well documented that endothelial activation contributes to the coagulation abnormalities observed in this disease. There is much evidence that the endothelial alterations in preeclampsia result from one or more circulating factors. The incubation of cultured endothelial cells with serum or plasma samples, taken from normal pregnant women and women with preeclampsia, results in marked alterations in cell behavior and metabolic processes. More recently, experiments employing myographic techniques have demonstrated convincingly the effects of a circulating factor(s) on the function of endothelial cells of resistance arteries. Vascular endothelial growth factor (VEGF) possesses many of the characteristics required of a candidate circulating factor. It contains a hydrophobic secretory signal sequence, exerts in vitro effects specific to vascular endothelial cell, and promotes endothelial expression of procoagulant activity. Circulating VEGF concentrations are elevated in women with preeclampsia, and VEGF increases microvascular endothelial cell prostacyclin production in a dose-dependent manner, analogous to the acute effects of plasma from patients with preeclampsia. Similarly, in myographic studies, when myometrial resistance arteries are incubated with VEGF, there are dose-dependent alterations in endothelium-dependent behavior, mirroring those found after incubation with plasma from patients with preeclampsia.

Endothelial Growth Factors↗

[Child neurology and neuronal apoptosis: introductory remarks].

Apoptosis is one type of cell death characterized morphologically by nuclear condensation and shrinkage of cell bodies. Thus, it is completely different from necrosis in features. Recently, it is suggested that apoptosis occurs in some neurodegenerative diseases of childhood as well as adulthood. Therefore, it is very important to reveal mechanisms of neuronal apoptosis. To the end, it is expected that new therapies will be developed to prevent the progress of neurodegenerative diseases. Based on such expectation, this symposium was organized to present recent progress in neuronal apoptosis research.

Apoptosis↗

Evidence on the participation of protein kinase C alpha in the proliferation of cultured myoblasts.

There is evidence involving protein kinase C (PKC) in the signal transduction pathways that regulate the differentiation of myoblasts into mature multinucleated muscle cells (myotubes). In order to obtain information on the possible role of individual PKC isozymes in myogenesis, in the present work we investigated the differential expression of PKC isoforms alpha, beta, delta, epsilon, and zeta during muscle cell development in vitro. Chick embryo myoblasts cultured from 1 to 6 days were used as experimental model. Morphological characterization and measurement of specific biochemical parameters in cultures, e.g., DNA synthesis, creatine kinase activity, and myosin levels, revealed a typical muscle cell developmental pattern consisting of an initial proliferation of myoblasts followed by their differentiation into myotubes. PKC activity was high at the proliferation stage, decreased as myoblasts elongated and fused, and increased again in differentiated myotubes. In proliferating myoblasts, the PKC inhibitors calphostin C and bisindolylmaleimide I decreased DNA synthesis whereas in myoblasts undergoing differentiation they exerted the opposite effect, suggesting that PKC plays a role at both stages of myogenesis. Western blot analysis of changes in the expression of PKC isoforms during muscle cell development showed high levels of PKC alpha in the proliferating phase which markedly decreased as myoblasts differentiated. Treatment with TPA of proliferative myoblasts inhibited DNA synthesis and selectively down-regulated PKC alpha, suggesting that this isozyme may have an important role in maintaining myoblast proliferation. On the other hand, an increase in the expression of PKC beta, delta, and epsilon was detected during myogenesis, suggesting that one or more of these isoforms may participate in the differentiation process of myoblasts.

Animals↗