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Biomedical subjects

Gerhard Schreiber

Publications and source records attributed to Gerhard Schreiber.

12 recordsLinked to original sources
PubMed2006

Characterization of a major secretory protein in the cane toad (Bufo marinus) choroid plexus as an amphibian lipocalin-type prostaglandin D synthase.

Here we report the enzymatic and ligand-binding properties of a major secretory protein in the choroid plexus of cane toad, Bufo marinus, whose protein is homologous with lipocalin-type prostaglandin (PG) D synthase (L-PGDS) and is recombinantly expressed in Xenopus A6 cells and Escherichia coli. The toad protein bound all-trans retinal, bile pigment, and thyroid hormones with high affinities (K(d)=0.17 to 2.00 microM). The toad protein also catalysed the L-PGDS activity, which was accelerated in the presence of GSH or DTT, similar to the mammalian enzyme. The K(m) value for PGH(2) (17 microM) of the toad protein was almost the same as that of rat L-PGDS (14 microM), whereas the turnover number (6 min(-1)) was approximately 28 fold lower than that of rat L-PGDS. Site-directed mutagenesis based on a modeled structure of the toad protein revealed that Cys(59) and Thr(61) residues were crucial for the PGDS activity. The quadruple Gly(39)Ser/Ala(75)Ser/Ser(140)Thr/Phe(142)Tyr mutant of the toad protein, resembling mouse L-PGDS, showed a 1.6 fold increase in the turnover number and a shift in the optimum pH for the PGDS activity from 9.0 to 8.5. Our results suggest that the toad protein is a prototype of L-PGDS with a highly functional ligand-binding pocket and yet with a primitive catalytic pocket.

Amino Acid Sequence↗
PubMed2006

Change in structure of the N-terminal region of transthyretin produces change in affinity of transthyretin to T4 and T3.

The relationship between the structure of the N-terminal sequence of transthyretin (TTR) and the binding of thyroid hormone was studied. A recombinant human TTR and two derivatives of Crocodylus porosus TTRs, one with the N-terminal sequence replaced by that of human TTR (human/crocTTR), the other with the N-terminal segment removed (truncated crocTTR), were synthesized in Pichia pastoris. Subunit mass, native molecular weight, tetramer formation, cross-reactivity to TTR antibodies and binding to retinol-binding protein of these recombinant TTRs were similar to TTRs found in nature. Analysis of the binding affinity to thyroid hormones of recombinant human TTR showed a dissociation constant (Kd) for triiodothyronine (T3) of 53.26+/-3.97 nM and for thyroxine (T4) of 19.73+/-0.13 nM. These values are similar to those found for TTR purified from human serum, and gave a Kd T3/T4 ratio of 2.70. The affinity for T4 of human/crocTTR (Kd=22.75+/-1.89 nM) was higher than those of both human TTR and C. porosus TTR, but the affinity for T3 (Kd=5.40+/-0.25 nM) was similar to C. porosus TTR, giving a Kd T3/T4 ratio of 0.24. A similar affinity for both T3 (Kd=57.78+/-5.65 nM) and T4 (Kd=59.72+/-3.38 nM), with a Kd T3/T4 ratio of 0.97, was observed for truncated crocTTR. The obtained results strongly confirm the hypothesis that the unstructured N-terminal region of TTR critically influences the specificity and affinity of thyroid hormone binding to TTR.

Alligators and Crocodiles↗
PubMed2006

Case report: primary carcinoid tumor of the testicle without metastases in combination with testicular atrophy and testosterone deficiency.

The first case of testicular carcinoid was represented as an element of a benign cystic teratoma by Simon et al. J Urol 1954; 72: 892-894. It is a rare disease accounting for less than 1% of all testicular neoplasms. We report a case of carcinoid of the testis without carcinoid syndrome and metastasis but with testosterone deficiency based on a bilateral testicular atrophy, which has not been previously reported.

Adult↗
PubMed2004

One-dimensional spatial soliton families in optimally engineered quasi-phase-matched lithium niobate waveguides.

The advantage for quadratic soliton generation of engineering the quasi-phase-matching period near the input of lithium niobate slab waveguides is demonstrated. This approach allows members of one-dimensional quadratic soliton families with different values of the wave-vector mismatch to be cleanly excited and to be characterized by quantitative intensity-profile measurements of both the fundamental and the second-harmonic soliton components.

Journal Article↗
PubMed2004

[Relapsing polychondritis as a rare different diagnosis of erysipelas].

A 76-year old patient with painful erythematous swelling of the right ear was initially treated with antibiotics under the suspected diagnosis of erysipelas. Her failure to respond and a history of previous laryngeal and nasal swelling suggested the possibility of relapsing polychondritis. High dose prednisolone therapy produced marked improvement. Relapsing polychondritis should be considered as a rare, but important differential diagnostic consideration for erysipelas.

Aged↗
PubMed2002

Developmental profile of thyroid hormone distributor proteins in a marsupial, the tammar wallaby Macropus eugenii.

The ontogeny of thyroxine distributor proteins in serum of the marsupial Macropus eugenii (tammar wallaby) was investigated from day 3 after birth until adulthood. The thyroxine distributor proteins in the serum of adult M. eugenii are transthyretin and albumin. Northern analysis of RNA prepared from liver showed that transthyretin mRNA levels were initially high (about adult levels at the earliest ages tested), reduced to about 60% adult levels (between days 50 and 150), and then steadily increased to adult levels (by days 200 to 250). Albumin mRNA levels were initially about 50% of adult levels (day 3) and steadily rose to 90% of adult levels by days 175 to 220. A globulin, "wallaby thyroxine-binding protein" (W-TBP), bound [(125)I]thyroxine from day 3 until about day 200. Of the protein-bound thyroxine, the proportion bound by transthyretin had a similar pattern to the transthyretin mRNA levels. From day 26 onward, about half of the protein-bound thyroxine was bound to albumin. On day 3, less than 10% was bound to W-TBP and the proportion steadily increased to a maximum of about 46% by about day 120 and then reduced to undetectable levels by around day 250. The developmentally regulated W-TBP was present throughout pouch life, when the pouch young is dependent on obtaining thyroxine required for normal growth and development from the mother. After the young tammar wallaby leaves its mother's pouch, a time when it has reached a level of physiological development approximately equivalent to that at the time of birth in precocious eutherian mammals such as cattle and sheep, W-TBP was no longer detected as a thyroxine distributor protein in serum.

Aging↗
PubMed2002

Crocodile transthyretin: structure, function, and evolution.

Structure and function were studied for Crocodylus porosus transthyretin (crocTTR), an important intermediate in TTR evolution. The cDNA for crocTTR mRNA was cloned and sequenced and the amino acid sequence of crocTTR was deduced. In contrast to mammalian TTRs, but similar to avian and lizard TTRs, the subunit of crocTTR had a long and hydrophobic NH(2)-terminal region. Different from the situation in mammals, triiodothyronine (T(3)) was bound by crocTTR with higher affinity than thyroxine (T(4)). Recombinant crocTTR and a chimeric construct, with the NH(2)-terminal region of crocTTR being replaced by that of Xenopus laevis TTR, were synthesized in the yeast Pichia pastoris. Analysis of the affinity of the chimeric TTRs showed that the NH(2)-terminal region modulates T(4) and T(3) binding characteristics of TTR. The structural differences of the NH(2)-terminal regions of reptilian and amphibian TTRs were caused by a shift in splice sites at the 5' end of exon 2. The comparison of crocodile and other vertebrate TTRs shows that TTR evolution is an example for positive Darwinian evolution and identifies its molecular mechanism.

Alligators and Crocodiles↗
PubMed2002

The evolution of transthyretin synthesis in the choroid plexus.

Choroid plexus has the highest concentration of transthyretin (TTR) mRNA in the body, 4.4 microg TTR mRNA/g wet weight tissue, compared with 0.39 microg in the liver. The proportion of TTR to total protein synthesis in choroid plexus is 12%. All newly synthesized TTR is secreted towards the ventricles. Net transfer of T4 occurs only towards the ventricle and depends on ongoing protein synthesis. Thyroxine-binding globulin (TBG), TTR and albumin form a "buffering" system for plasma [T4] because of their overlapping affinities and on/off rates for L-thyroxine (T4)-binding. The individual components of this network determining T4 distribution are functionally highly redundant. Absence of TBG (humans), or TTR (mice), or albumin (humans, rats) is not associated with hypothyroidism. Natural selection is based on small, inheritable alterations improving function. The study of these alterations can identify function. TTR genes were cloned and sequenced for a large number of vertebrate species. Systematic, stepwise changes during evolution occurred only in the N-terminal region, which became shorter and more hydrophilic. Simultaneously, a change in function occurred: TTR affinities for T4 are higher in mammals than in reptiles and birds. L-triiodothyronine (T3) affinities show the opposite trend. This favors site-specific regulation of thyroid hormones by tissue-specific deiodinases in the brain.

Animals↗