Two mutations remote from an exon/intron junction in the beta-hexosaminidase beta-subunit gene affect 3'-splice site selection and cause Sandhoff disease.

Four unrelated Japanese patients with infantile Sandhoff disease (beta-hexosaminidase beta-subunit deficiency) have been studied for the molecular basis of their severe phenotype. Two patients had complex base substitutions; one patient was homoallelic for a triple mutation (P417L, K121R, and S255R) and the other was a compound heterozygote of a double (P417L and K121R) mutation and the triple mutation. K121R is known to be a functional polymorphism, while P417L (exon 11, +8 C-->T) generates predominantly an abnormally spliced mRNA at base +112 of exon 11 and has been described in two patients with a juvenile form of the disease.

[Accumulation of a photosensitizer ATX-S 10 Na (II) to experimental corneal neovascularization].

In order to determine the most appropriate time point for laser irradiation in photodynamic therapy with a new photosensitizer, ATX-S 10 Na (II), which produces selective occlusion of new vessels, we investigated the time course of plasma levels of ATX-S 10 Na (II) after intravenous administration and degree of dye accumulation in the corneal neovascularization in rabbit eyes. Plasma ATX-S 10 Na (II) concentration decreased rapidly after injection and become virtually undetectable at 24 h, indicating rapid excretion from the body. Nitrogen-pulsed laser spectrofluorometry demonstrated that the amount of ATX-S 10 Na (II) in new corneal vessels increased and reached a maximal level 2 to 4 hours after dye injection.

[Disorders of choroidal circulation in diabetic maculopathy].

Diabetic maculopathy is classified into 3 types, namely, macular edema, ischemic maculopathy, and pigment epitheliopathy. Blood-retinal barrier disturbance and the influence of the posterior vitreous membrane have been reported as the cause of diabetic maculopathy. However, its association with the choroidal circulation feeding the outer layer of the retina which involves the outer blood-retinal barrier has not been clarified yet.

[The correlation between gap junction-mediated communication and cell proliferation among retinal pigment epithelial cells].

I investigated gap junction-mediated intercellular communication during cell proliferation of retinal pigment epithelium (RPE) following experimental retinal tear formation in albino rabbit eyes. I used a dye-coupling method with lucifer yellow CH. I also evaluated the expression of proliferating cell nuclear antigen (PCNA) in the RPE cells.

[The effectiveness of neoadjuvant chemotherapy for invasive bladder cancer].

Background: Sixteen patients with invasive bladder cancer were received neoadjuvant methotrexate, vinblastine, pirarubicin and cisplatin chemotherapy on our planning protocol.

Methods: The tumor was evaluated after 1 course of chemotherapy by radiographic examination, urine cytology, cystoscopy and random biopsy. If the response is CR or PR, one more course of chemotherapy was performed, and cystectomy was carried out.

[Acid lipase deficiency: Wolman disease and cholesteryl ester storage disease].

Wolman disease and cholesteryl ester storage disease (CESD) are caused by a deficiency of lysosomal acid lipase activity, resulting in massive accumulation of cholesteryl ester and triglycerides. Wolman disease occurs in infancy, with hepatosplenomegaly, steatorrhea and adrenal calcification. It is fatal before the age of 1 year.

[A sensitivity of CRP determination of cord blood and neonatal serum for neonatal infection].

CRP was determined for 110 cord bloods and peripheral blood of 36 newborns collected within 72 hours after delivery for the early diagnosis of newborn infection. The determination of CRP was done by a counting immunoassay method using PAMIA-30(Sysmex, Kobe, Japan). Sample volume needed was small and the time for determination was short.

[Embolization of varicocele with ethanol].

Embolization with ethanol was performed in 40 varicocele patients to prevent recurrence due to collateral formation. A prescribed amount of ethanol (0.5-4 ml) was injected slowly into the testicular vein with the catheter tip as close as possible to the inguinal region.

Effect of hyperthermia on tumor uptake of radiolabeled anti-neural cell adhesion molecule antibody in small-cell lung cancer xenografts.

Unlabelled: This study was performed to examine the effect of hyperthermia on the intratumor accumulation of a monoclonal antibody (Mab) in an animal model. Mab NE150 (IgG1) recognizes the neural cell adhesion molecule (NCAM) expressed by human small-cell lung cancer (SCLC) cells.

Methods: Athymic mice inoculated with NCI-H69, an SCLC cell line, received an intravenous injection of 125I- and 111In-NE150 and the serial changes of the biodistribution were determined.

[Systemic hemodynamics and renal blood flow in glycerol induced acute renal failure].

In our previous papers, we reported change in the systemic hemodynamics in rats with glycerol-induced acute renal failure, as estimated by the microsphere method. It was found that the development of acute renal failure related not only to renal blood flow, but also to the hepatic blood flow. In view of the liver playing an important role in the metabolism of substances, such as drugs, and in blood circulation, we examined changes in the systemic circulation and blood chemistry in rats with thioacetamide-induced liver cirrhotic, and those rats injected with glycerol.

The major mutation among Japanese patients with infantile Tay-Sachs disease: a G-to-T transversion at the acceptor site of intron 5 of the beta-hexosaminidase alpha gene.

A G-to-T substitution at the 3'-splice site of intron 5 in the beta-hexosaminidase alpha-subunit gene has been identified among Japanese patients with infantile Tay-Sachs disease. Of the 24 patients from 24 unrelated families, 15 were homozygous and 8 were heterozygous for this mutation (38/48 mutant alleles). The mutation causes a splicing abnormality, and the resultant mRNA lacks the exon 6 sequence.

Prostate cancer: arterial infusion chemotherapy and alteration of intrapelvic blood flow.

Twenty-one patients with prostate cancer underwent intermittent arterial infusion chemotherapy with an implanted reservoir and alteration of the intrapelvic blood flow. One internal iliac artery was embolized with steel coils so that the drugs would perfuse throughout the tumor through a single tube. Angiography performed after embolization showed distinct tumor vessels.

Segmental gut transit in diabetes mellitus: effect of cisapride.

Gut transit using radiopaque markers was assessed in 5 healthy subjects and 24 diabetic patients. In the diabetics, various parameters including duration of the disease and diabetic complications, such as neuropathy, retinopathy and nephropathy, were determined, and the relationships between gut transit times and these complications were evaluated. The effect of cisapride on gut transit was studied in 10 diabetic patients.

[Changes in blood pressure in two types (absolute and relative) of pregnancy induced hypertension (hypertensive type of toxemia)].

The criteria for pregnancy induced hypertension (PIH: hypertensive type of toxemia) have been determined by the Japanese Obstetrics and Gynecology Society. Mild PIH is classified into two types. One is "Absolute PIH (A-PIH)" diagnosed by (1) systolic blood pressure (SBP) greater than or equal to 140 mmHg and less than 160 mmHg or (2) diastolic blood pressure (DBP) greater than or equal to 90 mmHg and less than 110 mmHg.

Clinical evaluation of intermittent arterial infusion chemotherapy with an implanted reservoir for hepatocellular carcinoma.

A total of 45 patients with advanced hepatocellular carcinoma were treated at Osaka City University Hospital by intermittent arterial infusion chemotherapy with an implanted reservoir. The treatment consisted of intermittent infusion of doxorubicin (5-20 mg/body), mitomycin C (4-10 mg/body) or degradable starch microspheres (600-1200 mg/body) plus doxorubicin (30 mg/body). In all, 26% of the patients received this treatment for disease recurrence following transcatheter arterial embolization (TAE).

[Clinical backgrounds in two kinds (absolute and relative) of mild pregnancy induced hypertension].

The criteria for pregnancy induced hypertension (PIH) have been determined by the Japanese Obstetrics and Gynecology Society. Mild PIH is classified into two types. One is "Absolute-PIH (A-PIH)" diagnosed by 1) systolic blood pressure (SBP) greater than = 140mmHg and less than 160mmHg or 2) diastolic blood pressure (DBP) greater than = 90mmHg and less than 110mmg.

Effects of maternal postural change from supine to left-lateral on tocolysis, maternal cardiac function and pulsatility index of uterine artery.

In order to prove the usefulness of the left-lateral position (l-lat.) in preventing the cardiovascular complications associated with ritodrine, twenty-nine patients having preterm labor were employed as the subjects of this study. Before and during the administration of ritodrine, the cardiac function was recorded by impedance cardiography.