Novel Y283C mutation of the A subunit for coagulation factor XIII: molecular modelling predicts its impaired protein folding and dimer formation.

In an Italian patient with severe factor XIII deficiency, a novel mutation, Y283C (TAT to TGT), was identified heterozygously by nucleotide sequencing analysis in exon VII of the gene for the A subunit. The presence of this mutation was confirmed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis in the proband and his brother. Molecular modelling predicts that the mutant molecule would be misfolded. It is probable that the impaired folding of the mutant Y283C A subunit led to its instability, which is at least in part responsible for the factor XIII deficiency of this patient.

Fibrillin gene (FBN1) mutations in Japanese patients with Marfan syndrome.

Marfan syndrome (MFS; MIM #154700) is a connective tissue disorder characterized by cardiovascular, skeletal, and ocular abnormalities. The fibrillin-1 gene (FBN1; MIM no. 134797) on chromosome 15 was revealed to be the cause of Marfan syndrome. To date over 137 types of FBN1 mutations have been reported. In this study, two novel mutations and a recurrent de-novo mutation were identified in patients with MFS by means of single-strand conformational polymorphism (SSCP) analysis. The two novel mutations are a 4-bp deletion at nucleotide 2820-2823 and a G-to-T transversion at nucleotide 1421 (C474F), located on exon 23 and exon 11, respectively. A previously reported mutation at the splicing donor site of intron 2 (IVS2 G + 1A), which is predicted to cause exon skipping, was identified in a sporadic patient with classical MFS.

[Evaluation by MR imaging of neoadjuvant intra-arterial infusion chemotherapy in uterine cervical cancer].

Eight patients with uterine cervical cancer received two or three courses of neoadjuvant chemotherapy, including 254-S i.v. and CDDP i.a. Transcatheter arterial embolization (TAE) was added for seven patients. The therapeutic efficacy was evaluated by MR imaging and postoperative histopathological examination. Three patients achieved a complete response (CR) and five others were evaluated as a partial response (PR) on MR imaging. On postoperative histology, three of eight showed CR or PR, which coincided with MR findings. Viable cancer cells were shown in five patients. To detect these viable tumors, dynamic MR imaging was indispensable. However, because of limited spatial resolution, the detection of small residual tumors was not easy using dynamic MR imaging.

[Contrast-associated nephrotoxicity: ultrastructural and biochemical study in diabetic rats].

The present study was conducted to determine whether or not the pathologic state of diabetic mellitus serves as a risk factor for the induction of nephropathy by iodinated contrast medium (CM). CM was injected into experimentally induced diabetic rats showing early diabetic nephropathy and these animals were compared with normal rats administered CM. Various types of CM were injected into diabetic rats, and nephropathy was studied morphologically and biochemically. Electron microscopic ultrastructural study revealed vacuolar formation in the cytoplasm of the proximal tubular epithelial cells (PT cells) in both groups. However, some of these changes occurred less frequently in the diabetic group. In the diabetic group, activation of glomerular mesangial cells other than PT cells was observed with amidotrizoate, and retentive deposits in the mesangial areas were found with iopamidol. Biochemical study revealed abnormal values suggesting impaired PT cells in both the diabetic and normal groups. These findings corresponded to the results of electron microscopic ultrastructural observation. The above results suggested the possible occurrence of CM-associated nephrotoxicity in the pathologic stage of diabetic mellitus, even in mild nephropathy.

Quinidine enhances intracellular Ca2+ accumulation during rapid stimulation.

1. The quinidine-induced modification of intracellular Ca2+ concentration ([Ca2+]i) was studied in guinea-pig myocardium using fura-2. Quinidine reduced the systolic fluorescence signal level for [Ca2+]i and enhanced the end-diastolic signal level during a stimulation train. 2. The diastolic decay of [Ca2+]i fitted 2 exponential curves. Quinidine distorted the stimulation frequency-dependent acceleration of rapid [Ca2+]i decay, and prolonged the mean time constant of rapid decay after 2 Hz stimulation, from 154.4 to 205.3 msec (20 microM), and to 259.7 msec (60 microM quinidine). The time constant of slow recovery from [Ca2+]i accumulation after the stimulation train was not affected by stimulation frequency, or by quinidine, or caffeine. 3. These results suggest that quinidine modulates [Ca2+]i via a balance between the slowing of rapid [Ca2+]i decay and the reduction of the systolic [Ca2+]i. This effect may contribute to the anti-arrhythmic and pro-arrhythmic effects exerted by quinidine in some conditions.

[Effects of urography performed twice at a close interval with contrast media on renal function and morphology in rabbits].

This study was carried out in order to clarify the effects of rapid intravenous urography performed twice at a three-day interval with contrast medium on renal function and morphologic change in normal rabbits as a means to observe progress or to reexamine patients. The ionic high-osmolal amidotrizoate, non-ionic low-osmolal iopamidol, and ionic low-osmolal ioxaglate were used. A second urography was performed and curves of kidney density plotted against time and nephrograms were obtained. Serum BUN and creatinine were measured, and the kidneys were removed for histologic observations. Following amidotrizoate administration, curves of kidney density showed significantly slower clearance than with iopamidol and ioxaglate. Nephrograms at 40 seconds showed that opacification of the renal pelvis and urinary tracts also was poor. Serum creatinine following the second administration of amidotrizoate was significantly higher than the values before and at the first urography, and both serum BUN and creatinine were significantly higher than they were after iopamidol and ioxaglate. Although light microscopic changes were obscure, marked changes were observed by electron microscopy. In conclusion, intravenous urography conducted twice at a close interval with amidotrizoate induces impairment of glomerular function and morphologic change.