Gene expression profile of renal proximal tubules regulated by proteinuria

BACKGROUND: Proximal tubules activated by reabsorption of protein are thought to play significant roles in the progression of kidney diseases. Thus, identification of genes related to proteinuria should provide insights into the pathological process of tubulointerstitial fibrosis. METHOD: Gene expression profiles were constructed by means of direct sequencing procedures to identify genes induced in the mouse kidney proximal tubules (PT) exposed to proteinuria. RESULTS: By comparing the gene expression of control PT to that of disease model PT, the abundantly expressed genes in control PT were down-regulated presumably because of potentially toxic effects of proteinuria. From the more than 1000 up-regulated genes, an immunity related gene, thymic shared antigen-1 (TSA-1), and a novel gene, GS188, were selected for further characterization. The increased expression of TSA-1, a member of the Ly-6 family, and of GS188 in response to proteinuria was confirmed by Northern analysis, immunohistochemistry, in situ hybridization and laser microdissection along with real-time PCR analysis. Full length cloning of GS188 identified it as a family member of LR8 that was reported to express predominantly in fibroblasts. CONCLUSIONS: The gene expression profiles showed that the expression patterns in PT were changed dramatically by proteinuria. The profiles include novel genes that should be further characterized to aid the understanding of the pathophysiology of progressive kidney diseases.     

Mechanical analysis of the lumbar vertebrae in a three-dimensional finite element method model in which intradiscal pressure in the nucleus pulposus was used to establish the model

We established a three-dimensional finite element method (FEM) model of the 4th and 5th vertebrae, using computed tomography (CT) images (2-mm slice thickness) of a healthy 29-year-old man. Because of the lack of specific data regarding the material characteristics of the nucleus pulposus of intervertebral discs, we used intradiscal pressure in the nucleus pulposus to establish the model. We referred to data from Nachemson and from Sato et al. regarding intradiscal pressure and to the methods of Shirazi-Adl for data for other material characteristics (see text for these references). The mid-position model bears a load of 294 N in the vertical direction, while the models of the flexed and extended positions bear loads of 15 N-m. In addition, a degenerative disc model without intradiscal pressure was created for the standing model. The use of these models allowed the investigation of von Mises stress on the vertebral endplates and the annulus fibrosus. We also examined von Mises stress on the facet joint in normal and degenerative disc models. There was increased von Mises stress on the vertebral endplate in the anterior, center portions. von Mises stress on the annulus fibrosus increased in the posterior portion, the entrance to the neural foramen, and the exit of the neural foramen. von Mises stress was greater during flexion in the posterior portion; in particular, increasing to about 1.6 times the level seen with other postures. No changes were observed in von Mises stress on the vertebral endplates or annulus fibrosus in the degenerative disc model, but von Mises stress on the facet joints was about 2.5 times that seen in the normal disc model. Received: June 28, 2001 / Accepted: October 27, 2001     

Recovery of postural stability following conscious sedation with midazolam in the elderly

Purpose. To investigate the differences in recovery of postural stability, after obtaining similar intravenous sedation levels with midazolam, in elderly and younger patients undergoing dental surgery. Methods. We studied 15 elderly patients (>65 years) and 15 younger patients (<55 years) after intravenous sedation. Midazolam was carefully titrated over 4–5 min until slow response to verbal commands, ptosis of the eyelid, or slight slurring of speech was obtained. Parameters were postural balance tests and an addition test, as a psychomotor function test. Results. The dose of midazolam in the elderly group (0.045 ± 0.012 mg·kg⁻¹) was 62% of that in the younger group (0.074 ± 0.026 mg·kg⁻¹). In evaluation of the percentile rank of a balance test with a visual feedback system, which contained a dynamic balance element, recovery at 60 min in the elderly group was significantly slower than that in the younger group. However, the recovery times for the balance test and the addition test, at which the significantly changed values were restored to the baseline values, were 120 min and 90 min, respectively, in both groups. Conclusion. In the recovery from sedation, elderly patients had more difficulty in acquiring postural adjustment during movement than in maintaining a standing posture. If the dose is carefully administered, however, even elderly patients might be able to return home 2 h after midazolam administration, as could the younger patients. Received: November 6, 2001 / Accepted: April 22, 2002     

Resection of a mediastinal mature teratoma diagnosed owing to sudden chest pain with elevated preoperative serum CA19-9

Mediastinal teratomas are typically benign and asymptomatic, but they undergo sudden enlargement or rupture into neighboring organs in some patients owing to intratumoral hemorrhage, leading to serious complications. We report the case of a mediastinal mature teratoma that was discovered because of the sudden onset of chest pain accompanied by elevated preoperative serum CA19-9 levels. The patient was a 43-year-old man who experienced sudden chest pain and was brought to hospital in an ambulance. Chest radiography and computed tomography revealed a mediastinal tumor and a serum CA19-9 level that was elevated to 4377 U/ml. The tumor comprised soft tissue, fluid, and cystic components. The histological diagnosis was mature teratoma with peritumoral bleeding. Most epithelial components, including squamous epithelium and similar components in the bronchi, showed positive results for CA19-9 on immunohistological examination. The postoperative course was uneventful, and serum CA19-9 levels normalized.     

A case of paracecal hernia

A 63-year-old male patient suddenly suffered right lower abdominal pain. The patient had tenderness and rebound tenderness at the right lower abdomen. Marked small bowel dilatation and an intestinal obstruction were evident upon abdominal X-ray and abdominal computed tomography (CT) imaging. CT imaging also revealed a dilated small bowel cluster in a wrapped round shape in the right lower abdomen. The cecum and the ascending colon were displaced inward. Strangulation in the ileocecal region was suspected, and emergency surgery was performed. A part of the small bowel was incarcerated within the retrocecal recess, and the intestinal tract was strangulated in the hernia orifice, by which paracecal hernia was diagnosed. The strangulated intestinal tract was repositioned, and the orifice to the hernia was closed. Paracecal hernia is a rare disease; an internal hernia should always be considered in patients with ileus without a history of surgery.     

Treatment of lower limb deformities and limb-length discrepancies with the external fixator in Ollier's disease

Background In this study, we addressed two questions on the treatment for Ollier's disease: (1) how much callus formation occurs when an osteotomy is performed intralesionally and (2) how is the stability of the wires and half-pins that are inserted intralesionally. Methods Four children with Ollier's disease underwent treatment of 12 lower limb segments using distraction osteogenesis until completion of their growth. All osteotomies were performed at the centers of the deformities, resulting in a total of seven osteotomies performed intralesionally. Results Full correction of the deformity and full restoration of length were achieved in all cases, but a residual limb-length discrepancy of <10 mm remained. The mean external fixation index in the intralesional distraction osteogenesis group was 39.7 days/cm versus 30.8 days/cm in the extralesional distraction osteogenesis group. Conversion from abnormal cartilage to normal regenerate bone was seen in only one segment. Although approximately two-thirds of the wires and half-pins were inserted intralesionally, in all but one case (in which an iatrogenic fracture occurred) the wires and half-pins were well stabilized throughout the external fixation period. Conclusions Although deformity and limb-length discrepancies due to Ollier's disease were successfully resolved by distraction osteogenesis, enchondroma may arise in distracted calluses when osteotomized intralesionally. However, the stability of the external fixator was sufficient to lengthen limbs and correct deformities even when wires and half-pins were inserted intralesionally.     

Protective effect of sivelestat,a neutrophil elastase inhibitor,on ipsilateral and contralateral testes after unilateral testicular ischaemia–reperfusion injury in rats

What’s known on the subject? and What does the study add? Following ischemic damage, reperfusion may cause further injury paradoxically in the ischemic tissue, known as reperfusion injury. Decreased blood flow causes hypoxia, leading to increased levels of lactic acid, hypoxanthine, and lipid peroxides in ischemic tissues and subsequent increase in blood flow after lipid peroxidation produces reactive oxygen species. In addition, several experimental studies and clinical trials demonstrated that unilateral testicular torsion has a detrimental effect also to the contralateral testis. Although the basic pathological mechanism underlying testicular ischemia/reperfusion injury has not been completely understood, it has been shown that reactive oxygen species formed during ischemia/reperfusion play the key role in this process. In the international literature there is no information available regarding the effects of neutrophil elastase inhibitors such as sivelestat sodium aminoacetate tetrahydrate on the ischemia/reperfusion injury of the testis. In this study we investigated the effects of sivelestat in the testes bilaterally, after unilateral testicular ischemia/reperfusion injury using an experimental unilateral testicular ischemia/reperfusion rat model. We found that sivelestat reduces the oxidative stress and partially prevents the testicular damage both in the ischemic and in the contralateral testis.

OBJECTIVE

To investigate the effect of a neutrophil elastase inhibitor, sivelestat sodium hydrate, on testicular ischaemia–reperfusion (IR)‐injury.

MATERIAL AND METHODS

Eight‐week‐old male Sprague–Dawley rats were divided into four groups: sham‐operated control rats; IR rats (group IR); and IR rats that received intra‐abdominal administration of 15 mg/kg or 60 mg/kg sivelestat (group IR15 and group IR60, respectively). Right testicular vessels were clamped for 90 min in groups IR, IR15 and IR60. Sivelestat had been administered 45 min after the induction of the ischaemia in groups IR15 and IR60. In subpopulations of IR, IR15 and IR60 rats, reperfusion was performed after ischaemia for 2 h (groups IR‐A, IR15‐A and IR60‐A, respectively) or 48 h (groups IR‐B, IR15‐B and IR60‐B, respectively). At the end of the reperfusion period, blood samples were aspirated from both spermatic veins of each rat and testosterone was evaluated. Then both testes from all rats were collected and tissue levels of malondialdehyde (MDA), myeloperoxidase (MPO), and heat‐shock protein‐70(HSP‐70) were evaluated. Testicular tissue samples were also processed for histological evaluation and TUNEL staining.

RESULTS

MDA, MPO and HSP‐70 levels in the ischemic testis were significantly higher in the IR group compared with the control group. MDA and HSP‐70 in the contralateral testis were significantly higher in the IR group compared with the control group. Bilateral testosterone levels were lower in all rat groups in comparison with the control group. Bilateral testicular samples in group IR showed extensive histopathologic degenerative alterations and increased percentage of apoptotic cells. Sivelestat treatment lowered the MDA concentration and the percentage of apoptotic cells bilaterally and ameliorated the testicular histological pattern bilaterally.

CONCLUSIONS

Unilateral testicular ischaemia causes significant contralateral testicular damage. Sivelestat may be a novel adjunct tool for reducing oxidative stress and partially preventing bilateral testicular damage.     

Familial lateral temporal lobe epilepsy confirmed with intracranial electroencephalography and successfully treated by surgery

Documentation of familial epilepsy is of paramount importance for identification of epilepsy-associated genes, elucidation of pathomechanisms of epilepsy, and development of treatment of epilepsy. We report a Japanese family with 5 members with lateral temporal lobe epilepsy beginning around the second decade of life. All seizures were intractable to medical treatment, and four patients underwent surgical treatment following long-term monitoring by intracranial electroencephalography with subdural electrodes, which revealed neocortical origins for the seizure. These four patients were successfully treated with surgery. The clinical features of this familial temporal lobe epilepsy seem to be different from those of previously reported types of familial temporal lobe epilepsy.     

A case report of ureteropelvic junction obstruction and multiple renal stones associated with nutcracker syndrome

A 20 year-old man presented to emergency room with severe left-sided flank pain. Urinalysis showed hematuria and he was referred to the urology department. KUB, DIP and retrograde pyelography (RP) revealed multiple renal stones, left hydronephrosis (grade 2) and ureteropelvic junction obstruction (UPJO). Abdominal CT revealed shortened nutcracker distance and renal angiography showed left renal vein hypertension. From these findings, diagnosis of nutcracker syndrome was made. Transposition of the left renal vein, dismembered pyeloplasty and left pyelolithotomy were performed simultaneously. 2 months after the procedure, his symptom and hematuria disappeared. 3 months after the procedure, DIP revealed improvement of hydronephrosis (grade 1) and CT showed elongation of nutcracker distance. In 12 months follow-up, there was no recurrence of symptom and hydonephrosis. To the best our knowledge, there has been no report of UPJO associated with nutcracker syndrome and the simultaneous treatment for the both diseases.