Should the patient's rights of refusal override the doctor's Hippocratic Oath?
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Biomedical subjects
Publications and source records attributed to M Ono.
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Multiple-drug (OK-432, PSK and SPG) immunotherapy and chemotherapy provided remission of symptoms for 36 months in a patient aged 21 years suffering scirrhous gastric carcinoma associated with carcinomatous peritonitis in which direct infiltration to the pancreas, retroperitoneum and the left colon was observed. A remarkable improvement with time was observed by endoscopic and roentgenographic observation, and a substantial improvement was also observed in the NK-cell ratios of lymphocyte subsets of the OKT series in relation to immunologic parameters. A tumor necrosis factor [TNF]-like substance was thought to have been induced by multiimmunotherapy in this case.
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A colony-stimulating factor (CSF) has been purified to homogeneity from the serum-free medium conditioned by one of the human CSF-producing tumor cell lines, CHU-2. The molecule was a hydrophobic glycoprotein (mol. wt 19,000, pI = 6.1 as asialo form) with possible O-linked glycosides. Amino acid sequence determination of the molecule gave a single NH2-terminal sequence which had no homology to the corresponding sequence of the other CSFs previously reported. The biological activity was apparently specific for a neutrophilic granulocyte-lineage of both human and mouse bone marrow cells with a specific activity of 2.7 X 10(8) colonies/10(5) non-adherent human bone marrow cells/mg protein. The purified CSF can be regarded as a G-CSF of human origin and will become a useful material for investigation of regulatory mechanisms of human granulopoiesis.
Thioridazine, a phenothiazine calmodulin inhibitor, aggravated the cytotoxic effect of a conjugate (EGF-PE) of epidermal growth factor (EGF) coupled with Pseudomonas exotoxin against cultured HeLa cells. Other phenothiazine calmodulin inhibitors, trifluoperazine and chlorpromazine, also intensified the cytotoxic effect of EGF-PE, whereas N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide (W7) had no such effect. By using iodinated epidermal growth factor ( [125I]EGF), the effect of thioridazine on intracellular transport of EGF was examined. The release of radioactivity associated with [125I]EGF into medium was slow in the presence of thioridazine. The Percoll gradient centrifugation pattern showed that thioridazine delayed both the appearance of [125I]EGF in lysosomes and the disappearance of [125I]EGF from the lysosomes. The pH value in lysosomes was 5.28 in thioridazine-treated HeLa cells, while that in untreated cells was 5.15. Thioridazine was found to inhibit lysosomal enzyme activities of cathepsin B and acid phosphatase, but not beta-hexosaminidase when cell extracts were treated with the drug. Electron microscopy showed an increased number of electron-dense bodies, possibly autophagosomes/lysosomes in HeLa cells grown for 48 h with 3 micrograms/ml thioridazine. The potentiating action of EGF-PE by thioridazine is discussed in relation to the altered lysosomal function in treated cells.
Nineteen patients with unilateral supratentorial mass lesion and without any evident clinical signs of transtentorial herniation were studied with Computed Tomography (CT), brain-stem evoked potentials (BAEPs) and central conduction time (CCT) of short latency somatosensory evoked potentials (SEPs). Sixteen had tumours, two had intracranial haematoma and one had chronic subdural haematoma. CT detected the initial signs of transtentorial herniation in every case. Preoperative I-V interpeak latency (IPL) was significantly (M + 2SD) prolonged in 26% of cases on the lesion side and in 21% of cases on the opposite side. The mean I-V IPL was significantly prolonged both on the lesion side and the opposite side (P less than 0.01, P less than 0.02, respectively). Suppression of Wave V (M-2SD) was seen only in two cases, however, the mean amplitude of Wave V was significantly decreased both on the lesion side and on the opposite side (P less than 0.001, P less than 0.01, respectively). CCT of SEPs was significantly (M + 2SD) prolonged in 33% of cases on the lesion side and in only 13% on the opposite side. The mean CCT was, however, significantly prolonged both on the lesion and on the opposite side (P less than 0.001, P less than 0.02, respectively). Postoperative I-V IPL was significantly prolonged in only 11% of cases while the mean I-V IPL was still significantly prolonged (P less than 0.01) and the mean amplitude of Wave V was still suppressed (P less than 0.001) on the lesion side.(ABSTRACT TRUNCATED AT 250 WORDS)
We have recently isolated retinoic acid-resistant clones U-2 and U-3 from human breast cancer cell line MCF-7 (Ueda et al. (1985) Cancer Res. 45, 3332-3338). Growth of MCF-7 cells was found to be stimulated by estradiol but that of U-2 or U-3 was not. Cytosol from U-2 or U-3 cells contained no detectable estradiol receptor activity, whereas that from the parental MCF-7 cells showed estradiol receptor activity of 32 fmol/mg cytosol protein with a Kd of 2.6 X 10(-10) M by Scatchard analysis. Sucrose gradient centrifugation analysis of the cytosol fraction confirmed the presence of estradiol receptor activity in MCF-7 but not in U-2. Cytosol from MCF-7 and U-2 cells showed progesterone receptor activities of 106 fmol/mg protein with a Kd of 7.4 X 10(-10) M and 13 fmol/mg protein with a Kd of 9.9 X 10(-10) M, respectively. Addition of estradiol to the culture medium of the cells increased the level of progesterone receptor about 2-fold in MCF-7, but not in U-2. U-2 or U-3 cells showed about 5-fold higher resistance to an antiestrogen, tamoxifen, than MCF-7, and they were also 300- to 1,000-fold more resistant to other antiestrogens, epitiostanol and medroxyprogesterone, than MCF-7. The altered cellular sensitivity of U-2 or U-3 to the hormone antagonists is discussed in relation to the absence or presence of hormone receptors.
By using a DNA fragment primarily encoding the reverse transcriptase (pol) region of the Syrian hamster intracisternal A particle (IAP; type A retrovirus) gene as a probe, human endogenous retrovirus genes, tentatively termed HERV-K genes, were cloned from a fetal human liver gene library. Typical HERV-K genes were 9.1 or 9.4 kilobases in length, having long terminal repeats (LTRs) of ca. 970 base pairs. Many structural features commonly observed on the retrovirus LTRs, such as the TATAA box, polyadenylation signal, and terminal inverted repeats, were present on each LTR, and a lysine (K) tRNA having a CUU anticodon was identified as a presumed primer tRNA. The HERV-K LTR, however, had little sequence homology to either the IAP LTR or other typical oncovirus LTRs. By filter hybridization, the number of HERV-K genes was estimated to be ca. 50 copies per haploid human genome. The cloned mouse mammary tumor virus (type B) gene was found to hybridize with both the HERV-K and IAP genes to essentially the same extent.
We determined the complete nucleotide sequence of the human endogenous retrovirus genome HERV-K10 isolated as the sequence homologous to the Syrian hamster intracisternal A-particle (type A retrovirus) genome. HERV-K10 is 9,179 base pairs long with long terminal repeats of 968 base pairs at both ends; a sequence 290 base pairs long, however, was found to be deleted. It was concluded that a composite genome having the 290-base-pair fragment is the prototype HERV-K provirus gag (666 codons), protease (334 codons), pol (937 codons), and env (618 codons) genes. The size of the protease gene product of HERV-K is essentially the same as that of A- and D-type oncoviruses but nearly twice that of other retroviruses. A comparison of the deduced amino acid sequences encoded by the pol region showed HERV-K to be closely related to types A and D retroviruses and even more so to type B retrovirus. It was noted that the env gene product of HERV-K structurally resembles the mouse mammary tumor virus (type B retrovirus) env protein, and the possible expression of the HERV-K env gene in human breast cancer cells is discussed.
Susceptibility of Bacteroides gingivalis strains to the complement-mediated bactericidal activity of human serum was examined under anaerobic conditions. Serum containing high concentrations of IgG antibody to B. gingivalis enhanced the bactericidal activity. No enhancement was found in serum which did not contain the specific antibody or in serum absorbed with intact cells. The sensitivity to the killing by pooled serum differed among B. gingivalis strains. Cells of B. gingivalis activated the pooled human serum complement not only through the classic pathway but also through an alternative pathway. It was found that the susceptibility of B. gingivalis to the bactericidal activity was classic-pathway-dependent.
Spleen cells from tumor-bearing mice showed decreased natural killer (NK) activity and decreased binding to target cells with progression of the tumor. Treatment of spleen cells from tumor-bearing mice with vibrio cholerae neuraminidase (VCN) increased the cytotoxicity to a level twice or more as high as that of untreated cells, but the same treatment of spleen cells from normal mice had no or little effect. On the other hand, neither in spleen cells from tumor-bearing mice nor in those from normal mice, the VCN treatment had no effect on their binding to M-HeLa cells. The suppression of NK activity by preincubation with serum from tumor-bearing mice or prostaglandin E2 was completely abolished by VCN treatment. The above results indicate that VCN treatment of lymphocytes might augment NK activity by an antagonistic effect against an immune suppressive factor.