Binding-in: still a relevant concept?

Development of the maternal-fetal relationship was described by Rubin as an intimate "binding-in process." Recent technological advances enabled health care providers to observe, study, diagnose, and treat unborn children and led some to reconsider the relevance of the binding-in concept. Research has focused on prenatal attachment or bonding, maternal characteristics that influence prenatal attachment/bonding, and interventions to promote it. Before binding-in is dismissed as irrelevant, assessment of the prenatal attachment research, consideration of the impact of these ideas on pregnant women and their families, and the implications for maternity nurses must be examined.     

Studies on guanine adducts excreted in rat urine after benzene exposure

Investigations with [¹⁴C]benzene indicate the formation of baseadducts in vivo. Experiments to separate adducts from urineof [¹⁴C]benzene-exposed rats suggest the excretion of eightlabeled compounds different from benzene metabolites. In orderto obtain information about their structure we synthesized N7-,O⁶-, C8- and N²-phenylguanine. With regard to their chromatographicproperties we compared these phenylguanines with products obtainedby alkylation of guanine by metabolites of unlabeled and ¹⁴C-labeledbenzene in vivo with HPLC with UV detection and liquid scintillationcounting. Furthermore GC/MS and ELISA techniques were used todetect N7-phenylguanine. Phenylguanines could not be identifiedin collected DNA fractions. The labeled compounds detected inurine of [¹⁴C]benzene-exposed rats also showed deviations fromthe HPLC elution patterns of our reference substances. EvenN7-phenylguanine, formerly suspected to be a urinary metaboliteof benzene in the rat, could not be detected with these refinedHPLC methods. With GC/MS a compound was found in trace amountsin concentrated rat urine samples, which had a similar fragmentationpattern to N7-phenylguanine. These data could not be confirmedby a sensitive immunological assay (ELISA). No. N7-phenylguaninewas detected in purified rat urine samples. The results suggestthe excretion of a hydroxylated phenylguanine which may be formedin liver or bone marrow DNA by highly reactive hydroxylatedintermediates. The OH group might be lost because of the hightemperatures during GC/MS measurements. A hydroxy group at thephenyl-ring of N7-phenylguanine will cause other elution propertiesin HPLC compared to N7-phenylguanine.     

Properties of wr2721 (ethiofos) as modulator of Cisplatin-induced neurotoxicity studied at the ultrastructural level in the pond snail lymnaea-stagnalis

Modulating effects of WR2721 were studied on cisplatin-induced histological and ultrastructural changes in the ganglia of the central nervous system of the pond snail Lymnaea stagnalis. The relevance of the study was indicated by showing histochemically that alkaline phosphatase, the enzyme converting WR2721 into the active drug WR1065, is present in the snail brain. Central nervous systems of the snail were either preincubated in 5 mM WR2721 or in snail Ringer for 1 h and then postincubated for 10 or 20 h in: (i) Ringer (control), (ii) WR2721 (5 mM), (iii) cisplatin (0.4 mM), or (iv) cisplatin (0.4 mM) plus WR2721 (5 mM). The following parameters were studied: (i) general morphology, (ii) chromatin (number and mean clump size per unit surface ama, clump size frequency distribution), (iii) nucleoli (ratio of granular/fibrillar areas, (iv), Golgi zones (mean surface area, area containing electron dense material), (v) secretory granules (number), (vi) lysosomes (number per unit surface area of cytoplasm). The focus was on two types of identified neuroendocrine cells. Incubation in Ringer alone (controls) caused slight inactivation of the cells between 10 and 20 h of incubation (e.g. relative decrease of the granular part of the nucleoli). WR2721 alone had comparable effects on the tissue. In addition, in this group, a reduction in the electron dense material of the Golgi zones was observed. No major differences in number of secretory granules were observed in any of the groups. Treatment with cisplatin alone for 20 h caused a disappearance of the orange colour of the ganglia, swelling of axons and distension of intercellular spaces. Such changes were not observed in the group treated with cisplatin plus WR2721 or any of the other experimental groups. Both cisplatin alone and cisplatin plus WR2721 caused an increase in the number of chromatin clumps and a decrease in the mean chromatin clump size after 10 and 20 h of incubation. With regard to these parameters no differences were observed between the two groups. The chromatin clump size distribution curves of both groups were significantly different from the curve of the controls. Compared to that of the cisplatin group, the curve of the cisplatin plus WR2721 group, especially after 10 h, had shifted in the direction of that of the controls. Treatment with cisplatin alone induced drastic changes in nucleolar morphology. After 20 h of incubation the nucleoli had transformed into homogeneous dense structures. After 10 h of incubation in cisplatin plus WR2721 nucleoli still had a normal appearance. After 20 h those of the co-treated group had also become electron dense and appeared to contain numerous dark dots. Cisplatin caused a significant decrease in the extent of the Golgi zones. Co-treatment with WR2721 prevented this decrease to a certain degree. In both groups the electron dense material had disappeared from the Golgi zones. Furthermore, cisplatin alone induced an increase in the number of lysosomes. This increase was slightly (but not significantly) prevented by co-treatment with WR2721. The observations on the snail neurons show that WR2721 at the concentration studied induced only minor morphological changes. The drug modulates to some extent the pathological changes caused by cisplatin. The results support clinical data indicating that cisplatin-induced neurotoxicity is reduced by WR2721.     

A novel small-cell lung carcinoma-specific DNA-binding activity related to the transcription factor ap-1

A novel TRE-binding protein complex was detected specifically in 12 out of 13 small cell lung carcinoma (SCLC) cell lines. This complex was characterised by a lower electrophoretic mobility than the 'ubiquitous' complex present in all other carcinoma cell lines analysed. As shown by UV-crosslinking and South-Western blotting, the SCLC-specific complex contains a protein with an apparent M(r) > 100 kD, which is far bigger than all Fos and Jun proteins described to date. In addition, the DNA-binding specificity of this complex is different from the specificity of the 'ubiquitous' complex or a Fos/Jun heterodimer.     

The effect of infused fat emulsions on reticuloendothelial function in the rabbit

The effect of the infusion of different fat emulsions (Intralipid and MCT/LCT mixtures) on the reticuloendothelial function of the rabbit has been investigated. Emulsions containing 20% dispersed triglyceride were administered over 6 h to a total of 3 g/kg body weight. The extent of blockade of the reticuloendothelial system was measured using a labelled probe in the form of technetium-99m labelled albumin microspheres. Scintigraphic and blood and organ level determinations demonstrated that all emulsions caused an impairment of reticuloendoethlial function, but this was small.     

Differential expression of the neu transgene in murine mammary tissues

The mammary glands of control FVB and mice with MTV-LTR promoted transgenes were stained using immunohistochemistry to detect neu expression. Neu expression in the terminal end buds of developing mammary glands and during early pregnancy in FVB mice was confirmed by in situ hybridization. Neu was expressed in all tumors from mice with the neu transgene but not in tumors expressing transforming growth factor alpha (TGF alpha) or polyoma virus middle T (PyV-MT). Neu was also expressed sporadically in non-neoplastic mammary cells of transgenic neu mice. However, most mammary cells expressing neu were dysplastic. The differential expression of the neu transgene has important implications for the interpretation of transgenic biology.     

Correlation between apoptosis and tumor-associated macrophages in human invasive ductal breast carcinoma

The relationship between apoptosis and tumor-associated macrophages (TAM) was studied in situ in 60 breast carcinomas (18 G1, 28 G2 and 14 G3 carcinomas) using simultaneous apoptosis (TUNEL method) and macrophage staining (anti-CD68 antibody). Apoptotic tumor cell rate (ATCR), total TAM content (TAM(TOT)) and the proportion of TAM that had either cell-to-cell contact with apoptotic tumor cells or that were phagocytosing them (TAM/APO cells) were quantified. ATCR correlated significantly with TAM(TOT). Within all apoptotic tumor cells, the proportion of TAM/APO cells was lower than 20%. Considering the fact that cell-to-cell contact is essential for macrophage-mediated tumor cell killing, our data suggest that the majority of apoptoses occurring in breast cancer may not be caused by macrophage tumoricidal activity. TAM/APO cells accounted for only 1.7% of all TAM. Thus, tumor cell killing and apoptotic tumor cell phagocytosis seem to be quantitatively less important functions of TAM in human breast cancer in vivo.     

Aspergillosis of the cranial base

Aspergillus is an ubiquitous organism seldom pathogenic in normal hosts. Aspergillus osteomyelitis of the spine occurs rarely in immunocompromised patients as a result of hematogenous spread from distant foci. We present a case of Aspergillus osteomyelitis in the region of the jugular foramen in a previously healthy male with no antecedent event. He presented with dysphagia, hypophonia, and weight loss of several months duration. Diagnosis was delayed due to nonspecific results of various imaging tests. We review the clinical course of fungal osteomyelitis, including appearance on magnetic resonance imaging and computed tomography, culture characteristics, and gross appearance. Current treatment consists of surgical debridement and antifungal medications such as amphotericin B and itraconazole, and the efficacy of these are discussed.     

Rflp analysis of the L-myc oncogene in head and neck-cancer - relationship study with susceptibility and disease progression

The L-myc DNA restriction fragment length polymorphism (RFLF), revealed by EcoRI digestion, has been evaluated in a case-control study including 161 head and neck cancer (HNSCC) patients and 160 normal healthy individuals with similar smoking and alcohol habits. No significant difference in the distribution of L-myc genotypes (LL, LS or SS) was found between the two populations implying thus no predisposition to head and neck tumour by either allele. There was no significant association between L-myc genotypes and the usual clinicopathological features such as T staging, differentiation status and lymph node involvement. Moreover, follow-up data from 154 patients was obtained and correlated with the L-myc pattern. No significant difference was observed in metastasis occurrence, multiple cancer incidence and survival data in the patients classified according to the L-myc genotypes; only a trend to preferentially develop metastasis in lung for patients with S allele was noted. In conclusion, our data shows that the L-myc typing does not contribute to HNSCC risk or prognosis assessment. A review of L-myc RFLP published studies shows contradictory results even on the same type of tumour and emphasizes the lacunae in understanding the biological role of L-myc for valid interpretation of L-myc allelic associations with cancer susceptibility or prognosis.     

Alteration of the C-met oncogene locus in human head and neck-carcinoma

The c-met proto-oncogene encodes the receptor for the hepatocyte growth factor/scatter factor (HGF/SF) which induces eel proliferation and motility. We have analysed the genetic alteration involving the c-met locus on chromosome 7q31 using the pMet H polymorphic probe, in tumor and normal DNA from 87 patients with head and neck squamous cell carcinomas (HNSCC). We report the observation of loss of heterozygosity (LOH) at this locus in 23% of informative cases, contrasting with the previously reported 40% LOH detected in breast cancer. Further, gain of genetic material was also observed in 13% of the HNSCCs. The alterations of c-met gene were not significantly associated with standard pronostic features including tumor size and lymph node status. Involvement of the c-met locus in allelic imbalance, either loss or gain of genetic material, is relatively consistent with complex karyotype patterns detected in head and neck squamous cell carcinomas through previous cytogenetic studies.