Biomedical subjects
Publications and source records attributed to M Gallo.
Site-specific recombination reactions in higher eukaryotes are uncommon, perhaps because of the potential genomic instability that they may create. We focus this review on the issues of site-specificity, reaction fidelity and immunologic diversity in the V(D)J recombination reaction.
Adrenal androgens show a dual and apparently opposite effect on the growth of oestrogen-responsive breast cancer: they stimulate growth on their own, but counteract the growth-stimulatory effect of oestrogens. Focusing on the inhibitory action we have studied the effects of 5-en-androstene-3 beta,17 beta-diol (ADIOL) on the growth of oestrogen-responsive MCF-7 breast cancer cells in the presence of oestrogens (oestradiol and diethylstilboestrol), antiestrogens (tamoxifen) and antiandrogens (hydroxyflutamide). The inhibition of oestrogen-stimulated growth, attained with nanomolar concentrations of ADIOL, was not modified by increasing concentrations of diethylstilboestrol up to 100 nM. This inhibition was counteracted by antiandrogens, which were unable to block the ADIOL stimulatory effect in steroid-free medium. On the other hand, in the presence of tamoxifen ADIOL showed an additive antiproliferative activity also in steroid-free medium, rather than the usual stimulatory effect. These results suggest that ADIOL stimulates breast cancer cell growth via oestrogen receptors, but inhibits oestrogen-stimulated growth via androgen receptors.
The Sulfolobus solfataricus S12, S7 and S10 ribosomal proteins and the elongation factor 1 alpha genes are organized in a sequence analogous to that in the Escherichia coli str operon. Northern analysis showed that the S12 gene belongs to a transcript different from that corresponding to the other three genes. Compared to the Sulfolobus acidocaldarius S12 and to the Methanococcus vannielii S7 proteins, the S. solfataricus S12 and S7 proteins were 33 and 47 amino acids longer respectively. These differences were eliminated if the 5' flanking regions of the S. acidocaldarius S12 and the M. vannielii S7 genes were translated from a different start codon. Despite the structural similarities between the archaeal and the bacterial str operons the S. solfataricus ribosomal proteins S12, S7 and S10 are more similar to the eukaryotic counterparts.
The case is reported of an old woman with a myopathy syndrome. Upon differential diagnosis this myopathy was attributed to hypothyroidism. Treatment with low doses of L-thyroxine lead to complete remission of the clinical and serologic syndrome.
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Monoclonal antibody PR1 binds to the surface of normal prostate cells and to adenocarcinomas of the prostate. The cDNAs coding for the heavy and light chain variable regions of monoclonal antibody PR1 were cloned by PCR techniques. A recombinant toxin was then constructed that has the heavy chain variable region of monoclonal antibody PR1 connected to the light chain variable region by a flexible peptide linker to create a single-chain Fv; the Fv in turn is fused to a truncated form of Pseudomonas exotoxin. The resulting recombinant immunotoxin PR1(Fv)-PE38KDEL was produced in Escherichia coli and accumulated in inclusion bodies. After denaturation and renaturation, active monomeric molecules with a molecular mass of approximately 65 kDa were purified to homogeneity. PR1(Fv)-PE38KDEL binds specifically to cells containing the PR1 antigen and is very cytotoxic toward a subset of LNCaP cells that express the PR1 antigen on their surface.
A Sulfolobus solfataricus genomic library cloned in the EMBL3 phage was screened using as probes synthetic oligonucleotides designed from the known amino acid sequence of a peptide obtained from the purified glyceraldehyde-3-phosphate dehydrogenase (aGAPD) protein. The screening led to the isolation of six recombinant phages (lambda G1-lambda G6) and one of them (lambda G4) contained the entire GAPD gene. The deduced amino acid sequence accounts for a protein made of 341 amino acids and the initial methionine is encoded by a GTG triplet. Alignment of the S. solfataricus aGAPD sequence versus GAPD from archaea, eukarya, and bacteria showed that aGAPD is very similar to other archaebacterial but not to eukaryotic or eubacterial GAPD. For known archaebacterial GAPD sequences, the rate of nucleotide substitutions per site per year showed that these sequences are homologous not only at the amino acid but also at the nucleotide level. The evolutionary rates are nearly similar to those reported for other eukaryotic genes.
Lesions to the lateral parabrachial nucleus (PBN), one of the subnuclei that make up the pontine parabrachial complex, impairs the acquisition of taste aversion learning (TAL) with LiCl as the toxic stimulus. In this experiment, PBNl-lesioned and control rats were trained to learn a delayed task with a 15-min interval between presentation of the gustatory and the aversive stimulus. The impairment in learning observed after lesions of the PBNl is discussed in terms of disruption of the transmission of toxic stimuli (LiCl) processed by the humoral pathway and the area postrema (AP).
The effect of medullary afferent vagal axotomy on NaCl-induced short-term and long-term taste aversion learning (TAL) was examined to assess the relevance of the vagus nerve in drug-induced TAL. The results show that medullary afferent vagal axotomy disrupts NaCl-induced short-term (nondelayed) TAL, while having no effect on learning acquired with the same product in long-term (delayed) TAL protocols. Acquisition of learning in delayed discrimination tasks may be mediated by alternative mechanisms of nonvagal nature, e.g., the humoral system. The possibility that short-term and long-term TAL may be mediated by different neurobiological substrates is discussed.
The research about the neural basis of taste aversion learning (TAL) has pointed out the area postrema (AP) as a fundamental structure implied in the processing of certain toxic stimuli. Likewise, recent studies demonstrated that electric stimulation of the AP is an efficient substitute of the aversive stimulus. The lateral parabrachial nucleus (PBN1), one of the subnuclei of the parabrachial complex, is the main anatomic rostral connection of the AP. In the experiment presented here, we demonstrate that TAL induced by electric stimulation of the AP is interrupted when the PBN1 is lesioned, thus giving support to the functional role of this anatomic system (AP-PBN1) in the codification of aversive stimuli processed by the AP.
In 28 patients with systemic sclerosis interstitial lung involvement was investigated with high-resolution Computed Tomography (HRCT) in comparison with other diagnostic methods (respiratory function tests, lung scintigraphy and conventional radiography of the chest). The most frequent CT signs were: interlobular septal thickening, intralobular interstitial thickening, and ground-glass density. Their distribution was generally basal and posterior and high correlation was observed between the extent of lung disease and the cutaneous pattern of scleroderma. Pathological findings were present in 93% of cases: HRCT can must be considered more effective than the other methods in the evaluation of systemic sclerosis and should therefore be a fundamental diagnostic tool in the study and follow-up of interstitial diseases in the patients with systemic sclerosis.
Concentrations of total proteins, urea, total lipids in the blood plasma and glucose concentrations in the blood of beef bullocks were followed after their transition from winter feed rations to pasture, and in the subsequent grazing cycles within two years. Blood was taken by punctures from the vena jugularis from the same six bullocks all the time. In the 1st year of observation, blood sampling took place a week before the bullocks were moved to pasture, in the 2nd year of observation blood was taken twice in weekly intervals before pasture. During grazing, biological material was sampled in weekly intervals between 1st and 5th week (May--cycle I, June--cycle II), then in the tenth week (July--cycle III) and in the 14 week (August--pasture cycle IV). The concentrations of total proteins in the blood plasma of beef bullocks (Fig. 1) insignificantly increased after transition from indoor housing to pasture, this increase continued in the second year of observation for two weeks after transition to pasture, and in the first year of observation for four weeks with a break in the 2nd week. In the subsequent period, the concentrations of total proteins decreased to the values approaching the starting values. The concentrations of plasma urea in beef bullocks (Fig. 2) significantly increased in both years of observation after transition from stable fattening to pasture (p < 0.01 and p < 0.05, resp.). In the second week after transition to pasture, further highly significant increase in the concentrations of plasma urea was observed in both years of observation.(ABSTRACT TRUNCATED AT 250 WORDS)
Lesion studies of the role of the gustatory insular cortex (GC) and amygdala (Am) in conditioned taste aversion (CTA) are confounded by the irreversibility of the intervention. Functional ablation methods allow more specific influencing of different phases of CTA acquisition and retrieval. Bilateral tetrodotoxin (TTX) blockade of GC (10 ng) or Am (3 ng) before or after saccharin drinking in rats with chronically implanted intracerebral cannulae showed that GC is indispensable for the initial processing of the taste stimulus but not for the association of the gustatory trace with the symptoms of LiCl poisoning. Gustatory signals can by-pass the blocked Am, the inactivation of which, however, impairs the gustatory trace-poisoning association. TTX injection into both GC and Am impairs CTA retrieval more than isolated blockade of either of these structures. It is argued that GC and Am implement processing of gustatory and visceral signals, respectively, but that formation and consolidation of the CTA engram proceeds outside forebrain, probably at the level of the brainstem.
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In this study we investigated the calcitonin (CT) pattern both in basal conditions and after calcium infusion before and one month after oophorectomy in 17 premenopausal women. In addition, 13 oophorectomized women were randomly allocated to two groups, one given hormone replacement treatment and the other untreated, and CT response to hypercalcemia was reevaluated one year later. CT response to calcium infusion was significant only before oophorectomy and one year after estrogen-progestogen treatment, whereas there was no response one month after oophorectomy or after one year without hormone replacement therapy. Our data indicate that both estrogen secretion and replacement treatment may be important factors in CT response.
The present study describes how mass spectrometry was extensively applied to the characterization and quantification of modified amino acids within the polypeptide chain of Angiotensin I, chosen as model substrate, combining the use of fast atom bombardment mass spectrometry with gas chromatography--mass spectrometry. The reaction products after in vitro incubation of Angiotensin I with styrene oxide, a well known carcinogen, under different conditions, have been characterized: a prominent reactivity of several potential nucleophilic sites of Angiotensin I was shown, including two histidine residues and a tyrosine residue; it is worth noting that it has never been stated that tyrosine is highly reactive with styrene oxide. The results obtained demonstrate the usefulness of mass spectrometry for the structural determination of chemically modified amino acids in peptides and proteins, and the presence of a reliable relationship between reaction conditions and the production of alkylated amino acids. This characterization procedure offers the possibility of identifying reactive sites following exposure to unknown alkylating agents.
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