Positional cloning of the gene(WFS1) for Wolfram syndrome

Wolfram syndrome(DIDMOAD syndrome) is an autosomal recessive neurodegenerative disorder characterized by juvenile-onset, insulin-requiring diabetes mellitus and optic atrophy. Other symptoms including diabetes insipidus, neurosensory deafness, urinary tract and neurological abnormalities are often accompanied. In patients, beta-cells are selectively lost from their pancreatic islets of Langerhans. The gene was previously mapped to 4p16.1. By haplotype analysis and recombination mapping in 5 families, we localized the gene within a region less than 250 kb on chromosome 6p. In the region, we identified a novel gene(WFS1) encoding a putative transmembrane protein. Mutations were identified in all affected members of the families and these mutations were associated with disease phenotype. This finding was further confirmed by other investigators and to date, more than 50 mutations were identified in the WFS1 gene from the patients with Wolfram syndrome. The WFS1 gene encodes a protein of 100.3 kDa with 9 to 10 putative transmembrane domains. The protein appears to be important in the survival and maintenance of normal pancreatic beta-cells and neurons. Physiological function of the WFS1 protein and mechanisms by which defective WFS1 lead to the development of Wolfram syndrome need to be clarified.     

Immunoglobulin superfamily molecules in the nervous system.

Among the various types of membrane molecules involved in cell-cell interactions in the nervous system, we have focused in this review upon membrane proteins belonging to the immunoglobulin superfamily (IgSF). IgSF molecules are distinctive in that: (1) a large percentage of known neural adhesion molecules belongs to the IgSF; (2) they are homologous in structure (Ig domain), yet exhibit large variation of function in cell-cell interactions. The structure of IgSF molecules is briefly summarized in Section II, and each member of the IgSF which has been found in the nervous system is reviewed in Section III. In Section IV, we have discussed possible properties of yet-unknown nervous system IgSF molecules, on the assumption that nervous system IgSF molecules thus far discovered comprise only a small portion of those existing. Discussion is based upon an analogy with the immune system and upon knowledge of cell-cell interactions in the development of the nervous system. Our principal aims in this review are to summarize knowledge of neural IgSF molecules and to discuss the possibility that some IgSF molecules may encode in their structures instructions for recognizing, or for being recognized by, target neural cells. Further growth of knowledge of IgSF molecules may yield insights into the patterns of cell-cell interactions underlying the formation of neuronal circuits during development.     

Creation and use of a composite polyurethane-expanded polytetrafluoroethylene graft for hemodialysis access

The Thoratec (Vectra) polyurethane vascular access graft (TPVA) is among the most recent additions to the list of materials used to construct prosthetic grafts for vascular access during hemodialysis. We give the TPVA very high marks, and recognize the utility of such a graft for use in hemodialysis. However, the strong elasticity of this graft can lead to unexpected complications after suturing. We devised a new surgical method using a TPVA-ePTFE (expanded polytetrafluoroethylene) composite graft, substituting the anastomosis section of the TPVA with a portion of ePTFE graft material, and have been able to overcome most of the TPVA's potential problems. We herein describe the technique.     

Nucleotide deletion of T cell receptor V gamma 2 and J gamma 2 coding sequences at V gamma 2-J gamma 2 junctions in immature B cell lines.

Immature B cell lines transformed with a temperature-sensitive mutant of Abelson murine leukaemia virus undergo preferentially V gamma 2 to J gamma 2 joinings during culture at a non-permissive temperature (39 degrees C). Here we examined nucleotide addition and deletion at the V gamma 2-J gamma 2 junctions in these V gamma 2 to J gamma 2 joinings, in comparison with the V gamma 2-J gamma 2 junctional sequences reported previously in T cells. Forty-eight V gamma 2-J gamma 2 junctions were PCR-amplified and sequenced. Only three of 48 V gamma 2-J gamma 2 junctions had nucleotide addition. The average nucleotide deletion of V gamma 2 coding sequences at the V gamma 2-J gamma 2 junctions was 6.9 nucleotides in immature B cells and 5.1 nucleotides in T cells (p less than 0.05). Also, the average nucleotide deletion of J gamma 2 coding sequences at the V gamma 2-J gamma 2 junctions was 3.1 nucleotides in immature B cells and 1.9 nucleotides in T cells (p less than 0.01). The average of total number of the deleted nucleotides at the V gamma 2-J gamma 2 junctions was 10.0 nucleotides in immature B cells and 7.0 nucleotides in T cells (p less than 0.01). No correlation was found between the extent of the nucleotide deletion of the V gamma 2 coding sequence and that of the J gamma 2 coding sequence at each V gamma 2-J gamma 2 junction in immature B and T cells. These results demonstrated that nucleotide deletion at the V gamma 2-J gamma 2 junctions was significantly wider in immature B cells than in T cells.     

Regional cerebral blood flow (rCBF) in patients with ruptured cerebral aneurysm: site of aneurysm and rCBF

To investigate the relationship between the site of ruptured cerebral aneurysm and rCBF, 92 measurements of rCBF were conducted in 57 patients with ruptured cerebral aneurysm. Excluded from this study were patients with multiple aneurysms, intracerebral hematoma, and/or hydrocephalus. Twenty-four patients had the anterior communicating aneurysm (A-com), 20 patients had the internal carotid aneurysm (ICA), and 13 patients had the middle cerebral aneurysm (MCA). All patients underwent unilateral fronto-temporal craniotomy for clipping of the aneurysm and their rCBF measurements, using the xenon-133 inhalation method, were performed in the first three weeks after surgery. In each rCBF measurement, the hemispheric mean value of initial slope index (meanISI) was calculated in both cerebral hemispheres, that is, in the cerebral hemispheres ipsilateral and contralateral to craniotomy. The authors defined the "symmetry index of the meanISI (%): symmetry index" as the ratio of the meanISI in the cerebral hemisphere ipsilateral to craniotomy compared to the meanISI in the cerebral hemisphere contralateral to craniotomy. There was no significant relationship between the site of aneurysm and the meanISI in both hemispheres, and this result suggests that the site of aneurysm makes no difference in the incidence of vasospasm. In the postoperative first week, the "symmetry index" was 91.2 +/- 7.4% in MCA, 95.3 +/- 4.1% in ICA, and 97.9 +/- 8.2% in A-com; that is, MCA had significant asymmetry of meanCBF compared with A-com (p less than 0.05). In the second and third postoperative weeks, there was no significant relationship between the site of aneurysm and the asymmetry of meanCBF.(ABSTRACT TRUNCATED AT 250 WORDS)     

Natural killer activity and serum immunosuppressive acidic protein levels in esophageal and gastric cancers

The natural killer (NK) activity of peripheral blood mononuclear cells and serum immunosuppressive acidic protein (IAP) levels were examined in patients with esophageal or gastric cancer, before and after surgery. Patients with stage IV esophageal or stage IV gastric cancer had significantly lower NK activity (39.5±14.8% and 37±11.6%, respectively), and also higher serum IAP levels (778±264 g/mL and 633±156 g/mL, respectively), than the corresponding control values (50±5.6% and 375±26 g/mL, respectively). Patients with esophageal or gastric cancer who underwent curative resection had high NK activity (54.8±11.6% and 54.8±8.0%, respectively), and low IAP levels (471±116 g/mL and 490±42 g/mL, respectively), compared with those who underwent non-curative resection. Patients who underwent non-curative resection had lower NK activity and higher serum IAP levels than those who underwent curative resection, even 1 month after surgery. Mononuclear cells in the regional lymph nodes and tumor specimens showed significantly lower NK activity than those in the peripheral blood and spleen. Thus, NK activity and the IAP level reflected the immunocompetence, clinical course, and surgical curability of those patients. NK cells appeared not to have any significant antitumor activity in the regional lymph nodes or in the tumor itself, although they were still active in the peripheral blood.     

Significance of flow cytometric DNA analysis from freshly aspirated samples

The procedure of aspiration biopsy cytology by fine needle aspiration (ABC) is as option in establishing definitive diagnoses for breast cancers. In this series, a needle size of 21G was considered most suitable for ABC as well as flow cytometric DNA analysis. Histograms from fresh samples aspirated by fine needle clearly delineated a sharp peak in G&sup0;G(1) phases and also a better CV was obtained than with paraffin-embedded preparations. In addition, fresh samples gave more reliable DI and suggested the value of measuring nuclear DNA contents. It is believed that the prognoses of breast cancers are closely associated with DNA ploidy patterns. In this sense, flow cytometric DNA analysis of fresh samples of ABC is regarded as important in clinical use.     

Thymic cystectomy through subxyphoid by video-assisted thoracic surgery

In this paper we present a new technique for thymic cystectomy by video-assisted thoracic surgery. The thoracoscope was inserted using a Vein Harvest (Ethicon Endo-Surgery Co, Ltd, Cincinnati, OH) through a 5-cm subxyphoid incision. A Harmonic Scalpel (Ethicon Endo-Surgery) and Cherry Dissector (Ethicon Endo-Surgery) were used for dissection. The thymic cyst was successfully removed through the incision without thoracotomy. The advantage of this technique is that it is less invasive than video-assisted thoracic surgery through the thorax, removing the need for a thoracotomy.     

A case of crossed fused kidney with simple ureterocele

A 32-year-old man consulted Osaka National hospital with chief complaints of dysuria and macrohematuria. DIP and CT revealed that the right kidney deviated to the lower pole of the left kidney and they fused together. The right ureter crossed over the supine. The calcified shadow existed in the lower end of the left ureter with cobra head image. He had no external anomalies. Under diagnosing crossed fused kidney (inverted L shaped) complicated the left ureterocele with a stone, transurethral incision of ureterocele (TUI) was performed. We made transverse incision and extracted stone, 7 mm in size (calcium oxalate 96% and calcium phosphate 4%). Three months later after the operation, IVP, CG and VCG revealed the down-sized ureterocele and no VUR. Crossed renal ectopia complicated many anomalies about 50%. Among them anomalies of the urinary tract was most frequent about 30%. But crossed renal ectopia with ureterocele wasn't reported so far in Japanese literature.