EPIDEMIOLOGICAL CHARACTERISTICS OF PROSTATE CANCER IN GUNMA PREFECTURE, JAPAN

Background Prostate cancer is rare in Asia, but the number of patients is increasing in Japan. We conducted an epidemiological study of prostate cancer in Gunma Prefecture, Japan, to investigate the trends and characteristics of the disease.
Methods: The subjects were 1.411 prostate cancer patients newly diagnosed between 1985 and and 656 patients who died from prostate cancer between 1981 and 1992. The incidence and mortality rates were calculated by year, demographic region and age.
Results: The yearly incidence rate showed an increase but the mortality rate showed no marked fluctuations. There was no significant difference between urban and ruraI districts in either incidence or mortality rate. The incidence rate tended to be high in the northern part of the prefecture, but no marked variation in mortality rate was seen. The incidence and mortality rates in districts with a history of manganese mining were high compared to those in districts without mining. In contrast, the incidence and mortality rates in districts with a history of zinc mining were comparatively lower. Both incidence and mortality rates showed a marked increase with age. The age-specific incidence showed a double logarithmic relationship to age.
Conclusions: The increase of the yearly incidence rate might be due to changes in lifestyle and environmental factors, improved diagnostic techniques, and increased awareness among the general public regarding prostate disease. Further investigation is needed to clarify the pattern and the causes of regional differences in the incidence and mortality rates. The possibilities that manganese and zinc might be related to prostatic carcinogenesis are suggested. Int J Urol 1995:2:191–197     

Combination adoptive immunotherapy with chemoradiotherapy in oral carcinomas

Background The antitumor effects of adoptive immunotherapy in combination with chemoradiotherapy were investigated in patients with oral squamous cell carcinoma. Methods Inductive chemoradiotherapy with peplomycin, 5-fluorouracil and⁶⁰Co was given to 56 patients [CRI(−)group]. A local injection of adoptive lymphokine-activated killer (LAK) cells (≈2×10⁸ cells) and small doses of interleukin-2(≈3×10⁵ U) and interferon-gamma (≈2×10⁵U) was given to 40 other patients in combination with the chemoradiotherapy [CRI(+) group]. Results Clinically, CR, PR, and LR were observed in 15 (37.5%), 24 (60.0%), and 1 (2.5%) of the patients in the CRI (+) group, respectively; and in 14 (25.0%), 38 (67.9%), and 4 of the patients (7.1%) in the CRI (−) group. The histopathological effects were correlated with the tumor remission rate, with lethal degeneration (grades III and IV), and prominent degeneration (grade IIB) in the tumor cells noted in 20 (50.0%) and 16 (40.0%) of the CRI(+) patients, respectively; and in 21 (37.5%) and 29 (51.8%) of the CRI (−) patients. Immunohistochemically, a prominent decrease of proliferating cell nuclear antigenpositive cells with a reciprocal increase of Le^Y-positve cells was induced by the chemoradioimmunotherapy. DNA fragmentation was observed in the mutant type p53-negative tumors in the CRI(+) group. Conclusion Adoptive immunotherapy with LAK cells and cytokines in combination with chemoradiotherapy induces advantageous anticancer effects resulting from necrosis and apoptosis.     

Clinical similarities of hereditary progressive/dopa responsive dystonia caused by different types of mutations in the GTP cyclohydrolase I gene

OBJECTIVE—Hereditary progressive dystonia withpronounced diurnal fluctuation ((HPD)/dopa responsive dystonia (DRD))is a childhood onset dystonia which responds to levodopa. Variousclinical signs and symptoms of HPD/DRD have been recognised to date.Mutations in the GTP cyclohydrolase I (GTP-CH-I) gene were recentlyidentified as the cause of HPD/DRD. In the present study, the GTP-CH-Igene and the clinical features of eight HPD/DRD patients from sixfamilies were analysed to determine the correlationsbetween clinical expression and the mutations in the GTP-CH-I gene.
METHODS—The exons, exon-intron junctions, and anindispensable part of the 5' flanking region of the GTP-CH-I gene weresequenced in the eight clinically diagnosed patients with HPD/DRD andtheir asymptomatic parents.
RESULTS—Three independent mutations in theGTP-CH-I gene were found in three patients. One of the patients and herasymptomatic mother were heterozygous for a novel mutation at theinitiation codon. The three patients with dissimilar GTP-CH-I mutationsexhibited similar clinical features. The other five patients withnormal sequences presented several features not manifested by the three patients with the mutations. No mutation was found in the 5' flanking region of any patients or their parents.
CONCLUSIONS—A novel initiation codon mutation wasfound in a Japanese patient with HPD/DRD. The clinical manifestationscommon to the patients with HPD/DRD with a mutated GTP-CH-I gene werealso identified. Although focal manifestations of HPD/DRD associatedwith the mutations of this gene will be broadened, it is inferred thatthese clinical features are fundamental to HPD/DRD caused by mutationsin this gene.

     

Expression of intercellular adhesion molecule-1 on transitional cell cancer. Possible significance in immunity against tumor cells.

Immunohistochemical examination demonstrated expression of intercellular adhesion molecule-1 (ICAM-1) on 17 of 44 transitional cell cancers (TCCs) but not on normal transitional cells. ICAM-1 was frequently expressed in higher stage tumors, especially in those with abundant immune cells scattered within tumor. Analysis of infiltrating immune cells showed that they were composed mainly of T lymphocytes and a smaller number of macrophages bearing the lymphocyte function-associated antigen-1 (LFA-1). Expression of ICAM-1 on transitional cell cancer cell lines was augmented by in vitro treatment with interferon-gamma, tumor necrosis factor-alpha, and interleukin-1 beta. Furthermore, Northern blot analysis revealed higher quantities of a 3.3-kb RNA in T24 cells exposed to interferon-gamma or tumor necrosis factor-alpha. These results suggest that the expression of ICAM-1 on transitional cell cancers might be modified by cytokines produced by infiltrating immune cells, which might facilitate immune responses against cancer cells.     

Effects of sodium nitroprusside (MR7S1) and nitroglycerin on the systemic,renal, cerebral,and coronary circulation of dogs anesthetized with enflurane

Summary In beagle dogs anesthetized with enfluranenitrous oxide, effects of sodium nitroprusside (SNP; MR7S1) and nitroglycerin (NTG) on hemodynamics and main organ circulation were studied to evaluate their effectiveness and safety as hypotensive agents during anesthesia. SNP (MR7S1) infusion (1–10 g/kg/min) decreased arterial blood pressure in a dose-dependent manner. The hypotension was stable during the infusion. After discontinuation of infusion, the blood pressure rapidly returned to the initial level. The hypotension was associated with decreases in cardiac output and total peripheral resistance. NTG infusion (3–10 g/kg/min) decreased arterial blood pressure, too, but the hypotension was less marked and not dose dependent, and the recovery was slower. Neither drug changed the heart rate. Infusion of SNP (MR7S1) and NTG did not change the hypotension induced by the injection of adenosine, SNP, and NTG. Furthermore, cerebral blood flow, cerebral oxygen consumption, and renal blood flow were unchanged during the hypotension produced by either drug. Coronary blood flow was decreased, but this was due to decreases in cardiac oxygen consumption. In conclusion, SNP (MR7S1) is superior to NTG as a hypotensive agent during anesthesia in efficacy, clear dose dependency, and rapid recovery. The hypotension induced by NTG as well as SNP (MR7S1) seems to have no undesirable effects on the circulation of important organs.     

Colon bladder replacement after total cystectomy

Although ileal conduit diversion is widely accepted in the treatment of the patients undergoing radical cystectomy, many patients would prefer other alternatives which allow continence. and urination through the urethra. We describe a new procedure in which a segment of detuburalized right colon is used as a continent reservoir. Eight patients, 7 after radical cystectomy for bladder cancer and one after total exenteration for rectal cancer, have undergone colon bladder replacement. New created bladder had a capacity of 300 to 600 ml. All patients could pass urine through the urethra but one is on self-catheterization. Five of the 8 patients had no residual urine. Three months after operations 4 were totally continent and 3 were satisfactorily dry during daytime but slightly enuretic. Excretory urography showed no abnormalities in their upper urinary tract. Considering the "quality of life' of a patient, this procedure can be an ideal option for selected patients.     

Drug Binding to α1-Acid Glycoprotein Studied by Circular Dichroism

The interactions of acidic and basic drugs with ₁-acid glycoprotein (₁-AGP) were investigated using circular dichroism (CD) measurements. Extrinsic Cotton effects were generated by the binding of drugs to ₁-AGP. The CD data suggested the presence of a single binding site on the ₁-AGP molecule. The induced ellipticities of the acidic drug–₁-AGP system decreased with increasing pH, while the ellipticities for the basic drugs increased with pH. The ellipticities for all drugs were reduced by the addition of fatty acids. Furthermore, the induced ellipticities decreased in the presence of cesium chloride for basic drugs bound to ₁-AGP. The extrinsic Cotton effects therefore appear to result from hydrophobic interaction with ₁-AGP for the acidic drugs and from hydrophobic and electrostatic interactions for the basic drugs.     

WIDESPREAD ECZEMA VACCINATUM ACQUIRED BY CONTACTS A Report of an Autopsy Case

A4-moth-old male infant predisposed to allergic dermatitis acquired widespread eczema vaccinatum by contacts with a recently vaccinated sibling. He died of acute purulent peritonitis following a perforation of multiple duodenal ulcers. Fluorescence immunocytochemical and electron microscopic studies on the skin lesions revealed the presence of viral antigens and numerous virus particles compatible morphologically with those of the mature form from the same batch of smallpox vaccine given to the sibling. A large number of virus particles in the developmental form were also predominantly scattered in the cytoplasm of cells at the stratum malpighii of the epidermis as well as in neutrophils and macrophages in the skin lesions. The virus isolation from the skin lesions was done by using the HeLa cells and the human embryonic lung fibroblasts. No abnormal laboratory data were noted in immunoglobulins. On the basis of atrophy of the thymus and other lymphatic tissues and an appearance of large pyroninophilic cells in association with blastoid transformation, the authors discussed a possible participation of the disturbance of cellular immunity secondary to the virus infection in the development of the disease. ACTA PATH. JAP. 29 : 435–455, 1979.     

Surface antigenic specificities of human thymus-derived lymphocytes.

Surface antigenic specificities of human thymus-derived (T) lymphocytes were studied by cytotoxicity tests using a heterologous rabbit anti-human thymus serum. This serum showed higher cytotoxic titres on thymocytes by comparison with peripheral lymphocytes. After proper absorption the antiserum was non-toxic for chronic lymphatic leukaemia cells, but lysed the majority of thymocytes. It also lysed some of peripheral lymphocytes, corresponding to those lymphocytes which bound sheep erythrocytes (E) but not erythrocyte-antibody-complement complexes (EAC). Pretreatment of lymphocytes with the absorbed antiserum and complement completely abrogated rosette formation with E but spared EAC-binding lymphocytes. It also eliminated their reactivity to phytohaemagglutinin and concanavalin A. These findings indicate that the absorbed serum causes selective lysis of T cells. The results obtained from quantitative absorption studies suggest that a certain loss of T-cell antigens is brought about during the differentiation of thymocytes into peripheral T cells.     

GIANT CELL CARCINOMA OF THE PANCREAS

A case of giant cell carcinom of the pancreas is reported herein. The patient is a 67-year-old Japanese woman complaining of ascites, general fatigue, loss of weight, abdominal distention, nausea, and vomiting. Cytological diagnosis of ascites revealed adenocarcinoma. At autopsy, a whitish tumor measuring around 5 cm in diameter was found at the head of the pancreas. Metastasis was seen only in the liver. Histological examination displayed bizarre multinucleated giant cells occasionally phagocytosing the tumor cells and neutrophils.