Bone marrow involvement in small cell lung cancer: Prognostic significance and correlation with hematological and biochemical parameters

The more metastatic sites and bone marrow metastasis in small cell lung cancer (SCLC), the worse the prognosis. Diagnosing the bone marrow invasion at the beginning of the therapy is important for determining of the prognosis and planning the treatment. Abnormalities of some blood parameters may help to estimate the extent of bone marrow invasion by cancer cells. In this retrospective review, the changes in routine laboratory tests that may indicate bone marrow invasion, the predictive values of these tests, and the prognostic importance of bone marrow invasion were evaluated in SCLC patients who were being followed up according to a protocol. One hundred and forty‐four patients with SCLC were enrolled in this study. Retrospectively, it was evaluated that 25 (17.4%) of the patients had bone marrow metastasis. According to univariate analysis, there was a significant difference between hemoglobin, white blood cell count, platelet count, lactate dehydrogenase, alkaline phosphatase and uric acid of the patients with and without bone marrow involvement. Among the biochemical parameters, the elevated LDH and AP had the highest sensitivity and specificity as indicators of bone marrow invasion (0.80–0.82 and 0.84–0.78, respectively). The median overall survival of extensive‐stage disease with and without bone marrow metastasis were 4.0 ± 1.0 months (95% CI 2.2–5.7) and 7.0 ± 1.2 months (95% CI 4.7–9.3), respectively (P = 0.03). Bone marrow metastasis was found to be an indicator of a bad prognosis. Bone marrow biopsy, that is an invasive procedure, can be performed on selected patients who have changes of routine laboratory tests suggesting bone marrow invasion.     

Molecular cloning and characterization of receptors for the mammalian bombesin-like peptides

The bombesin-like peptides comprise a large family of peptides common to both amphibians and mammals that function as growth factors, neurotransmitters, and paracrine hormones. GRP, the mammalian homolog of bombesin and its receptor, as well as NMB, the mammalian homolog of ranatensin, are expressed in human neoplasms and, in particular, in small cell lung carcinomas (SCLC). To better characterize the physiological roles of bombesin-like peptides, our laboratory has cloned the receptors for GRP in murines, rats, and humans. The 3T3 GRP receptor was isolated and characterized using the two-electrode-voltage-clamp analysis and acquorinemission methods in xenopus oocytes expression system. The rat and human GRP and NMB receptors were cloned by hybridization at low stringency, using the mouse cDNA receptor probe. Sequence analysis of the receptors showed 384 and 390 amino acids for GRP and NMB receptors, respectively. The homology between the two receptors is 60% and between species in the same receptor, 90%. The receptors belong to the 7-membrane spanning domains superfamily. The specific GRP-R antagonist blocked the response to bombesin in oocytes injected with GRP-R, but failed to do so in oocytes injected with NMB-R. The two receptors differ in their distribution of tissue expression. RNA blot and RNase protection analysis showed the same size of mRNA without alteration in the receptors. RT + PCR analysis performed on genomic DNA revealed similarity between normal and cell DNAs, suggesting no major gene deletion or rearrangement. Southern blot analysis indicated the absence of gene amplification. Sequence analysis of the exonic segments of the receptor genes displayed identical amino acids to the respective cDNAs. None of the genes had classic TATAA box. Somatic cell hybrids localized the GRP-R on the X-chromosome and the NMB-R on chromosome 6. The same sequence of normal genes and cDNAs of GRP and NMB receptors, together with the gene characterization, demonstrated that SCLC cell lines do not require a structural change in receptor protein or genomic rearrangement.     

Potentiation of fibroblast DNA synthesis by a phenytoin-induced mononuclear cell derived factor in vitro

Abstract – Human mononuclear cells purified by Lymphoprep flotation were incubated with phenytoin (PHT) (20 μg/ml) or its metabolite p-HPPH (2 μg/ml) in the presence of Concanaval-in A (10 μg/ml) in vitro. The results indicate that phenytoin and its metabolite p-HPPH induce the release of a mononuclear cell factor(s) that activates quiescent human gingival fibroblast to synthesize DNA.     

Intra-arterial digital subtraction angiography of the spinal cord

Digital subtraction angiography (DSA) of the spinal cord was performed in 6 patients using selective intra-arterial injections of contrast material. Two arteriovenous malformations of the spinal cord, 1 dural fistula, and 1 case of multiple hemangioblastomas were studied. Contrast and spatial resolution were satisfactory for defining normal and abnormal vascularity while reducing examination time, contrast dosage, patient discomfort, and film cost. The only significant limitation was misregistration artifacts seen on lateral views encompassing the diaphragm.     

Effects of malnutrition on the erythrocyte fatty acid composition and plasma vitamin E levels of Pakistani children

Abstract Erythrocyte fatty acids and plasma vitamin E concentrations were determined in 47 grade 2 and 21 grade 3 malnourished Pakistani children (ages 4–56 months). Data were compared with those of 26 age- and sex-matched apparently healthy controls. Evaluation with three statistical approaches revealed that both grade 2 and grade 3 malnourished children had decreased erythrocyte ω6 fatty acids and to a lesser extent decreased ω3 fatty acids. These decreases were compensated for by increased ω9 fatty acids. The patients tended to have lower plasma vitamin E concentrations. We conclude that malnourished Pakistani children have low essential fatty acid status, notably those of the ω6 series. The combination of low erythrocyte 22:6ω3 and a low 22:5ω6/22:4ω6 ratio in grade 2 patients suggests low Δ4-desaturation activity, which may be due to impaired peroxisomal β-oxidation.     

Influence of bacterial cell concentration and inorganic anions on lysis of Streptococcus mutans BHT by salivary lysozyme

The aim of this work was to study the influence of bacterial cell concentrations and inorganic anions on lysis of Streptococcus mutans BHT by human salivary lysozyme (HSL). HSL was partly purified from saliva by ion exchange chromatography. The bacteria were grown in a synthetic medium containing ³H-thymidine to monitor DNA release. The experiments demonstrated that release ³H-thymidine was dependent on the bacterial cell concentration and an apparent K_m-value corresponding to approximately 2.9 × 10⁸ cells/ml was calculated. The influence of I^?, Br^?, Cl^?, F^?, HCO₃^? and SCN^? on bacteriolysis was studied. All anions tested were slightly inhibitory on the action of HSL. The inhibition varied from 7 to 76% depending on the ion and ionic strength. The order of addition of HSL and sodium chloride caused different lytic responses. This was reflected by the amount of HSL adsorbed by the bacteria.