Quantitative analysis of the suppressive effect on the light rise of the hypertonic solution

We previously reported the hyperosmolarity response (a decrease of the ocular standing potential by hyperosmolarity) as a new clinical test of the retinal pigment epithelium (RPE) activity. In the present study a hypertonic solution (Fructmanit, 1.4 × 10³ m0sm/1) was intravenously injected for 20 min in proportion to a subject's total blood volume (TBV). At the injection speed of 5, 10, and 15% of the subjects' TBV per hour the mean amplitude of the hyperosmolarity response in normal subjects was 19.7, 30.1 and 36.4% respectively. The amplitude of the hyperosmolarity response depends on the logarithm of the dose of the hypertonic solution within the range of the dose tested.We previously found that hyperosmolarity suppresses the light rise. The present study investigated this suppressive effect in a quantitative manner. The light rise (a full-field illumination of 1.2 × 10³ cdl/m²) was dose-dependently suppressed by Fructmanit. The mean of the light rise to dark trough ratio in normal subjects was 1.81 with no osmotic stress, and 1.64, 1.41 and 1.29 respectively at the injection speeds of 5, 10, and 15%. The suppression of the light rise by hyperosmolarity is compatible with the view that the hyperosmolarity response and the light rise share the basal membrane of the RPE as the main site of their generation.     

A case of Machado-Joseph disease--cerebral blood flow and cerebral metabolic rate of oxygen]

A 51-year-old woman, with progressive gait disturbance and dysarthria, had been diagnosed as Menzel-type spinocerebellar degeneration. Later, she developed dystonic posture of upper limbs and bulging eyes. She was diagnosed as Machado-Joseph disease from neurological findings, which consisted of cerebellar signs, pyramidal tract signs and extrapyramidal tract signs and peripheral neuropathy. She died suddenly of unknown origin. Her illness lasted about 13 years. Neuropathological findings showed moderate neuronal loss with gliosis in the subthalamic nucleus, globus pallidus, substantia nigra, dentate nucleus, oculomotor and hypoglossal nucleus and anterior horn. Positron emission tomography (PET) using 15O steady state inhalation technique revealed reduction of cerebral blood flow and cerebral metabolic rate of oxygen in not only cerebellum but also cerebral cortex. These findings are different from typical PET findings of spinocerebellar degeneration.     

Experimental model of chronic tonsillar herniation associated with early stage syringomyelia

This report describes an experimental model of chronic tonsillar herniation and its effects on the spinal cord. In ten rats, a small piece of chemically induced mammary cancer was transplanted to the supraoccipital bone. In all cases, the transplanted cancers grew into the posterior fossa, destroying the supraoccipital bone and compressing the cerebellum extradurally. In six of the ten rats, tonsillar herniation was observed at 8–14 weeks after transplantation. Transdural infiltration of the tumor cells was not apparent in any animal. In those rats with tonsillar herniation (n=6), the spinal cord from the C5 to the T8 segments showed enlargement of the central canal without exception. Histological examination revealed the following changes: stretching and thinning of the ependymal cells; swelling of the astrocytic processes; and extracellular edema, predominantly in the dorsal gray matter, but also in the ventral inner portion of the dorsal column. In the control group (n=4) and those rats without tonsillar herniation (n=4), such histological changes of the spinal cord were not observed. Although the lesions can not be regarded as representing mature syringomyelia, they most likely constitute an earlier evolutionary stage.     

Clinical study of penile cancer]

Recent progress in molecular biology suggests a certain relationship between penile cancer and human papilloma virus infection. However, the treatment for penile cancer has not been established since each institute has experienced only a small number of patients. We analyzed the result of our treatment for 14 penile cancer patients during past twenty years. Ten of the 14 patients were initially treated for the primary lesion with a combination of peplomycin (PEP) or bleomycin (BLM) and radiation therapy. Of these, 9 were found not to have residual viable cancer cells in their primary lesions. No local recurrence was found in all 7 patients in whom the penis was preserved. This result suggests that combination of PEP (BLM) and radiation preserves the penis without increasing the risk of local recurrence. Penile cancer-related death did not occur in patients without lymph node metastasis. However, this cancer death did occur in 4 out of 7 patients with lymph node metastasis, suggesting that metastasis is one of the important prognostic factors. PEP (BLM) and radiation therapy with or without regional lymph node dissection did not improve the prognosis of patients with advanced penile carcinoma, such as with pN2, pN3 or distant metastasis. More effective management may be necessary for these patients.     

Long-term follow-up study of 268 diabetic patients undergoing haemodialysis, with special attention to visual acuity and heterogeneity

We studied the long-term outcome of 268 patients suffering fromdiabetic end-stage renal disease (DM-ESRD) treated with long-termhaemodialysis between 1978 and 1991, with special emphasis onvisual acuity as well as the heterogeneity of DM-ESRD The 50%patient survival on haemodialysis was 60 months. Visual disturbanceswere found in 73.1% (392/536) of eyes at the start of haemodialysis.Chronological assess ment of visual acuity demonstrated thestabilization of visual acuity and 87.1% (364/418) of eyes werestable, 4.8% (20/418) were improved, and 8.1% (34/418) wereaggravated in the long term respectively. The change of visualacuity was frequently seen in the short term, and rapid shiftsof body fluid to correct overhydration induced abrupt changesof glycaemic control as well as retraction of macular oedema.Hence it might be one of the factors affecting rapid changeof visual acuity in the short term. Meanwhile, long-term deterioration of visual acuity resulted from either hyperten sionunresponsive to medical treatment or poor glycaemic control.Some DM-ESRD patients had only background retinopathy at thestart of haemodialysis and these were likely to have the nephroscleroticglomerular lesion. They were old, not nephrotic and had a milddegree of diabetes during the predialysis stage. Thus, DM-ESRDpatients seem to have some heterogeneity in their clinical characteristics,and old DM-ESRD patients with only background retinopathy havethe appearance of diabetic macroangiopathy rather than microangiopathy.     

Improvement in the Treatment of Childhood Cancer: Analysis of Survival Data from the National Children's Hospital (1965-1987)

Developments in the treatment of childhood cancer have beenevaluated in patients who had been treated in the National Children'sHospital from 1965 to 1987. The total number of patients was867, of which leukemia accounted for 376, malignant lymphoma61, neuroblastoma 174, Wilms' tumor 55, yolk sac tumor 29, rhabdomyosarcoma36 and hepatoblastoma 30. Patients were divided into three timeintervals: the 1960s, 1970s and 1980s. A marked improvementin five-year survival was recognized in Wilms' tumor and yolksac tumor, amounting to 80%, followed by rhabdomyosarcoma, acutelymphoblastic leukemia and malignant lymphoma. There was noimprovement in patients with acute non-lymphoblastic leukemia,neuroblastoma and hepatoblastoma. Prognostic factors for neuroblastomawere further analyzed, and the age of onset and stage of diseasewere found to have remained constant for 23 years. Factors relatingto the improvement of survival were discussed.     

SOLITARY PLASMACYTOMA OF THE SUBMANDIBULAR LYMPH NODE WITH STROMAL AMYLOID DEPOSITS

This report concerns a case of solitary extramedullary plasmacytoma of the left submandibular lymph node in a 56-year-old man. The tumor showed monoclonal proliferation of abnormal plasma cells which revealed highly positive stainings of both methylgreen pyronin and kappa light chain using the immunoperoxidase technique in the cytoplasms, and further revealed massive'.amyloid'deposits in the stroma, which suggested the possibility of sequential amyloid formation upon the secretion of paraprotein by tumor cells.     

Bcl11b is required for differentiation and survival of alphabeta T lymphocytes

The gene Bcl11b, which encodes zinc finger proteins, and its paralog, Bcl11a, are associated with immune-system malignancies. We have generated Bcl11b-deficient mice that show a block at the CD4-CD8- double-negative stage of thymocyte development without any impairment in cells of B- or gammadelta T cell lineages. The Bcl11b-/- thymocytes showed unsuccessful recombination of V(beta) to D(beta) and lacked the pre-T cell receptor (TCR) complex on the cell surface, owing to the absence of Tcrb mRNA expression. In addition, we saw profound apoptosis in the thymus of neonatal Bcl11b-/- mice. These results suggest that Bcl11b is a key regulator of both differentiation and survival during thymocyte development.