[Statistical review of adrenal cortical carcinoma].
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Biomedical subjects
Publications and source records attributed to T Ichikawa.
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Semen quality and endocrine parameters after spermatic cord torsion were investigated. Of 24 patients evaluated following spermatic cord torsion 12 were treated with bilateral orchiopexy (orchiopexy group), and 12 were treated with ipsilateral orchiectomy and contralateral orchiopexy (orchiectomy group). The average sperm density and the average total sperm count in the orchiectomy group were significantly lower than those in the orchiopexy group (p < 0.05, p < 0.05, respectively). The mean serum follicle stimulating hormone level in the orchiectomy group was significantly higher than that in the orchiopexy group (p < 0.05). These findings suggest a significant decrease in testicular function in the orchiectomy group. All the patients in the orchiopexy group demonstrated a normal semen quality and endocrine parameters during followup. Four of the 8 patients in the orchiectomy group whose duration of followup was more than two years still demonstrated oligozoospermia (< 20 x 10(6)/ml, one of 4 was azoospermia). The average age at operation of these four patients with abnormal semen quality was significantly higher than that of the other 4 patients with normal semen quality (p < 0.05), whereas no significant difference in duration of torsion preceding surgical therapy was observed between these two groups. These findings suggest that subsequent semen quality is likely to remain within normal limits with early surgical treatment by bilateral orchiopexy. Ipsilateral orchiectomy in the younger generation seems to result in less damage of the contralateral testis than in the older generation.
Glycerol enhances pulmonary tumorigenesis in mice treated with 4-nitroquinoline 1-oxide (4NQO). The present study shows that active oxygen formation by glycerol may be responsible for this enhanced tumorigenesis. Male ddY mice were treated with 4NQO and given a 5% glycerol solution instead of drinking water for up to 4 weeks after 4NQO injection. There was no difference in NADH-dependent active oxygen formation of the mitochondria between the 4NQO- and 4NQO-plus-glycerol-treated groups but the ratios of NADH- and NADPH-dependent active oxygen formation of the microsomes and nuclei of the 4NQO-plus-glycerol-treated group to the 4NQO-treated group increased with increasing time after 4NQO injection. Significant differences in the maximum NADH- and NADPH-dependent active oxygen formation were observed 2 or 4 weeks after 4NQO injection.
Previous studies using somatic cell hybridization of highly metastatic and nonmetastatic rat prostatic cancer cells demonstrated that the resultant hybrids were nonmetastatic if all of the parental chromosomes were retained. Somatic hybrid segregants which underwent nonrandom chromosomal losses reexpressed high metastatic ability. These results demonstrated that there are gene(s) the expression of which can suppress metastatic ability of prostatic cancer cells. To identify the location of homologous gene(s) in the human, specific human chromosomes were introduced into highly metastatic rat prostatic cancer cells using the microcell-mediated chromosome transfer. Introduction of human chromosome 11 into highly metastatic rat prostate cancer cells results in suppression of metastatic ability without suppression of the in vivo growth rate or tumorigenicity of the hybrid cells. Spontaneous deletion of portions of human chromosome 11 in some of the clones delineated the minimal portion of human chromosome 11 capable of suppressing prostatic cancer metastases as the region between 11p11.2-13 but not including the Wilms' tumor-1 locus.
Linomide (N-phenylmethyl-1,2-dihydro-4-hydroxyl-1-methyl-2-oxo-quinoline-3- carboxamide) is a quinoline 3-carboxamide which previously has been demonstrated to produce immunomodulator and antitumor effects when given in vivo. To test the possible antitumor effects of linomide against prostatic cancers, rats bearing five distinct Dunning R-3327 rat prostatic cancer sublines were treated daily with i.p. injections of linomide. These studies demonstrated that linomide has a reproducible antitumor effect against all of the prostatic cancers tested regardless of their growth rate, degree of morphologic differentiation, metastatic ability, or androgen responsiveness. This antitumor effect is observed only in vivo, not in vitro, and involves a cytotoxic response of the prostatic cancer cells. This cytotoxic response results in the retardation of the growth rate (i.e., increased tumor volume doubling time) of primary prostatic cancers and in metastatic lesions. Linomide's growth retardation is reversible, and thus continuous daily treatment with linomide is required for maximal antitumor response. Pretreatment of rats with linomide before tumor inoculation has no effect in addition to that produced by initiating linomide treatment at the time of tumor inoculation. No enhancement of either natural killer cell number or natural killer cell cytotoxic activity is induced by linomide treatment in the tumor-bearing rats. In addition, depletion of natural killer cell activity via injections of asialo-GM1 antiserum does not prevent the antitumor effects of linomide in vivo. Likewise, the antitumor effects of linomide are also produced in prostatic cancer-bearing athymic nude rats. These results suggest that the requirement for host involvement in the antitumor effects of linomide against rat prostatic cancers may involve both immune and nonimmune host mechanism(s) (e.g., antiangiogenesis).
Cadherins represent a family of Ca(2+)-dependent cell adhesion molecules involved in homotypic, homophilic cell-cell interactions. Recent studies have shown that the cadherins can play a role in invasive and metastatic behavior. Using the established Dunning R-3327 model system of serially transplantable rat prostate cancers, the expression of E- and P-cadherin in rat prostatic cancer was studied. Analysis within this system demonstrated that whereas E-cadherin was expressed in the normal rat prostate and the well- or moderately differentiated, noninvasive Dunning tumors, no expression, either at the mRNA or at the protein level, could be detected in the invasive sublines. Since not all invasive Dunning tumors studied have metastatic ability, these results suggest that a decreased expression of E-cadherin is correlated with invasive behavior rather than with metastatic ability. Recently, genetic instability occurred in an animal bearing the well differentiated, androgen-responsive, slow growing, nonmetastatic Dunning R-3327-H rat prostate cancer resulting in the progression to an anaplastic, androgen-independent, fast growing, highly metastatic state. This spontaneously arising tumor, termed the AT6 subline, in its original host was heterogeneously composed of both a well differentiated and an anaplastic population of cancer cells in which areas of squamous cell differentiation were occasionally observed. The original animal bearing this heterogeneous AT6 cancer developed multiple metastases, the lung metastases being heterogeneously composed of anaplastic and squamous cell populations. Cytogenetic analysis demonstrated that the lung metastases were derived from a specific subpopulation of cancer cells present in the original AT6 primary tumor. Immunohistochemical studies demonstrated that only the area of lung metastases displaying squamous morphology were positive for E-cadherin. In contrast, the anaplastic areas of the lung metastases and the metastases in other organs were E-cadherin negative. By the first passage of the AT6 tumor only the anaplastic cells were present and no detectable E-cadherin mRNA or protein was found in the primary tumor and metastatic deposits. These results suggest that a decreased expression of E-cadherin is associated with the progression of prostatic cancer.
We investigated the therapeutic effect of anti-lymphocyte serum (ALS) on clinically overt diabetes by using a nonobese diabetic (NOD) mouse model of type I diabetes mellitus. ALS given within 14 days of disease onset gradually reversed hyperglycemia with a 76% cumulative incidence of remission. Combined use of anti-CD4 and anti-CD8 monoclonal antibodies, but not anti-CD4 or anti-CD8 antibody alone, was also effective with overall 64% remission. Diabetic NOD mice that failed to respond to ALS treatment accepted subsequent islet isografts for a prolonged period (mostly greater than 100 days), whereas islet isografts in diabetic NOD mice previously treated with normal rabbit serum were all destroyed as acutely as isografts in untreated diabetic NOD mice. These results suggest that persistence of diabetes was due to irreversible beta-cell destruction and that ALS has indeed abrogated autoimmunity. In addition, ALS treatment at the time of islet isografting achieved significant prolongation of graft survival with 8 of 13 mice maintaining euglycemia for greater than 100 days. Although ALS prolonged islet allograft survival in diabetic NOD mice, the degree of prolongation was much less for allografts than for isografts, suggesting that ALS is capable of suppressing autoimmunity more effectively than allograft responses.
Eclosion hormone (EH) is a peptide triggering ecdysis in insects. Injection of Lucifer dye into EH producing cells in the silkworm at various stages of adult development revealed that after pupation the EH cells produced many axon collaterals to form a new neurohaemal structure in the corpora cardiaca (CC), the corpora allata and the associated nerves of the CC. The axon collaterals may serve as a major release site of EH at adult ecdysis.
Following v-Ha-ras transfection of nonmetastatic dimethylbenz(( a ))anthracene-induced rat mammary cancer (RMC1) cells, occasional transfectants were isolated that acquired high metastatic ability. High metastatic ability is not a simple process regulated by v-Ha-ras p21 levels alone in these v-Ha-ras transfectants but involves the development of cytogenetic changes. If such cytogenetic changes involve only gain in gene expression, then all hybrids formed by fusing highly metastatic v-Ha-ras RMC1 transfectants with the parental nonmetastatic RMC1 should be highly metastatic. If loss of a metastatic suppressor gene(s) is also involved, then such hybrids should be nonmetastatic since chromosomes from the nonmetastatic parental cells should supply the suppressor function. To test this possibility, a highly metastatic cloned v-Ha-ras transfectant was fused with the nonmetastatic parental RMC1 cells. Five hybrid clones were isolated that conserved the chromosomes from their parental cells. When these hybrid clones were injected into animals, primary tumors developed with the same tumor-doubling time as that of the highly metastatic parental v-Ha-ras transfectant (i.e., approximately 2 days). High metastatic ability was, however, suppressed in these hybrid clones. All hybrid clones continued to express v-Ha-ras p21. Thus, suppression of metastatic ability in the hybrids can occur even in the presence of an elevated v-Ha-ras p21 level. This suggests that the acquisition of metastatic ability following v-Ha-ras transfection involves loss of metastasis suppressor gene function in rat mammary cancer cells.
We report a first case of malignant peritoneal mesothelioma examined by radioimmune (RI) angiography with technetium-99m human serum albumin. The RI angiography clearly demonstrated the characteristic findings including hypertrophic gastroepiploic arteries and dilated omental branches. These findings may be very helpful in distinguishing malignant peritoneal mesotheliomas from peritoneal carcinomatosis.
We isolated three glial fibrillary acidic protein (GFAP) cDNA clones from a glioma cell line, U-251 MG. One clone isolated from a U-251 MG cDNA library was long, but lacked both ends. Using poly(A)+ RNA and primers synthesized according to the sequence of this clone, we used the polymerase chain reaction-assisted rapid amplification of cDNA ends (PCR-RACE) method, which is a strategy to isolate cDNA ends, and obtained cDNA clones for the 5' and 3' ends. From the sequences of these overlapping clones, the complete nucleotide sequence of human GFAP cDNA was established. The start (ATG) and the stop (TGA) signals were seen at nucleotide positions 15 and 1311, respectively, and divided the entire sequence of 3027 bp into 14 bp of 5' non-coding, 1296 bp of coding and 1717 bp of 3' non-coding regions. Using cDNA probes made from both the coding and the 3' non-coding regions, Northern blot hybridization was performed with two different stringencies on RNAs from human and rodent brains and human GFAP-positive and -negative cells. It was shown that the 3' non-coding region probe was more specific for human GFAP than the coding region probe which was specific only under higher stringency conditions. This was also suggested by homology analysis of the sequence with those of various intermediate filament proteins. Based on these findings, we performed spot blot hybridization of sorted human chromosomes and Southern blot hybridization of PCR-amplified DNAs of a panel of hamster-human somatic cell hybrids and localized the human GFAP gene to chromosome 17.
We report herein a case of successfully treated advanced, nonfunctioning islet cell carcinoma associated with left-sided portal hypertension. The splenic vein was obstructed by a huge intravenous tumor thrombus developing from the main pancreatic tumor. Direct invasion to adjacent organs such as the spleen, colon, left kidney and stomach was also observed, although liver metastasis was not present. Radical resection was carried out with removal of these five involved organs and the patient is alive without recurrence more than 5 years after surgery.
Brain natriuretic peptide (BNP), a family of peptides with structural and biologic homologies to previously identified atrial natriuretic peptide (ANP), has been found in human cardiac tissue and plasma. To examine the secretion mechanism of these peptides, we have studied the relationship between their plasma concentrations and hemodynamic parameters before and at 0.5 and 24 hours after percutaneous transvenous mitral commissurotomy (PTMC) in 14 patients with mitral stenosis. We have also investigated the validity of measuring plasma natriuretic peptides as a means for estimating changes in hemodynamic parameters after PTMC. The procedure decreased left atrial pressure (p < 0.01) with an elevation in left ventricular end-diastolic pressure (p < 0.05). Plasma ANP levels decreased significantly after PTMC (before, 64.1 +/- 33.7 fmol/ml; at 0.5 hour, 58.9 +/- 27.7 fmol/ml; at 24 hours, 45.7 +/- 18.3 fmol/ml; p < 0.01), whereas plasma BNP levels remained unchanged after the procedure (before, 5.3 +/- 1.5 fmol/ml; at 0.5 hour, 5.6 +/- 1.9 fmol/ml; at 24 hours, 5.0 +/- 1.9 fmol/ml; p = NS). There was a significant relationship between basal plasma ANP and left atrial pressure (r = 0.88; p < 0.001), and changes in plasma ANP were correlated with those in left atrial pressure (r = 0.69; p < 0.01). Basal plasma BNP was significantly correlated with basal left ventricular end-diastolic pressure (r = 0.65; p < 0.05) but not with the other measured hemodynamic parameters or with plasma volume.(ABSTRACT TRUNCATED AT 250 WORDS)
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Telomeres are the physical ends of eukaryotic chromosomes. In view of reports of the reduction of telomeric repeats in human malignant tumors, we measured the lengths of telomeric repeats in 55 primary neuroblastomas. The average lengths of telomeric repeats in these tumors fell in a wide range (from 1.1 kb to more than 23 kb) relative to those in ganglioneuromas and normal peripheral mononuclear cells. The reduction of telomeric repeats was significantly correlated with advanced stages of tumor development, poor prognosis, and increased S-phase fractions in tumor cells. On the other hand, three cases of Stage IV-S tumors showed the reduction of telomeric repeats and low percentage of S-phase fractions. These Stage IV-S patients had a good prognosis with spontaneous regression of metastatic tumors.
Auditory brain stem responses were recorded in 20 patients with anorexia nervosa and 10 normal control subjects. Twenty patients were studied during two phases of illness, 1) anorexia nervosa group with under weight (U-AN group), and 2) anorexia nervosa group with recovered normal weight (N-AN group). Absolute latencies, interwave latencies, absolute amplitudes, and amplitude ratios were investigated. A nonsignificant difference was found among these groups as far as the latencies were concerned. Both the patients in the U-AN group and those in the N-AN group had significantly smaller amplitude ratios (III/I, IV.V/I) and absolute amplitude (V) than did the control subjects. Furthermore, a nonsignificant difference was found between the U-AN group and the N-AN group. It suggests that some dysfunction might exist in the region of the brain stem.
We have reported a 38-year-old female who did not show clinical seizures during continuous spikes in the left occipital area over a period of 18 years. As to the neurological findings, visual disturbance, optic nerve atrophy and right hemianopsia were almost always present. The low density area distributing from the left occipital area to the left temporal one on the CT revealed to be porencephaly. From the clinical findings obtained in this case, the lesion responsible for the occipital continuous spikes could be ascribed to be functional abnormality of the visual pathway connecting the left lateral geniculate body with the left occipital cortex.
Alexithymia and depression in family members of alcoholics were examined among 48 families. Results were as follows: (1) The prevalence of alexithymia was 47.9% (23 cases), whereas that of depression was only 6.3% (3 cases); (2) no significant correlation between alexithymia and depression was noted; (3) expressiveness and conflict were significantly lower in families with alcoholics than in healthy families without alcoholics, although families with alcoholics do have strong conflicts. The results suggest the possibility that half of them forcefully suppress their conflicts, unconsciously deny the existence of alcoholics, and finally manifest secondary alexithymia.