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Pseudohypoparathyroidism 1b (PHP 1b) is characterized by specific resistance of target tissues to PTH, but no mutations in the PTH/PTH-related peptide (PTHrP) receptor gene have been identified. To investigate the basis for defective PTH signaling, we used polymorphic markers in or near the genes encoding PTH and its receptors to perform linkage analysis between these loci and PHP 1b. Two multiplex PHP 1b families (families M and K) were informative for an intragenic polymorphism in exon 13 of the PTH/PTHrP receptor gene detected by PCR amplification and resolved by denaturing gradient gel electrophoresis. Linkage analysis revealed discordance of the PTH/PTHrP receptor with PHP1b. One PHP 1b kindred (family M) was informative for a intragenic polymorphism in exon 3 of the PTH gene detected by PCR amplification and resolved by denaturing gradient gel electrophoresis. The PTH gene polymorphism segregation was discordant with PHP 1b. Probands from each family had normal PTH genes by direct sequence analysis. In three PHP 1b kindreds, we analyzed simple sequence polymorphisms in three microsatellite markers flanking the PTH type 2 receptor locus located at 2q33. Linkage analysis demonstrated no linkage. In conclusion, neither the PTH gene nor the PTH receptor genes (type 1 and 2) are linked to PHP 1b.

Albright hereditary osteodystrophy (AHO) is characterized by multiple somatic defects secondary to mutations in the GNAS1 gene. AHO patients with mutations on maternally inherited alleles are resistant to multiple hormones (e.g., PTH, TSH), a variant termed pseudohypoparathyroidism (PHP) type 1a, due to presumed tissue-specific paternal imprinting of the a chain of Gs as demonstrated in murine renal proximal tubule and fat cells. Studies in human tissues thus far revealed imprinting only in pituitary. Because mild hypothyroidism due to TSH resistance occurs in most PHP type 1a patients, we investigated whether Gas is imprinted in thyroid. Examination of eight normal thyroids demonstrated significantly greater expression from the maternal GNAS1 allele, with paternal Gas transcripts accounting for only 25.9–40.4%. Expression of NESP55, XLas, and 1A was uniallelic. We conclude that Gas is incompletely imprinted in the thyroid, which provides an explanation for mild TSH resistance in PHP type 1a. 2002 Elsevier Science (USA). All rights reserved.

We design an acoustic metamaterial (AM) with multi-band of negative modulus composed of different sized split hollow spheres (SHSs). From acoustic transmitted experiment, the AM exhibits simultaneously negative modulus at frequencies 914, 1298 and 1514 Hz. Based on the multi-band designed concept, broadband AM is fabricated by arraying gradually sized SHS. The transmission results indicate that this medium can achieve negative modulus at the frequency range from 900 to 1500 Hz. This kind of broadband AM is very convenient to couple with other structures to gain the double-negative AM.

Phototransduction is mediated by cGMP, a second messenger that gates a cation channel in the rod outer segment membrane. The level of cGMP in photoreceptor cells is regulated by cGMP phosphodiesterase (PDE), a G-protein-coupled enzyme that is stimulated by light activation of rhodopsin. The cGMP PDE has two catalytic units, alpha and beta, a third subunit, gamma, is inhibitory, and when released facilitates activation of PDE activity. Illumination of vertebrate photoreceptor cells produces transient hyperpolarization due to the closure of a cGMP-gated channel in the rod outer segment membrane. In the dark, photoreceptors are depolarized as the cGMP-gated channels are opened. The retinal rod cGMP channel is a member of a growing family of ligand-gated channels that are regulated by a direct interaction with cyclic nucleotides. The gene encoding the human retinal rod cGMP channel has been cloned recently and preliminarily localized to chromosome 4 using somatic cell hybrid panels. The authors report here confirmation of the mapping to chromosome 4 and refine the map location by chromosomal in situ hybridization. 8 refs., 1 fig.