Present status of apheresis technologies: part 4. Leukocyte filter.

This article is the fourth of a 4 part series describing the currently available apheresis devices and technologies. The sections include the following: Part 1, Membrane Plasma Separator (published in Vol. 1, No. 1); Part 2, Membrane Plasma Fractionator (published in Vol. 1, No. 2); Part 3, Adsorbent (published in Vol. 1, No. 3); and Part 4, Leukocyte Filter.     

Evaluation of the radiologic findings on hysterosalpingography by selective hydrotubation with flexible hysterofiberscope

Purpose The objective of this study was to assess further the significance and accuracy of hysterosalpingography (HSG) by comparing the radiologic findings on HSG to selective hydrotubation (SHT) using a hysterofiberscope in 106 women with tubal occlusion.Results Patency was successfully observed by SHT in 72 of 134 tubes and 62 of 106 patients. Proximal obstruction was divided into three groups according to the shape of cornual obstruction (sharp, dull, defect) on HSG. The success rate for SHT in unilateral obstruction (64%) were significantly higher than those in bilateral obstruction (39%). In the three groups of proximal obstruction, the success rates for SHT were 24, 75, and 30% in sharp, dull, and defect, respectively. The group of dull had significantly higher success rate than the groups of sharp and defect. Thirteen of 62 patients who successfully recanalized became pregnant at 9-month follow-up interval.Conclusion Careful evaluation of the cornual obstruction in radiologic findings on HSG may be important for the decision on further treatment. Furthermore, SHT using a hysterofiberscope is an effective method for evaluating tubal obstruction and for managing it in a selected group of patients with tubal obstruction.Presented at the 50th Annual Meeting of the American Fertility Society, San Antonio, Texas. November 5–10, 1994.     

Urinary cytodiagnostic abnormality in a patient with malignant lymphoma

A 69-year-old man was admitted due to chronic subdural hematoma. He had lymphadenopathies in the neck. The diagnosis of non-Hodgkin lymphoma (diffuse, large, B cell type) was made by a cervical lymph node biopsy. The renal failure by obstruction of the urinary tract developed gradually, and the tumor cells were found by urinary cytodiagnosis. He was treated immediately with chemotherapy. After the treatment, the urine volume increased and the general conditions improved. It was indicated from this case that the urinary cytodiagnosis is useful for the detection of urinary tract infiltration by lymphoma cell. The urinary cytodiagnostic abnormalities in patients with non-Hodgkin lymphomas were discussed from the literature, including this case.     

Significance of heterogeneous nuclear ribonucleoprotein B1 as a new early detection marker for oral squamous cell carcinoma.

The development of an early tumor detection marker for oral cancer is an obvious need due to the high recurrence rate and poor survival rate. Based on our previous report that overexpression of heterogeneous nuclear ribonucleoprotein (hnRNP) B1 protein was found in 100% of squamous cell carcinomas of human lung, we applied the same immunohistochemical method, using anti-hnRNP B1 antibody, to human oral squamous cell carcinoma (OSCC). Seven human tissue sections of OSCC showed strong staining with anti-hnRNP B1 antibody, and hnRNP B1 protein of 37 kDa was identified in protein fractions isolated from six of the cancerous tissue sections, while it was not found in adjacent noncancerous tissue. Moreover, three non-homogeneous (nodular) leukoplakia sections showed significant anti-hnRNP B1 staining. The results suggest that this antibody detects precancerous lesions as well as advanced lesions (stages I to IV) of OSCC. We also present positive results of cytodiagnosis for two smear specimens. All of the above results indicate that hnRNP B1 is a new and useful marker for early detection of OSCC.     

Haplotype analysis of the estrogen receptor 1 gene in male genital and reproductive abnormalities

BACKGROUND: We have recently suggested that homozygosity for a specific 'AGATA' haplotype within a approximately 50 kb linkage disequilibrium (LD) block of the gene for estrogen receptor alpha (ESR1) may raise the susceptibility to cryptorchidism by enhancing estrogenic effects of environmental endocrine disruptors (EEDs). METHODS: Haplotype analysis of ESR1 was performed in 328 Japanese subjects, i.e. 70 patients with micropenis (MP), 43 patients with hypospadias (HS), 80 patients with spermatogenic failure (SF) and 135 control males. Genotyping was performed by the 5' nuclease assay. RESULTS: The LD block was identified in each of the patient groups and in the control males. The frequency of homozygotes for the specific 'AGATA' haplotype was markedly higher in the HS patients [P = 0.0000033, odds ratio [OR] = 11.26] and slightly higher in the MP patients (P = 0.034, OR = 3.64) than in the control males, and the 'AGATA' haplotype was strongly associated with HS (P = 0.0000022, OR = 11.26) and weakly associated with MP (P = 0.040, OR = 3.64) in a recessive mode. There was no significant difference between the SF patients and the control males. CONCLUSIONS: Our results support the hypothesis that homozygosity for the specific ESR1 'AGATA' haplotype may increase the susceptibility to the development of male genital abnormalities in response to estrogenic EEDs.     

PAX9 and TGFB3 are linked to susceptibility to nonsyndromic cleft lip with or without cleft palate in the Japanese: population-based and family-based candidate gene analyses

The prevalence of nonsyndromic cleft lip with or without cleft palate (CL/P) and cleft palate only (CPO) are believed to be higher in the Japanese than in Americans, Europeans or Africans. The purpose of this study was to investigate, in a Japanese population, relationships between CL/P or CPO and seven candidate genes (TGFB3, DLX3, PAX9, CLPTM1, TBX10, PVRL1, TBX22) that showed positive associations in other populations and are expressed in the oral/lip region in developing mice. We first searched for mutations in these genes among 112 CL/P and 16 CPO patients, and found a heterozygous missense mutation (640A>G, S214G) in exon 3 of PAX9 in two sibs with CL/P and their phenotypically normal mother from a Japanese family. A population-based case-control analysis and a family-based transmission disequilibrium test (TDT), using single nucleotide polymorphisms (SNPs), and two-SNP haplotypes of the genes, between the 112 CL/P cases with their parents and 192 controls indicated a significant association at one SNP site, IVS1+5321, in TGFB3 with a P-value of 0.0016. Population-based haplotyping revealed that the association was most significant for haplotype A/A consisting of IVS1+5321 and IVS1–1572; TDT also gave a P-value of 0.0252 in this haplotype.     

Efficient Isolation of Swine Influenza Viruses by Age-Targeted Specimen Collection

The control of swine influenza virus (SIV) infection is paramount for increasing the productivity of pig farming and minimizing the threat of pandemic outbreaks. Thus, SIV surveillance should be conducted by region and on a regular basis. Here, we established a microneutralization assay specific for SIV seroprevalence surveillance by using reporter gene-expressing recombinant influenza viruses. Growth-based SIV seroprevalence revealed that most sows and piglets were positive for neutralizing antibodies against influenza viruses. In contrast, the 90-day-old growing pigs exhibited limited neutralizing activity in their sera, suggesting that this particular age of population is most susceptible to SIV infection and thus is an ideal age group for SIV isolation. From nasal swab specimens of healthy pigs in this age population, we were able to isolate SIVs at a higher incidence (5.3%) than those of previous reports. Nucleotide sequencing and phylogenetic analysis of the hemagglutinin (HA) genes revealed that the isolated SIVs have circulated and evolved in pigs but not have been recently introduced from humans, implying that a large number of SIV lineages may remain “undiscovered” in the global porcine populations. We propose that the 90-day-old growing pig-targeted nasal swab collection presented in this study facilitates global SIV surveillance and contributes to the detection and control of SIV infection.     

Disaccharide Esters Screened for Inhibition of Tumor Necrosis Factor-α Release Are New Anti-cancer Agents

Tumor necrosis factor-α (TNF-α) is a proinflammatory cytokine playing a part in various pathological states. Non-toxic inhibitors of TNF-α release are thought to be promising agents for cancer prevention. We found that the acetone fraction of the tobacco leaf surface lipid containing glucose esters and sucrose esters inhibited both TNF-α release from BALB/3T3 and KATO III cells induced by okadaic acid and tumor promotion by okadaic acid on mouse skin initiated with 7,12-dimethylbenz(a)anthracene (DMBA). Next, we investigated the inhibition of TNF-α release with synthetic disaccharide esters, such as 6,6′-di-0-alkanoyl-α,α-trehaloses (6,6′-diester-trehaloses), 4,4′-di-0-alkanoyl-α,α-trehaloses (4,4′-diester-trehaloses) and 6,6′-diamino-6,6′-dideoxy-N, N′-dial-kanoyl-α,α-trehaloses (6,6′-diamide-trehaloses) bearing fatty acids of various chain lengths, and n- dodecyl-β-D-maltoside as a disaccharide monoester. 6,6′-Diester-trehaloses and 4,4′-diester-treha-loses of C₈ to C₁₄ fatty acids, 6,6′-diamide-trehaloses of C₈ to C₁₄ fatty acids, and n-dodecyl-β-D-maltoside all inhibited TNF-α release in a dose-dependent manner. The IC₅₀ values are 7.4-14.8 μM for 6,6′-diester-trehaloses (C₈ to C₁₂), 14.6-21.6 μM 4,4′-diester-trehaloses (C₈ to C₁₂), 2.9-15.0 μM for 6,6′-diamide-trehaloses (C₈ to C₁₄) and 23 μM for dodecyl-β-D-maltoside. Both 6,6′-di-O-octanoyl-α,α-trehalose (C₈, designated as SS555) and n-dodecyl-β-D-maltoside (C₁₂) inhibited tumor promotion by okadaic acid on mouse skin initiated with DMBA. Percentages of tumor-bearing mice in week 15 of tumor promotion were reduced from 60.0 to 13.3 with SS555, and to 46.7 with n-dodecyl-β-D-maltoside. Moreover, SS555 inhibited TNF-α gene expression mediated through inhibition of AP-1 activation, but not NF-αB activation. This paper reports that diester-trehaloses of C₈ to C₁₂ fatty acids and mimics of disaccharide monoesters such as n-dodecyl-β-D-maltoside appear to be potential cancer-preventive agents of a new type.     

hnRNP B1 protein may be a possible prognostic factor in squamous cell carcinoma of the lung

Heterogeneous nuclear ribonucleoprotein (hnRNP) B1 is an RNA-binding protein that is required for the maturation of mRNA precursor. It was previously reported that hnRNP A2/B1 was overexpressed at the early clinical stage of lung cancer, and that hnRNP B1 protein, a splicing variant of hnRNP A2 mRNA, was elevated in lung cancer tissues. In this study, we applied the immunohistochemical method, using anti-hnRNP B1 antibody to analyze the usefulness of the hnRNP B1 antibody as a prognostic marker and also as a marker useful for early detection. A total of 206 specimens were examined. Histological examination revealed this protein to be positive in 79 (71.2%) of 111 squamous cell carcinomas and in 45 (64.3%) of 70 adenocarcinomas, respectively. This protein was also expressed in 24 (63.2%) of 38 roentgenographically occult carcinomas and in seven (63.6%) of 11 dysplastic lesions. These findings suggest the possible participation of this protein in early carcinogenesis. Furthermore, the survival curve of the squamous cell carcinoma patients with hnRNP B1 overexpresseion showed a better prognosis compared with that of the patients without hnRNP B1 expression (P=0.014), whereas in adenocarcinoma patients, there was no such a difference between them (P=0.889). These findings indicate that hnRNP B1 could be a useful marker for the early detection of bronchogenic squamous cell carcinoma and that it may be a prognostic factor in this cell type.