Correlation between deletion patterns of SMN and NAIP genes and the clinical features of spinal muscular atrophy in Japanese patients

We conducted molecular analysis of two candidate genes for spinal muscular atrophy (SMA), the survival motor neuron gene (SMN) and the neuronal apoptosis inhibitory protein gene (NAIP), in 16 Japanese patients with SMA and compared the phenotypic features of SMA in these patients with the corresponding genotypes. Exons 7 and/or 8 of SMN were homozygously deleted in 11 SMA type I (Werdnig-Hoffmann disease) patients, two SMA type II patients and one SMA type III patient. Exons 5 and 6 of NAIP were homozygously deleted in six SMA type I patients. No patient had a deletion in NAIP without a deletion in SMN. Mechanical ventilation was required during the first 7 months of life in the SMA type I patients who had a deletion in both SMN and NAIP. Ventilatory support was initiated within 2 years after birth in patients who had a deletion in SMN but not in NAIP. We detected homozygous deletion of exon 5 of NAIP in the unaffected mothers of two SMA type I patients. In these families, the patients exhibited a deletion in both SMN and NAIP. The parents and unaffected siblings of these patients did not have a deletion in SMN. The present findings support the hypothesis that SMN deletion plays an important role in the development of SMA and suggest that combined deletion of both SMN and NAIP may be relevant for determining the disease severity.     

Two color flow cytometric analysis of lymphocytes in HTLV-I-carrier children

Phenotypic changes in lymphocytes from healthy children with antibody for human T lymphotrophic virus type I (HTLV-I) were studied using two color flow cytometry. The subjects were high school students within a small district of Kyushu, Japan. In the carrier group, a subset of lymphocytes which expressed CD8⁺CD57⁺ was significantly lower in percentage (P < 0.01) and in number (P < 0.05). There was no significant difference between carriers and non-carriers in the percentage and number of CD4⁺ Leu8⁺cells or CD4⁺ HLA-DR⁺ cells. The IgG levels were slightly higher in carriers than in non-carriers (P < 0.05). These findings suggest that HTLV-I-infected cells may affect the immune system in healthy carrier children.     

Eicosanoid production and levels of newly characterized eicosanoid-forming enzymes in glomeruli and tubules of rat kidneys

Summary: We examined the production of prostaglandin (P0) E₂, 6-keto PGF_1α and thromboxane (Tx) B₂, the mass of cyclooxygenase (COX) isoenzymes and the activities of phospholipases A₂ and C in glomeruli, cortical tubules and medullary tubules of rat kidneys. Medullary tubules produced significantly greater amounts of PGE₂, 6-keto PGF1α. and TxB2 than glomeruli or cortical tubules. the most abundant eicosanoid in medullary tubules was 6-keto PGF1_α. By contrast, glomeruli and cortical tubules predominantly produced POE₂ (glomeruli > cortical tubules). Levels of COX 1 were markedly greater in medullary tubules than in glomeruli or cortical tubules. Glomeruli had significantly greater amounts of COX 1 than cortical tubules. Detectable amounts of COX 2 were not present in the three preparations. the activity of phospholipase (PL) A₂ against phosphatidyicholine (PC) was significantly greater in tubules (medullary tubules > cortical tubules) than in glomeruli. By contrast, there was a significant increase in the activity of PLA₂ against phosphatidylethanolamine (PE) in glomeruli as compared to tubules (medullary tubules > cortical tubules). the activity of PLC was the Weatest in medullary tubules. Glomeruli had significantly greater activity of PLC than cortical tubules. the order of magnitude for the total activity of the three phospholipases in membranes was medullary tubules> glomeruli> cortical tubules. the total production rate of POE₂, 6-keto PGF1α and TxB₂ was in parallel with the amount of COX 1 and the total activity of membranous phospholipases A₂ and C in the three preparations. In conclusion, there are differences in the production of PGE₂, 6.-keto PGF1α and TxB₂, the ainount of COX 1 and the activities of phospholipases A₂ andC among glomeruli, cortical tubules and medullary tubules of rat kidneys; and the different aspects of COX 1 and phospholipases A₂ and C have a key role in the control of eicosanoid production in the three preparations.     

A pilot study evaluating a new questionnaire for prostatic symptom scoring, the SPSS, and its sensitivity as constructed to objective measures of outflow obstruction

AIM: To evaluate the extent to which our newly developed questionnaire, the Saitama Prostate Symptom Score (SPSS), for prostatic symptom scoring reflects objective findings in benign prostatic hyperplasia (clinical BPH) and to compare it with the International Prostate Symptom Score (IPSS) with regard to diagnostic sensitivity in clinical BPH. METHODS: In this study, both the SPSS and the IPSS were self-administered by patients. Free uroflowmetry, a pressure-flow study and the measurement of prostatic volume were carried out. RESULTS: There was no significant correlation between the results of the IPSS questionnaire and the urethral obstruction grade estimated by Schaefer or Abrams-Griffiths nomograms. The total score of the SPSS was correlated with these nomograms (P = 0.0487 and P = 0.0413, respectively). There was no significant correlation between the results of the IPSS questionnaire and the total volume or transition zone volume of the prostate, whereas the total score of the SPSS correlated with the total volume of the gland and transition zone volume (P = 0.0044 and P= 0.0051, respectively). CONCLUSION: This study revealed the SPSS to correlate with objective findings satisfactorily. However, there are still several aspects of the SPSS which need to be improved upon, and the questionnaire should be studied in larger numbers of patients suffering from lower urinary tract symptoms.     

Optimal dosage and differences in therapeutic efficacy of IGIV in Kawasaki disease

In an initial study, three groups of patients with Kawasaki disease received either aspirin alone or alkylated immunoglobulin G intravenous preparation (IGIV) 200 mg/kg daily x3 days + aspirin, or 400 mg/kg alkylated IGIV daily x3 days + aspirin. In a second study, three groups of patients were treated with either 100, 200 or 400 mg/kg of native IGIV in combination with aspirin daily for 5 days. While the regimen of 200 mg/kg native IGIV daily x 5 days was found to be effective, the incidence of coronary artery lesions (CAL) was even less on a regimen of 400 mg/kg daily x 5 days. It is therefore suggested that a better therapeutic effect can be achieved with a 400 mg/kg dose of native IGIV. Based on the results from these two studies, it is assumed that native IGIV is more effective in inhibiting CAL formation and persistence than the chemically modified preparation in which the biological activity of the Fc region in the immunoglobulin G molecule is altered.