Distribution of radiolabeled 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitros ourea hydrochloride in rat brain tumor: intraarterial versus intravenous administration

To assess the rationale of intraarterial (i.a.) 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea chemotherapy, distribution of 14C-labeled 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)- 3-nitrosourea in rat glioma was studied after i.a. or i.v. infusion. Immediately after infusion, the tumor located in the hemisphere of intracarotid infusion received 4.6-fold higher radioactivity than the tumor located contralaterally to intracarotid infusion and 2.8-fold higher radioactivity than i.v. infusion. The difference was kept up to 30 min after i.a. infusion. Autoradiographic observation indicated rather uniform distribution of the tracer in the central portion of i.a. infusion. However, in the periphery of i.a. infusion, distribution of the tracer was nonhomogenous. The results indicate that i.a. 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea chemotherapy is useful when the tumor has high blood flow and is located in the center of an infused area.     

Use of antisera in the isolation of human specific conjugates of haloperidol

1. Three conjugated metabolites of haloperidol were isolated from urine of patients on haloperidol and purified by h.p.l.c. with immunological detection, using three types of anti-haloperidol antisera. 2. Structures of the metabolites were: a sulphate conjugate of the 2-hydroxylated 4-fluorophenyl ring of reduced haloperidol (MH-1), a glucuronide conjugate at the same position as MH-1 (MH-2), and a glucuronide conjugate of the hydroxy group of haloperidol (MH-3). 3. MH-3 was the main urinary metabolite in volunteers receiving haloperidol, who excreted 18% of the dose in the 24 h urine as MH-3, while other conjugates were less than 1%. MH-3 could not be hydrolysed with beta-glucuronidase, due to steric hindrance. 4. Immunological detection of conjugated metabolites is very useful in metabolic studies in humans because of its sensitivity and specificity.     

Breast cancer detected by mass screening using physical examination alone

In Tokushima prefecture, mass screening for breast cancer has been conducted using physical examination alone since 1970. Breast cancer was detected in 116 of 111,571 screened women up until 1984. The detection rate was 0.08 per cent in total examinees, 0.13 per cent in initial examinees, and 0.04 per cent in subsequent examinees. The patients with breast cancer were divided into three groups, i.e., 62 cases detected at initial screening, 28 cases detected at subsequent screenings, and 26 interval cancer cases. 510 patients with breast cancer in the outpatient clinic were serving as controls. The stage classification and nodal involvement were significantly different between the mass screening group and the control group, but not significantly different among the three groups. The interval cases were detected at an early stage. The survival rates were not significantly different between the three groups and the control group. Efforts should be doubled to educate women about the proper method of breast self-examination in order to promote the early detection of breast cancer.     

Pancreatic tumor antigen in transplantable adenocarcinomas induced by N-bis(2-hydroxypropyl)nitrosamine in hamsters

An attempt was made to detect a pancreatic tumor antigen (PTA) in transplantable pancreatic adenocarcinomas induced by N-bis(2-hydroxypropyl)nitrosamine (DHPN) in hamsters. Antibody against antigenic protein was raised by immunizing rabbits with whole homogenate of the tumors transplanted into the back of hamsters. PTA was purified by affinity chromatography and shown to have the physicochemical properties of a glycoprotein with a molecular weight of 800,000, migrating in the beta regions upon agarose gel electrophoresis. Loss of immunological properties was observed after heating at 65 degrees C for 30 min. Enzyme immunoassay revealed that the levels of PTA in the serum and tissue showed a positive correlation with the induction of the presence of tumor, and size of the tumor. It is tentatively suggested that PTA values above 150 ng/ml serum are indicators of tumors, because in normal hamsters the PTA range is from 25 to 130 ng/ml serum. Immunohistochemically, PTA was demonstrated to be localized within the cytoplasm of epithelial tumor cells of well-differentiated tubular adenocarcinomas.     

THE HISTOLOGIC FEATURES AND HISTOGENESIS OF MALIGNANT OVARIAN BRENNER TUMOR

Eight cases of malignant and 12 0f benign Bren- ner tumor are reported, patient ages ranged 31 69 and 39-53 years. The malignant tumor was bilateral in 6 0f 8 cases, and the benign in l of 12. The greatest diameter of the malignant tumors averaged around 11 cm, and the benign 10. Six of the malignant Brenner tumor patients died, one was lost to follow up, and one survived for 10 years. Pathologic and microscopic findings were pre- sented in some detail. Based on the analysis of the association between the histologic features and type of Mullerian epithelium, we believe that the so called Brenner tumor is in effect a tumor arising from the Mullerian epithelium with a tendency to differentiate into vaginocervical type epithelium.     

Experimental autoimmune uveoretinitis (EAU) in rats: isolation of S-antigen, EAU susceptibility of rat strains, genetic control of EAU induction, and effects of cyclophosphamide and irradiation on EAU

Highly purified S-antigen was isolated from bovine retinas by high performance liquid chromatography (HPLC), and was used to induce experimental autoimmune uveoretinitis (EAU) in various rat strains. Studies were then made of the genetic control of EAU, the effects of cyclophosphamide or irradiation on EAU, and the correlation between the EAU incidence and the serum levels of antibody to S-antigen. Lewis rats were the most susceptible to EAU followed by Wistar rats. F344 rats and BN rats were resistant to EAU. (Lewis X BN)F1 rats and (LBNF1 X Lewis) rats were susceptible to EAU, while (LBNF1 X BN) rats were resistant. These results indicate that susceptibility to EAU was inherited as an autosomal dominant trait. Treatment of rats with cyclophosphamide or irradiation (200 rad/rat) on the day before immunization markedly suppressed EAU development. On the other hand, the same dose of irradiation 7 days after the immunization did not affect the disease induction, yet the antibody levels to S-antigen were very high in the rats. In addition, BN rats resistant to EAU exhibited very high levels of antibody to S-antigen. Therefore, the antibody to S-antigen seems to play a minor role, if any, in the immunopathogenic mechanisms of EAU.     

Noninvasive Estimation of Blood Alcohol Concentrations: Ethanol Vapor Above the Eye

The present study describes, in animals, a novel approach to the in vivo, noninvasive determination of alcohol in the body. The concentration of ethanol in vapor above the lacrimal fluid in the eye was analyzed in situ by the use of a fast (1-min) gas sensor method developed previously for biological liquids. After an oral dose of 1 g/kg to 11 animals, eye vapor measurements and blood samples were obtained over 4 hr. The correlation of 61 blood ethanol concentrations obtained by the two methods yielded a correlation coefficient of 0.92 and a slope of 0.99. The metabolic rates of ethanol determined by gas chromatographic analysis of blood and by ethanol eye vapor analysis are virtually identical. The data suggest that ethanol eye vapor analysis may be an attractive, noninvasive method for the determination of ethanol in animals. The method is not subject to false high readings due to alcohol in the buccal cavity and thus might constitute an alternative to breath analysis in the human. In a separate series, ethanol was determined by head space gas chromatography in samples of blood and lacrimal fluid while the animals were under ketamine anesthesia. The correlation of ethanol concentrations in blood and lacrimal fluid (r = 0.99) shows that ethanol is distributed in lacrimal fluid which comprises part of total body water.     

Study on distribution of epidermal growth factor (EGF) in rat tissues

Tissue distribution of epidermal growth-factor (EGF) in rat was investigated using a human EGF (hEGF) radioimmunoassay system. Antisera generated against hEGF reacted with hEGF and [21Leu] hEGF but not with mouse EGF, fibroblast growth factor (FGF), nerve growth factor (NGF), platelet derived growth factor (PDGF), and endothelial cell growth supplement (ECGS). Similar amounts of EGF immunoreactivity (EGF-IR) were found in the rat submandibular gland (32.8 +/- 4.59 ng/g tissue, n = 5) and duodenum (39.9 +/- 18.7 ng/g tissue, n = 9), whereas little EGF was detected in other tissues. No sex difference was observed in submandibular and duodenal EGF-IR, being different from the case of mouse in which ten times higher concentration of EGF-IR was found in male submandibular gland. Sephadex G-50 gel chromatography of submandibular and duodenal extracts revealed that each consisted of at least three different immunoreactive forms. The predominant EGF-IR was coeluted with 125I-EGF, significant amounts of EGF-IR was observed in the void volume fractions, and only small peaks of EGF-IR were present near Vt. These data clarified the presence of EGF-IR in rat submandibular and duodenal tissues and the molecular heterogeneity of EGF-IR and suggest some important role of EGF in the gastrointestinal function.