Enhancement of rat urinary bladder tumorigenesis by lipopolysaccharide-induced inflammation.

Chronic inflammation of the urinary tract is a significant risk factor for the development of urinary bladder cancer in humans. We previously demonstrated that weekly treatment with killed Escherichia coli enhanced rat urinary bladder tumorigenesis initiated by the carcinogen N-methyl-N-nitrosourea. We conducted the present study to determine whether lipopolysaccharide (LPS), a major cell wall component of E. coli, had a tumor-enhancing effect. LPS was instilled twice a week at three doses (100, 1.0, and 0.01 microgram/ml) into heterotopically transplanted rat urinary bladders which were treated with a single low dose (0.25 mg) of N-methyl-N-nitrosourea or vehicle. Rats treated with 100 micrograms/ml of LPS showed a significant increase in the incidence and number of tumors in the bladders pretreated with N-methyl-N-nitrosourea. Treatment with LPS alone did not induce tumors. The enhancing effects were associated with a marked increase in the numbers of polymorphonuclear leukocytes and an increase in the H2O2 concentration in the bladder lumen. Oxidative stress by reactive oxygen intermediates and a proliferative response of the carcinogen-exposed urothelium to the inflammatory stimulation appeared to play a significant role in tumor enhancement by LPS.

Increased renal retention of 99mTc-methylene diphosphonate after nephron-sparing surgery.

UNLABELLED: Nephron-sparing surgery has become established as an effective treatment for localized renal cell carcinoma when preservation of renal function is necessary. The surgery usually requires temporary renal artery occlusion and may induce ischemic renal damage. In this study, we retrospectively evaluated renal activity on bone scintigraphy after nephron-sparing surgery. METHODS: Eleven patients who underwent nephron-sparing surgery for renal cell carcinoma and had a normal contralateral kidney were studied. A total of 12 bone scintigraphy images with 99mTc-labeled methylene diphosphonate were obtained within 1 y after surgery in these patients to assess skeletal metastasis. Activity in the spared renal parenchyma was compared visually with that in the contralateral normal kidney. RESULTS: The tumor was successfully resected in every patient, and no clinically significant complications occurred. Activity in the spared renal parenchyma was elevated in six of seven examinations performed within 21 d after surgery. In three examinations, the increase in renal activity was heterogeneous, being relatively prominent near the surgical margin. Increased renal activity was not observed on five examinations performed 3 mo or more after surgery. CONCLUSION: Renal retention of bone-seeking agents is elevated in the early period after nephron-sparing surgery, probably as a result of ischemic insult during the surgical procedure. Bone scintigraphy may aid in evaluating the presence and degree of ischemic damage of the spared renal parenchyma.

Differential expression of keratin 5 gene in non-tumorigenic and tumorigenic rat bladder cell lines.

In this study, we attempted to find a gene or genes which were differentially expressed between a non-tumorigenic rat bladder cell line and a highly tumorigenic/metastatic bladder carcinoma cell line that was derived from the former after treatment in vitro with N-methyl-N-nitrosourea. We cloned a rat keratin 5 cDNA by a differential hybridization technique and found that all of the non-tumorigenic cells (7/7) and normal bladder tissue expressed keratin 5, but most of the tumorigenic cells (8/10) did not express keratin 5. Furthermore, in a spontaneously transformed cell line, keratin 5 expression was lost during the transformation process. These results suggest that loss of keratin 5 expression is closely associated with acquisition of a tumorigenic phenotype by rat bladder non-tumorigenic cells.

Cytotoxic effect of a fusion protein from transforming growth factor alpha and Pseudomonas exotoxin on rat and human bladder carcinoma cells in vitro.

A protein formed by fusion of transforming growth factor alpha with Pseudomonas exotoxin (TGF alpha-PE40) has been shown to have the ability to kill or inhibit the growth of several carcinoma cell lines. This study was designed to evaluate the in vitro cytotoxic effects of TGF alpha-PE40 on rat and human bladder carcinoma cell lines with different biological potential, and normal rat urothelial cells. The rat cell lines used were D44c, LMC19, and MYU3L, which were established in our laboratory. Human cell lines used were RT4, T24, and 253J. As a normal control, we used the first-passage culture of normal rat bladder urothelium (RU-P1). We examined the number and affinity of epidermal growth factor receptors (EGFR) in these cells, the ability of TGF alpha-PE40 to bind EGFR, and the cytotoxic effect of TGF alpha-PE40 and PE40. Rat cell lines, D44c, LMC19, and MYU3L (EGFR = 4.9 x 10(3)-11.4 x 10(3)/cell) had ED50 values (the concentration of TGF alpha-PE40 needed to reduce the viable cell population by 50%) of 180 pM, 540 pM and 6000 pM respectively; for cI (the concentration required to achieve complete inhibition of growth under continuous serum stimulation) TGF alpha-PE40 concentrations of 10(4) pM, 10(4) pM and higher than 10(4) pM respectively were required. Human cell lines, RT4, T24, and 253J (EGFR = 32 x 10(3)-126 x 10(3)/cell) had ED50 values of 20 pM, 66 pM, and 330 pM respectively and T24 showed cI values of 10(3) pM. RU-P1 (EGFR = 92.6 x 10(3)/cell) had the highest ED50 value of 8000 pM. These data indicate that the susceptibility to TGF alpha-PE40 does not always depend on the number of EGFR, that cells having a relatively small number of EGFR respond well to TGF alpha-PE40, and that normal urothelial cells are more resistant to TGF alpha-PE40 than are cancer cells. The differential effect of TGF alpha-PE40 on normal and neoplastic cells provides a rational basis for its use in vivo to control tumor growth.

Biochemical characteristics of cardiac myosin: the pH dependence of Ca-ATPase activity, and that of the absorption spectrum of 2,4,6-trinitrophenyl groups attached to myosin.

For both cardiac and skeletal myosin, the Ca-ATPase activity of myosin at acidic pH was shown to be different from that at alkaline pH, in the susceptibility to heat-inactivation, the effects of organic solvents, and the effect of trinitrophenylation of the myosin. It is therefore suggested that there are two different types of Ca-ATPase of both cardiac and skeletal myosin. Differences in the Ca-ATPase activity were also found between cardiac and skeletal myosins. (a) The Ca-ATPase activity of cardiac myosin was more susceptible to heat-inactivation at alkaline pH than at acidic pH. In contrast, the activity of skeletal myosin was more susceptible to heat-inactivation at acidic pH than at alkaline pH. (b) Dioxane weakly stimulated the activity of cardiac myosin at acidic pH, but strongly activated that of skeletal myosin at acidic pH. Acetone very strongly inhibited the activity of cardiac myosin at alkaline pH, but not so strongly that of skeletal myosin at alkaline pH. (c) Trinitrophenylation of the myosin resulted in loss of the activity optimum at acidic pH with skeletal myosin but not with cardiac myosin. As reported by Srivastava et al. (J. Biochem. 86, 725-731, 1979), 1 mol of lysine residue per mol of cardiac myosin quickly reacted with 2,4,6-trinitrobenzene sulfonate (TNBS) either in the absence or presence of inorganic pyrophosphate (PPi). However, trinitrophenyl (TNP) groups bound to cardiac myosin in the presence of PPi were significantly different, in the pH dependence of the absorption spectrum, from those bound (to cardiac myosin) in the absence of PPi.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of T-kinin on microvascular permeability and its modulation by peptidases in rat airways.

T-kinin (Ile-Ser-bradykinin), the product of T-kininogen, has been found in rat plasma during systemic inflammation, but the effect of this kinin on airway inflammatory response is unknown. We examined the effect of T-kinin on vascular permeability in airways of anesthetized rats in vivo by using photometric measurement of the extravasated Evans blue. Intravenous injection of T-kinin (0.1-10 mumol/kg) increased dye extravasation in a dose-dependent manner, with 134% for trachea and 117% for bronchi by 1 mumol/kg. Pretreatment with bradykinin B2-receptor antagonist Hoe-140 (100 nmol/kg), but not the B1-receptor antagonist des-Arg9-Leu8-bradykinin (5 mg/kg), abolished plasma extravasation evoked by T-kinin (1 mumol/kg). NK1 tachykinin-receptor antagonist CP-99994 (4 mg/kg) did not affect T-kinin-induced vascular leakage. Pretreatment with captopril (2.5 mg/kg), angiotensin-converting enzyme inhibitor, potentiated T-kinin (100 nmol/kg)-induced plasma extravasation, whereas phosphoramidon (2.5 mg/kg), a neutral endopeptidase inhibitor, had no effect. We conclude that T-kinin produces airway vascular extravasation via stimulation of B2 receptors. The effect is modulated by endogenous angiotensin-converting enzyme and is not mediated via activation of sensory nerve.

Patients with temporal lobe epilepsy show an increase in brain-derived neurotrophic factor protein and its correlation with neuropeptide Y.

Model studies on animal seizures have proposed potential involvement of the neurotrophins, BDNF and NGF, in human epilepsy. However, their biological significance in this disease itself remains to be evaluated. Here we demonstrate that patients with intractable temporal lobe epilepsy show a marked increase in protein levels of BDNF (2.6-fold, p<0.01) but not other neurotrophins. Moreover, the specific BDNF increase was significantly correlated with contents of neuropeptide Y. Thus, these results indicate the activity-dependent expression of BDNF in human subjects and its potential contribution to the pathophysiology of human epilepsy via neuropeptide Y.

Surgical treatment of renal cell carcinoma associated with Budd-Chiari syndrome: report of four cases and review of the literature.

AIMS: Renal cell carcinoma is sometimes associated with inferior vena caval tumour thrombus, but occlusion of hepatic veins by the tumour thrombus causing liver dysfunction, the so-called Budd Chiari syndrome, is relatively uncommon. There are only a few reports in the literature which discuss this condition. METHODS: Four cases admitted to our hospital over a 7-year period and eight cases reported in detail in the English and the Japanese literature were included in this study. They are classified into two groups: mild/silent, without liver failure, and severe, with liver failure. RESULTS: Five patients were classified as mild/silent and seven as severe. Clinical manifestations were mild in the former cases and acute in the latter. Surgery was performed in four of the former cases but only in one case of the latter cases. CONCLUSIONS: In mild cases, surgical treatment seems to avoid imminent hepatic failure effectively and should be performed as soon as possible. In such cases Budd Chiari syndrome in itself does not affect the prognosis. In severe cases, however, surgical treatment is very difficult and risky due to the existing hepatic failure.

Natural history of intracranial cavernous malformations.

The authors have reviewed the clinical records of 110 patients with intracranial cavernous malformations diagnosed by histological examination and/or magnetic resonance imaging over a mean follow-up period of 4.71 years. These cases were divided, based on their presentation, into a hemorrhage group, a seizure group, and an incidentally diagnosed group. The rate of subsequent symptomatic bleeding was investigated in relation to age at onset, sex, and location of the initial lesion. A high rate of subsequent symptomatic bleeding episodes was found in the hemorrhage group, especially among younger females. The nonhemorrhagic-onset cases had a very low incidence of bleeding. The outcome was generally good, except in patients with lesions in the basal ganglia and brainstem. These findings will be helpful in planning a rational therapeutic strategy for intracranial cavernous malformations.

Comparison of the results of bilateral total knee arthroplasty with and without patellar replacement for rheumatoid arthritis. A follow-up note.

Simultaneous bilateral total knee arthroplasty was performed in twenty-six patients who had rheumatoid arthritis, and a patellar replacement was performed concurrently in one randomly selected knee in each patient. A lateral retinacular release was performed in all knees. The patients were followed for at least six years (mean, 6.6 years; range, 6.0 to 7.5 years), and the postoperative status of the patients was evaluated with the knee score of The Hospital for Special Surgery. Pain on standing and on ascending or descending stairs as well as tenderness of the patellofemoral joint also were assessed. The over-all score and the individual scores for pain, function, range of motion, muscle strength, flexion contracture, and instability were not significantly different between the knees that had had a patellar replacement and those that had not. However, pain on standing and on ascending or descending stairs as well as tenderness of the patellofemoral joint were only noted in knees that had not had a patellar replacement. These findings suggest that, in order to diminish pain on standing and on using stairs, replacement of the patella during total knee arthroplasty is preferable for patients who have rheumatoid arthritis.

Assay in mice for low levels of Clostridium botulinum toxin.

When botulinum toxin at a low level such as 0.1 to 1.0 mouse intraperitoneal LD50 was injected subcutaneously into a mouse at the inguinocrual region, abdominal ptosis with local palsy developed. If this symptom is taken as a marker, 1.0 mouse intraperitoneal LD50 can be detected within 6 h and 0.1 LD50 within 24 h. The severity of symptoms and the time-to-death in days after injection of toxin were converted into scores to quantify the toxic activity. Over a wide range of dose, between 0.075 and 38.4 mouse intraperitoneal LD50, a linear relationship was obtained between the log dose and the score. By use of this method, low levels of toxin such as 0.1 mouse intraperitoneal LD50 can be titrated accurately and easily.

Temporal lobe lesion demonstrating features of dysembryoplastic neuroepithelial tumor and ganglioglioma: a transitional form?

We report an unusual multimodular glioneuronal lesion found in a temporal lobe from a 17-year-old boy with complex partial seizure. Histologically, this lesion was located within the cortex of the middle temporal gyrus and consisted of multinodular foci and the surrounding cortical dysplasia, resembling dysembryoplastic neuroepithelial tumor (DNT). However, it was quite different in the following respects from usual DNT: 1 nodule found in the subpial area consisted entirely of mature atypical neuronal cells separated by a reticulin fiber network connecting to the pia mater and the area around and between the above nodule, whereas another neighboring nodule, which contained many oligodondroglia-like round cells as well as occasional neuronal cells and fibrillary astrocytic cells, showed scattered neuronal cells in the well-differentiated fibrillary astrocytic stroma, the histological features being those of ganglioglioma (GG). We consider that the present case is a good example of the transitional form between DNT and GG. At 25 months following total lesion extirpation, the patient is healthy and free from seizures.

Full recovery from deafness after removal of a large acoustic neurinoma associated with neurofibromatosis 2: case report.

The first case of full recovery from deafness after radical intracapsular removal of a large acoustic neurinoma, more than 4 cm in diameter, is reported. The patient, a 17-year-old woman, had multiple intracranial and intraspinal tumors in addition to bilateral acoustic neurinomas. Radical intracapsular removal is a useful technique to preserve nerves in patients with large acoustic neurinoma. When identifiable evoked potentials are preserved in brain stem auditory evoked potential, hearing preservation should be tried despite preoperative hearing level.

Two cases of symptomatic interhemispheric arachnoid cyst in the elderly.

We recently experienced two cases of symptomatic interhemispheric arachnoid cyst (IHAC) in the elderly, both extending into the frontoparietal region. Both patients presented with more than an 8-year history of progressive hemiparesis and underwent capsule resection in combination with internal drainage to the pericallosal cistern via the interhemispheric approach. Postoperatively, the cyst cavities were greatly reduced in size, and neurologic signs and symptoms were markedly improved. A discussion of the diagnosis, mechanism of symptom onset, and management of symptomatic IHAC in the elderly is presented.

Interhemispheric epithelial cyst. Case report.

We report a rare case of a 54-year-old woman with an interhemispheric epithelial cyst. This will be the first report of an interhemispheric epithelial cyst without callosal agenesis. A partial excision of the cyst wall has led to her recovery with no evidence of recurrence. Ultrastructural studies suggest that the cyst was derived from the primitive neuroepithelium. We discuss the pathogenesis of the interhemispheric epithelial cyst.

Obstructive hydrocephalus due to a giant aneurysm of the internal carotid bifurcation.

A rare case of obstructive hydrocephalus associated with a giant aneurysm of the internal carotid artery is presented. The giant aneurysm, which was located in the prepontine cistern, was initially thought to be of basilar artery origin. Cerebral computed angiotomography had the most diagnostic value in disclosing the partially thrombosed giant aneurysm and its relationship with the surrounding arteries. After undergoing a ventriculoperitoneal shunt operation, the patient's clinical symptoms markedly improved.

Functional posterior rhizotomy for severely disabled children with mixed type cerebral palsy.

The authors evaluated the impact of functional posterior rhizotomy (FPR) for children with severely disabled mixed type cerebral palsy (CP). Three quadriplegic children at the age of 3, 4, and 10 years underwent FPR. They were classified as mixed type CP based on the clinical presentation of marked spasticity with dystonic posture. Preoperative Ashworth score of the lower extremity was 3.5, 4.5, 4.8 respectively. Two children showed prominent opisthotonus and all showed severe subluxation of the hip joint. Advanced scoliosis was associated in two children. FPR was performed from L2 to S1 in one child, L2 to S2 in one and L2 to S1/S2 in one based on the result of pudendal mapping. Rootlet cutting rate ranged from 66 to 75%. Postoperatively, Ashworth score dropped to 1.4, 1.2, 1.3, respectively. Functional improvement of the upper extremity and urination were confirmed in two children. Hip subluxation was reduced in one child and remained stable in two. A one-year follow-up review confirmed no relapse of spasticity among them. FPR achieved highly satisfactory surgical effects in children with severe mixed type CP. Although long-term follow-up is mandatory since there was a report of relapsed spasticity after FPR in this particular population of CP, FPR could be a choice of surgery in severely disabled children with mixed type CP.

Extravasation from anterior choroidal artery in a child with moyamoya disease--case report.

A rare association of moyamoya disease with intra- and periventricular hemorrhage in an 8-year-old girl is presented. Angiography showed that the cause of hemorrhage was extravasation from the dilated anterior choroidal artery. Ventriculoperitoneal shunt and encephalomyosynangiosis have prevented clinical or neurological deficits for over 6 years.

Ruptured distal anterior inferior cerebellar artery aneurysm--case report.

A 62-year-old female presented with a distal anterior inferior cerebellar artery (AICA) aneurysm showing severe involvement of the facial and acoustic nerves manifesting as progressive left hearing disturbance and left facial nerve paresis. She was admitted to our hospital 2 months after the onset. A saccular aneurysm arising from the meatal loop of AICA was found between the facial and acoustic nerves which were damaged directly by the aneurysm. Magnetic resonance imaging demonstrated a vascular anomaly, differentiating this disorder from cerebellopontine angle tumor, and evidence of an old subarachnoid clot. These characteristics were extremely helpful for the differential diagnosis. Neck clipping and aneurysmectomy were performed to achieve decompression of the cranial nerves. One year and 2 months later full function of the facial nerve returned but the hearing disturbance persisted.

Peritumoral edema and seizure in patients with cerebral convexity and parasagittal meningiomas.

Epileptogenic factors associated with cerebral convexity or parasagittal meningiomas were investigated by retrospective analysis of clinical symptoms and computed tomographic findings in 83 consecutive patients. The patients were divided into Group A consisting of 27 patients presenting with epilepsy as the first symptom, and Group B consisting of 56 patients presenting with other symptoms. Tumor location, tumor size, histological subtype, and the amount of peritumoral edema were compared between the groups. Tumor size, location, and histological subtype did not differ significantly between the two groups, but the area of peritumoral edema was significantly greater in Group A than in Group B. Similar results were found in subgroups of patients with frontal meningioma, central meningioma, and fibroblastic meningioma. Generalized seizures tended to occur in patients with frontal or fibroblastic meningioma, and partial seizures in those with central or parietal meningioma. Peritumoral edema is a significant epileptogenic factor associated with both cerebral convexity and parasagittal meningiomas, and may be especially related to the occurrence of secondarily generalized seizures in frontal and fibroblastic meningiomas.