Hyaluronate receptors mediating glioma cell migration and proliferation.

The extracellular matrix (ECM) of the central nervous system (CNS) is enriched in hyaluronate (HA). Ubiquitous receptors for HA are CD44 and the Receptor for HA-Mediated Motility known as RHAMM. In the present study, we have investigated the potential role of CD44 and RHAMM in the migration and proliferation of human astrocytoma cells. HA-receptor expression in brain tumor cell lines and surgical specimens was determined by immunocytochemistry and western blot analyses. The ability of RHAMM to bind ligand was determined through cetylpyridinium chloride (CPC) precipitations of brain tumor lysates in HA-binding assays. The effects of HA, CD44 blocking antibodies, and RHAMM soluble peptide on astrocytoma cell growth and migration was determined using MTT and migration assays. Our results show that the expression of the HA-receptors, CD44, and RHAMM, is virtually ubiquitous amongst glioma cell lines, and glioma tumor specimens. There was a gradient of expression amongst gliomas with high grade gliomas expressing more RHAMM and CD44 than did lower grade lesions or did normal human astrocytes or non-neoplastic specimens of human brain. Specific RHAMM variants of 85- and 58-kDa size were shown to bind avidly to HA following CPC precipitations. RHAMM soluble peptide inhibited glioma cell line proliferation in a dose-dependent fashion. Finally, while anti-CD44 antibodies did not inhibit the migration of human glioma cells, soluble peptides directed at the HA-binding domain of RHAMM inhibited glioma migration both on and off an HA-based ECM. These data support the notion that HA-receptors contribute to brain tumor adhesion, proliferation, and migration, biological features which must be better understood before more effective treatment strategies for these tumors can be found.

Cerebellopontine angle meningioma with a high jugular bulb.

A cerebellopontine angle meningioma originating from the skull base over a high jugular bulb is quite rare. We report a case of a 68-year-old woman who had a right cerebellopontine angle meningioma with a prominent high jugular bulb. CT and MRI revealed a round tumour which attached to a bony prominence over the high jugular bulb. The apex of the jugular bulb was 3 mm higher than the floor of the internal auditory canal. The tumour was removed via a suboccipital retrosigmoid approach. The bony projection was drilled off carefully using a diamond drill; the jugular bulb became visible through the thinned bone. When a meningioma of this type is removed including bony changes, special attention is needed to avoid injury to the jugular bulb.

Endodermal cyst in the cerebellopontine angle with immunohistochemical reactivity for CA19-9.

We present a rare case of the endodermal cyst in the cerebellopontine angle with positive immunohistochemical reactivity for CA19-9. The patient was a 67-year-old woman with an endodermal cyst in the cerebellopontine angle who presented with progressive gait disturbance. A magnetic resonance image showed a cerebellopontine angle which was low in signal on T1-weighted, and high on T2-weighted image without gadolinium enhancement. The preoperative diagnosis was an epidermoid or arachnoid cyst. The patient underwent surgery. Since the intraoperative histological diagnosis by frozen section was endodermal cyst, total removal of the cyst wall was achieved for preventing recurrence. The postoperative definitive histological diagnosis was endodermal cyst, type A by Wilkins-Odom classification, lined by mucinous epithelium with an immunohistochemical reactivity for CA 19-9 protein and cytokeratin. This is the first reported case of a huge endodermal cyst in the cerebellopontine angle of an elderly woman which exclusively showed a differentiation toward the midgut epithelium. The histological diagnosis during surgery by frozen section should be performed for proper treatment.

Ion heating and high-energy-particle production by ion-cyclotron heating in the large helical device

Ion-cyclotron heating was applied to the Large Helical Device. When the proton-cyclotron resonance was near the saddle point of the magnetic field-strength plane, strong ion-cyclotron damping occurred. Under these conditions efficient plasma heating was achieved for more than one minute. A high-energy ion tail was observed, and the effective tail temperature was determined by a balance between the wave acceleration and the electron-drag relaxation. There was no apparent sign of particle orbit loss effect in the investigated density range of 0.8-1.3x10(19) m(-3).

Characterization of iris pigment epithelial cell for auto cell transplantation.

To establish auto iris pigment epithelial (IPE) transplantation, we characterized the properties of IPE cells and the method of culture using auto serum. Monkey and human IPE cells were obtained and cultured in several conditions, using auto, mouse, rabbit, bovine, or human serum. Immunocytochemical study was performed to confirm that the cells were epithelial in origin. The proliferation rate of the IPE was also calculated from fresh human IPE cells, which were obtained during filtering glaucoma surgery. Proliferation rate was also compared to that of retinal pigment epithelial (RPE) cells. Reverse-transcriptase and polymerase chain reaction for melanogenesis was performed, and the amount of pigment in the IPE cells was also calculated. Mouse and rabbit sera were not effective for the monkey IPE cell culture. Conversely, the cells grew well in the medium with auto, bovine, or human serum. Human IPE cells grew exponentially by the described methods and reached to 60,000 cells after about 4-5 weeks. When we compared them by proliferation rate, IPE cells were less proliferative than RPE cells. The gene expression for melanogenesis and the amount of pigment in the IPE gradually decreased through successive passages. Transplantation has been tried for the treatment of age-related macular degeneration using RPE from fetus or from eye bank eyes. However, focal rejection may play an important role in the clinical results. The establishment of auto IPE cell transplantation may improve the problem of rejection. In the present study, we established auto IPE cell culture using auto serum. The cultured IPE cell showed pigment epithelial cell properties until around five passages in both human and monkey.

Cytokine gene expression after subretinal transplantation.

Transplantation study of neural retina, retinal pigment epithelial (RPE), or iris pigment epithelial (IPE) cells have been performed not only in animal model but in human age-related macular degeneration, and some of the findings reported with cystoid macular edema may have been due to graft rejection. In this investigation, we examined cytokine gene expression by reverse transcriptase-polymerase chain reaction at the transplanted subretinal space. Transplantation was performed in normal Royal College of Surgeon's rats using cultured human RPE and rat IPE. They were followed without immunosupression. Gene expression for melanogenesis of transplanted human RPE was observed only in the early days after transplantation. Rat interleukin (IL)-1alpha, -1beta1, -2, -6, interferon gamma, and tumor necrosis factor alpha (TNF alpha) genes were also expressed after the early days of transplantation. Cytokine expression was observed not only after cell transplantation but also after vehicle-only injection, which was considered a reaction to the surgical trauma. However, statistically significant amount of expressions of IL-1alpha, -1beta, and -6 were observed after the early days of transplantation of human RPE or IL-1alpha, -1beta, and TNF alpha of rat IPE, if we compare them to vehicle-only injection. These cytokines may play an important role for the local reaction after transplantation.

Quantitative analysis of major histocompatibility complex class II-positive cells in posterior segment of Royal College of Surgeons rat eyes.

Potential antigen-presenting cells in the posterior segment of Royal College of Surgeons (RCS) rat eyes were analyzed quantitatively. Light microscopic immunohistochemistry was performed at postnatal days (P) 10, 20, 28, 42, 63, and 140 in the eyes of RCS rats and their congenic counterparts. Immunohistochemical studies were carried out using monoclonal antibodies against major histocompatibility complex (MHC) class II antigen (OX6), a cytoplasmic antigen in bone marrow-derived macrophages (ED1), a membrane antigen on resident tissue macrophages (ED2), and a microglia/macrophage marker (OX42). Some sections were stained by a double-labeling method using these antibodies. No MHC class II-positive cells were seen in dystrophic RCS rat retinas at P10. They were found, however, in the outer nuclear layer and debris of outer segments at P20. From P20 to P42 the number of cells increased, then decreased until P140. Congenic controls, however, showed no MHC class II-positive cells in the retina. Cells double-labeled with OX6 and ED1 were present in the outer nuclear layer at P42, but no OX6 or OX42 double-labeled cells were detected. Also, no ED2-positive cells were detected. Our results suggest that MHC class II-positive cells may play some role in retinal dystrophy.

Epidural spinal cord compression as an initial symptom in childhood acute lymphoblastic leukemia: rapid decompression by local irradiation and systemic chemotherapy.

We treated an 11-year-old girl with spinal cord compression near an epidural tumor. Bone marrow examination confirmed the diagnosis of acute lymphoblastic leukemia (ALL). To reduce the compression we treated her immediately with high-dose dexamethasone and vincristine administered intravenously along with local irradiation. Three days later, radiation was discontinued because magnetic resonance imaging showed that the spinal cord compression was reduced. Complete remission has continued without evidence of neurologic sequelae for more than 3 years since diagnosis. Rapid reduction of the blasts resulted in tumor lysis syndrome, which was treated with conventional management and additional diuresis without hemodialysis. Epidural spinal cord compression in childhood ALL can be treated effectively with systemic chemotherapy and local radiotherapy without laminectomy.

Clinical course and outcome of idiopathic membranous nephropathy in Japanese children.

We retrospectively studied 12 Japanese children (8 boys, 4 girls) with idiopathic membranous nephropathy (IMN), aged 2.9-15.8 (mean 7.7) years at onset. All patients were identified through either screening or a routine urinalysis; proteinuria was present in all, haematuria, which was macroscopic in 4, in 11. Three had nephrotic syndrome (NS) at or soon after onset. Stages on electron microscopy, performed in 10 patients, were I in 3, II in 5 and III in 2. Steroids alone or with cyclophosphamide were administered to 5 patients, including the 3 patients showing NS. Complete remission of proteinuria occurred in 8 patients 0.3-1.6 (mean 0.6) years after onset, and proteinuria did not recur. After a follow-up of 1.6-11.6 (mean 5.9) years, these 8 patients were in complete remission and the remaining 4 had only mild proteinuria; none had hypertension or impaired renal function. Thus, we infer that IMN in Japanese children may have a better course and outcome than IMN in non-Japanese children. Based on a comparative study of Japanese (previously reported cases added to ours) and non-Japanese (mostly Caucasian) children with IMN, this was confirmed; it is possible that steroid therapy in Japanese patients is more effective in inducing remission of NS and preserving renal function.

Prevention and control of nosocomial infection caused by methicillin-resistant Staphylococcus aureus in a premature infant ward--preventive effect of a povidone-iodine wipe of neonatal skin.

In early 1983 we experienced a small scale epidemic of Staphylococcus aureus coagulase type IV in the premature infants unit. Children had bacteraemia or impetigo. The microorganism was resistant to methicillin, erythromycin and lincomycin and was susceptible to tetracycline, chloramphenicol and cefmetazole. The results of coagulase typing and antimicrobial sensitivities indicated that these cases represented nosocomial infection with MRSA. The source and route of the infection were investigated, and measures were taken to prevent bacterial spread from carriers and to keep instruments and environments clean. As the source of infection was not identified, we tried wiping the body surface of the premature infants with a diluted IsodineR solution (10% povidone-iodine; 1:100 dilution) in order to prevent colonization of the microorganism on the body surface. As a result, no additional MRSA infection occurred in the premature infant unit. During the subsequent 6 years of frequent surveys of carriers and wiping the appropriate body surface with diluted IsodineR solution we have had no recurrence of MRSA. None of the premature infants wiped with IsodineR solution showed any objective abnormalities, although laboratory testing disclosed an elevated blood iodine level and a transient mild reduction of T4 in some infants.

Entrapment of left renal vein in children with orthostatic proteinuria.

We found that patients with orthostatic protein-uria had entrapment of the left renal vein (LRV) by the aorta and superior mesenteric artery (SMA). Of 15 patients studied, ultrasonographic examination showed 13 cases of typical LRV entrapment with prestenotic dilatation, and 2 cases of mild LRV compression between the aorta and SMA. Intra-arterial digital subtraction angiography and monitoring of pull-back pressure from LRV to the inferior vena cava (IVC) were performed on 2 patients with 4+ proteinuria. Accumulation of contrast medium was seen with mild back-flow to the collateral veins, and pressure gradients between LRV and IVC were 4 mmHg and 8 mmHg, respectively. Eighty school-children formed a control group and were investigated ultrasonically. Nine showed typical LRV entrapment, among whom 3 had moderate to massive orthostatic proteinuria. The discovery of LRV entrapment in patients with orthostatic proteinuria gives definite evidence of LRV congestion and may be possibly a cause of massive protein secretion from the left kidney.

[Prevention and control of nosocomial infection caused by methicillin resistant Staphylococcus aureus in premature infant ward--prevention effect of "povidone iodine solution" wipe of neonatal skin].

In January 1983, a number of premature infants under management in the premature infants' unit of our hospital were found to have bacteremia due to Staphylococcus aureus. By the end of February of the same year, 4 of these infants, who had been treated in the same unit, developed impetigo. The S. aureus responsible for this condition was classified as type IV by a coagulase typing. In a subsequent antimicrobial susceptibility test using the disk diffusion method, this microorganism was found to be resistant to methicillin, erythromycin and lincomycin, and to be susceptible to tetracycline, chloramphenicol and cefmetazole, indicating that it was a methicillin resistant S. aureus (MRSA). Because the result from the coagulase typing agreed with the antimicrobial susceptibility pattern in all cases, we concluded that these cases represented nosocomial infection with MRSA. The source and route of the infection were investigated, and measures taken to prevent bacterial spread from carriers and to keep instruments and environments clean. Although the source of infection was not identified. Then, we tried wiping the body surface of the premature infants with an Isodine solution (10% PVP-I, 1:100 dilution) in order to prevent colonization of the microorganism on the body surface. With this application+, MRSA was no longer detected from the body surface of the premature infants, and no additional MRSA infection occurred in the premature infants' unit. Data collected for premature infants' managed at our hospital in the subsequent 6 years allows us to conclude that MRSA infection can be almost completely controlled by frequent surveys of carriers and appropriate body surface wiping with Isodine solution.(ABSTRACT TRUNCATED AT 250 WORDS)

A case of pyloric atresia associated with junctional epidermolysis bullosa.

We describe an infant with congenital pyloric atresia associated with junctional epidermolysis bullosa, which is now recognized as an autosomal recessive syndrome. Laparotomy revealed a membrane in the pyloric antrum. Clinical manifestations included intractable diarrhoea and malnutrition due to protein-losing gastroenteropathy. A satisfactory nutritional state could not be obtained during the clinical course and the child died.

Intra-arterial digital subtraction angiography for children with idiopathic renal bleeding: a diagnosis of nutcracker phenomenon.

Among children with asymptomatic hematuria, 28 cases of nonglomerular idiopathic renal bleeding were subjected to this series of study. Intra-arterial digital subtraction angiography (DSA) and/or renal venography were performed to investigate the hematuria of unknown etiology. DSA clearly demonstrated the entrapment of the left renal vein (LRV), or nutcracker phenomenon in the majority of our patients (22 out of 28 cases): obstruction of the LRV with well-developed collaterals were found in 8 cases, and in the remaining 14 cases, various degrees of LRV compression were demonstrated. A characteristic real-time DSA image was the congestion of LRV associated with collaterals and/or intermittent venous flow at the compressed segment of LRV. The pullback pressures from LRV to the inferior vena cava (IVC) that were obtained from 5 of these patients demonstrated gradients of 2 mmHg (3 cases), 3 mmHg (1 case), and 5 mmHg (1 case), respectively. The parallel application of ultrasonography has given positive signs for LRV entrapment, although they have not necessarily coincided with the existing criteria of nutcracker phenomenon. Considering the high incidence of LRV entrapment among children with nonglomerular hematuria, most nutcracker phenomenon should be diagnosed on ultrasonography. However, intra-arterial DSA is an important tool to establish the disease entity and ultrasonic criteria.

Transient neonatal hyperthyroidism and maternal thyroid stimulating immunoglobulins.

Serum thyroid stimulating hormone binding inhibitor immunoglobulins (TBII) and thyroid stimulating antibody (TSAb) concentrations were measured in three pregnant women with hyperthyroidism and then in their infants. The results suggested that TBII concentrations in infants in the neonatal period or from mothers during the third trimester of pregnancy showed a good correlation with the development of neonatal hyperthyroidism.

Carcinoma of the pancreas with endocrine component in childhood. A case report.

A case of pancreatic tumor in a six-year-old girl is presented. The tumor had histologic characteristics of acinar cell carcinoma with endocrine component. Grossly, it was encapsulated and attached to the tail of the pancreas, measuring 8 cm in the greatest diameter. Histologically, the tumor was composed of medium-sized tumor cells, with mild pleomorphism showing mainly acinar structures. Many of these tumor cell contained fine granules that were periodic acid-Schiff positive, diastase resistant, and positive with dimethylaminobenzaldehyde nitrite strain for tryptophan, and some contained granules that were positive with Grimelius stain and positive with peroxidase-antiperoxidase technic for gastrin. Electron microscopy revealed two types of membrane-bound granules in the tumor cells. The larger granules measured 400-700 nm in diameter and appeared to be zymogen granules, while the smaller ones measured 100-200 nm in diameter and appeared to be neuroendocrine granules. Some cells contained both granules. The postoperative course of the patient was excellent, and she was alive and well 13 years after operation. This may be the second reported case of acinar-endocrine cell tumor of the pancreas.

An unusual case of metaphyseal chondrodysplasia with an abnormal perilacunar matrix associated with agranulocytosis and hypoplasia of the thymus.

We report herein an unusual skeletal dysplasia in a 6-month-old boy characterized by metaphyseal dysplasia associated with agranulocytosis and hypoplasia of the thymus. A radiological survey revealed generalized metaphyseal abnormalities showing widening and increased density. Pathological changes in the chondro-osseous tissues were unusual and distinctive. There was widespread evidence of abnormal chondrocytes with an abnormal perilacunar matrix containing a PAS-positive, diastase resistant substance. Chondrocyte maturation and regular columnar arrangement were absent in most growth plates with only scattered ball-like nests of chrondrocytes showing incomplete maturation. This case is a newly described form of osteochondrodysplasia.