Examination of PPP1R3B as a candidate gene for the type 2 diabetes and MODY loci on chromosome 8p23.

The product of the PPP1R3B gene (G(L)) is the regulatory subunit of PP1 - a serine/threonine phosphatase involved in the modulation of glycogen synthesis in the liver and skeletal muscle. The PPP1R3B gene is located on chromosome 8p23 in a region that has been linked with type 2 diabetes and maturity-onset diabetes of the young (MODY). We examined whether sequence variants at the PPP1R3B locus are responsible for the linkage with diabetes observed at this location. RT-PCR analysis revealed the existence of two alternative promoters. These and the two exons of this gene were sequenced in the probands of 13 Joslin families showing the strongest evidence of linkage at 8p23. A total of 20 variants were observed: two in the 5' flanking region, one in the intron (9 bp 5' of exon 2), and 17 in the 3' UTR. The intronic variant generated a new acceptor splice site, resulting in an alternative splice variant with a longer 5' UTR. However, neither this nor other variants segregated with diabetes in the 13 'linked' families. Furthermore, allele frequencies were similar in 90 family probands from the Joslin Study and 347 unrelated controls. Thus, genetic variability in the PPP1R3B gene does not appear to contribute to diabetes in our mostly Caucasian families. However, a role cannot be excluded in other populations such as the Japanese, among whom linkage to diabetes is also observed at 8p23 and a non-synonymous mutation has been detected in the PPP1R3B gene.

Hydropic degenerating leiomyoma presenting as pseudo-Meigs syndrome with elevated CA 125.

BACKGROUND: Leiomyomas rarely cause pseudo-Meigs syndrome. Increased levels of CA 125 often are associated with some types of malignancy. No reported case of pseudo-Meigs syndrome presenting with hydropic degeneration of uterine leiomyoma and an elevated CA 125 level could be found on a MEDLINE search. CASE: A 46-year-old woman presented with a pleural effusion and a pelvic mass measuring 30 x 18 cm. Preoperative evaluation was remarkable for a CA 125 level of 254 U/mL. At laparotomy, the diagnosis was a benign leiomyoma with focal hyaline and extensive hydropic degeneration. Her pleural effusion resolved completely by 4 months postoperatively. CONCLUSION: Pseudo-Meigs syndrome can present with an elevated CA 125 level.

The abdominal muscles and vertebral stability.

It has been suggested that the muscles of the anterolateral abdominal wall increase the stability of the lumbar region of the vertebral column by tensing the thoracolumbar fascia and by raising intra-abdominal pressure. In this report these new mechanisms are reviewed and their contribution to vertebral stability assessed. The thoracolumbar fascia consists of two principal layers of dense fibrous tissue that attach the abdominal muscles to the vertebral column. Each of these layers was dissected in fresh and fixed material and samples chosen for light and scanning electron microscopy to study the arrangement of the component fibers. Computed axial tomography in volunteers showed the changes in spatial organization that occur during flexion of the back and during the Valsalva maneuver. The fascia was then tensed experimentally in isolated unfixed motion segments. The results suggested that the stabilizing action of the thoracolumbar fascia is less than had been thought previously but was consistent with calculations based on the more accurate structural and mechanical information that had been derived from the current study. Abdominal muscle contraction was simulated in whole cadavers in both the flexed and lateral bending positions to compare the stabilizing effect of the thoracolumbar fascia and intra-abdominal pressure mechanisms. These definitive experiments showed that the resistance to bending in the sagittal plane offered by the abdominal muscles acting through fascial tension was of a similar magnitude to that offered by a raised intra-abdominal pressure, both being relatively small in the fully flexed position. The stabilizing influence of the middle layer of the thoracolumbar fascia in lateral bending was clearly demonstrated and warrants further study in vivo.

Tissue residues from feeding pentachloronitrobenzene (quintozene) to White Leghorn chickens.

One-day-old White Leghorn chicks were fed graded levels (0, 10, 50, 100 and 1,000 ppm) of pentachloronitrobenzene (PCNB; quintozene) up to 8 weeks. Each treatment group consisted of 90 randomly selected birds (2 replications of 45 birds each). Body weight gains were significantly lower at the 1,000-ppm treatment level. Histopathologic examination of brain, liver, pancreas, small intestine, gizzard, spleen, kidney, lung, and heart failed to reveal lesions in either control or treated groups. Bioaccumulation of PCNB or its metabolites (pentachloroaniline and pentachlorophenylmethylsulfide) in tissues only occurred in trace or very low concentrations. However, trace contaminating of PCNB, eg, hexachlorobenzene (HCB) and pentachlorobenzene (PCB) accumulated in tissues to a significant degree. Tetrachloronitrobenzene, another contaminant of PCNB, was found in only the adipose and cardiac tissues following the feeding of 1,000 ppm PCNB. Storage of PCNB, HCB, and PCB in adipose and other tissues was linearly related to the amount of PCNB in the ration.

The accumulation and elimination of tissue residues after feeding pentachloronitrobenzene to White Leghorn cockerels.

Day-old White Leghorn cockerels were fed graded levels (10, 50, 100, and 1000 ppm) of pentachloronitrobenzene (PCNB) containing pentachlorobenzene (PCB), tetrachloronitrobenzene (TCNB), and hexachlorobenzene (HCB) at trace contaminants, for 12 weeks. Bioaccumulation of PCNB and its metabolites in tissues does not appear to occur to any major extent. The contaminants of PCNB, HCB, and PCB were found to accumulate to a greater degree in adipose tissue than does PCNB itself. TCNB was also detected in adipose tissue and in trace amounts in other tissues. PCNB accumulated to the highest concentration in body fat followed by gizzard and kidney. Only traces of PCNB were found in heart, liver, leg, and heart muscle. Metabolites, pentachloroaniline (PCA), and pentachlorphenylmethylsulfide (PCMS) were found in only trace quantities following the feeding of 1000 ppm PCNB. Half-life values for the depletion of the contaminants of PCNB, PCB, and HCB were determined in adipose tissue of cockerels; values as high as 53 and 95 days were found for PCB and HCB, respectively.