A case of bilateral aldosterone-producing adenomas differentiated by segmental adrenal venous sampling for bilateral adrenal sparing surgery.

Primary aldosteronism due to unilateral aldosterone-producing adenoma (APA) is a surgically curable form of hypertension. Bilateral APA can also be surgically curable in theory but few successful cases can be found in the literature. It has been reported that even using successful adrenal venous sampling (AVS) via bilateral adrenal central veins, it is extremely difficult to differentiate bilateral APA from bilateral idiopathic hyperaldosteronism (IHA) harbouring computed tomography (CT)-detectable bilateral adrenocortical nodules. We report a case of bilateral APA diagnosed by segmental AVS (S-AVS) and blood sampling via intra-adrenal first-degree tributary veins to localize the sites of intra-adrenal hormone production. A 36-year-old man with marked long-standing hypertension was referred to us with a clinical diagnosis of bilateral APA. He had typical clinical and laboratory profiles of marked hypertension, hypokalaemia, elevated plasma aldosterone concentration (PAC) of 45.1 ng dl(-1) and aldosterone renin activity ratio of 90.2 (ng dl(-1) per ng ml(-1 )h(-1)), which was still high after 50 mg-captopril loading. CT revealed bilateral adrenocortical tumours of 10 and 12 mm in diameter on the right and left sides, respectively. S-AVS confirmed excess aldosterone secretion from a tumour segment vein and suppressed secretion from a non-tumour segment vein bilaterally, leading to the diagnosis of bilateral APA. The patient underwent simultaneous bilateral sparing adrenalectomy. Histopathological analysis of the resected adrenals together with decreased blood pressure and PAC of 5.2 ng dl(-1) confirmed the removal of bilateral APA. S-AVS was reliable to differentiate bilateral APA from IHA by direct evaluation of intra-adrenal hormone production.

Primary aldosteronism as a cause of severe postpartum hypertension in two women.

Two women who first had the clinical features of primary aldosteronism in the postpartum period are described. Their gestations were virtually uneventful. After delivery, however, progressively severe hypertension (Joint National Committee VI, stage 3) with hypokalemia developed. Pregnancy may conceal the clinical symptoms of primary aldosteronism that causes unexpected severe hypertension in the postpartum period.

Identification of a novel promoter and exons of the c-ERBB-2 gene.

The c-ERBB-2 gene is frequently amplified in various cancers. During the course of studies on the structural characterization of the amplification units, we isolated four cDNA clones, A39, GRB7, C51 and CAB1 with corresponding genes localized on the c-ERBB-2 locus. A tentative gene, C51, was located at about 12 kb upstream of the c-ERBB-2 gene. By molecular cloning of a full-length cDNA clone of C51 and the reverse transcription PCR (RT-PCR) method, we identified a novel transcript of c-ERBB-2 containing new 5' sequences including the C51 sequence, demonstrating that the c-ERBB-2 gene has a novel promoter and new exons. The structural organization of the novel promoter and exons of c-ERBB-2 was revealed by complete sequence analysis of a total size of about 20 kb of genomic DNA clones containing the 5'-flanking region of the previously described c-ERBB-2 gene. Transient expression of the newly identified promoter-reporter gene constructs in breast cancer cell line MCF-7 showed that the elements responsible for promoter activity were contained in a 697 bp region upstream of the transcriptional start site. The new transcript may encode a protein different in the portion of the extracellular domain. Although the presence of the predicted protein product was not examined, this report is important in that it provides a new aspect of the c-ERBB-2 protooncogene products.

Deletion of the carboxyl-terminal exons of K-sam/FGFR2 by short homology-mediated recombination, generating preferential expression of specific messenger RNAs.

The K-sam gene was first identified as an amplified gene from human gastric cancer cell line KATOIII, and its product is identical to fibroblast growth factor receptor 2. The K-sam gene is located on human chromosome 10q26 and is preferentially amplified in the poorly differentiated types, especially in the scirrhous type, of gastric cancers. During the course of studies on the structural characterization of the amplification units, we found that the carboxyl-terminal exons of K-sam were deleted in three of four of the scirrhous type of gastric cancer cell lines. These deletions generate preferential expression of mRNAs encoding K-sam proteins lacking the carboxyl-terminal region containing the tyrosine residues at positions 780, 784, and 813. The carboxyl-terminal region has been reported to have a sequence required for the inhibition of NIH3T3 transformation, indicating that cells with amplification of the truncated K-sam gene have a growth advantage during the carcinogenic process for the scirrhous type of gastric cancers. This is the first report showing the deletion of the carboxyl-terminal exons of the receptor-type of the protein tyrosine kinase gene. Sequence analysis of the DNA sequences surrounding the deletion junctions shows the presence of unique sequences and indicates the involvement of short homology-mediated recombination in the generation of these deletions.

Transition Dipole Moments for the Vibrational Fundamentals of HNC Determined from the Herman-Wallis Effect.

The nu1 and nu3 fundamental bands of HNC are recorded with a Fourier transform infrared spectrometer with a resolution of 0.008 cm-1. Hydrogen isocyanide is generated in situ by dc discharge in a mixture of CH3CN ( approximately 40 mTorr), H2 ( approximately 160 mTorr), and Ar ( approximately 160 mTorr). The transition dipole moments for these fundamental bands are determined from the analysis of the Herman-Wallis effect, and they are compared with ab initio calculated values. It is found that the ab initio values for the nu1 and nu3 bands are about 50 and 30% larger, respectively. The transition dipole moments determined are to be of use for determination of the abundance of HNC in reaction systems such as the dissociative recombination reaction of HCNH+ with electrons. Copyright 1998 Academic Press.

Presence of Streptococcus anginosus DNA in esophageal cancer, dysplasia of esophagus, and gastric cancer.

We recently reported cloning of Streptococcus anginosus (S. anginosus) DNA fragments containing the 16S ribosomal gene from DNA samples of surgical specimens of gastric cancers. To investigate the specificity of S. anginosus infection, Southern blot analysis with S. anginosus 16S ribosomal DNA probe and PCR analysis with S. anginosus-specific primers were performed in DNA samples prepared from 15 esophageal cancers, 43 gastric cancers, 16 lung cancers, 10 cervical cancers, 14 renal cell carcinomas, 10 colorectal cancers, and 19 bladder cancers. We frequently found S. anginosus DNA sequences in DNA samples from esophageal cancer and gastric cancer tissues, as well as in those from dysplasia of the esophagus of esophageal cancer patients. No S. anginosus DNA bands were detected by Southern blot analysis on DNAs from the noncancerous portions of the esophagus or the stomach. By PCR analysis with 35 cycles, only 7% of the noncancerous portion of the esophagus was shown to contain S. anginosus sequences. No S. anginosus sequences were found in DNAs from cancers in lung, cervix, and kidney, but they were found in 1 of 10 colon cancers.

[The combination therapy with vinca-alkaloid slow infusion and cholchicine was effective to refractory idiopathic thrombocytopenic purpura. The patient could receive femoral head replacement in safety].

A 46-year-old man with idiopathic thrombocytopenic purpura (ITP) refractory to corticosteroid, splenectomy and other drugs was admitted to our hospital in August, 1994, because of aseptic necrosis of the right femoral head. Although high-dose intravenous gamma-globulin was ineffective, the platelet count was increased within two weeks by the combination therapy that consisted of 0.02 mg/kg vincristine alternating with 0.1 mg/kg vinblastine by slow infusion at a 1-week interval, and oral 1.5 mg/day colchicine. He subsequently underwent the femoral head replacement. This combination therapy seems to be useful for refractory ITP in preparation for surgery.

Cell membrane fluidity in K562 cells and its relation to receptor expression.

Cell membrane fluidity (CMF) and transferrin receptor (Tf-R) expression were investigated in K562 cells, a human chronic myelocytic leukemia cell line, treated by gamma-interferon (IFN-gamma). CMF was increased using spin-labeled electron spin resonance techniques, and Tf-R expression was measured by flow cytometric analysis with an EPICS-750 flow cytometer/cell sorter. Treatment of K562 cells in suspension culture with IFN-gamma for as long a time as 6 hr caused an increase in CMF, and then returned to the level of control cells at 12 hr. Conversely, by 24 hr after the beginning of treatment, the rigidity of CMF was increased. Thus, the changes of IFN-gamma-induced CMF was biphasic. While the early change of CMF is related to signal generation and transmission, the later change may reflect changes in lipid compositions and/or cytoskeletal complexes of the plasma cell membrane. A significant increase of Tf-R after 6 hr and 24 hr in number was obtained by treatment of K562 cells with IFN-gamma, but at 12 hr the number of Tf-R did not differ from the control. These results suggested that the early phase of upregulation of Tf-R induced by IFN-gamma was caused by increased CMF, and the late phase of upregulation of Tf-R was due to increased rigidity of CMF. In conclusion, the state of CMF associated with a certain receptor expression in cells is not rigid and can be modulated to some extent by exogenous influences. This may open possibilities of some adjuvant therapeutic measures in malignant diseases by increasing the antigenicity of tumor cells.

Tumour necrosis factor-alpha upregulates transferrin receptors in K 562 cells.

The effects of tumour necrosis factor-alpha on transferrin receptor expression in a human chronic myelocytic leukaemia cell line, K 562 cells, were studied. Cytofluorometry studies showed that the numbers of transferrin receptors in exponentially growing K 562 cells were increased when the cells were incubated with tumour necrosis factor-alpha for 24 h. The induction of transferrin receptors by tumour necrosis factor-alpha may be mediated by a mechanism that is independent of growth since cell growth in treated cultures did not differ from that in the controls. The DNA contents of K 562 cells treated with tumour necrosis factor-alpha showed that after 24 h there were less cells in the G1 and S phases and more cells in the G2/M phase than in the control group. The phase of upregulation of transferrin receptors induced by tumour necrosis factor-alpha may be dependent on the cell cycle. This new evidence that tumour necrosis factor-alpha upregulates transferrin receptors suggests a cancer-anaemia cascade in which the cancer burden state activates macrophage release of tumour necrosis factor-alpha as a result of transferrin receptor expression.

Anti-proliferative effect of combined tumour necrosis factor-alpha and interferon-alpha on human pancreatic cancer in vitro and in vivo.

The anti-proliferative effects of tumour necrosis factor-alpha (TNF-alpha) and interferon-alpha (IFN-alpha), alone or in combination, on human pancreatic cancer cells lines (PANC-1, MIA PaCa-2 and BxPC-3) and human pancreatic cancer tumour (Exp-58), were investigated in vitro and in vivo. The anti-proliferative effect was determined using the dye uptake method and the subcutaneous tumour model. Combined TNF-alpha and IFN-alpha demonstrated marked synergistic and/or additive effects in comparison with their effects as single agents. These results suggest that combined cytokine therapy of TNF-alpha and IFN-alpha may make possible some improvement in the treatment of pancreatic carcinoma patients in the future.

Occlusion of a postoperative rectoabdominocutaneous fistula with fibrin clot: a case report.

A 56 year-old rectal cancer patient who developed a chronic rectoabdominocutaneous fistula postoperatively was treated with fibrin clot, and the fistula healed completely. Occlusion of chronic postoperative fistulas with fibrin clot appears to be a useful technique.

Antitumor activities of IKP-104, a 4(1H)-pyrizinone derivative, on cultured and implanted tumors.

Antitumor activities of IKP-104, a 4(1H)-pyrizinone derivative, were investigated with cultured tumor cell lines and implanted tumors in mice. IKP-104 inhibited the growth of cultured murine tumor cell lines (L1210 leukemia, Lewis lung carcinoma and B16 melanoma) and human tumor cell lines (K562 leukemia and HeLa cervical carcinoma). It also had antitumor effects on implanted murine ascitic tumors (L1210 leukemia and sarcoma 180) and a murine solid tumor (Lewis lung carcinoma). IKP-104 could be classified as a phase-dependent cytostatic drug based on the mode of growth inhibition of cultured B16 melanoma cells compared with those of several other antitumor agents. The effect of IKP-104 on the cell cycle traverse of cultured B16 melanoma cells was estimated by morphological and flow cytometric analyses. Cells accumulated in the mitotic phase, and abortive mitosis or polyploidy or multinucleation was induced from 6 h after exposure to IKP-104. Based on these results, IKP-104 is expected to be useful for the treatment of tumors, and its mode of action seemed to be similar to that of metaphase arrestants such as colchicine or vinca alkaloids.

The effects of epinephrine on norepinephrine release in essential hypertension.

The effects of endogenous epinephrine (E), released by glucagon injection, and exogenously infused E on plasma norepinephrine (NE) and cardiovascular responses before and after beta-blockade were studied in patients with essential hypertension and in age-matched normotensive controls. The resting plasma NE and E levels were significantly higher in the borderline hypertensive subjects (NE: 251 +/- 21 pg/ml [SEM], p less than 0.005; E: 57 +/- 5, p less than 0.05, n = 18) than in controls (NE: 129 +/- 12; E: 39 +/- 5, n = 18). An intravenous injection of glucagon (1.0 mg) induced a transient rise of both plasma catecholamine levels and blood pressure in every subject studied. Plasma E levels rose transiently and returned to the basal levels by 20 minutes after the injection, whereas plasma NE levels showed a more prolonged rise over 20 minutes. beta-Blockade with propranolol did not affect the plasma E response to glucagon, but inhibited the prolonged rise of plasma NE levels. An intravenous infusion of exogenous E (1.25-1.50 micrograms/min) for 30 minutes caused an apparent rise of both plasma NE levels and blood pressure, which lasted more than 60 minutes after stopping the E infusion. Propranolol did not affect the time course of plasma E but again inhibited the prolonged rise of both plasma NE levels and blood pressure. No significant differences could be observed in the cardiovascular or plasma NE responses to glucagon or to E infusion between normal and hypertensive subjects. These findings lend support to the view that plasma E can act physiologically as a sustained stimulator of presynaptic beta-adrenergic receptors, which leads to an enhanced NE release from peripheral sympathetic nerve terminals and a rise of blood pressure in humans.