Comparative cytotoxicity of exogenous cadmium-metallothionein and cadmium ion in cultured vascular endothelial cells.
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Biomedical subjects
Publications and source records attributed to M Sakamoto.
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A 59-year-old male with history of sigmoid colon cancer had a high serum-CEA level and was referred for the evaluation of metastatic liver disease. Ultrasonography and computerized tomography showed two tumours in the liver. Macroscopically, these were in segment 4 (S4) and 2 (S2). Histologically, the tumour in S4 showed a number of bile ductules with variable amounts of stroma, an appearance compatible with bile duct adenoma (BDA). There were markedly atypical ductules of various sizes, the epithelium of which had coarsely granular/hyperchromatic large nuclei, in some areas of the lesion. These atypical ductules showed invasive growth into the liver parenchyma. Some cystically dilated ductules with bile plugs resembling bile duct hamartoma (BDH) were also seen. The other tumour in S2, was a metastatic adenocarcinoma from sigmoid colon and showed strongly positive staining for CEA. Since the lesion in S4 of our case is solitary and most of histological features are similar to those of BDA with markedly atypical bile ductules, we consider that this may be the first case of cholangiocarcinoma associated with BDA with focal area of BDH. It is possible that the adenoma-carcinoma sequence occurs in biliary tumours.
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This study evaluates the toxicity of lead in the presence or absence of cadmium on the maintenance of a monolayer of cultured bovine aortic endothelial cells. It was histologically shown that lead at 50 microM or less induced a slight formation of de-endothelialized areas on the monolayer after a 24-h incubation. Although lead accumulated in endothelial cells in a dose-dependent manner, the cytotoxicity (evaluated by the [3H]adenine release assay) was not detected. However, cadmium (1.0 or 2.0 microM)-induced de-endothelialized areas on the monolayer was considerably larger in the presence of lead at 10 microM; the cytotoxicity of cadmium was significantly enhanced by lead. It was concluded that vascular endothelial cell monolayer is severely destroyed by a greater cytotoxicity of combination of cadmium with lead.
Using our scoring system, we studied the production of monokines (interleukin-1 alpha, interleukin-1 beta, tumor necrosis factor-alpha, and interleukin-6) by lipopolysaccharide-stimulated peripheral whole blood in 34 patients with chronic hepatitis C during the interferon-alpha/beta therapy. It decreased in 25.7% (9/35 group A), fluctuated in 60.0% (21/35, group B), and increased in 14.3% (5/35, group C). The patients in group A were younger than those in group B (P < 0.05). The histological grade of injury was milder in group A than in group B or C. The rate of sustained response was 66.7% (6/9) in group A, 19.0% (4/21) in group B, and 40.0% (2/5) in group C(P = 0.0184, group A versus group B). In summary, monokine production by peripheral whole blood varied during interferon therapy for chronic hepatitis C patients. No significant change was noted in 60% of the patients. However, patients with decreased monokine production were younger, with a mild histological grade, and likely to respond to the interferon therapy.
The pretreatment bone scintigrams of 58 patients with prostate cancer with bone metastasis were reviewed and the prognostic value of the initial extent of bone involvement was compared with that of other pretreatment characteristics. The extent of bone metastasis revealed by the scan was related to survival. The serum level of alkaline phosphatase at pretreatment and pathological grade also had some predictive value. Although the pathological grade of primary tumours was related to prognosis, the survival of patients with the same histological grade differed according to the initial extent of disease; patients with extensive disease along with raised serum alkaline phosphatase (twice or more as high as the cut-off value) had poorer prognosis than did those with lower alkaline phosphatase or smaller extent of disease. The extent of bone involvement in combination with serum alkaline phosphatase level therefore apparently has higher prognostic value than does disease extent alone.
We investigated the cytotoxicity of cadmium in cultured vascular endothelial cells from bovine aorta pretreated with zinc. The cytotoxicity was evaluated by the [3H]adenine release assay. It was shown that the increase in the [3H]adenine release after challenge with cadmium was significantly prevented by pretreatment with zinc. It was histologically observed that cadmium-induced occurrence of the de-endothelialized areas was reduced in zinc-pretreated cell layer. Intracellular accumulation of cadmium was significantly less but that of zinc was more in zinc-pretreated cells. The content of cadmium in both the particulate and the cytosol fraction was decreased by zinc pretreatment; however, metallothionein content after challenge with cadmium was not changed. It was therefore concluded that zinc is capable of inducing a tolerance to cadmium cytotoxicity in cultured vascular endothelial cells; this tolerance is postulated to be due to a decrease in the intracellular cadmium accumulation rather than a metallothionein induction.
PURPOSE: We attempt to determine the long-term success rate of the modified Pereyra bladder neck suspension, identify preoperative factors predictive of long-term outcome, and investigate the influence of method and length of followup on reported continence status after modified Pereyra bladder neck suspension. MATERIALS AND METHODS: The charts of 177 patients who underwent modified Pereyra bladder neck suspension at our institution more than 5 years ago were reviewed. An attempt was made to contact all patients either by mail or telephone to complete a patient survey questionnaire. RESULTS: Of 177 patients 125 (71%) completed the patient survey with a mean followup of 9.8 years. At survey followup 20% of the patients reported no incontinence of any type and 51% reported stress urinary incontinence with or without urge incontinence. Of the patients 71% reported significant improvement in the incontinence and 73% were satisfied with the results of the procedure. No accurate preoperative predictors of long-term outcome were identified. The method and length of followup had significant impact on reported continence status after modified Pereyra bladder neck suspension. CONCLUSIONS: This long-term study using outcomes analysis reveals a high rate of recurrent stress incontinence after modified Pereyra bladder neck suspension. However, most patients maintain significant subjective improvement and remain satisfied with the results of the operation.
BACKGROUND: Behçet disease is a chronic, recurrent, inflammatory disorder characterized by the triad of oral and genital ulcers and ocular lesions. The etiology is unknown. Although many of these patients become blind, some have good vision all their life. METHODS: To attain more accurate data on the prognosis of these patients, the authors studied 52 Japanese patients (101 eyes) seen at Kyushu University Hospital between 1980 and 1990. At the first visit, patients ranged in age from 21 to 61 years; at onset, they ranged in age from 17 to 55 years; and the disease duration at first visit was from 0 to 22 years. Thirty-five of the 101 eyes had a visual loss of more than five lines or the patients became blind. The authors divided the subjects into two groups--favorable group and unfavorable group. If an eye had more than five lines of visual loss or the patient became blind 3 years after the first visit, it was placed in the unfavorable group, and if not, it was classed in the favorable group. Thirty-two factors determined from clinical records were used to select statistically significant risk factors for visual loss, using univariate analysis and multivariate logistic regression analysis. RESULTS: Univariate analysis showed the following four factors that were significantly different between favorable and unfavorable groups: sex, disease interval, other complications, and skin lesions (first year). Multivariate analysis showed that the following seven factors had mutually independent contributions to visual loss: skin lesions; arthritis; posterior attacks; other complications (experienced), including gastrointestinal, vascular, and central nervous system lesions; female sex; disease interval; and anterior attacks. The first four factors have effects of losing vision, whereas the others are related to vision retention. CONCLUSION: The authors find that skin lesions, arthritis, posterior attacks, and other complications are linked to loss of vision, whereas female sex, disease interval, and anterior attacks are related to retention of vision.
OBJECTIVE: The authors determined an appropriate surgical treatment for liver metastases from colorectal cancers. Clinicopathologic features of metastatic lesions of colorectal cancers were studied. SUMMARY BACKGROUND DATA: Major hepatic resection is the usual procedure for treatment of hepatic metastases from colorectal cancers. METHODS: Forty consecutive patients who underwent hepatic resections were prospectively studied, for a total of 89 metastatic liver tumors. RESULTS: Metastatic tumor often extended along Glisson's capsule, including invasion to the portal vein (9 cases), the hepatic vein (3 cases), the bile duct (16 cases), and the nerve (6 cases). The main tumor had small satellite nodules in only one patient, and there were no microscopic deposits in the parenchyma, even within 10 mm from the metastatic tumors. Fibrous pseudocapsule formation was observed in 28 patients. DISCUSSION: The rarity of intrahepatic metastasis from metastatic tumor supports nonanatomic limited hepatic resection as the procedure of choice for metastatic colorectal cancer in the liver. The spread via Glisson's capsule should be taken into consideration for complete tumor clearance.
Surgical specimens obtained from 21 patients with renal pelvic cancer, in which the tumor was located on the side of the renal parenchyma, were reviewed with special reference to tumor involvement with renal collecting ducts and/or renal parenchyma. Four distinct entities were found: 1) 4 tumors that involved the collecting ducts without invasion of renal parenchyma, 2) 4 tumors that involved the collecting ducts with microscopic invasion of renal parenchyma, 3) 5 tumors that invaded the renal parenchyma by less than 5 mm. and were microscopically identified as being without ductal involvement and 4) 6 tumors that exhibited extensive renal parenchymal invasion. The patients with intraductal tumors had good prognosis as did those with microscopic invasion except for 1 who died of lymph nodes metastases. Conversely, 6 patients with extensive invasion had a poor prognosis, 5 (88%) of whom died of recurrent tumor or distant metastases. The differences in these 4 entities may be important, especially if large numbers of patients are examined, and they may ultimately be shown to have a different prognosis.
Itraconazole has been shown to be highly effective against a broad spectrum of fungi, particularly aspergillus. In order to achieve the desired pharmacological effect, the itraconazole plasma concentration should be > 250 ng/ml. We developed a high-performance liquid chromatography assay for the rapid determination of plasma itraconazole concentration using solid-phase extraction and small sample volume. The assay possessed linearity up to 5,000 ng/ml, sensitivity of 50 ng/ml, average recovery of 100.8%, and run-to-run precision (n = 10) for concentrations of 100, 200, and 500 ng/ml of 12, 6.6, and 5.8%, respectively. Furthermore, the assay proved to be free of interference from 48 commonly prescribed and some over-the-counter medications. We conclude that the method described here is ideally suited for the therapeutic monitoring of itraconazole.
1. ATP-sensitive K+ channels (KATP) are activated either by decreased intracellular ATP content or ATP/ADP ratio during ischaemia. We examined the role of a cerebral KATP in arterial pressure regulation during acute cerebral ischaemia using SHR and WKY rats. Thirteen week old male SHR or WKY rats were anaesthetized with urethane, and arterial pressure and heart rate were recorded under an artificial ventilation. 2. Intracerebroventricular (i.c.v.) injections of glibenclamide, a specific inhibitor of KATP, elicited dose-dependent vasopressor responses in WKY with bilateral ligation of carotid arteries, whereas it caused smaller vasopressor responses in SHR than WKY. 3. Systemic administration of AVP V1 receptor antagonist, OPC-21268, abolished the vasopressor responses of i.c.v. injections of glibenclamide in WKY but not in SHR. 4. Intracerebroventricular injections of glibenclamide caused both the increase in plasma concentration of AVP and the decrease in pituitary AVP content in WKY with bilateral ligation of carotid arteries, whereas it elicited no significant change in plasma and pituitary concentration of AVP in SHR with bilateral ligation of carotid arteries. 5. Cerebral KATP may play a role in the protection of excess hypertension by inhibiting AVP release from the pituitary glands during acute ischaemia in WKY, but this mechanism might not work in SHR during acute cerebral ischaemia.
We reported a 53-year-old female who was admitted due to partial loss of consciousness. She had been diagnosed as old pulmonary tuberculosis and diabetes mellitus. She was diagnosed as diabetic keto-acidosis on admission. We isolated Escherichia coli in the blood, transtracheal aspiration (TTA) and from the urine. We have experienced 6 cases where the same bacteria was isolated from the blood and TTA at the same time. In all 6 cases, we have found single bacteria in the blood and a few other bacteria in TTA. Blood culture is the most certain method to detect the origin of infectious diseases. But the compromised host, as in this case, has multifocal infections in many cases. In order to understand the pathological aspects of the infection, we must obtain many kinds of samples and as many as possible.
We measured the chemiluminescent activity (CL-index) in both the whole blood and isolated neutrophils from 12 patients with acute respiratory infection (7 cases; pneumonia, 4 cases; in the exacerbated phase, chronic lower tract infection, and one; acute bronchitis) two times per each case: before and after chemotherapy. Before the initiation of chemotherapy, neutrophil and whole blood CL was high but whole blood CL was higher. After the completion of chemotherapy, whole blood CL was decreased more significantly than neutrophil CL. There was no correlation between neutrophil CL and whole blood CL. However the neutrophil CL-index.N (neutrophil numbers x neutrophil CL-index) was correlated with the whole blood CL. Thus, we think the number of neutrophils is a critical factor for phagocytic function of neutrophils as determined by CL.
PURPOSE: To use computed tomography (CT) during arterial portography (CTAP) and CT arteriography to compare the hemodynamic properties of early hepatocellular carcinoma (HCC) with those of small HCC. MATERIALS AND METHODS: Forty-four early HCCs (mean diameter, 1.5 cm) in 37 patients (26 men and 11 women aged 52-74 years; mean age, 59.2 years) were studied. CTAP was performed on 35 early HCCs, CT arteriography on 20, and both studies on 11. CTAP, CT arteriography, or both were performed on 90 small HCCs (mean diameter, 2.0 cm) in 57 patients (44 men and 13 women aged 48-71 years; mean age, 61 years). The findings for small HCC were compared with those for early HCC. RESULTS: CTAP depicted 23 early HCCs as hypoattenuating masses and 12 as isoattenuating. CT arteriography depicted 11 early HCCs as hypoattenuating masses, six as isoattenuating, and three as hyperattenuating. CTAP depicted 85 of 88 small HCCs as hypoattenuating masses and three as isoattenuating. CT arteriography depicted 13 of 14 small HCCs as hyperattenuating masses. CONCLUSION: CTAP, the standard of reference for the detection of small HCC, is not sensitive enough for the detection of early HCC.
The ATP-sensitive potassium channels (KATP) are activated either by a decrease in intracellular ATP content or by a lowering of the ATP-ADP ratio such as during stroke. We studied the role of cerebral KATP on arterial pressure during acute reduction of cerebral blood flow in 12-week-old male Wistar rats anesthetized with urethane by recording arterial pressure and heart rate continuously. After bilateral ligation of the common carotid arteries, glibenclamide, a specific blocker of KATP, was injected intracerebroventricularly into the cerebral lateral ventricle. Glibenclamide elicited a sustained vasopressor response in a dose-dependent manner in rats with bilateral carotid artery ligation (10 nmol, +15 +/- 2 mm Hg; 1 nmol, +5 +/- 1 mm Hg, P < .01 versus vehicle), but hemodynamic alterations were barely recorded with glibenclamide in sham-operated control rats. The abdominal sympathetic discharge was not increased significantly enough to explain the pressor mechanism. Similarly, pretreatments with intravenous injections of bunazosin, an alpha 1-adrenoceptor antagonist, did not affect the pressor response of intracerebroventricular glibenclamide. To investigate the vasopressor mechanism further, we measured plasma and pituitary concentrations of arginine vasopressin and determined the effects of vasopressin receptor antagonists. The intracerebroventricular injections of glibenclamide significantly increased the plasma concentration of vasopressin (P < .05) and significantly decreased the pituitary concentration of vasopressin (P < .05) in rats with bilateral carotid artery ligation. Intravenous pretreatment with the vasopressin V1 receptor antagonist OPC-21268 abolished the vasopressor response to intracerebroventricular glibenclamide (+16 +/- 2 versus +1 +/- 1 mm Hg, P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)
The interaction of zinc sulfate with thrombospondin (TSP) derived from bovine platelets, on the proliferation of bovine aortic smooth muscle cells was investigated using cell culture. Zinc alone has no effect but potentiates the stimulatory effect of TSP on the incorporation of [3H]thymidine into the acid-insoluble cell fraction. Other heavy metals including copper, lead, manganese and nickel did not exhibit a similar effect. In bovine aortic endothelial cells, [3H]thymidine incorporation was stimulated by zinc alone and suppressed by TSP alone; the stimulation by zinc was significantly reduced by TSP. In human fibroblastic IMR-90 cells, [3H]thymidine incorporation was stimulated by either zinc or TSP; a simultaneous treatment with zinc and TSP showed an additive effect. The present data suggest that zinc may be a unique heavy metal that potentiates the proliferation of vascular smooth muscle cells stimulated by TSP; in addition, such an interaction was observed selectively in this cell type. Since a large amount of TSP is released from alpha-granules of aggregated platelets, zinc may augment TSP activity which is involved in the physiology of vascular tissues.