Mutation analysis of a Japanese patient with fucosidosis

Fucosidosis is a rare autosomal recessive disorder resulting from a deficiency of α-L-fucosidase. Recently, various mutations have been reported in this disease, but it is difficult to elucidate the phenotype from the genetic mutations. We report a patient with chronic infantile type fucosidosis, with a compound heterozygote of a nonsense mutation (W148X, Trp at codon 148 to stop codon) and a large deletion, including all exons. This is the first report of a large deletion demonstrated in fucosidosis. It is interesting that this patient has a relatively mild clinical course despite the absence of the mRNA. This case also indicates the difficulty in determining the phenotype from the genotype in fucosidosis. Received: February 19, 1999 / Accepted: April 16, 1999     

Responses of bradykinin sensitive tooth-pulp driven neurons in cat cerebral cortex

Summary The properties of single cortical neurons responding to electrical stimulation of the tooth-pulp and to intrapulpal application of bradykinin were studied in the cat. The activities of tooth-pulp driven neurons (TPNs) were recorded from the middle and anterior parts of the coronal gyrus of the cerebral cortex. Bradykinin-sensitive tooth-pulp driven neurons (BK-TPNs) were located in layer IV of area 3b of the anterior part of the coronal gyrus. These neurons had a large cutaneous oro-facial receptive field and received a nociceptive input from the facial skin as well as from the tooth-pulp. The BK-TPNs had a higher threshold and longer latency to electrical stimulation than TPNs insensitive to bradykinin (non BK-TPNs). These findings suggest that BK-TPNs in this cortical area may be involved in sensory processing of noxious information from trigeminal regions.     

Effect of an endogenous satiety substance, 2-buten-4-olide, on gastric acid secretion and experimental ulceration in rats

The involvement of a feeding-related endogenous sugar acid, 2-buten-4-olide (2-B4O) on central regulation of gastric acid secretion, and its antiulcer effects on several gastric and duodenal experimental ulcer models were investigated in rats. Spontaneous gastric acid secretion was not affected by 2-B4O at doses below 10 mg/kg. The peripheral secretagogue-stimulated gastric secretions were significantly increased by pretreatment with 2-B4O. Gastric acid secretion induced by 2-deoxy-D-glucose (2-DG) was significantly suppressed by pretreatment with 2-B4O at doses between 0.1 and 100 mg/kg. Gastric and duodenal ulcerations induced by cold stress plus indomethacin, restraint and water immersion stress, pylorus ligation or cysteamine were also inhibited by pretreatment with 2-B4O. The results suggest that antiulcer effects of 2-B4O are due to suppression of gastric acid secretion via reduction of activity of the vagus nerve and gastric-related hypothalamic neurons. Thus, 2-B4O may be useful for treatment of gastroduodenal ulcer.     

Antibodies to large glycopeptides in sera from patients with ovarian germ cell tumours

Antibodies reactive with a murine teratocarcinoma cell line (F9) were detected by immunofluorescence staining in sera from patients bearing ovarian germ cell tumour. Immunochemical studies revealed that antibodies binding to the cell surface of F9 cells react with large glycopeptides which are known to be components of F9 antigens defined by murine anti-F9 antibodies. In addition, treatment of F9 cells with retinoic acid, which induces differentiation of embryonal carcinoma cells, distinctly reduced both the ability of these antibodies to stain F9 cells and the biosynthesis of large glycopeptides by the cells. These findings indicate that the large glycopeptides precipitable by the patients' antibodies are differentiation associated antigens on characteristic embryonic cells.     

Gene therapy of Parkinson's disease using adeno-associated virus (AAV) vectors

Parkinson's disease (PD) is characterized by the progressive loss of the dopaminergic neurons in the substantia nigra and a severe decrease in dopamine in the striatum. A promising approach to the gene therapy of PD is intrastriatal expression of dopamine-synthesizing enzymes [tyrosine hydroxylase (TH) and aromatic L-amino acid decarboxylase (AADC)]. The most appropriate gene-delivery vehicles for neurons are adeno-associated virus (AAV) vectors, which are derived from non-pathogenic virus. Therefore, TH and AADC genes were introduced into the striatum in the lesioned side using separate AAV vectors in parkinsonian rats, and the coexpression of TH and AADC resulted in better behavioral recovery compared with TH alone. Another strategy for gene therapy of PD is the protection of dopaminergic neurons in the substantia nigra using an AAV vector containing a glial cell line-derived neurotrophic factor (GDNF) gene. Combination of dopamine-supplement gene therapy and GDNF gene therapy would be a logical approach to the treatment of PD.     

Cytologic diagnosis of endosalpingiosis with pregnant women presenting in peritoneal fluid: a case report

The cytologic appearance of endosalpingiosis in peritoneal fluid cytology smears has not been extensively described. We report a case of endosalpingiosis in a 29-year-old pregnant female who presented with peritoneal fluid. Dense papillary epithelial clusters with indistinct ciliated cells were found in the Papanicolaou-stained smears. However, long and delicate cilia were obvious in papillary cluster with scanning electron microscopy. Cell nuclei were oval, with finely dispersed chromatin and uniform nuclear membrane. Peritoneal fluid cytology with these findings may be helpful to suggest the probable preoperative diagnosis of endosalpingiosis or benign glandular inclusions involving the pelvic peritoneum.     

Characterization of Pseudomonas aeruginosa isolates from patients with urinary tract infections during antibiotic therapy

We characterized susceptibilities and genotypes in a series of Pseudomonas aeruginosa isolates from five cases of urinary tract infections (UTIs) to evaluate clonal shifts of carbapenem resistance. In one case, a series of isolates showed different susceptibility patterns for carbapenems but an identical genotype. In another case, genotypes varied among 4 P. aeruginosa isolates from recurrent UTIs over 9 months. Although the patient had been treated with no antibiotic immediately before isolation, the susceptibility patterns for carbapenems and ceftazidime varied. Further analysis in these two cases of outer membrane protein profiles showed that loss of OprD production resulted in reduced susceptibilities to carbapenems in all of the carbapenem-resistant isolates. Loss of OprD production was likely due to oprD gene inactivation in both of cases, since the carbapenem-resistant isolates showed no cross resistance to levofloxacin and chloramphenicol compared with the carbapenem-susceptible isolates. There was another case in which all isolates showed similar susceptibility patterns for carbapenems and ceftazidime, and an identical genotype during the intermittent use of antibiotics over 5 months. In two cases, a single course of antibiotic therapy resulted in eradication of P. aeruginosa. Our results suggest that clonal shifts of carbapenem resistance in P. aeruginosa may result from loss of OprD during antibiotic treatment. Therefore, it is important for clinicians to monitor susceptibilities to antibiotics, especially carbapenems, in P. aeruginosa isolated during therapy.