Kinetics of histologic changes in human melanoma after local immunotherapy with BCG

Summary BCG was injected directly into multiple metastatic cutaneous melanomas. Individual metastases were excised sequentially at planned intervals. We found that a progressive necrosis of tumor cells was followed first by a severe exudative reaction and subsequently by the formation of BCG granulomas which completely replaced the tumor mass. No changes were observed in noninjected subcutaneous nodules excised simultaneously with injected nodules at 36 hrs.Supported in part by USPHS Grant Number 7 R10 CA18044-01 and Hematopathology Tutorials, Inc.     

Gene-based anchoring of the rat genetic linkage and cytogenetic maps: new regional localizations, orientation of the linkage groups, and insights into mammalian chromosome evolution

In order to generate anchor points connecting the rat cytogenetic and genetic maps, the cytogenetic position of 62 rat markers (including 55 genes) already localized genetically was determined by fluorescence in situ hybridization. Whenever possible, markers located near one end of the linkage groups were included. These new localizations allowed us to unambiguously orient the 20 autosomal and the X chromosome linkage groups. The position of the centromere in the linkage map could also be determined in the case of several metacentric chromosomes. In addition, the regional localization of 15 other rat genes was determined. These new data bring useful information with respect to comparative mapping with the mouse and the human and to mammalian evolution. They illustrate, for instance, that groups of genes can remain syntenic during mammalian evolution while being subjected to intrachromosomal rearrangements in some lineages (synteny is conserved while gene order is not). This analysis also disclosed cases of synteny conservation in one the two rodent species and the human, while the synteny is split in the other rodent species: such configurations are likely examples of lineage-specific interchromosomal rearrangements associated with speciation. Received: 20 April 1998 / Accepted: 26 May 1998     

Interaction of Doxorubicin with phospholipid monolayer and liposomes

The effect of Doxorubicin which is (an anthracycline antibiotic with a broad spectrum of antitumor activity) on the monolayer and bilayer in the form of large Multilamellar Vesicles (MLV's) of Dipalmitoyl phosphatidylcholine (DPPC) were studied by means of monolayer techniques (surface pressure, penetration kinetics, and association constant) and light scattering technique. The monolayer technique showed that addition of DXR to a lipid film composed of (DPPC/CHOL/PEG-PE) at a molar ratio of (100:0:0) produced a less condensed Monolayer. In the (π-A) curves, DXR induced shift towards larger area/molecule, where the area/molecule was shifted from 61 to 89 A², and 116 A² in the presence of 20 and 40 nM DXR, respectively. The three curves collapsed at a pressure π = 45 mN/m. In penetration kinetics experiment (Δπ-t), the change in pressure with time was 8 and 14 mN/m for a DXR concentration of 20 and 40 nM, respectively, and the increase in surface pressure presented a plateau over a period of 30 min. The measured association constant (K) was found to be 5 × 10⁵/M. In the light scattering experiment, there was a shift of the transition temperature (T_m) of (MLV's) of the same composition of the monolayer towards a smaller value from 40.5° to 34.5°C. Incorporation of CHOL and PEG-PE as DPPC/CHOL/PEG-PE at a molar ratio of (100:20:0), (100:0:4) and (100:20:4) greatly counteracted the effect of DXR and made the lipid membrane more condense and rigid. Moreover, the penetration of DXR into the membrane was greatly reduced. There was a very small shift for the (π-A) and (Δπ-t) curves, and the association constant of the drug for these different lipid compositions was greatly reduced down to 2.5 × 10⁵/M and the transition temperature (T_m) was increased up to (42.5°C) in the presence of 40 nM DXR. Our results suggest that DXR has a great effect on the phospholipid membrane, and that addition of CHOL or PEG-PE to the phospholipid membrane causes stabilization for the membrane, and reduces the interaction with Doxorubicin.     

Plankton and primary productivity of Lake Manzala,Egypt

Primary production and distribution and abundance of phyto- and zooplankton of lake Manzala were investigated from June 1985 to June 1986.Primary production varied from 4.1 to 28.7 g O₂ m^–2 d^–1 with the highest values 24.2 and 28.7 g O₂ m^–2 d^–1 recorded in the eastern and southern sectors and the lowest value 4.1 g O₂ m^–2 d^–1 recorded in the northern sector. The seasonal mean production for the lake was estimated at 13.3 g O₂ m^–2 d^–1.Mean phytoplankton abundance ranged from 32.7 10⁷ to 76.1 10⁷ cells m^–3 with a mean value of 48.10⁷ cells m^–3. Diatoms were the dominant phytoplankton group comprising 52 to 90 % by number. The greatest relative abundance (87 to 90%) was recorded in the southern sector.Mean zooplankton abundance ranged from 30.1 10³ to 44.4 10³ organisms m^–3 in the eastern sector to 5.5.10³ in the northern sector. In response of eutrophication, the species composition changed significantly over the last 20 years. Cladocerans represented less than 1% of zooplankton during 1959/60, but 75% in 1985/86. Rotifers constituted 40% in 1959/60, and only 1% in 1985/86. Cirriped larvae declined from 21% to 1%.     

Higher diagnostic accuracy with the ThinPrep method in a simulated intraoperative environment

Objective:  To compare the accuracy of intraoperative fine needle aspiration cytology samples prepared by the ThinPrep method to conventional cytological methods. Specimen adequacy and turn around time (TAT) were also assessed.
Methods:  Fifty consecutive fresh tumours submitted for histological analysis were aspirated and each prepared as follows: (i) direct smear with H&E stain, (ii) direct smear with Pap stain, (iii) ThinPrep slide with H&E stain, and (iv) ThinPrep slide with Pap stain. The slides were randomly distributed to three cytopathologists for interpretation. The quality of the preparation, the diagnosis and the time needed for interpretation were recorded.
Results:  Accuracy was measured as the percentage of absolute agreement between the cytological and the histopathological diagnoses of the lesions. Histologically, there were 43 malignant and six benign lesions and one atypical lipoma. The TAT began when the slides/cytolyte specimens arrived at the lab and ended with the pathologist's diagnosis.
Conclusions:  In terms of accuracy and specimen adequacy, ThinPrep slides with Pap stain is the best procedure. This advantage however is offset by the longer testing time.     

Heterocellular interaction enhances recruitment of alpha and beta-catenins and ZO-2 into functional gap-junction complexes and induces gap junction-dependant differentiation of mammary epithelial cells

Gap junctions (GJ) are required for mammary epithelial differentiation. Using epithelial (SCp2) and myoepithelial-like (SCg6) mouse-derived mammary cells, the role of heterocellular interaction in assembly of GJ complexes and functional differentiation (β-casein expression) was evaluated. Heterocellular interaction is critical for β-casein expression, independent of exogenous basement membrane or cell anchoring substrata. Functional differentiation of SCp2, co-cultured with SCg6, is more sensitive to GJ inhibition relative to homocellular SCp2 cultures differentiated by exogenous basement membrane. Connexin (Cx)32 and Cx43 levels were not regulated across culture conditions; however, GJ functionality was enhanced under differentiation-permissive conditions. Immunoprecipitation studies demonstrated association of junctional complex components (α-catenin, β-catenin and ZO−2) with Cx32 and Cx43, in differentiation conditions, and additionally with Cx30 in heterocellular cultures. Although β-catenin did not shuttle between cadherin and GJ complexes, increased association between connexins and β-catenin in heterocellular cultures was observed. This was concomitant with reduced nuclear β-catenin, suggesting that differentiation in heterocellular cultures involves sequestration of β-catenin in GJ complexes.