A case of resectable lung adenocarcinoma associated with sarcoidosis

A 71-year-old woman with uveitis was referred to our hospital for further examination of the possible underlying diseases. In roentgenological examination with plain X-ray and CT scan, hilar and mediastinal lymphadenopathy and a mass shadow in the right upper lung field was observed, whereas fibrotic changes were not obvious in both lung fields. Transbronchial lung biopsy with fiberoptic bronchoscope revealed granulomatous interstitial pneumonia. CD4-positive lymphocytes were increased in bronchoalveolar lavage. The patient was diagnosed as having sarcoidosis. Subsequently, right upper lobectomy was performed, and Stage I lung adenocarcinoma was diagnosed. The patient is under follow up without medication and the disease has been stable for two years. A relationship between epithelioid granulomatosis and malignant diseases is discussed and a review of the literature is given. Since it is still controversial as to the incidence of malignant diseases in sarcoidosis patients, it is important to accumulate data on these associations.     

Comparative analysis of the priming effect of human interferon-gamma, -alpha, and -beta on synergism with muramyl dipeptide analog for anti-tumor expression of human blood monocytes

Freshly isolated human peripheral blood monocytes from healthy volunteers were not cytotoxic to allogeneic A375 melanoma cells, but they were activated to the cytotoxic state by incubation in vitro with either des-methyl muramyl dipeptide (norMDP; minimal effective dose, 0.5 micrograms/ml) or recombinant human interferon-gamma (rIFN-gamma; minimal effective dose, 1 U/ml). A combination of subthreshold concentrations of these agents (norMDP, 0.5 micrograms/ml; rIFN-gamma, 10 U/ml) also induced significant cytotoxicity, indicating that the effects of norMDP and rIFN-gamma in monocyte activation are synergistic. Natural human IFN-gamma (nIFN-gamma) and norMDP also had similar synergistic effects. Pretreatment of rIFN-gamma with anti-IFN-gamma antibody completely inhibited its synergistic effect with norMDP in monocyte activation. Because pretreatment of rIFN-gamma and norMDP with polymyxin B did not interfere with their effects in monocyte activation, the preparations were not contaminated with lipopolysaccharide. Moreover, because pretreatment of monocyte monolayers with anti-Leu-11b antibody (anti-natural killer (NK) cell antibody) and complement did not interfere with the synergistic effects of norMDP and rIFN-gamma, whereas pretreatment with anti-Leu-M1 antibody (anti-monocyte antibody) caused complete inhibition of their effects, the observed tumor cytotoxicity of monocyte-rich monolayers was probably not due to a small number of adherent NK cells, but to the stimulation of the monocytes. Natural and recombinant IFN-alpha and IFN-beta at concentrations of greater than or equal to 100 U/ml also induced tumoricidal activity of monocytes, but unlike IFN-gamma, their effects were additive with norMDP, and they had less priming effect than IFN-gamma when they were added before norMDP to monocytes. These findings suggest that recombinant human IFN-gamma has much more synergistic potential with norMDP than IFN-alpha or IFN-beta, and this synergism of rIFN-gamma and norMDP for monocyte activation could be of clinical value in treatment of disseminated malignant diseases, because these compounds are readily available at standardized concentrations.     

Novel racemosin B derivatives as new therapeutic agents for aggressive breast cancer

Carbazole derivatives show anti-cancer activity and are of great interest for drug development. In this study, we synthesized and analyzed several new alkylamide derivatives of racemocin B, a natural indolo[3,2-a]carbazole molecule originally isolated from the green alga Caulerpa racemose. Several alkylamide derivatives were found to exhibit moderate to strong growth inhibition against human breast cancer cell lines. They induced G2/M cell cycle arrest and apoptosis in the aggressive triple-negative breast cancer cell line MDA-MB-231. Among these derivatives, compound 25 with the lowest IC₅₀ induced cell death by suppressing autophagy. This was accompanied by inhibition of autophagic flux and accumulation of autophagy protein 1 light chain 3, LC3II, and p62. The novel alkylamide derivative offers a potential new treatment for human breast cancer.     

Asymptomatic Plasmodium malariae infections in children from suburban areas of Yaoundé, Cameroon

The gold standard for malaria diagnosis is the microscopic examination of Giemsa stained thick blood smears though microscopy mostly may not detect the presence of Plasmodium species infections in asymptomatic samples. In the reported study, we used two diagnostic methods viz. the conventional microscopic examination and polymerase chain reaction (PCR) assay to analyse the asymptomatic malaria samples. PCR assay amplifying 18S small-subunit ribosomal RNA (SSU rRNA) gene of Plasmodium in 122 samples confirmed 68% of isolates as asymptomatic P. falciparum infections; with 87.9% mono-infections. We observed that the P. malariae positive samples were not diagnosed in microscopic examination of the blood smears but the PCR based diagnostic method revealed the presence of 12% P. malariae infections in asymptomatic samples from Yaoundé region of Cameroon where no official cases of P. malariae have been reported for over a decade. The sequence analysis further confirmed the presence of 12% P. malariae in malaria positive samples with three base pair deletions and five substitutions in the SSU rRNA gene.     

Generation of killer activity by interleukin-12 of mononuclear cells in malignant pleural effusions due to lung cancer

 In the present study, we examined the ability of interleukin (IL)-12 to generate an antitumor effect in the tumor-growing site. Mononuclear cells (MNC) were obtained from 12 malignant pleural effusions due to lung cancer in the tumor-growing site. Non-major-histocompatibility-complex-restricted killer activity, examined by 4-h ⁵¹Cr release assay against Daudi lymphoma cells as well as various lung cancer cell lines (H69 and PC-9), and in vitro production of interferon γ (IFNγ), measured by enzyme immunoassay, were investigated as mediators of antitumor effects of host cells activated by IL-12. IL-12 induced killer activity of MNC in pleural effusions (pleural MNC) dose-dependently. Moreover, pleural MNC produced a signficant amount of IFNγ in response to IL-12. The killer activities of IL-12-activated blood MNC were higher than those of pleural MNC. The supernatants of pleural effusions of these untreated patients suppressed killer induction by IL-12 of blood MNC of healthy volunteers. These observations suggest that MNC present at the site of growing tumors may act as effector cells against lung cancer in the presence of IL-12. Received: 31 December 1996 / Accepted: 10 September 1997     

Artificial model of photosynthetic oxygen evolving complex: catalytic O2 production from water by di-mu-oxo manganese dimers supported by clay compounds

Adsorption of [(OH(2))(terpy)Mn(mu-O)(2)Mn(terpy)(OH(2))](3+) (terpy=2,2':6',2"-terpyridine) (1) onto montmorillonite K10 (MK10) yielded catalytic dioxygen (O(2)) evolution from water using a Ce(IV) oxidant. The Mn K-edge X-ray absorption near edge structure (XANES) of the 1/MK10 hybrid suggested that the oxidation state of the di-mu-oxo Mn(2) core could be Mn(III)-Mn(IV). However the pre-edge peak in the XANES spectrum of 1 adsorbed on MK10 is different from the neat 1 powder. The kinetic analysis of O(2) evolution showed that the catalysis requires cooperation of two equivalents of 1 adsorbed on MK10. The reaction of the [(bpy)(2)Mn(mu-O)(2)Mn(bpy)(2)](3+) (bpy=2,2'-bipyridine) (2)/MK10 hybrid with a Ce(IV) oxidant evolved O(2). However, the turnover number value was less than unity for 2/MK10, showing that 2 adsorbed on MK10 does not work as a catalyst. The terminal water ligands could be an important for the catalysis by adsorbed 1. The mechanism of O(2) production by photosynthetic oxygen evolving complex is discussed based on catalytic O(2) evolution by 1 adsorbed on MK10.     

Intravascular macrophage depletion attenuates endotoxin lung injury in anesthetized sheep.

We recently showed that we can selectively and safely deplete most (average 85%) of the pulmonary intravascular macrophages in sheep by intravenously infusing liposomes containing dichloromethylene bisphosphonate. After a 1-h stable baseline, we made a 6-h comparison after a 30-min intravenous endotoxin infusion (1 microg/kg) between six anesthetized control lambs and six anesthetized lambs in which the intravascular macrophages had been depleted 24 h previously. Three of the control lambs had been macrophage depleted and allowed to recover their intravascular macrophage population for >/=2 wk. After depletion, both the early and late pulmonary arterial pressure rises were dramatically attenuated. Our main interest, however, was in the acute lung microvascular injury response. The early and late rises in lung lymph flow and the increase in lung lymph protein clearance (lymph flow x lymph-to-plasma protein concentration ratio) were >90% attenuated. We conclude the pulmonary intravascular macrophages are responsible for most of the endotoxin-induced pulmonary hypertension and increased lung microvascular leakiness in sheep, although the unavoidable injury of other intravascular macrophages by the depletion regime may also contribute something.     

A method for the synthesis of an oseltamivir PET tracer

A protocol applicable for the synthesis of an oseltamivir positron emission tomography (PET) tracer was developed. Acetylation of amine 3 with CH(3)COCl, followed by deprotection and aqueous workup, produced oseltamivir 4 from 3 within 10 min. The obtained 4 was sufficiently pure for PET studies. This method can be extended to PET tracer synthesis using CH(3)(11)COCl.     

Molecular Cloning and Expression of a Novel Cholinephosphotransferase Involved in Glycoglycerophospholipid Biosynthesis of <Emphasis Type="Italic">Mycoplasma fermentans</Emphasis>

A gene, mf1, encoding a novel cholinephosphotransferase in glycoglycerophospholipid (GGPL) biosynthesis of Mycoplasma fermentans PG18 was identified by genomic analysis, cloned, and expressed in Escherichia coli. The mf1 gene comprises an open reading frame of 777 bp encoding 258 amino acids. The mf1 gene product, Mf1, has 23% amino acid homology with LicD of Haemophilus influenzae but no homology with genes of other Mycoplasma species in the GenBank database. The reaction product of Mf1 using α-glucopyranosyl-1,2-dipalmitoilglycerol and cytidine 5′-diphosphocholine (CDP-choline) as substrates showed the specific protonated molecule at m/z 896, which corresponded to GGPL-I as determined by matrix-assisted laser desorption/ionization–time-of-flight mass spectrometry (MALDI-TOF MS). Furthermore, the product ions of choline, phosphocholine, and hexose-bound phosphocholine were detected by tandem mass spectrometry (MS) analysis of protonated molecules at m/z 896. These results identified mf1 as a novel cholinephosphotransferase and showed that the phosphocholine transfer step is involved in the GGPL biosynthesis pathway of M. fermentans. This is the first report of a GGPL biosynthesis enzyme.