Treatment of delayed brain injury after pituitary irradiation

Treatment for delayed brain injury after pituitary irradiation is discussed. Six cases with delayed brain injury were treated with a combination of dexamethasone or betamethasone, with heparin, glycerol, dextran 40 and some vasodilators. Two cases with temporal lobe syndrome were treated in the early stages of brain injury for a period of over 12 months were almost completely cured, another two cases with chiasma syndrome were treated in the relatively late stages, showed a partial improvement. One case which was irradiated 120 GY during 13 years did not improve. The final case treated with steroids for a short period also resulted in failure and the patient underwent an operation for the removal of the necrotic mass three years after the radiotherapy. Steroid therapy started in the early stages of brain injury after irradiation for over the 12 months is thought to be effective. Heparin therapy was also effective in one out of three cases, but in one of the cases subarachnoid hemorrhage from a traumatic aneurysm occurred during the therapy. In an acute phase, showing edematous change of the injured brain, the administration of glycerol is also thought to be useful. But the effectiveness of the other medicines containing some vasodilators was obscure or doubtful. We propose the following: (1) A meticulous observation is essential for the patients who received high doses of irradiation to diagnose brain injury in the early reversible stage. (2) Steroids should be given immediately in this reversible stage of brain injury before the irreversible "necrosis" occurs. (3) Steroids should be maintained for a long period over 12 months.(ABSTRACT TRUNCATED AT 250 WORDS)     

Colon bladder replacement after total cystectomy

Although ileal conduit diversion is widely accepted in the treatment of the patients undergoing radical cystectomy, many patients would prefer other alternatives which allow continence. and urination through the urethra. We describe a new procedure in which a segment of detuburalized right colon is used as a continent reservoir. Eight patients, 7 after radical cystectomy for bladder cancer and one after total exenteration for rectal cancer, have undergone colon bladder replacement. New created bladder had a capacity of 300 to 600 ml. All patients could pass urine through the urethra but one is on self-catheterization. Five of the 8 patients had no residual urine. Three months after operations 4 were totally continent and 3 were satisfactorily dry during daytime but slightly enuretic. Excretory urography showed no abnormalities in their upper urinary tract. Considering the "quality of life' of a patient, this procedure can be an ideal option for selected patients.     

CD154-CD40-independent up-regulation of B7-2 on splenic antigen-presenting cells and efficient T cell priming by staphylococcal enterotoxin A

It has been demonstrated that in vivo T cell priming requires CD154-CD40 interaction, which is suggested to be critical in the induction of co-stimulatory activities on antigen-presenting cells (APC). In the current study, we demonstrate that in vivo administration of a high dose of a superantigen, staphylococcal enterotoxin A (SEA), could up-regulate B7-2 on most splenic APC independently of the CD154-CD40 interaction, followed by efficient expansion of SEA-reactive V(beta)3(+) T cells in CD154- or CD40-deficient mice. However, the CD154-CD40 interaction may be involved in SEA-mediated T cell activation, since a contribution of the CD154-CD40 interaction was observed when a lower dose of SEA was injected. CD154-independent T cell priming by SEA appeared also independent of the TRANCE-RANK pathway, which was shown to be capable of mediating CD154-independent activation of naive T cells during the infection of some viruses. These results indicate that SEA, which provokes rapid and efficient T cell responses without adjuvant, could utilize multiple CD154/TRANCE-independent pathways, to prime T cells.     

IgG HEAVY CHAIN ALLOTYPES (Gm) IN ATROPHIC AND GOITROUS THYROIDITIS

We typed coded sera from 135 healthy controls, seventy-six patients with autoimmne goitrous and seventy-three with atrophic thyroiditis for IgG heavy chain markers (Gm). All subjects were Caucasian from Newfoundland. An increase in the Gm phenotype ag was found in the 149 patients with thyroiditis compared to controls (X₁²= 5.82, P <0.01); significance was, however, not maintained after correction for the number of variables tested. The difference in ag phenotype was more pronounced among the seventy-three patients with atrophic thyroiditis (X₁²= 8.80 corrected P < 0.05). Because the haplotype ag was not significantly increased in this group, we conclude that homozygotes for Gm ag are at an increased risk of developing atrophic thyroiditis.     

Cone cGMP-gated channel mutations and clinical findings in patients with achromatopsia, macular degeneration, and other hereditary cone diseases

Unrelated patients with achromatopsia, macular degeneration with onset under age 50 years, cone degeneration or dysfunction, cone-rod degeneration, or macular malfunction were screened for mutations in the three genes known to be associated with achromatopsia: the GNAT2 gene encoding the alpha subunit of cone transducin and the CNGA3 and CNGB3 genes encoding the alpha and beta subunits of the cone cGMP-gated cation channel. We found no examples of patients with GNAT2 mutations. Out of 36 achromats, 12 (33%) had mutations in CNGA3 (13 different mutations including five novel mutations) and 12 (33%) had mutations in CNGB3 (six different mutations including four novel mutations). All achromats with CNG mutations had residual, presumably cone function as determined by computer-averaged 30-Hz electroretinograms (ERGs). There was considerable variability in acuity and color vision, with most patients having acuities of 20/200-20/400 and complete absence of color perception, and others having acuities of 20/25-20/40 and some color vision. Two pseudodominant achromatopsia cases were uncovered, both with CNGA3 mutations, including one family in which some compound heterozygotes with achromatopsia mutations were clinically unaffected. We found two novel CNGB3 changes in three patients with juvenile macular degeneration, a phenotype not previously associated with mutations in the cone channel subunits. These patients had subnormal acuity (20/30-20/60), normal to subnormal color vision, and normal to subnormal full-field cone ERG amplitudes. Our results indicate that some patients with channel protein mutations retain residual foveal cone function. Based on our findings, CNGB3 should be considered as a candidate gene to be evaluated in patients with forms of cone dysfunction, including macular degeneration.     

A promoter variant of the ATP-binding cassette transporter A1 gene alters the HDL cholesterol level in the general Japanese population

To investigate the effects of polymorphisms in the ATP-binding cassette transporter A1 (ABCA1) gene on the high-density lipoprotein cholesterol (HDL-C) level and the incidence of myocardial infarction (MI), we performed association studies. Sequence analysis identified 14 polymorphisms in the promoter region of ABCA1. After considering linkage disequilibrium, three polymorphisms in the promoter region and 11 polymorphisms from the JSNP database were determined in 1,880 subjects recruited from the Suita Study, representing the general population in Japan. We evaluated the association between the ABCA1 genotype and HDL-C level adjusted not only for standard factors, but also for genetic factors including ApoA1 and ApoE genotypes. Of the 14 polymorphisms tested, the G(–273)C (P=0.0074), C(–297)T (P=0.0195), and IMS-JST071749 (P=0.0093) polymorphisms were significantly associated with the HDL-C level in the Suita population. We could reconfirm that the G(–273)C genotype was influential in another set of subjects (P=0.0310, n=743). However, the distribution of the ABCA1 G(–273)C genotype in subjects with MI (n=598) was not different from that in the control population (n=801). These results indicate that ABCA1 G(–273)C has a significant effect on the HDL-C level in the general Japanese population, but not on the incidence of MI.     

Occlusion and subsequent re-canalization in early duodenal development of human embryos: integrated organogenesis and histogenesis through a possible epithelial-mesenchymal interaction

Histogenesis of the duodenum, especially changes in the epithelium in relation to temporal occlusion and re-canalization of the lumen, was investigated by light microscopy together with morphometric analysis, as well as by scanning and transmission electron microscopy of 133 externally normal human embryos ranging from Carnegie stage 12 to 23. A series of morphogenetic events passed the duodenum in a cranio-caudal (proximo-distal) wave like fashion during the period examined. They included: (1) a decrease in the caliber and area of the lumen, (2) ’occlusion’ of the lumen, (3) vacuole formation, (4) ’re-canalization’ and villi formation. The only exemption to this rule was that, in the upper part of the duodenum, the lumen was not obliterated in the embryos examined. Morphometric analyses revealed that both the area of the epithelium and the number of epithelial cells decreased during the ’occlusion’ phase. This result suggests that, unlike the classical view, epithelial cell proliferation does not play an important role in occluding the lumen, but the predominant morphogenetic event during this phase is convergence of the epithelial cells to elongate the duodenum. Apoptosis, contrary to some classical views, decreased during the ’re-canalization’ phase, and it appeared to be involved in the formation of the small lumens in the epithelial ’plug’ and in villi formation, but not in enlarging the secondary lumens. The secondary small lumens in the occluded lumen were frequently formed near the border between the central ’plug’ and peripheral basal cells on the basement membrane. This and other findings of concentric differentiation in both the epithelial and mesenchymal layers suggested a possible control mechanism by the epithelium-mesenchymal interaction on human duodenal morphogenesis and histogenesis. The present electron microscopic observations also provided details on the mechanisms involved in the enlargement of the secondary lumen and differentiation of villi. The implications of these findings to duodenal anomalies are also discussed. Accepted: 12 November 2001     

TUMOR CELL PHAGOCYTOSIS AND CYTOTOXICITY OF LYMPHOBLASTOID CELLS FOLLOWING CONCANAVALIN A TREATMENT

Cell-to-cell interaction was investigated in various malignant tumor cells (human ovarial tumor, lung cancer, carcinoma of larynx and hamster melanoma cell) and in human lymphoblastoid cells (T-cell (MOLT-4 cell), thymoma cells and B-cells (Burkitt lymphoma cell)). Live lymphoblastoid cells did not adhere to the cell surfaces of tumor cells nor the lymphoblastoid cells were ingested by tumor cells wihout immunologic and specific treatment. Tumor cells as well as T-cells and B-cells had receptors to concanavalin A on their surfaces, and they showed marked cell binding of tumor cells and lymphoblastoid cells. Moreover, tumor cells that phagocytized lymphoblasts underwent marked cell destruction within 4 hours of cell binding. The cytolytic mechanism of the target tumor cell was probably related to contact with the lymphoblastoid cells and was increased by ingestive activity, and metabolic disturbance by lymphotoxin in tumor cells.     

Maternal and fetal nitric oxide synthesis is decreased in pregnancies with small for gestational age infants

Our purpose was to evaluate whether maternal and fetal nitric oxide synthesis in pregnancies with small for gestational age (SGA) infants are different from those in pregnancies with appropriate for gestational age (AGA) infants. Maternal and fetal circulating nitrate and nitrite concentrations were compared between 30 pregnancies with AGA and 10 pregnancies with SGA at birth. End-products of nitric oxide synthesis were measured in maternal and cord venous blood samples using a fluorometric assay. Umbilical artery blood pH and PO2 were also measured. Maternal circulating nitrite and nitrate concentrations (6.91 +/- 1.27 microM) in pregnancies with SGA were significantly lower than those (11.69 +/- 1.33 microM) in pregnancies with AGA (P = 0.015). Fetal circulating nitrite and nitrate concentrations (7.54 +/- 1.09 microM) in pregnancies with SGA were also significantly lower than those (11.24 +/- 1.08 microM) in pregnancies with AGA (P = 0.024). There were no significant differences in umbilical artery blood pH and PO2 between the two groups. These results suggest that maternal and fetal nitric oxide synthesis are decreased in pregnancies with SGA infants.