A case of polycythemia vera complicated by chronic renal failure under hemodialysis requiring parathyroidectomy for secondary hyperparathyroidisim

A case of polycythemia vera complicated by chronic renal failure under maintenance hemodialysis requiring parathyroidectory (PTH) for secondary hyperparathyroidism (2° HPT) is reported. A 62 year old female presented with 75000 white blood cells (WBC)/μl, 703×10⁴ red blood cells (RBC)/μl, 23×10⁴ platelets (PLT)/μl, hyperuricemia and hypertension in 1970 and the diagnosis of polycythemia vera was made. Hemodialysis was started in October 1974 for chronic renal failure. Blood cells in peripheral blood rapidly decreased in number after the beginning of dialysis, reaching the level of 10000∼20000 WBC/μl, and 150∼250×10⁴RBC/μl. In August 1988, marked bone resorption in X-ray picture and high serum alkaline phosphatase and parathyroid hormone (PTH) noted along with 17400 WBC/μl, 370×10⁴RBC/μl and 35.9×10⁴PLT/μl. After subtotal PTX removing 3.21g parathyroid gland, serum PTH rapidly fell. At 3 months after PTX, WBC rose to 23600/μl, RBC 372×10⁴/μl and PLT 94.0×10⁴/μl. At 6 months, WBC was to 31000/μl, RBC 429×10⁴/μl and PLT 78.0×10⁴/μl, suggesting an inhibitory action of PTH on not only RBC, but also WBC and PLT.     

Immediate changes in subcellular structures of transplanted tumors following photodynamic and laser hyperthermic therapy

Background and Objective: To further understand the precise process of the tumor cell degeneration after photodynamic therapy (PDT), laser hyperthermic therapy (LH), and combined treatments using an Nd:YAG laser. It is important to examine initial morphological alteration of tumor cells after these treatments. Study Design/Materials and Methods: In this study, nude mice bearing HeLa cell tumors were treated with PDT, LH, and combined treatments of the two. Tumor tissues obtained immediately after these treatments were analyzed using electron microscopy and morphometry. Results: In the combined treatments, which produced more severe effects on tumor cells, morphological features of apoptosis such as cytoplasmic condensation, blebs, and apoptotic bodies appeared in the cells, although the typical alteration in the nuclear chromatin was not seen. Conclusion: Cytoplasmic alterations may proceed more rapidly than nuclear alterations in the cellular degeneration induced by the single or combined treatments of PDT and LH.     

Development of GFAP-positive cells and reactive changes associated with cystic lesions in HTX rat brain.

HTX rat, a congenital hydrocephalic strain, develops ventricular dilatation and cystic cavities in the cerebral white matter after birth. To investigate the reactive changes in glial cells around these cavities, immunohistochemical staining for glial fibrillary acidic protein (GFAP), a specific marker protein of astrocytes, and bromodeoxyuridine (BrdU), a thymidine analogue, was carried out on 107 Wistar and HTX rat brains from birth to postnatal day (P) 26. Animals were divided into three groups: Group A, Wistar rats as normal controls; Group B, HTX rats with a normal structure or only mild ventricular dilatation without any lesion in the white matter; and Group C, HTX rats with severe ventricular dilatation and cyst formation in the white matter. Group B rats showed similar development of GFAP-positive (GFAP+) cells to that in Group A rats, both morphologically and quantitatively. On the other hand, Group C rats showed definite structural changes in GFAP+ cells around the cystic cavities from P5. These included enriched cytoplasm and thickened cell processes with increased GFAP expression, and enveloped most cyst walls from P10. However, quantitative examination of the percentage of GFAP+ cells in Group C rats showed a similar developmental profile to those in Group A and B rats. Furthermore, the labeling index of BrdU-positive cells, indicating S-phase cells, in the white matter in Group C rats showed a similar decreasing pattern to that in Group A and B rats from P1 to P26.(ABSTRACT TRUNCATED AT 250 WORDS)     

Association of Vascular Endothelial Growth Factor Expression with Tumor Angiogenesis and with Early Relapse in Primary Breast Cancer

Angiogenesis is an independent prognostic indicator in breast cancer. In this report, the relationship between expression of vascular endothclial growth factor (VEGF; a selective mitogen for endothelial cells) and the microvessel density was examined in 103 primary breast cancers. The expression of VEGF was evaluated by immunocytochemical staining using anti-VEGF antibody. The microvessel density, which was determined by immunostaining for factor VIII antigen, in VEGF-rich tumors was clearly higher than that in VEGF-poor tumors ( P <0.01). There was a good correlation between VEGF expression and the increment of microvessel density. Furthermore, postoperative survey demonstrated that the relapse-free survival rate of VEGF-rich tumors was significantly worse than that of VEGF-poor tumors. It was suggested that the expression of VEGF is closely associated with the promotion of angiogenesis and with early relapse in primary breast cancer.     

Inhibition by a novel azole antifungal agent with a geranyl group on lanosterol 14 alpha-demethylase of yeast.

AFK-108 (1-[2-(2,4-dichlorophenyl)-2-((2E)-3,7-dimethylocta-2,6- dienyloxy)ethyl]-1H-imidazole) is a new imidazole derivative characterized by a geranyl substituent showing strong antifungal activity. Azole antifungal agents are known to be potent inhibitors of lanosterol 14 alpha-demethylase (P450(14)DM) of fungi. The role of the geranyl group of AFK-108 on interaction of AFK-108 with the target was studied by using Saccharomyces cerevisiae P450(14)DM as the model enzyme. AFK-108 and some of its derivatives bound to oxidized P450(14)DM with one-to-one stoichiometry and inhibited the demethylase activity. AFK-108 derivatives having the longer farnesyl or the shorter prenyl group showed lower affinity than AFK-108 for the enzyme. AFK-108 caused 100% inhibition at the equivalent concentration to P450(14)DM in the reaction mixture (0.07 microM), while the farnesyl derivative inhibited the activity by 60% at the same concentration. AFK-108 interfered with the binding of CO to the ferrous P450(14)DM. However, the interfering effect of the prenyl derivative was lower than that of AFK-108. Another AFK-108 derivative having the saturated 3,7-dimethyloctyl group was also a weaker inhibitor than AFK-108. These experiments suggest that the geranyl group of AFK-108 interacts with the substrate binding site of P450(14)DM that recognises the side chain of the substrate. AFK-108 is the first example of an azole derivative interacting with the side chain recognising region of the substrate binding site of P450(14)DM.     

Molecular genetics of human aldehyde dehydrogenase.

Four non-allelic genes, which encode four different aldehyde dehydrogenase (ALDH) isozymes, have been cloned and characterized at the present time. The coding nucleotide sequences, and organization of introns and exons of these genes have been elucidated. The ALDH1 gene encodes the major cytosolic ALDH1 existing in the liver and other tissues. The genetic deficiency of this isozyme was found at a low frequency (< 10%) in both Caucasians and Orientals. The deficiency and alcohol sensitivity character are inherited together in one large Caucasian family examined. The ALDH1 gene contains two hormone response elements in its upstream 5' region. The ALDH2 gene encodes the major liver mitochondrial ALDH2 which has a very low Km for acetaldehyde. The atypical ALDH2(2) allele is common (about 30%) in Orientals; and subjects with ALDH2(2) allele, both homozygous and heterozygous status, lack ALDH activity. These individuals are alcohol sensitive and have a markedly reduced risk in developing alcoholism and alcoholic liver diseases. The ALDH3 gene produces a cytosolic ALDH3 isozyme existing in the stomach and liver carcinoma but hardly in normal liver. The ALDH3 locus is polymorphic in Orientals and presumably other populations. The ALDH5 gene, which is expressed in testes and liver, is highly polymorphic in both Caucasians and Orientals. The variation of these two loci may affect the development of alcohol-related problems.     

Vasodilator effects of C-type natriuretic peptide on cerebral arterioles in rats

The vasodilator effects of C-type natriuretic peptide (CNP) were investigated in isolated rat cerebral arterioles. CNP caused dose-dependent vasodilation, maximally by 10.0±2.2% at 10⁻⁶ M. The median effective concentration (EC₅₀) was 5.2×10⁻¹⁰ M. In contrast, atrial natriuretic peptide and B-type natriuretic peptide, other members of the natriuretic peptide family, produced little or no vasodilation. Pretreatment with methylene blue (10⁻⁴ M) abolished CNP-induced vasodilation, whereas pretreatment with N^G-monomethyl-

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-arginine or indomethacin did not inhibit vasodilation. Thus, CNP is suggested to cause significant vasodilation in cerebral arterioles via a cyclic guanosine monophosphate-dependent mechanism. © 1997 Elsevier Science B.V. All rights reserved.     

Cyclic AMP-dependent phosphorylation of the rat brain ryanodine receptor.

Phosphorylation of the rat brain ryanodine receptor was studied using a monoclonal antibody, Ry-1, against the cardiac ryanodine receptor. A large polypeptide with the same SDS-PAGE mobility as that of the canine cardiac receptor was detected in rat brain membranes by immunoblotting. The brain ryanodine receptor was solubilized from the microsomal membranes with 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonic acid (CHAPS), and more than 85% of the solubilized receptor was immunoprecipitated by Ry-1. Immunoprecipitated receptors were phosphorylated by cAMP-dependent protein kinase. The ryanodine receptor was also expressed in cultured fetal rat brain neurons and was phosphorylated by treating the cells with dibutyryl cAMP. The number of cells showing a caffeine-induced Ca2+ transient was increased significantly in the phosphorylating condition. These results suggest that the Ca channel activity of the brain ryanodine receptor is regulated by cAMP-dependent phosphorylation.     

Correlation of Nuclear Morphometry and Immunostaining for p53 and Proliferating Cell Nuclear Antigen in Transitional Cell Carcinoma of the Bladder

Background :
In an attempt to determine the biological significance of nuclear morphometric findings, measurements of mean nuclear volume (MNV) and nuclear roundness factor (NRF) were compared to the immunoreactivityof p53 expression and proliferating cell nuclear antigen (PCNA) in human bladder cancer.
Methods :
MNV and NRF were measured using stereological methods. Expression of p53 and PCNA were determined by immunohistochemical staining. Specimens from 111 patients with previously untreated bladder cancer were analyzed.
Results :
The mean MNV was 235.8 ± 1 33.6 μm³ for the 81 patients with p53-labeling index (LI) less than 10% and 337.2 ± 141.0 μn³ for the 30 patients with p53 LI greater than 10% (P = 0.008). There was Resign if icant correlation between NRF and expression of p53. The mean MNV was 220.1 ± 1 20.5 μm³ for the 67 patients with PCNA LI less than 28% (the mean value of PCNA LI) and 328.9 ± 149.2 μm³ in 44 patients with PCNA LI greater than 28% (P= 0.0001). The mean NRF was 80.7 ± 4.2 for the 67 patients with PCNA LI less than 28%, and 82.3 ± 3.4 for the 44 patients with PCNA LI more than 28% (P= 0.04). Conclusion: Nuclear morphometric findings may reflect the proliferative potential of cancer eel Is of the bladder, as indicated by findings of immunostaining for p53 and PCNA.     

Human recombinant erythropoietin directly stimulates B cell immunoglobulin production and proliferation in serum-free medium.

The effect of human recombinant erythropoietin (Epo) on B cell responses was studied in a serum-free medium. Epo enhanced IgM production and thymidine uptake by a human IgM-producing lymphoblastoid cell line, CBL. This effect was specific to Epo since enhancement was blocked by anti-Epo antibody but not by control antibody. Among the various cytokines, interleukin-4 (IL-4) enhanced IgM production and thymidine uptake while IL-6 enhanced IgM production without affecting thymidine uptake. In contrast, other cytokines including IL-1 beta, IL-2, IL-5, interferon-alpha (IFN-alpha), interferon-gamma (IFN-gamma), or granulocyte/macrophage colony-stimulating factor (GM-CSF) were without effect. However, the enhancing effect of Epo is different from that of IL-4 or IL-6, since Epo effect was not blocked by anti-IL-4 antibody or anti-IL-6 antibody. Moreover, specific binding of Epo was detected on CBL cells. Epo also enhanced immunoglobulin (IgG, IgM and IgA) production and thymidine uptake by purified tonsil small resting B cells stimulated by Staphylococcus aureus Cowan strain I (SAC) or by large activated B cells. In contrast, Epo had no effect on unstimulated small resting B cells. These results indicate that Epo could directly stimulate activated and differentiated B cells and could enhance B cell immunoglobulin production and proliferation.