Genetic selection for high acute inflammatory response confers resistance to lung carcinogenesis in the mouse

Mice selected for a high acute inflammatory response (AIRmax) are resistant to chemically induced lung tumorigenesis, whereas the low responders (AIRmin) are susceptible. In urethane-treated mice, anti-inflammatory drugs increased the tumor incidence in AIRmax but not AIRmin mice, and an inverse correlation (P<.001) between the degree of acute inflammatory response (AIR) and lung tumorigenesis was found in an F2 (AIRmax x AIRmin) intercross population. The results provide evidence for the involvement of lung tumor modifier loci in AIR regulation and implicate AIR quantitative trait loci in the inherited predisposition to lung cancer.     

Ultrastructural localization of nonspecific esterase activity in guinea pig and human monocytes, macrophages, and lymphocytes

Using either hexazotized pararosaniline or new fuchsin as coupling agents, we investigated the ultrastructural localization of alpha- naphthyl acetate esterase (ANAE) activity in guinea pig bone marrow and peritoneal exudates, and in human peripheral blood cells. DFP- inhibitable ANAE activity was present on the cell surface of lymphocytes, monocytes, macrophages, neutrophils, eosinophils, basophils, megakaryocytes, platelets, and blasts. Demarcation lines in megakaryocytes and the perinuclear cisternae in normoblasts were also positive. In addition, lymphocytes, monocytes, and macrophages displayed ANAE activity associated with cytoplasmic-vesicle clusters (CVC). Reaction product was always present on the cytoplasmic surfaces of these vesicles and in the adjacent cytoplasm; vesicle interiors were invariably ANAE-negative. Small lymphocytes generally had a single large paranuclear ANAE-positive CVC, whereas mononuclear phagocytes had multiple discrete foci of similar appearing ANAE-positive CVC that sometime became confluent. ANAE activity was also found in the Gall bodies of human lymphocytes and in coated vesicles of macrophages. Cytoplasmic ANAE activity was increased in oil-induced guinea pig peritoneal macrophages. Both surface and cytoplasmic esterase activities had a neutral pH optimum. An identical distribution of reaction product was observed when alpha-naphthyl butyrate was employed as substrate. The function of these esterases, and their relation to known surface and cytoplasmic neutral proteases, awaits further investigation.     

Late or delayed induced or spontaneous puberty in girls with Turner syndrome treated with growth hormone does not affect final height

Although it has been well established that GH treatment increases final height (FH) in girls with Turner syndrome (TS), the optimal ages to start GH therapy and introduce estrogens for pubertal induction have not been defined. We evaluated retrospectively the influence of the age at onset of GH treatment and age at onset of puberty on FH of 186 adult TS women treated during childhood with GH. Puberty started spontaneously in 38 patients, and it was induced in 148 girls with ethinyl estradiol (mean +/- SD starting dose, 66 +/- 32 ng/kg.d). Patients with spontaneous or induced puberty were divided into quartiles on the basis of age at initiation of GH treatment (3-10, 10-12, 12-14, and 14-19 yr). FH was 151.7 +/- 6.0 cm; there were no FH differences between patients with induced or spontaneous puberty, nor were there differences between the age quartiles. Puberty started earlier in the girls with spontaneous puberty than in those with induced puberty (12.4 +/- 1.3 yr vs. 14.5 +/- 1.9 yr; P < 0.0001). The age at onset of puberty was not related to FH. Pubertal growth was 15.4 +/- 4.6 cm in the girls with spontaneous puberty and 8.6 +/- 4.3 cm in the girls with induced puberty (P < 0.0001). We conclude that GH treatment results in a significant increase in FH in most TS girls. Under the conditions of GH treatment and induction of puberty that we have used, the age at start of GH treatment was not related to FH; in addition, late or delayed induced or spontaneous puberty did not affect FH.     

Fulminant Epstein–Barr virus‐associated hemophagocytic syndrome in a renal transplant patient and review of the literature

We describe a rare fulminant case of Epstein–Barr virus‐associated hemophagocytic syndrome (HPS) in a 37‐year‐old female renal transplant patient, indistinguishable from severe sepsis clinically and in the laboratory. HPS involves rapidly escalating immune system activation, resulting in a cytokine cascade, which can, especially in immunocompromised patients, lead to multi‐organ failure, and even death. Thirty‐two Herpesviridae‐associated HPS cases in renal transplant patients have been reported and are reviewed. Overall mortality is 47% (15/32 cases).     

Pheochromocytoma associated with adrenocortical tumor in the same gland. Two case reports and literature review

Pheochromocytomas are catecholamine-producing neuroendocrine tumours arising from chromaffin cells of the adrenal medulla or extra-adrenal paraganglionic system that show 2 distinctive features, rarity and clinical variability. Pheochromocytoma occasionally is associated with pathological lesions of the adrenal cortex. We present 2 cases of patients referred to our hospital with a finding of clinical suspected pheochromocytoma. Both of them were hypertensive; the first patient with typical symptoms of pheochromocytoma and the second patient with chest pain and hypertension resistant to pharmacological treatment. The diagnosis of pheochromocytoma was confirmed in both cases with laboratory analysis and the lesion was achieved by employing 3 imaging techniques: computed tomography (CT), magnetic resonance imaging (MRI) and scintigraphy with (123)I-metaiodobenzilguanidine (MIBG). The patients underwent adrenalectomy and in the same adrenal gland we found a pheochromocytoma associated with a nonfunctioning cortical adenoma. As far as we know few cases with this association are available in the literature.     

The Kernel Energy Method: application to a tRNA

The Kernel Energy Method (KEM) may be used to calculate quantum mechanical molecular energy by the use of several model chemistries. Simplification is obtained by mathematically breaking a large molecule into smaller parts, called kernels. The full molecule is reassembled from calculations carried out on the kernels. KEM is as yet untested for RNA, and such a test is the purpose here. The basic kernel for RNA is a nucleotide that in general may differ from those of DNA. RNA is a single strand rather than the double helix of DNA. KEM energy has been calculated for a tRNA, whose crystal structure is known, and which contains 2,565 atoms. The energy is calculated to be E = -108,995.1668 (a.u.), in the Hartree-Fock approximation, using a limited basis. Interaction energies are found to be consistent with the hydrogen-bonding scheme previously found. In this paper, the range of biochemical molecules, susceptible of quantum studies by means of the KEM, have been broadened to include RNA.     

Long-term follow-up of blood donors with indeterminate human immunodeficiency virus type 1 results on Western blot

BACKGROUND: At present, tens of thousands of United States blood donors who are at low risk for human immunodeficiency virus type 1 (HIV-1) infection are indefinitely deferred. These persons are repeatably reactive for HIV-1 antibody in enzyme immunoassay (EIA) and are indeterminate in Western blot. STUDY DESIGN AND METHODS: To determine the significance and persistence of anti-HIV-1 reactivity in plasma from volunteer blood donors with HIV-1-indeterminate Western blots, 66 donors were retested for HIV-1 antibody by the same manufacturers' EIA and Western blot 5 to 7 years after the initial Western blot. In addition, donors' peripheral blood mononuclear cells were tested by polymerase chain reaction (PCR) for HIV-1 DNA gag sequences. RESULTS: Thirty-five (53%) of 66 donors were still repeatedly reactive for HIV-1 on EIA and indeterminate on Western blot, 23 (35%) were negative on EIA and indeterminate on Western blot, 7 (11%) were negative in EIA and Western blot, and 1 (2%) was repeatedly reactive on EIA and negative on Western blot. Donors with persistently indeterminate Western blots had a band pattern nearly identical to that on the original Western blot. No donor was positive in Western blot, p24 antigen, or PCR testing. No donor had signs or symptoms of HIV-1 infection. CONCLUSION: Long-term follow-up of Western blot-indeterminate blood donors does not reveal evidence of HIV-infection. A mechanism to return these donors to the donor pool should be considered.     

Deletion of the human retinoblastoma gene in primary leukemias

As an initial step in evaluating the role of tumor suppressor genes in leukemogenesis, we surveyed primary leukemia cells from 130 patients for possible deletion of the retinoblastoma susceptibility (Rb) gene by Southern blot analysis. Two of them clearly showed homozygous deletion of Rb alleles. The first patient was a pre-B acute lymphoid leukemia (ALL) associated with a cytogenetic translocation: t(14;16)(q24;q22). The deletion was located at the 3' portion of the Rb gene, very close to the site of Rb gene deletion recently identified in an ALL cell line. The absence of Rb110 protein was further confirmed by Western blot analysis. The second patient was a chronic myelomonocytic leukemia (CMMoL), terminated in acute blastic transformation. Deletion of the 5' portion of Rb gene was found in leukemic cells in the chronic stage. The results indicated that inactivation of the Rb gene occurred in certain cases of leukemia. Its significance warrants further study.     

How cytokines can influence the brain: a role for chemokines?

Following inflammation or infection, cytokines are released in the blood. Besides their effect on the immune system, cytokines can also act in the brain to modulate our behaviors, inducing for example anorexia when produced in large amount. This review focuses on our current knowledge on how cytokines can influence the brain and the behaviors through several possible pathways: modulating peripheral neurons which project to the brain through the vagus nerve, modulating the levels of hormones such as leptin which can act to the brain through the humoral pathway and possibly acting directly in the brain, through the local production of cytokines and chemokines such as SDF-1alpha/CXCL12.