Graft-versus-host disease after intraoperative blood transfusion: a rare and lethal condition.
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Aged↗
Biomedical subjects
K Shimamura
Publications and source records attributed to K Shimamura.
A case of gastrointestinal stromal tumor of the stomach.
In a 55-year-old man, a tumor about 3 cm in diameter was detected in the upper abdomen by abdominal ultrasound screening during follow-up of chronic hepatitis C discovered in 1990. There were no symptoms and no abnormalities on physical examination. Tests for tumor markers were negative. By barium meal and gastroscopy, submucosal tumor was found on the lesser curvature of the stomach, with bridging fold in the absence of central ulceration. Biopsy revealed no tumor tissue. Under the diagnosis of submucosal tumor of the stomach, either a leiomyoma or leiomyosarcoma, partial resection of stomach was performed. Direct invasion of the surrounding organs, lymph node metastasis or distant metastasis was not observed grossly in the operation. Histologic examination of the resected specimen revealed proliferation of spindle cells and oval cells in an interlacing pattern. Immunohistochemistry for CD34, vimentin and c-kit protein was strongly positive, while smooth muscle actin, S-100 protein, desmin and p53 protein were negative. The proliferating cell nuclear antigen index was about 50%, while the MIB-1 index was < or = 1%. From these findings, this tumor was diagnosed as a gastrointestinal stromal tumor of the uncommitted type.
Follow-Up Studies↗
Allelic loss on chromosome 9 in bladder cancer tissues and urine samples detected by blunt-end single-strand DNA conformation polymorphism.
Allelic loss on chromosome 9 is the most frequent and earliest genetic event in bladder carcinogenesis, and its detection in urine samples would be useful for detecting bladder cancer. A highly sensitive method to detect loss of heterozygosity (LOH) at 5 polymorphic loci on chromosome 9p and 9q was developed by the use of blunt-end single-strand DNA conformation polymorphism (blunt-end SSCP) analysis. Tumor tissues, urine samples and peripheral blood lymphocytes from 34 patients with transitional cell carcinoma of the bladder were analyzed. LOHs on 9p and/or 9q were found in 24 (71%) of 34 tumor samples and 23 (70%) of 33 urine samples, while no allelic loss was detected in 20 urine samples from benign urothelial diseases. The frequency of allelic loss in tumor tissues was 67%, 71% and 80% in the pTa, pT1 and > or = pT2 stages and 50%, 80% and 79% in G1, G2 and G3 tumors, respectively. In comparison with a urine cytological examination, LOH on chromosome 9 was detected in 70% of urine samples diagnosed as transitional cell carcinoma, 67% of those as atypia and 70% of those as no malignant cells. Thus, detection of LOH on chromosome 9 from urine samples by blunt-end SSCP is a more sensitive diagnostic modality than cytologic examination for detecting bladder cancer. It would be useful for postoperative management of bladder cancer, particularly when the allelic loss is revealed in the tumor tissues obtained at first surgery.
Carcinoma, Transitional Cell↗
FGF and Shh signals control dopaminergic and serotonergic cell fate in the anterior neural plate.
During development, distinct classes of neurons are specified in precise locations along the dorso-ventral and anterior-posterior axes of the neural tube. We provide evidence that intersections of Shh, which is expressed along the ventral neural tube, and FGF8, which is locally produced at the mid/hindbrain boundary and in the rostral forebrain, create induction sites for dopaminergic neurons in the midbrain and forebrain. The same intersection, when preceded by a third signal, FGF4, which is expressed in the primitive streak, defines an inductive center for hindbrain 5-HT neurons. These findings illustrate that cell patterning in the neural plate is a multistep process in which early inducers, which initially divide the neural plate into crude compartments, are replaced by multiple local organizing centers, which specify distinct neuronal cell types within these compartments.
Animals↗
Altered expression of alpha-actin, smooth muscle myosin heavy chain-1 and calponin in cultured smooth muscle cells by oxidized low density lipoproteins.
The expression of the contractile proteins, alpha-actin, smooth muscle myosin heavy chain-1 (SM1) and calponin present in smooth muscle cells (SMC) in the presence of oxidized low density lipoproteins (oxLDL) was investigated in two different cell cultures: the mouse smooth muscle cell line SVSC and rat smooth muscle cells (RSMC). Exposure of the cells to 187 microg protein/ml oxLDL for 24 h reduced the expression of all three contractile proteins in both cell cultures when compared to cells incubated in the presence of native LDL. This investigation of the response of SMC contractile proteins to oxLDL may provide further insights into the mechanisms by which oxidatively modified LDL is atherogenic and suggests that oxLDL may contribute to the regulation of the expression of the genes responsible for the synthesis of smooth muscle cell contractile proteins.
Actins↗
Membrane potential of mesenteric artery from carvedilol-treated spontaneously hypertensive rats.
The effects of chronic treatment of stroke-prone spontaneously hypertensive rats (SHRSP) with carvedilol, an antihypertensive agent which has both alpha- and beta-adrenoceptor-blocking actions, on membrane potential and relaxation of mesenteric resistant artery were studied. Five-week old SHRSP were treated with carvedilol for three months. At 16 weeks, the resting membrane potential of arteries from carvedilol-treated SHRSP was more negative than that of arteries from untreated SHRSP. The magnitude of acetylcholine-induced hyperpolarization in arteries from carvedilol-treated SHRSP was not different from that of arteries from untreated SHRSP. In the presence of noradrenaline, the membrane potential of arteries from carvedilol-treated SHRSP was more negative than that of arteries from untreated SHRSP. The membrane potential of arteries from carvedilol-treated SHRSP in the presence of noradrenaline and acetylcholine was more negative than that of arteries from untreated SHRSP. The acetylcholine-induced relaxation in noradrenaline-precontracted preparations from carvedilol-treated SHRSP was greater than that in preparations from untreated SHRSP and was smaller than that in preparations from Wistar Kyoto rats. Scanning electronmicroscopy showed that carvedilol-treatment decreased the structural abnormalities of the endothelium of arteries from SHRSP. These results indicate that chronic carvedilol treatment made the membrane potential of smooth muscle more negative and improved endothelial function in the mesenteric artery of SHRSP, which may contribute to the antihypertensive effect of carvedilol.
Animals↗
Cytokine dependent growth of human TF-1 leukemic cell line in human GM-CSF and IL-3 producing transgenic SCID mice.
Although severe combined immunodeficient (SCID) mice are considered useful as an animal model for human hematopoietic diseases, the complete reconstruction of human hematopoietic cells can not be established even in these mice. This appears to be because human cytokines, adhesion molecules and extracellular matrices which support differentiation and growth of human hematopoietic cells differ from those in animals. To improve this animal model, we attempted to produce transgenic (Tg) mice producing human interleukin 3 (hIL-3) and human granulocyte macrophage colony stimulating factor (hGM-CSF) with the homozygote of the scid gene. We established two Tg mouse lines, one releasing both 0.5-1 ng/ml of hIL-3 and 0.05-0.2 ng/ml of hGM-CSF in their sera and another releasing only high (2-10 ng/ml) levels of hGM-CSF. When human cytokine-dependent myeloid cell line, TF-1, was subcutaneously transplanted into these two Tg-SCID mouse lines, TF-1 could be successfully engrafted and grew in all lines of Tg-SCID mice but not in control mice. We also observed that TF-1 grows in GM-CSF Tg-SCID mice in a dose dependent manner in vivo and IL-3 shows an additive effect on its growth. These results indicated that these Tg-SCID mice were an useful in vivo model for investigating human leukemogenesis, especially the role of IL-3 and GM-CSF in leukemogenesis.
Animals↗
Histological and immunocytochemical studies of human psoriatic lesions transplanted onto SCID mice.
To investigate the pathology of psoriasis, we developed an animal model for this disease using severe combined immunodeficiency (SCID) mice. These mice possess neither B nor T Lymphocytes so that both cellular and humoral immunities are impaired. For the in vivo study of psoriasis, human psoriatic skin was grafted on SCID mice. Long-term morphological and immunohistochemical changes in the grafted skin ware examined for up to 22 weeks after transplantation. The human skin graft were generally well maintained during this period, but the histological and immunohistochemical findings characteristic of psoriasis, except for acanthosis and hyperkeratosis, gradually disappeared as lymphocytic infiltration of the psoriatic lesions declined.
Adult↗
Interaction of cultured keratinocytes and fibroblasts from human psoriatic and normal skin in immunodeficient mice.
Clarification of the pathogenesis of psoriasis requires separate studies of the epidermis, dermis, and inflammatory cells. We previously subcutaneously transplanted a mixture of cultured human keratinocytes and fibroblasts into mice to develop cysts with human skin structures. Using this method, we separately cultured psoriatic and normal keratinocytes and fibroblasts. Four mixtures were prepared: normal keratinocytes and normal fibroblasts (NK/NF); psoriatic keratinocytes and normal fibroblasts (PK/NF); normal keratinocytes and psoriatic fibroblasts (NK/PF); and psoriatic keratinocytes and psoriatic fibroblasts (PK/PF). Each mixture was transplanted into immunodeficient mice to observe formation of cysts and histological changes. The cysts varied in structure depending on the mixture, which suggests that psoriatic keratinocytes and fibroblasts had some abnormalities. Psoriatic fibroblasts may be partially responsible for thickening of the epidermis. Cell differentiation might have been accelerated in psoriatic keratinocytes after transplantation, resulting in the loss of epidermis structures.
Animals↗
Control of anteroposterior and dorsoventral domains of Nkx-6.1 gene expression relative to other Nkx genes during vertebrate CNS development.
Here we report the isolation, sequence and developmental expression in the central nervous system of several members of the chicken and mouse Nkx gene family. These are among the earliest genes to be regionally expressed in the neural plate; they are expressed just above the axial mesendoderm (prechordal mesendoderm and notochord). Each Nkx gene has a distinct spatial pattern of expression along the anterior-posterior axis of the ventral central nervous system: Nkx-2. 2 is expressed along the entire axis, whereas Nkx-2.1 is restricted to the forebrain, and Nkx-6.1 and Nkx-6.2 are largely excluded from the forebrain. They are also expressed in distinct patterns along the dorsal-ventral axis. These genes are expressed in both the ventricular and mantle zones; in the mantle zone Nkx-6.1 is co-expressed with Islet-1 in a subset of motor neurons. Like other Nkx genes, expression of Nkx-6.1 is induced by the axial mesendoderm and by sonic hedgehog protein. BMP-7 represses Nkx-6.1 expression. While the notochord can induce Nkx-6.1 expression in the anterior neural plate, sonic hedgehog protein does not, suggesting that the notochord produces additional molecules that can regulate ventral patterning.
Amino Acid Sequence↗
Regionalization of the prosencephalic neural plate.
Recent embryological studies are beginning to establish that the underlying organization of the forebrain may be reduced to relatively simple elements that are common to all vertebrates. We begin this chapter by reviewing studies that describe the similarities in prospective fate and molecular organization of the developing neural plate in fish, frogs, chickens, and mice. The chapter next addresses mechanisms that regulate regional specification in the anterior central nervous system. There is now evidence that the axial mesendoderm anterior to the notochord (the prechordal plate) has a central role in induction of the floor and basal plate primordia (hypothalamus) of the forebrain. Patterning of the anterolateral neural plate (telencephalon) may be regulated by FGF8 produced in the anterior neural ridge. Thus, the synthesis of information from fate mapping and experimental embryological and genetic studies is illuminating the mechanisms that generate the different components of the forebrain.
Animals↗
Detection of alterations in chromosomes 16 and 1 by fluorescence in situ hybridization in breast tumors cytologically or histologically equivocal for malignancy.
Structural and numerical alterations, and fusion of chromosomes 16 and 1 have been shown to occur frequently in low-grade breast carcinoma, but not in benign papilloma by fluorescence in situ hybridization (FISH). We carried out FISH analysis of 11 benign tumors and 3 breast tumors for which the preoperative diagnosis was equivocal for cancer. In 11 benign lesions and 1 benign phyllode tumor which was cytologically equivocal for malignancy, alteration of the chromosome 16 or 1 signal was not detected as a predominant cell clone. On the other hand, in 1 grade 1 invasive ductal carcinoma which was judged as equivocal for malignancy and 1 marked adenosis with atypia which was judged as malignant by fine-needle aspiration cytology, the majority of constituent tumor cells showed fusion of chromosomes 16 and 1. Detection of alterations in chromosomes 16 and 1 as a predominant clone was suggested to be an indicator of lesion malignancy even though the grade of malignancy may not be high. As a supportive diagnostic procedure, FISH analysis may give information about the nature of lesions, when the lesions are clinically or pathologically equivocal for cancer.
Biopsy, Needle↗
Role of endothelium and adventitia on eugenol-induced relaxation of rabbit ear artery precontracted by histamine.
Eugenol (> or = 0.1 mM) inhibited the contractions induced by various stimulants, such as 90 mM extracellular K+ solution ([K+]0), histamine and noradrenaline in the rabbit ear artery. Inhibitory actions of eugenol occurred in a concentration-dependent manner, however, eugenol more dominantly inhibited the histamine-induced contraction than those induced by either 90 mM [K+]0 solution or noradrenaline. Removal of both endothelium and adventitia did not change the inhibitory actions of eugenol on the 90 mM [K+]0- and noradrenaline-induced contractions, however, attenuated those on the histamine-induced contraction. Chlorphenylamine abolished the histamine-induced contraction, but neither cimetidine, ranitidine nor thioperamide modified the eugenol actions on the contractions induced by histamine. Pretreatment with nitric oxide syntheses inhibitor NG-nitro-L-arginine (LNNA; 100 microM), but not soluble guanylate cyclase inhibitor methylene blue (MB; 10 microM), prevented endothelium/adventitia-dependent augmentation of the eugenol-induced relaxation on the histamine-induced contraction. When an intact tissue, but not an endothelium/adventitia-denuded tissue, was placed at the up-stream close to the other denuded preparation (test preparation), histamine-induced contraction observed in the test preparation tended to be augmented. Similarly, eugenol-induced relaxation was also augmented by the same treatment. Eugenol (0.3 mM) inhibited the excitatory junction potentials (EJPs) without hyperpolarization of the membrane. However, a high concentration of eugenol (1 mM) slightly hyperpolarized the membrane (ca. 5 mV). No transient enhancement of amplitude of EJP was recorded. These results suggest that eugenol may inhibit the histamine-induced muscle contraction directly, and the inhibition is augmented by the adventitia and endothelium partly by vasoactive substances, which were released from the adventitia/endothelium-derived substances in rabbit ear artery.
Animals↗
Ca(2+)-sensitivity of portal vein circular muscle from normotensive and hypertensive rats.
Contractile sensitivity to Ca2+ was studied in rat portal vein circular muscle isolated from normotensive Wistar Kyoto rats (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP). There was no difference in resting membrane potential between WKY and SHRSP. Elevation of extracellular K+ concentration induced similar increase in tension in preparations from WKY and SHRSP. High K(+)-depolarized preparation developed tension increase when extracellular Ca2+ concentration was increased. The sensitivity to extracellular Ca2+ was similar in preparations from WKY and SHRSP. Permeabilized preparation contracted when free Ca2+ concentration was increased. Sensitivity of permeabilized preparation to Ca2+ was similar in preparations from WKY and SHRSP. These results indicate that regulation of contraction by Ca2+ was similar between WKY and SHRSP. Since there was no change in high K-induced contraction in intact preparations or Ca-induced contraction in permeabilized preparations, there seemed to be no difference in Ca2+ influx via voltage-dependent channels in portal vein circular muscle from WKY and SHRSP.
Animals↗
[A single dose toxicity study of magnesium sulfate in rats and dogs].
A single dose toxicity study of magnesium sulfate by intravenous administration was conducted in rats and dogs. The results are summarized in the following. Magnesium sulfate was administered once at dose levels of 90, 130, 200, 300 and 450 mg/kg to Crj:CD(SD) rats at 6 weeks of age. Deaths occurred in the 200 mg/kg and above groups in both sexes. The LD50 values were 206 mg/kg for males and 174 mg/kg for females. In the surviving animals, in the 130 mg/kg and above groups, tonic convulsions, abnormal gait and tachypnea were seen. However, these signs disappeared gradually and all animals returned to a normal state by 15 min after dosing. There were no treatment-related changes in the body weight or gross pathology. Magnesium sulfate was infused for 6 hr at dose levels of 75, 300 and 1200 mg/kg (12.5, 50 and 200 mg/kg/hr) to female beagle dogs at 6 months of age. No deaths were observed in any of the dose groups and it was considered that the lethal dose level would be higher than 1200 mg/kg(200 mg/kg/hr). In the 1200 mg/kg group, vomiting, decreased spontaneous movement, staggering gait, prone position and flush of the conjunctiva and ear auricles were seen. However, these signs disappeared gradually and animals returned to a normal state by 1 hr after dosing. There were no treatment-related changes in the body weight, food consumption or gross pathology.
Animals↗
[A 2-week toxicity study of magnesium sulfate administered by 24-hr intravenous infusion in beagle dogs followed by 2-week recovery period].
A 2-week toxicity study of magnesium sulfate administered by a 24-hr intravenous infusion at the dosage levels of 0, 12.5, 50, 100 and 200 mg/kg/hr in female beagle dogs was conducted, with 2-week follow-up observation after drug withdrawal. One of 2 animals in the 200 mg/kg/hr group died approx. 32 hr after the start of infusion. At the same time, the remaining 1 animal of the same group was sacrificed in a moribund state. Changes attributable to the treatment of magnesium sulfate were decreased food consumption and body weight gain, anemia, mild prolongation of conduction time in electrocardiogram and tubular basophilia in the kidneys in the animals treated with 100 mg/kg/hr. Furthermore, decreased calcium level was recorded in the animals treated with 50 mg/kg/hr or more. However, these changes disappeared after drug withdrawal, and reversibility was suggested. Judging from the mode of occurrence, since the change in calcium level observed in the group treated with 50 mg/kg/hr was slight, it was considered to be toxicologically insignificant. In conclusion, the nontoxic dosage level of magnesium sulfate was judged to be 50 mg/kg/hr under the condition of the present study.
Anemia↗
[A 4-week toxicity study of magnesium sulfate administered by 24-hr intravenous infusion in beagle dogs].
A 4-week toxicity study of magnesium sulfate administered by 24-hr intravenous infusion at the dosage levels of 0, 12.5, 50 and 100 mg/kg/hr in female beagle dogs was conducted. No death occurred in any group. Changes attributable to the treatment with magnesium sulfate were decreased food consumption and body weight gain, anemic change, increased urine volume, decreased serum calcium level, increased inorganic phosphorus level, slight prolongation of conduction time in electrocardiogram and tubular basophilia in the kidneys in the group treated with 100 mg/kg/hr. In addition, essentially similar changes were also observed at the same dosage level in the 2-week study of this drug, in which recoverability was recognized with 2-week follow-up observation after drug withdrawal. In conclusion, the nontoxic dosage level was judged to be 50 mg/kg/hr under the condition of the present study.
Anemia↗
[A study for effects on pre- and postnatal development, including maternal function in rats treated subcutaneously with magnesium sulfate].
Magnesium sulfate, at dose levels of 250, 500 and 1000 mg/kg, was administered subcutaneously three times daily to Crj:CD(SD) female rats from day 15 through day 20 of gestation. The effects of the compound on dams and F1 animals were examined. In the dams, decreased food consumption was observed in the 500 and 1000 mg/kg groups. Hypolocomotion, pronation, bradypnea and decreased body weight gain were observed in the 1000 mg/kg group. But there were no effects on the delivery or lactation conditions and necropsy from administration of the test article. In the F1 animals, low body weight, delays in differentiation (eruption of lower incisor, opening of eyelid) and reversible change in ribs (wavy rib) were observed in the 1000 mg/kg group. But there were no effects from administration of the test article in viability, functional examinations, behavior tests or reproductive ability. Based on the above results, under the conditions of this study, it was concluded that the non-toxic dose levels for general toxicological effects on dams was 3 x 250 mg/kg/day, for reproductive ability of dams was 3 x 1000 mg/kg/day, and for development of F1 animals was 3 x 500 mg/kg/day.
Animals↗