Gene conversion is a likely cause of mutation in PKD1

Approximately 70% of the gene responsible for the most common form of autosomal dominant polycystic kidney disease ( PKD1 ) is replicated in several highly homologous copies located more proximally on chromosome 16. We recently have described a novel technique for mutation detection in the duplicated region of PKD1 that circumvents the difficulties posed by these homologs. We have used this method to identify two patients with a nearly identical cluster of base pair substitutions in exon 23. Since pseudogenes are known to be reservoirs for mutation via gene conversion events for a number of other diseases, we decided to test whether these sequence differences in PKD1 could have arisen as a result of this mechanism. Using changes in restriction digest patterns, we were able to show that these sequence substitutions are also present in N23HA, a rodent-human somatic cell hybrid that contains only the PKD1 homologs. Moreover, these changes were also detected in total DNA from several affected and unaffected individuals that did not harbor this mutation in their PKD1 gene copy. This is the first example of gene conversion in PKD1 , and our findings highlight the importance of using gene-specific reagents in defining PKD1 mutations.      

Frontal lobe in vivo (31)P-MRS reveals gender differences in healthy controls, not in schizophrenics

Phosphorus-31 magnetic resonance spectroscopy ((31)P-MRS) has gained much interest in schizophrenia research in recent years since it allows the non-invasive measurement of high-energy phosphates and phospholipids in vivo. However, until now only differences in metabolite concentrations between certain brain areas of schizophrenic patients and healthy controls have been examined. We investigated the influence of gender on the concentrations of different phosphorus compounds. For this purpose, well-defined volumes in the frontal lobe of 32 healthy controls and 51 schizophrenic in-patients were examined with an image selected in vivo spectroscopy (ISIS) sequence on a whole-body scanner at 1.5 T. Healthy females exhibited increased values of inorganic phosphate (P(i)) and decreased values of phosphocreatine (PCr) in comparison to their male counterparts. In schizophrenic patients such gender differences were not present. Thus, the results can be interpreted in the sense that frontal energy demanding processes are enhanced in female compared to male healthy volunteers; schizophrenia seems to reduce these gender differences.     

Dynamic and static phantoms for evaluation of digital subtraction angiographic systems

Two types of phantoms were developed with which to evaluate the overall performance of digital subtraction angiography (DSA) systems. A dynamic phantom, called a "fish bone" phantom, consists of polyethylene tubes that simulate blood vessels with various lesions, such as stenoses, ulcers, and aneurysms. With this phantom, washout curves were obtained representing the relationship between iodine content and time. It will be useful for qualitative assessment of DSA images, evaluation of different image-processing schemes, and studies of blood flow analysis. A static phantom, called a "C-D" phantom, can be used for measurement of quantitative contrast-detail (C-D) diagrams and for daily monitoring of DSA systems. This was constructed of tubes of seven different diameters (2.15-0.28 mm) and 14 different concentrations of contrast medium (100%-1.1% Renografin-76 [meglumine and sodium diatrizoate]). The C-D diagrams were determined from an observer performance study using C-D phantom images obtained at four different DSA settings.     

Gabapentin leads to remission of somatoform pain disorder with major depression

Gabapentin, a novel antiepileptic drug, is effective in the treatment of partial seizures with and without secondary generalization. Evidence suggests that it may have mood-stabilizing and possibly antidepressant properties in bipolar depression. We report on a 48-year-old woman who had recurrent major depressive disorder. Following inguinal herniorrhaphy, she developed severe stabbing pain in the lower abdomen and inguinal area that progressed to constant pain in her whole body. She was depressive, hopeless, and had given up her social activities. A diagnosis of major depressive disorder and somatoform pain disorder was made. Antidepressants and carbamazepine were ineffective, and she had attempted suicide. Gabapentin resulted in remission of both the pain and the depressive mood at a dose of 1.800 mg/day.