Phase II study with methyl-6[[[2-chloroethyl) nitrosoamino] carbonyl] amino]-6-deoxy-alpha-D-glucopyranoside (MCNU) in hematological malignancies

A total of 117 cases with hematological malignancies were treated with MCNU at doses of 70-100 mg/m2. Following are the results obtained. 1. MCNU showed a marked depression of cells in the cases with CML, polycythemia vera and thrombocythemia. The low level of cells was maintained for 2 to 7 months. 2. A good response was observed in several cases with blastic crises of CML. 3. No response was observed in two cases with acute leukemia. 4. Although a fair response was observed in several cases with malignant lymphoma or multiple myeloma, moderate bone marrow suppression was observed in a majority of the cases.     

Characteristics of alpha adrenoceptors of lymphatics and their physiological significance

We studied isolated bovine mesenteric lymphatics to investigate the pharmacological properties of the postjunctional-adrenoceptors. Rings of the lymph vessels were mounted for isometric tension recording in organ chambers filled with Krebs-Ringer bicarbonate solution. The lymph vessels contracted when exposed to phenylephrine and clonidine. The relative sensitivity of the vessels to clonidine was larger than to phenylephrine. Yohimbine was a competitive antagonist against phenylephrine and clonidine in the lymph vessels. Prazosin caused a parallel shift to the right of the dose-response curve to phenylephrine, and not to clonidine in the vessels. The Schild's plot for yohimbine in the lymph vessels suggests that the presence of both alpha 1- and alpha 2-like adrenoceptors on lymphatic smooth muscle cells.     

Hypothalamic hamartoma with precocious puberty--a case report

A case of hypothalamic hamartoma with precocious puberty is presented and the literature of reported cases is reviewed. An 8-year-old boy was admitted to our hospital because of precocious puberty and mental retardation. His genital development was Tanner's stage 4 and pubic hair was Tanner's stage 3. Bone age was 11 years. Plain CT showed an isodense mass in the suprasellar cistern which was not enhanced following contrast administration. Metrizamide CT cisternography showed a filling defect in the suprasellar cistern. Endocrinological evaluation revealed high levels of serum luteinizing hormone (LH) and testosterone with a marked response of LH to LH-RH injection. A left frontotemporal craniotomy was performed and the tumor was partially removed. The tumor was gray, firm and well-circumscribed with poor vascularity. Postoperatively, a right oculomotor palsy and transient diabetes insipidus developed. He was discharged ambulatory one month later. Serum LH and testosterone returned to normal and the response of LH to LH-RH injection became normal. Hamartoma was diagnosed on histological examination. Electron micrographic study showed numerous dense granules with approximately 0.1 mu in diameter, in which Judge proved LH-RH by immunofluorescent study in 1977. Our case supports the hypothesis that hypothalamic hamartoma may cause precocious puberty by autonomous secretion of LH-RH and we consider that neurosurgical treatment is recommended.     

The B region-associated antigens and MLR phenotypes in the Japanese inbred strains of rats

Seven different alloantisera absorbed with red blood cells (RBC) from appropriate strains of rats detected a series of B cell alloantigenic specificities that could be divided into two groups, presumably coded for by at least two different closely-linked loci in the rat major histocompatibility complex (MHC), RT1. The one locus had two allele codes for a broad specificity and the other locus codes for a unique specificity that was found only in the restricted strains of rats that shared the same mixed lymphocyte reaction (MLR) phenotype. RBC-absorbed alloantisera were monitored against a panel of B cell fractions obtained from sixteen inbred strains. Two alloantisera, ACI anti-W and W anti-TO detected two broad specificities, into either of which all inbred strains tested were classified. Two broad RT1-B region-associated specificities were thus designated provisionally as Ba-1.1 and -1.2. Another five alloantisera detected four respective specificities which have a narrower strain distribution. Sixteen inbred strains were classified into one of five specificities detected by W and F344, F344 anti-SDJ, WKA anti-ACI, W anti-BUF and ACI anti-W absorbed with LEJ lymph node cells. Each specificity was designated provisionally as Ba-2.1, -2.2, -2.4, -2.6, -2.7, respectively. A complete association of Ba-2 specificities with MLR phenotype was observed. Antigenic specificities of Ba-2.2, -2.2 and -2.4 were all classified in a group of Ba-1.1 specificity, whereas Ba-2.6 and -2.7 specificities were associated with Ba-1.2 specificity. This relationship suggested a linkage disequilibrium between the two loci for the Ba antigens.     

Down-regulation of ASY/Nogo transcription associated with progression of adult T-cell leukemia/lymphoma

Adult T-cell leukemia/lymphoma (ATLL) is an aggressive form of human leukemia/lymphoma. Although this disease is initiated by infection with human T-lymphotropic virus type 1 (HTLV-1), many HTLV-1 carriers survive for a long period without aggressive illness, suggesting that other factors may play roles in the progression of ATLL to an aggressive state. However, the mechanism involved in this progression still remains unclear. Previously, we have reported that ASY/Nogo mRNA was markedly down-regulated in human small-cell lung carcinomas, whereas it was expressed in normal tissues and other lung carcinomas, such as adenocarcinoma and squamous cell carcinoma. To understand whether or not ASY/Nogo gene is involved in the progression of ATLL, we examined the expression of ASY/Nogo mRNA in smoldering, chronic and aggressive ATLL, and found that the expression level of ASY/Nogo mRNA was markedly reduced in clinically aggressive ATLL. HTLV-1 Tax expression was not affected by the down-regulation of ASY/Nogo mRNA. These results indicate that the ASY/Nogo gene may act as a suppressor against ATLL progression, independent of Tax expression.     

Isolated, blood-perfused canine arteries: different vasoconstrictor responses of internal and external carotid arteries to 5-hydroxytryptamine

Canine carotid arteries were isolated, suspended in a bath and perfused under a constant flow rate with arterial blood led from a support dog. Resting perfusion pressure was set at a constant level over 50 mm Hg. Drugs were administered into the endothelial side of the artery through a cannulated tubing and the response was obtained as pressure changes. This preparation was proved to be superior to usual isolated arterial strips, since its reactivity was kept in a stable condition over 5-10 hours at 37 degrees C. Using this preparation, effects of 5-hydroxytryptamine (5-HT) on the internal and external carotid arteries were investigated in comparison with effects of norepinephrine. In the internal carotid artery, 5-HT caused a much more potent vasoconstriction than norepinephrine. On the other hand, in the external carotid artery, 5-HT caused only slight vasoconstriction, while norepinephrine produced a marked vasoconstriction.