The immunological cross‐reactivity of several peptides with specific pattern‐property characteristics related to the epitopes of human immunodeficiency virus type 1 (HIV‐1) gp160/ 120 envelope proteins has been investigated. Proteins with similar primary structures can be expected to show functional or topographic similarities, such as specific epitopes which may cross‐react with antibodies derived from the immunisation of animals with other members of the same protein family. These structure‐function characteristics may be revealed as periodicities derived from presentations based on the discrete Fourier transformation of the distributions of various physico‐chemical amino acid descriptors, constituting the polypeptide backbone and amino acid side‐chains of the protein molecule. Such approaches, for example, have permitted prediction of periodicities corresponding to secondary structural motifs, including amphipathic α‐helices and β‐sheets, within protein sequences, and have helped to clarify potential binding sites for ligands, substrates or cofactors with interacting macromolecules. Based on this approach, characteristic periodicities have been identified which represent common Fourier transform spectral properties of the envelope (ENV) gpl60/120 glycoproteins from a range of HIV‐1 isolates. In addition, similar periodicities have been detected as components of the discrete Fourier transform representation of the corresponding amino acid descriptors of the CD4 binding domain of gpl20. Accordingly, we have synthesised several peptides having periodic characteristics in their discrete Fourier transform representations similar to these HIV‐1 proteins. These nonhomologous synthetic peptides induced cross‐reactive antibodies in New Zealand White rabbits. Polyclonal antibodies raised to one of these peptides reacted with HIV‐1 ENV gpl20‐related proteins, as determined by enzyme‐linked immunosorbent assay and Western blotting techniques. These findings provide further evidence for a role of immunological cross‐reactivity and molecular biomimicry in the development of peptide‐based vaccines directed against viral or bacterial pathogens.

Nitric oxide (NO) from astrocytes is one of the signalers used by the brain's extensive glial-neuronal-vascular network, but its excessive production by pro-inflammatory cytokine-stimulated glial cells can be cytodestructive. Here, we show how three pro-inflammatory cytokines (IL-1beta, TNF-alpha, and IFN-gamma) together stimulated the activation, but not the prior expression, of NOS-2 protein via a mechanism involving MEK-ERKs protein kinases in astrocytes from adult human cerebral temporal cortex. The cytokines triggered a transient burst of p38 MAPK activity and the production of NOS-2 mRNA which were followed by bursts of MEK-ERK activities, synthesis of the NOS-2 co-factor tetrahydrobiopterin (BH(4)), a build-up of NOS-2 protein and from it active NOS-2 enzyme. Selectively inhibiting MEK1/MEK2, but not the earlier burst of p38 MAPK activity, with a brief exposure to U0126 between 24 and 24.5 h after adding the cytokine triad affected neither NOS-2 expression nor NOS-2 protein accumulation but stopped BH(4) synthesis and the assembly of the NOS-2 protein into active NOS-2 enzyme. The complete blockage of active NOS-2 production by the brief exposure to U0126 was bypassed by simply adding BH(4) to the culture medium. Therefore, this cytokine triad triggered two completely separable, tandem operating mechanisms in normal human astrocytes, the first being NOS-2 gene expression and accumulation of NOS-2 protein and the second being the synthesis of the BH(4) factor needed to dimerize the NOS-2 protein into active, NO-making NOS-2 enzyme.

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Partial hepatectomy induces increases in the synthesis of both messenger (poly(A)+) and ribosomal (poly(A)-) RNA, which precede the initiation of DNA synthesis. The increase in poly(A)+RNA, which commences soon after surgery and reaches a peak 1-3 hours later is particularly striking. Disruption of this early increase in poly(A)+RNA synthesis by colchicine (and other microtubule disrupters) or indomethacin results in a failure to initiate DNA synthesis. This suggests that prostaglandins and the microtubules are involved in the mechanism of proliferative activation. Hypocalcemia, which also prevents the initiation of DNA synthesis, has no effect on the prereplicative changes in either messenger or ribosomal RNA synthesis. These results help to define the critical stages of prereplicative development and give some insight into their regulation.

There is a marked increase in the concentration of putrescine during the first ten hours following partial hepatectomy in rats. The concentration of spermidine also increases but to a smaller degree. Putrescine levels return to normal between 10 and 24 hours after the operation, whereas the increased spermidine level is maintained. The production of putrescine and spermidine appears to be initiated by the induction of ornithine decarboxylase which shows a single peak of activity at four hours after hepatectomy. The activity of S-adenosylmethionine decarboxylase shows little change following hepatectomy. The changes in polyamine levels and the activities of the enzymes of polyamine metabolism are not affected by thyroparathyroidectomy 72 hours prior to hepatectomy. Thus although these hypocalcemic conditions considerably reduce and delay DNA synthesis and mitosis, the prereplicative changes in polyamine metabolism still occur. These data suggest that the hepatocytes in hypocalcemic animals have become activated and moved to an advanced stage of prereplicative development before being blocked.