Recurrent goiter, hyperthyroidism, galactorrhea and amenorrhea due to a thyrotropin and prolactin-producing pituitary tumor

A 22-year-old woman with recurrent goiter, hyperthyroidism, galactorrhea, and amenorrhea due to a pituitary tumor is described. She had been treated surgically twice for recurrent goiter with tracheal compression. Despite clinical signs of hyperthyroidism and slightly elevated plasma thyroid hormone levels (T4: 11 mug/dl; T3: 189 ng/dl), without thyroid hormone replacement therapy the basal TSH level was elevated up to 23 muU/ml and could not be suppressed by exogenous thyroid hormones: even when the serum thyroid hormone levels were raised into the thyrotoxic range (T4: 16.2 mug/dl T3: 392 ng/dl), the basal TSH fluctuated between 12 and 29 muU/ml. The basal PRL level was elevated up to 6000 muU/ml. The administration of TRH (200 mug iv) led only to small increments of TSH and PRL levels. Bromocriptin (5 mg p.o.) or l-dopa (0.5 g p.o.) suppressed TSH and PRL values significantly. After transsphenoidal hypophysectomy, TSH and PRL were below normal and the patient development panhypopituitarism. The adenoma showed two cell types which could be identified as lactotrophs and thyrotrophs by electronmicroscopy and immunofluorescence. From these data we conclude that the patient had a pituitary tumor with an overproduction of thyrotropin and prolactin.     

The interaction of acetoxy-dimethylnitrosamine, a proximate metabolite of the carcinogenic amine, and bacteriophages R17 and T7

The biological and physicochemical effects of reacting bacteriophages R17 and T7 with acetoxy-dimethylnitrosamine (ADMN) have been studied. The rate-determining step in the reactions appeared to be the loss of the acetoxy group by hydrolysis, the hydroxymethyl-methylnitrosamine generated decomposing rapidly to give a methyldiazonium ion and formaldehyde. In experiments with bacteriophage suspended in phosphate buffer the biological inactivation observed was the sum of the effects of the formaldehyde and of alkylation by the methylcarbonium ion produced from the diazonium ion. In experiments with bacteriophage suspended in Tris--HCl buffer the effects of formaldehyde were eliminated by its reaction with the buffer component. Alkylation by the carbonium ion produced unstable phosphotriesters in the bacteriophage RNA which on hydrolysis led to degradation of the molecule. In phosphate buffer the formaldehyde cross-linked the protein coat of the bacteriophage blocking the extraction of the RNA. Estimates of the mean lethal dose and of the extent of degradation of the RNA following reaction in Tris--HCl buffer were fairly close to those observed in experiments with N-methyl-N-nitrosourea (MNUA).     

Comparison of the structures and the crystal contacts of trypanosomal triosephosphate isomerase in four different crystal forms

Triosephosphate isomerase (TIM) is a dimeric enzyme consisting of 2 identical subunits. Trypanosomal TIM can be crystallized in 4 different spacegroups: P2(1)2(1)2(1), C2(big cell), C2(small cell), and P1. The P1 crystal form only grows in the presence of 1.4 M DMSO; there are 2 DMSO binding sites per subunit. The structures have been refined at a resolution of 1.83 A, 2.10 A, 2.13 A, and 1.80 A, respectively. In the 4 different spacegroups the TIM subunit can be observed in the context of 7 different crystallographic environments. In the C2 cells, the dimer 2-fold axis coincides with a crystallographic 2-fold axis. The similarities and differences of the 7 subunits are discussed. In 6 subunits the flexible loop (loop 6) is open, whereas in the P2(1)2(1)2(1) cell, the flexible loop of subunit 2 is in an almost closed conformation. The crystal contacts in the 4 different crystal forms are predominantly generated by polar residues in loops. A statistical analysis of the residues involved in crystal contacts shows that, in particular, serines are frequently involved in these interactions; 19% of the exposed serines are involved in crystal contacts.     

Study of proteases and other enzymes of Vibrio cholerae 01 E2 Tor and 0139 serotypes isolated in Yavatmal (Maharashtra)

A critical issue in the field of signal transduction is how signaling molecules are organized into different pathways within the same cell. The importance of assembling signaling molecules into architecturally defined complexes is emerging as an essential cellular strategy to ensure specificity and selectivity of signaling. Scaffold proteins function as the pillars of these transduction complexes, bringing together a diversity of signaling components into defined ultramicrodomains of signaling.     

Sequential expression of transforming growth factor-beta1 by T-cells, macrophages, and microglia in rat spinal cord during autoimmune inflammation

Transforming growth factor-beta1 (TGF-beta1) is crucially involved in regulating inflammatory events during experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis. Despite accumulating evidence for local expression of TGF-beta1 in the inflamed nervous system, uncertainty remains regarding its cellular source. We have investigated the temporospatial distribution of TGF-beta1 gene expression in rat spinal cord during EAE. In actively induced EAE, in situ hybridization revealed strong expression of TGF-beta1 in meningeal and perivascular mononuclear infiltrates at onset of the disease, continued expression in perivascular infiltrates and scattered mononuclear cells at maximal disease severity, and expression in scattered parenchymal cells during recovery. Double labeling studies revealed subpopulations of infiltrating T-cells to be the major source of TGF-beta1 early in the disease, followed by macrophages at peak severity and microglial cells during the recovery phase of EAE. Astrocytes and neurons did not express TGF-beta1. Quantification of mRNA by Northern blot analysis revealed that cellular expression of TGF-beta1 by T-cells, macrophages, and microglia sums up to a long-lasting elevation of TGF-beta1 mRNA extending well into the recovery phase. Our data indicate cellular diversity and suggest functional diversity of TGF-beta1 gene expression during EAE. While TGF-beta1 expressed early in the disease by T-cells may contribute to inflammatory lesion development, microglial cells may potentially contribute to recovery by expressing immunosuppressive TGF-beta1 during remission.