Yeast ribosomal proteins: XI. Molecular analysis of two genes encoding YL41, an extremely small and basic ribosomal protein,from Saccharomyces cerevisiae

Summary Two genes encoding ribosomal protein YL41 were cloned from Saccharomyces cerevisiae chromosomal DNA. Both genes contain an uniterrupted region of only 75 nucleotides coding for a protein of 3.3 kD. Within the coding regions the nucleotide sequences are virtually identical, whereas in both the 5-and 3-flanking regions the two genes differ significantly from each other. The deduced protein shows an arginine and lysine content of 68 percent, i.e., 17 out of 25 residues, and the basic residues are evenly distributed over the molecule. When compared to the ribosomal protein sequences currently available no counterpart to YL41 could be found in prokaryotes and it seems likely that YL41 is a eukaryotespecific ribosomal protein.     

Mucosal carcinoma within a colonic diverticulum

We report a case of a mucosal carcinoma and adenoma within a diverticulum in the cecum. Radiographic, endoscopic, and pathologic evaluation of the tumor is presented. Surgical resection was undertaken because of the size and shape of the lesion, risk of perforation, and the possibility of malignancy. A recent review of the literature with respect to clinical signs, diagnosis, growth of the carcinoma, and treatment of tumors around or within diverticula is also presented. A carcinoma or adenoma arising within the diverticulum is very rare. Endoscopic resection of the tumor could entail the risk of perforation, because of the lack of muscular coats in the diverticula. Surgical treatment may be the procedure of choice for lesions near or within the diverticula. Received: November 19, 1998 / Accepted: March 26, 1999     

Do panty liners promote vulvovaginal candidiasis or urinary tract infections?: A review of the scientific evidence

Panty liners are used to absorb light menstrual flow, vaginal discharge, or urine leakage, or to maintain a clean, dry feeling. Allegations that panty liners may trap heat and moisture to promote vulvovaginal candidiasis (VVC) or promote colonization by microbes that contribute to urinary tract infections appear to be unfounded. As reviewed herein, measurements of the impact of panty liners on skin temperature and skin surface moisture had no clinically meaningful effect on cell densities of genital microflora. Epidemiological investigations of a potential link to VVC were either negative or were inconclusive because of confounding factors. Although enteric microbes reside on the vulva and perineum, no evidence exists that panty liner use promotes urethral colonization by enteric microbes. Moreover, a series of 13 randomized prospective trials of panty liners or ultra-thin pads demonstrated no clinically significant adverse effects either on the skin or on isolation frequencies or cell densities of representative genital microflora. Post-market surveillance systems suggest a low incidence of complaints. Evidence from vulvar clinic patients reveals no significant contribution of these products to persistent vulvar symptoms. Taken together, the scientific evidence supports the conclusion that panty liners are safe when used as intended and do not promote VVC or urinary tract infections.     

Lesion of the isthmo-optic nucleus impairs target selection for visually guided reaching

Flavonoids, which are polyphenolic compounds, have been reported to possess remarkable antioxidant and anti-inflammatory activities. Among the dietary flavonoids, fisetin (3,3′,4′,7-tetrahydroxyflavone) possesses a significant spectrum of biochemical and pharmacological actions. The present study aimed to investigate the antidepressant potential of fisetin and its possible mechanism. Two mouse models of despair tests were used to evaluate the antidepressant-like effect of fisetin. The results suggested that fisetin (10 and 20 mg/kg, p.o.) dose dependently inhibited the immobility time in both behavioral tests, while the doses that affected the immobile response did not affect locomotor activity. Two behavioral models, reserpine-induced hypothermia and ptosis, and p-chlorophenylalanine (PCPA)-induced depletion of serotonin, were used to explore the possible involvement of fisetin in the noradrenergic and serotonergic system. The higher dose of fisetin was found to effectively antagonize the hypothermia, but not ptosis, induced by reserpine. Pre-treatment with PCPA abolished the anti-immobility effect of fisetin in the forced swimming and tail suspension tests. Moreover, neurochemical assays showed that fisetin produced an increase in serotonin and noradrenaline levels in the frontal cortex and hippocampus. Monoamine oxidase (MAO) activity in the mouse brain was inhibited by 14.7% after treatment with fisetin, while MAO-B activity was not affected. These findings indicate that the antidepressant-like effect of fisetin involves the regulation of the central serotonin and noradrenaline levels.     

Biallelic loss‐of‐function UBA5 mutations in a patient with intractable West syndrome and profound failure to thrive

Mutation of the gene encoding ubiquitin‐like modifier‐activating enzyme 5 (UBA5) causes autosomal recessive early‐onset epileptic encephalopathy. UBA5 acts as an E1‐activating enzyme in the ubiquitin‐fold modifier 1 pathway, which is important for unfolded protein elimination and regulation of apoptosis, and has been linked to human diseases. We identified biallelic mutations in UBA5 in a Japanese boy with intractable West syndrome, profound failure to thrive, and severe cerebral and cerebellar atrophy. The boy presented with epileptic spasms and hypsarrhythmia at the age of three months. He was diagnosed with West syndrome, however, treatments with adrenocorticotropic hormone and several antiepileptic drugs were ineffective. MRI findings were initially normal, but subsequently showed a progression of cerebellar and cerebral atrophy. By the age of seven years, he had not achieved any developmental milestones; he had daily epileptic spasms and tonic seizures and profound failure to thrive. Gene analysis revealed novel compound heterozygous mutations in UBA5; a microdeletion encompassing the entire UBA5 gene and a putative disease‐causing missense mutation in the catalytic domain. These biallelic variants may have caused loss of function, accounting for the observed clinical symptoms. Intractable infantile epileptic spasms, failure to thrive, and severe neurological impairment may be characteristic of patients with UBA5 mutations.     

Reduced Foxp3 expression with increased cytomegalovirus-specific CTL in HTLV-I-associated myelopathy

Human T-lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients show high immune responses to HTLV-I. However, it is unclear whether the cytotoxic T lymphocyte (CTL) responses to other chronic viruses also increase. We investigated the responses in the peripheral blood by using HLA-A*0201/peptide pentamers. The frequency of cytomegalovirus (CMV)-specific CTL tended to be higher in HAM/TSP patients than in healthy controls (HCs). The frequency of CMV-specific CTL positively correlated with that of HTLV-I Tax-specific CTL. The frequency of Foxp3+ cells in CD4+ lymphocytes tended to be higher in HAM/TSP patients than in ACs and HCs. The expression level of Foxp3 was lower in HAM/TSP patients than in HCs and was inversely correlated with the CMV-specific CTL frequency. A percentage of Foxp3+ cells showed a positive correlation with the HTLV-I proviral load. These results suggest that a decrease in the Foxp3 expression may contribute to the high immune response to CMV and that the Foxp3+ regulatory T cells may play a role in the immune surveillance of HTLV-I.     

A case of hematomyelia caused by coagulation--fibrinolysis abnormality accompanied with colon cancer and its metastasis]

A 76-year-old woman developed weakness and sensory loss in the lower limbs and urinary disturbance in four days. She had a history of operation for the ascending colon cancer and lung metastasis one year ago. Neurological examination revealed flaccid paraplegia, absent Achilles tendon reflex, severe disturbance of superficial and deep sensation below the L3 level, and vesicorectal abnormality. Magnetic resonance imaging (MRI) studies showed an intramedullary T1-iso, T2-low lesion with Gd-DTPA contrast enhancement in conus medullaris at LI level. The laboratory examination revealed the elevated level of serum FDP. D-dimer and TAT. She was diagnosed as hematomyelia, which may be caused by the activation of coagulation and fibrinolysis system. We suggested that the ascending colon cancer and lung metastasis may contribute to the coagulation-fibrinolysis abnormality.     

Identification of novel low molecular weight CXCR4 antagonists by structural tuning of cyclic tetrapeptide scaffolds

A highly potent CXCR4 antagonist, compound 2, was previously found by using two orthogonal cyclic pentapeptide libraries involving conformation-based and sequence-based libraries based on the pharmacophore of a 14-mer peptidic antagonist, 1. Herein, cyclic tetrapeptides derived from replacements of the dipeptide unit (Nal-Gly) with a gamma-amino acid and pseudopeptides cyclized by disulfide and olefin bridges were synthesized to find novel scaffold structures different from that of cyclic pentapeptides. These compounds contain a reduced number of peptide bonds compared to compound 2. Furthermore, several analogues with chemical modification of the side chain of Arg(4) in 2 were also prepared. From these, several new leads possessing high to moderate CXCR4-antagonistic activity were characterized.