Isolated relapse of acute lymphoblastic leukemia in the breast of a young female.

A 20-year-old female developed a relapse of B-precursor acute lymphoblastic leukemia (ALL) as a mass in her left breast after 6 years of maintained continuous complete remission. No leukemic lesions were identified in other sites such as the bone marrow or cerebrospinal fluid. The relapsed leukemic cells in the breast revealed the same immunophenotypes (CD10(+), CD19(+), CD20(+), HLA-DR(+), CD34(+)) as those of the onset ALL cells in the bone marrow. A literature survey found 10 other cases of ALL relapse in the breast without bone marrow involvement, mostly consisting of adolescent girls. Including the present report, a total of 11 cases were analyzed; the onset ages of ALL were a median of 16.5 (range 5-50) years old and the ages of relapse in the breast a median of 20 (range 12-51) years old. Data suggest that, although rare, the breast could become one of the extramedullary relapse sites of ALL developed in adolescent girls.

Pivalate affects carnitine status but causes no severe metabolic changes in rat liver.

To investigate the carnitine deficiency induced by pivalate, rats had free access to drinking water with or without pivalate. Consumption of 20 mmol/L pivalate for 1 wk decreased the levels of both free and total carnitine in plasma to approximately 20% of levels before treatment. After 4 wk, the concentrations of free carnitine in the liver, heart and muscle of pivalate-treated rats were approximately 60-80% of the control, and in the kidney, 26% of the control. Fractional excretion of free carnitine (FEFC) in pivalate-treated rats was measured; however, the treatment for 3 or 8 d did not affect the values relative to those obtained before treatment. Treatment with pivalate for 4 wk did not affect plasma concentrations of glucose, ammonia and free fatty acids (FFA) in the rats; however, the concentration of 3-hydroxybutyrate (3-OHB) was higher, and the FFA/3-OHB ratio was lower than those of controls. In a liver perfusion study, ketogenesis from oleate and gluconeogenesis from lactate and pyruvate in rats treated with pivalate for 4 wk were not different from controls. These results suggest that administration of pivalate did not induce the excessive excretion of free carnitine in urine, and secondary carnitine deficiency induced by intake of 20 mmol/L pivalate for 4 wk did not cause severe metabolic changes in rat liver.

Glycogenolytic effect of adenosine involves ATP from hepatocytes and eicosanoids from Kupffer cells.

In the perfused liver, infusion of adenosine (50 microM) caused an increase in portal pressure and glucose output as well as a brief increase in oxygen uptake followed by a transient decrease within 1 min. Half-maximal glycogenolytic effect was observed with approximately 20 microM adenosine, and the stimulation was maximal at concentrations > 50 microM. The effect of adenosine was blocked when Kupffer cells were destroyed with gadolinium chloride treatment (10 mg/kg iv), supporting the hypothesis that eicosanoid release from Kupffer cells participates in the effect of adenosine in the liver. Although adenosine has been reported to increase eicosanoid release from perfused liver (S. vom Dahl, M. Wettstein, W. Gerok, and D. Hüssinger, Biochem. J. 270: 39-44, 1990), in this study adenosine failed to stimulate prostaglandin release from cultured Kupffer cells at concentrations ranging from 1 microM to 1 mM, casting doubt on the hypothesis that Kupffer cells are totally responsible for the effect of adenosine. In contrast, adenosine increased ATP transiently from 4 to 15 nM in effluent from perfused livers concomitant with a transient increase in carbohydrate output and portal pressure. To assess which type of hepatic cells released ATP after addition of adenosine, parenchymal, Kupffer, and endothelial cells were isolated and incubated with adenosine. Adenosine increased ATP concentrations in culture media of parenchymal cells but not from Kupffer or endothelial cells. Furthermore, ATP stimulated prostaglandin release from cultured Kupffer cells, whereas ATP (10 microM) infusion caused glucose release with kinetics similar to adenosine in perfused livers, an effect that was blocked by destroying Kupffer cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Transient activation of hepatic glycogenolysis by thrombin in perfused rat livers.

Thrombin, a peptide with native protease activity, caused a rapid (less than 1 min) increase in glycogenolysis of about 30%, assessed from rates of production of glucose+lactate+pyruvate, and in oxygen uptake in perfused rat liver. These increases were followed by a rapid return to basal values within 5 min. The effect of thrombin on glycogenolysis was dose-dependent and was maximal at perfusate concentrations around 1 U/ml. Interestingly, the effect of thrombin on glycogenolysis could be elicited only once in any given liver. The activation of glycogenolysis by thrombin was diminished nearly 50% by prior infusion of the protease inhibitor, diisopropyl fluorophosphate (10 microM), and over 90% when thrombin was treated with diisopropyl fluorophosphate prior to infusion. The stimulation of glycogenolysis by thrombin could be detected in isolated hepatocytes or in livers stored for 24 h in cold Euro-Collins solution, a treatment which destroys endothelial cells. Further, thrombin stimulated production of prostaglandin D2 from arachidonic acid in cultured hepatic endothelial but not Kupffer cells. The effect of thrombin on carbohydrate output was also blocked by a phospholipase A2 inhibitor (quinacrine, 50 microM) and by an inhibitor of the cyclooxygenase (indomethacin, 20 microM), suggesting the involvement of cyclooxygenase in the mechanism of action of thrombin. In support of this idea, the transient kinetics of stimulation of glycogenolysis by thrombin and arachidonic acid was nearly identical to release of thromboxane B2 (80-420 pg/ml) and prostaglandin D2 (300-900 pg/ml) from the perfused liver. Further, a second addition of thrombin failed to increase thromboxane and prostaglandin D2 release as well as carbohydrate production, supporting a causal link between these phenomena. Taken together, these data support the hypothesis that thrombin interacts with receptors in the liver, possibly on endothelial cells, leading to activation of phospholipase A2 and subsequent transient production of prostaglandins and thromboxanes. These mediators subsequently interact with receptors on parenchymal cells, leading to a transient stimulation of glycogenolysis.

Evidence that free radicals are involved in graft failure following orthotopic liver transplantation in the rat--an electron paramagnetic resonance spin trapping study.

The purpose of these studies was to determine whether free radicals were formed as a consequence of reperfusion during orthotopic liver transplantation and whether their formation was related to graft failure. Grafts were stored for 18 hr in Euro-Collins solution or for 48 hr in University of Wisconsin solution (nonsurvival conditions) and reperfused with blood containing the spin trap alpha-phenyl N-tert-butylnitrone (PBN). Venous blood samples (4-5 ml) were collected, and serum was extracted with chloroform and methanol (2:1) and analyzed for radical adducts by electron paramagnetic resonance (EPR) spectroscopy. In samples from livers stored under nonsurvival conditions, EPR spectra were detected indicating the presence of PBN radical adducts. In contrast, radical adduct formation was 3- to 4-fold lower in similar experiments performed with untransplanted livers or with livers stored under survival conditions (1 hr in Ringer's solution or 24 hr in UW solution). Oxygen radicals are more likely involved in the production of radical adducts because formation was nearly completely prevented by superoxide dismutase plus catalase or Carolina rinse, which contains glutathione, desferrioxamine mesylate, and allopurinol. Radical adduct formation was much greater in a blood-free perfusion system where oxygen delivery was high, suggesting that blood elements are not necessary for radical adduct formation. An inverse correlation between survival of livers stored in UW solution and radical adduct signal was observed in this study. Thus, it is concluded that free radicals formed during reperfusion are involved in the mechanism of graft failure following liver transplantation in the rat.

Hormones increase oxygen uptake in periportal and pericentral regions of the liver lobule.

The effect of several hormones known to alter intracellular free Ca2+ on rates of O2 uptake in periportal and pericentral regions of the liver lobule was studied in the perfused liver. Regional O2 uptake was measured by stopping the flow and monitoring the decrease in O2 concentration. When perfusion was in the anterograde direction, basal rates of O2 uptake were two to three times higher in periportal than in pericentral regions, and phosphorylase alpha activity, which increases as a function of intracellular free Ca2+ levels, was higher in periportal regions. In contrast, when perfusion was in the retrograde direction, rates of O2 uptake were two to three times greater in pericentral regions. Infusion of epinephrine (0.1 microM) or angiotensin II (5 nM) increased the rate of O2 uptake nearly exclusively in downstream areas of the lobule where O2 tension was low. When perfusions were in the anterograde direction, epinephrine increased phosphorylase alpha activity significantly only in pericentral regions. Stimulation of O2 uptake by epinephrine was blocked by the alpha-adrenergic receptor blocker phentolamine (1 microM) but not by the beta-receptor blocker propranolol. Thus hormones that increase intracellular calcium stimulate O2 uptake predominantly in regions of the liver lobule where O2 tension is lowest, supporting the hypothesis that oxygen tension regulates O2 uptake in the liver via mechanisms involving intracellular free Ca2+.

Activation of Kupffer cells on reperfusion following hypoxia: particle phagocytosis in a low-flow, reflow model.

Hypoxia is produced selectively in pericentral regions of the liver lobule with a low-flow, reflow perfusion model in which the flow rate is reduced to approximately one-third to one-fourth of normal. This model was used to monitor carbon particle phagocytosis by Kupffer cells during hypoxia and reoxygenation. At normal flow rates, oxygen uptake was 131 mumol.g-1.h-1, pressure was 7.5 cmH2O, and carbon uptake was 150 mg.g-1.h-1. During the low-flow period, oxygen uptake, pressure, and carbon uptake decreased to values of 54 mumol.g-1.h-1, 6.4 cmH2O and 83 mg.g-1.h-1, respectively. Upon reflow, oxygen uptake and pressure increased to 141 mumol.g-1.h-1 and 10.3 cmH2O, respectively. In addition, carbon uptake was elevated approximately threefold to 234 mg.g-1.h-1, indicating activation of Kupffer cells. This activation was prevented by pretreatment with methyl palmitate, a known inhibitor of Kupffer cells. Histological examination revealed significantly more Kupffer cells laden with carbon particles in untreated livers after reflow than in livers from methyl palmitate-treated or untreated rats. Electron microscopic analysis of livers at reflow revealed Kupffer cells with numerous pseudopodia and lamellapodia, reflecting an activated state. These changes were absent in controls or in livers perfused under low-flow conditions. This study demonstrates that Kupffer cells are activated on reoxygenation after hypoxia.

Bacterial meningitis caused by Veillonella parvula.

A three-year-old girl injured her right eyelid with a toothbrush. The wound was sutured. Swelling of the eyelid, high fever and vomiting developed in spite of oral antibiotics for seven days. The findings of the cerebrospinal fluid (CSF) were white blood cells (WBC) 26,368/mm3 (90% polymorphs), protein 127 mg/dl, and sugar 0 mg/dl. Although Gram negative organisms were seen on the smear, aerobic culture was sterile. Later culture of CSF on admission grew anaerobic bacteria: Veillonella parvula. Intravenous administration of penicillins with cefotaxime (CTX), or of fosfomycin (FOM) were ineffective. Chloramphenicol (CP) cured the patient without neurological sequelae. There were no abnormal findings on brain CT scan. This is the first report of Veillonella meningitis. V. parvula appeared to have invaded the CSF from the abscess of the eyelid. It is necessary to consider anaerobic meningitis when there is a preceding pyogenic infection in the head.

A case of incomplete DiGeorge syndrome associated with partial monosomy 22q11.1 due to maternal 14;22 translocation.

We report a boy with some clinical symptoms compatible with a diagnosis of incomplete DiGeorge syndrome. He had a dismorphic face, micrognathia, cleft palate, and heart anomalies similar to DiGeorge syndrome, but lacked aplasia of the thymus or hypoparathyroidism typical of the syndrome. High-resolution banding analysis revealed that his karyotype was 45,XY,-14,-22, +der(14)(14pter----14q32.32::22q11.21----22qter), the consequence of a maternal reciprocal translocation between chromosomes 14 and 22. Precise localization of the gene responsible for the present DiGeorge syndrome was assigned to subband 22q11.1.

[Malignant lymphoma of the central nervous system in a boy with immotile cilia syndrome].

Malignant lymphoma of the central nervous system in a thirteen-year-old boy with immotile cilia syndrome (ICS) is reported. He had frequent upper respiratory tract infections, chronic sinusitis and pneumonia during in childhood. Bronchiectasis was demonstrated by bronchography. The diagnosis of ICS was confirmed by the lack of dynein arms of cila in the nasal mucosa with electronmicroscopy. In 1987, he complained of headache and vomiting and a space occupied mass lesion in the left frontoparietal lobe was found by head CT scan, which was subtotally resected. Histological studies showed large cell type non-Hodgikin lymphoma of B-cell phenotype. He received radiotherapy (41Gy) to the whole brain and systemic chemotherapy consisting of adriamycin, cyclophosphamide, vincristine, prednisolone, L-asparaginase and intrathecal methotrexate, and the patient maintained complete remission for eight months. However, relapse occurred and the patient died twelve months after the initiation of treatment.

Ciliated mucous cells found in the nasal mucosa of a patient with Kartagener's syndrome.

Transmission electron microscopy revealed the presence of ciliated cells containing many mucous secretory granules in the nasal surface epithelium of a 13-year-old patient suffering from Kartagener's syndrome. In these cells, mucous secretory granules were accumulated in the apical cytoplasm, and the Golgi apparatus was well developed in the supranuclear region. Mucous secretory granules were discharged infrequently through the apical cell membranes by single or compound exocytosis. The cells were considered to be ciliated mucous cells, which have already been reported to be present in the lower respiratory tract but not in the upper respiratory tract.