Activation of Fas and perforin pathways in rat liver allograft rejection.
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Biomedical subjects
Publications and source records attributed to A Tamura.
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A female patient received a renal transplantation from an unrelated cadaver donor, and five years later developed myelodysplastic syndrome (MDS) with immunological abnormalities. Chromosomal analysis showed trisomy 8 in bone marrow cells. FISH analysis indicated that trisomy 8 was present in 4% of CD19 + cells, suggesting that the MDS clone involved B lymphocytes. Polymerase chain reaction of the human androgen receptor gene indicated B cell clonality (54%) and granulocyte clonality (63%). There have been no previous reports of secondary MDS following renal transplantation in which the MDS clone involved the B cell lineage. The abnormal MDS B cell clone may have caused the immunological abnormalities.
A series of cephalosporin derivatives with various bicyclic heterocycles at the C-3 position was synthesized and evaluated for antibacterial activity. Among them CP0467 (3a) showed excellent antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) (MIC90 = 6.25 microg/mL), and extremely high affinity for the penicillin binding protein 2' of MRSA (I50 = 0.49 microg/mL). Furthermore, 3a showed a long-acting pharmacokinetic profile in mice (AUC(infinity) = 482.3 microg/h/mL and T(1/2) = 1.9 h).
A series of cephalosporin derivatives with a thiazolopyridinium group at the 3-position was synthesized and evaluated for antibacterial activity. Some of these cephalosporin derivatives having a (5-alkylthiazolo[4,5-c]pyridinium-2-yl)thiomethyl group at the 3-position showed strong activity against Gram-positive and Gram-negative bacteria, including Pseudomonas aeruginosa. Among them, 5a showed a good antibacterial spectrum in vitro, and also showed a similar or slightly superior activity to that of ceftazidime in vivo against P. aeruginosa.
An improved new method for the simultaneous visualization of mRNA and encoded protein in LR White resin-embedded specimens is described. This pre-embedding electron microscopical in situ hybridization (procedure) localized rat growth hormone mRNA specifically as high electron-density products on the polysomes of the rough endoplasmic reticulum. A subsequent post-embedding immunoreaction, using protein A colloidal gold particles, identified growth hormone as gold particles both in the cisternae of the rough endoplasmic reticulum and on the secretory granules. In our previous report, we used Epon resin for tissue embedment, which required an etching process using hydrogen peroxide or sodium periodate for immunoreactivity retrieval. In general, osmification and embedment in Epon resin are reported to decrease the immunoreactivity of the targeted protein, and the etching process using hydrogen peroxide or sodium periodate results in deosmification and shades off the signals of mRNA. To resolve these problems, we have recently used LR White resin for tissue embedment. In LR White resin-embedded tissues, retrieval of immunoreactivity using hydrogen peroxide or sodium periodate is not required, and, therefore, the gradation of the signals of mRNA can be avoided.
We report a 40-year-old Japanese man with a creeping eruption caused by a larva of the nematode suborder Spirurina type X. He had eaten raw small squid (hotaruika) 4 weeks before the serpiginous erythematous eruption appeared on his abdomen. Routine laboratory tests revealed only slight eosinophilia in his peripheral blood. Although we could not find the larva in an excised skin specimen, an indirect immunofluorescence test confirmed the presence of antibodies against larvae of the suborder Spirurina type X. We review 28 reported cases in Japan which showed that creeping eruption caused by larvae of the suborder Spirurina type X has the following clinical characteristics: an incubation time of 1-4 weeks; a migratory, well-defined, narrow, serpiginous erythematous eruption; and only slight peripheral blood eosinophilia. Excision of the advancing end of the track was curative in our patient.
Hidradenitis suppurativa (HS) represents a chronic, recurrent, deep-seated folliculitis resulting in abscesses followed by the formation of sinus tracts and scarring. It is an uncommon disorder frequently involving the perianal region. We review the clinical and pathological features of 12 patients (10 men and two women) with perianal HS (PHS). The mean age at presentation was 43 years (range 24-65), and the mean duration of illness was 14 years (range 2-30). Two patients exhibited multiple areas of involvement, including the axilla and the nape of the neck, in addition to the perianal region. Histological examinations showed epidermis-lined sinuses surrounded by dense plasma cell infiltration in four of nine specimens. The complications related with PHS included anal fistula (seven patients), diabetes mellitus (four), malignant tumour (two) and sepsis (one). Three patients died of the complications. Eight patients underwent wide local excision. The defects were managed with a meshed split-thickness skin graft in five patients, and open treatment in the remainder. New lesions developed in untreated skin of two patients. However, no patient relapsed in the surgically treated sites. PHS is frequently complicated with anal fistula and is occasionally life-threatening as a result of the occurrence of malignant tumours or sepsis. Early surgical excision followed by meshed split-thickness skin graft can successfully cure the lesion without functional disturbance.
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AIMS: This study was conducted to clarify the significance of abnormal Q-wave regression in anterior wall acute myocardial infarction. METHODS: A total of 74 patients who presented with a first anterior wall acute myocardial infarction within 6 h of onset were divided into two groups according to the presence (group A, n = 29) or absence (group B, n = 45) of regression of abnormal Q waves. Regression of abnormal Q waves was defined as the disappearance of the Q wave and the reappearance of the r wave > or = 0.1 mV in at least one of leads I, aVL, and V1 to V6. RESULTS: Emergency coronary arteriography revealed that group A had a higher incidence of spontaneous recanalization or good collateral circulation than group B (55% vs 31%, P < 0.05). Peak creatine kinase activity tended to be lower in group A than in group B (2358 +/- 1796 vs 3092 +/- 1946 IU.L-1, P = 0.09). Group A had a greater left ventricular ejection fraction and better regional wall motion at 1 and 6 months after acute myocardial infarction than group B. The degree of improvement of left ventricular ejection fraction and regional wall motion between 1 and 6 months after acute myocardial infarction was significantly greater in group A than in group B. CONCLUSION: Patients with anterior wall acute myocardial infarction showing Q-wave regression had a trend towards a smaller amount of necrotic myocardium and a significantly larger amount of stunned myocardium.
BACKGROUND: Obstructive pneumonia, a synonym for endogenous lipoid pneumonia, is often seen in patients with lung cancer, but details of this condition are still uncertain. METHODS: To elucidate the features of obstructive pneumonia, we radiopathologically studied 147 patients with lung cancer that had been resected. RESULTS: Gross inspection of the resected materials revealed evidence of endogenous lipoid pneumonia in 33 of the 147 patients with radiography that corresponded to obstructive pneumonia. We classified the 33 cases into three types as follows: (1) type I lipoid pneumonia, localized to the lung parenchyma distal to an airway obstructed by a tumor (23 cases); (2) type II lipoid pneumonia, features of type I lipoid pneumonia and consecutively spreading to the adjacent segment whose airway was not affected (five cases); (3) type III lipoid pneumonia, features of type II lipoid pneumonia and spreading to the isolated segments (five cases). Lipoid pneumonia was found in 16 of 89 (18%) adenocarcinoma cases and in 17 of 55 (31%) squamous cell carcinoma cases. In type I lipoid pneumonia, squamous cell carcinoma cases were predominant over adenocarcinoma cases (14 vs nine cases), but in type III lipoid pneumonia, adenocarcinoma cases predominated (four vs one case). Further, in cases of type III lipoid pneumonia, radiographs frequently revealed that lung cancers were cavitated. CONCLUSION: Lipoid pneumonia in lung cancer may be associated with factors that play a larger role than the cancer alone. It can be speculated that transbronchial dissemination of breakdown products of adenocarcinoma cells, including mucin, may contribute to the spread of the non-obstructive component of lipoid pneumonia, because the local physical effect of obstructed bronchus does not affect the non-obstructive component.
To determine whether human luteal cells can utilize very low density lipoproteins (VLDL)-carried cholesterol for steroidogenesis, we investigated the expression of VLDL receptor mRNA in human ovarian tissues and progesterone production by human luteinized granulosa cells after the addition of VLDL. The production of progesterone in the presence of human chorionic gonadotrophin (HCG) was increased significantly (P < 0.05) by VLDL (2479 +/- 1477 ng/10(5) cells, mean +/- SD, n = 6) and low density lipoproteins (LDL) (2726 +/- 1287), in comparison with the level in the absence of these lipoproteins (1350 +/- 739). Northern blot analysis revealed that the levels of expression of VLDL and LDL receptor mRNA in granulosa cells were almost equal to those in whole ovarian tissue. VLDL receptor mRNA was abundant in granulosa cells of preovulatory follicles and cells of the corpus luteum. Preovulatory thecal cells and stromal cells expressed lower amounts of VLDL receptor mRNA than granulosa cells of preovulatory follicles and cells of the corpus luteum. From the present study, it might be suggested that VLDL is utilized for steroidogenesis in human luteinized granulosa cells.
Preconditioning with sublethal ischemia induces tolerance to subsequent lethal ischemia in neurons. We investigated electrophysiologic aspects of the ischemic tolerance phenomenon in the gerbil hippocampus. Gerbils were subjected to 2 minutes of forebrain ischemia (preconditioning ischemia). Some of them were subjected to a subsequent 5 minutes of forebrain ischemia 2 to 3 days after the preconditioning ischemia (double ischemia). Hippocampal slices were prepared from these gerbils subjected to the preconditioning or double ischemia, and field excitatory postsynaptic potentials were recorded from CA1 pyramidal neurons. Capacity for long-term potentiation triggered by tetanic stimulation (tetanic LTP) was transiently inhibited 1 to 2 days after the double ischemia but then recovered. Latency of anoxic depolarization was not significantly different between slices from preconditioned gerbils and those from sham-operated gerbils when these slices were subjected to in vitro anoxia. Postanoxic potentiation of N-methyl-D-aspartate (NMDA) receptor-mediated transmission (anoxic LTP) was inhibited in slices from gerbils 2 to 3 days after the preconditioning ischemia, whereas it was observed in slices from sham-operated gerbils and gerbils 9 days after the preconditioning ischemia. These results suggest that protection by induced tolerance is (1) not only morphologic but also functional, and (2) expressed in inhibiting postischemic overactivation of NMDA receptor-mediated synaptic responses.
It is well known that hemiplegia is frequently observed in cerebral ischemia. It is important for the pathophysiologic study and development of drug therapies to establish a precise method investigating impairment of motor function with animal models. To develop a quantitative and objective method for evaluating impairment of motor function, we examined an inclined plane test after chronic focal cerebral ischemia in the rat. Standard scoring of neurologic deficits has limitations, including problems with quantification and objectivity. The purpose of this study was to establish a novel method for evaluating impairment of motor function in middle cerebral artery (MCA) occluded rats. The left MCA was permanently occluded at a proximal site, and sensorimotor performance was evaluated at the fifth day and every week for 11 weeks thereafter. The ability to maintain body position on an inclined plane was measured when rats were placed on a stainless steel slope in left-headed, right-headed, and up-headed positions. Neurologic examination based on hemiparesis and abnormal posture was also performed. After all behavioral examinations were completed, the degree of shrinkage of the left hemisphere to the contralateral was measured. The ability of MCA-occluded rats to maintain position on an inclined plane in the left-headed position was significantly restricted when compared with that of sham-operated rats throughout the test period (maximum angle of 37 degrees versus 45 degrees, respectively). Minimal natural recovery was observed for all position measurements. MCA-occluded rats showed a significantly higher neurologic score with natural recovery. The ability to maintain position on an inclined plane after MCA occlusion (MCAO) was significantly correlated with the degree of the shrinkage of the ischemic hemisphere and neurologic score. The angle for the left-headed position was most strongly correlated with ipsilateral shrinkage. In the present study, long-lasting impairment of motor function was detected in rats with MCAO, which correlated with the shrinkage of the ischemic hemisphere. Furthermore, a difference in performance depending on body position (left-headed versus right-headed) was also detected. The left-headed position was found to be most sensitive for evaluating this model. The inclined plane test is a quantitative, objective, and sensitive method for evaluating motor deficits after chronic focal cerebral ischemia in rats, and this method may be useful to investigate changes in motor function in hemiplegia.
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A case of multiple cutaneous epithelioid hemangioendothelioma (EH) in a Japanese male is reported. The patient was a 52-year-old Japanese bureaucrat. Clinically, about 10 purplish-red, elastic soft or hard papules and nodules had appeared on both lower extremities and the left buttock over the past 20 years. They were excised, but some of them recurred. Histologically, the papules and nodules were well-circumscribed tumors located in the superficial and deep dermis. They appeared to arise from medium-sized vessels and were composed of proliferations of characteristic epithelioid endothelial cells with intracytoplasmic vacuolization and spindle cells. No other extracutaneous tumors were found. We diagnosed the present case as multiple cutaneous EH with spindle cells. The presence of epithelioid endothelial cells and absence of pleomorphism and mitoses of nuclei of spindle cells made differential diagnosis from Kaposi's sarcoma possible. The protracted clinical course seems characteristic of EH in various organs including skin.
The insulin content in mouse insulinoma MIN6 cells was determined using matrix-assisted laser desorption ionization (MALDI) time-of-flight mass spectrometry (TOF/MS). A mass spectrum of cellular insulin was obtained with a cell burst of MIN6 by hypotonic water. Signal intensities of intracellular insulin were proportional to the number of MIN6 cells. The present method was applied to the determination of intracellular insulin content of MIN6 before and after glucose stimulation.