In murine ontogeny, macrophage precursor cells develop in the yolk sac and fetal liver. Primitive macrophages also appear in the yolk sac, migrate to various tissues, and differentiate into several fetal macrophage populations. Because the development of the monocytic cell lineage is incomplete in the early stage of fetal hematopoiesis, primitive/fetal macrophages are considered to originate from granulocyte-macrophage colony forming cells or earlier macrophage precursors, bypassing the early monocytic cell series. In adult mice rendered severely monocytopenic by administration of strontium-89, resident macrophages are maintained by self-renewal. In contrast, administration of liposome-encapsulated dichloromethylene diphosphonate (clodronate) results in the elimination of various tissue macrophage populations. The repopulation of affected macrophages is dependent on the increase of precursors in the liver and spleen during the period of macrophage depletion. Such precursors reconstitute heterogeneous macrophage subpopulations. In mice homozygous for the osteopetrosis (op) mutation, the absence of macrophage colony-stimulating factor (M-CSF) activity results in a deficiency of monocytes and monocyte-derived macrophages. However, immature macrophages are present in various tissues. Administration of M-CSF to op/op mice induces the increased proliferative capacity and the morphological maturation of macrophages. However, the responses of individual tissue macrophage subpopulations to M-CSF are different. These results indicate that macrophage development, differentiation, and proliferation are regulated by the tissue microenvironment including the in situ production of macrophage growth factors in both fetal and adult life.

The first total synthesis of garsubellin A, a neurotrophic compound with potent choline acetyltransferase-inducing activity, is described. Keys for success were (1) stereoselective intermolecular aldol reaction at the C-4 position with acetaldehyde, (2) stereoelective Claisen rearrangement to introduce an allyl group to the most sterically crowded position at C-6, (3) ring-closing metathesis to construct the B-ring, and (4) Wacker-type oxidative C-ring formation. This synthetic route can be extended to an asymmetric synthesis of garsubellin A using the Koga catalytic enantioselective alkylation, which produced enantioenriched alpha-prenyl cyclohexenone with excellent enantioselectivity (95% ee).

Aim-To compare the incidence of squamous cell carcinoma (SCC) of the lung in Okinawa with that in Niigata on the mainland. Methods-All patients presenting with SCC ofthe lung in Okinawa and Niigata in 1993 were included in the study. Diagnoses were confirmed by conventional histological examination of paraffin wax sections. Human papillomavirus (HPV) was detected by non-isotopic in situ hybridisation (NISH) and polymerase chain reaction (PCR) amplification with primers specific for the E6 and E7 regions of the HPV genome. PCR products were analysed by Southern and dot blotting. Results-The incidence of well differentiated SCC of the lung was high in patients from Okinawa compared with moderately and poorly differentiated types, and compared with the incidence of SCC in patients from Niigata. This is despite similar patterns of age, sex (predominatly male), and smoking habit. More patients from Okinawa, however, were positive for HPV DNA by PCR (79%) and NISH (53%). Many patients haboured HPV types 6, 16, and 18. Only 30% of patients from Niigata were positive for HPV DNA by PCR and 20% by NISH. These patients all harboured one HPV type only. Conclusion-Surprisingly large numbers ofpatients from Okinawa were positive for HPV DNA. The detection of HPV DNA was strongly associated with well differentiated SCC. This was particularly true for HPV types 6 and 16. There was no correlation between either smoking and detection of HPV DNA, or smoking and histological differentiation. (J Clin Pathol 1996;49:810-817) Keywords: human papillomavirus, in situ hybridisation, PCR, squamous cell carcinoma of the lung.

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A new method for the catalytic enantioselective Strecker reaction (cyanation) of N-diphenylphosphinoyl ketoimines is described. The asymmetric catalyst is a chiral gadolinium complex prepared from Gd(OiPr)3 and the d-glucose-derived ligand 3 in a 1:2 ratio. The reaction has a broad substrate generality, giving high enantioselectivity from aromatic, ethyl, primary alkyl, and alpha,beta-unsaturated ketoimines. The products could be easily converted to disubstituted alpha-amino acids and their derivatives.