Carcinogenicity of 1,2-dimethylhydrazine dihydrochloride in BALB/c mice

Summary The carcinogenicity of 1,2-dimethylhydrazine dihydrochloride (DMH) by oral, intragastric and subcutaneous administration was examined in 339 BALB/c mice. Subcutaneous injection of DMH induced intestinal tumors in the lower colon of all mice. After oral administration it induced a high incidence of vascular tumors in the liver and soft tissues, but colon tumors were found in only 2 mice when given at a high dosage. On intragastric administration, it induced a fairly high incidence both of colon and vascular tumors. The sites and incidences of vascular tumors and squamous cell carcinomas of the perianal glands were also described.This work was supported in part by a Grant-in Aid for Cancer Research from the Ministry of Education, Japan.     

Serum cholesterol levels as a risk factor of cardiovascular disease

By summing up a series of epidemiological evidence a continuous elevation of total serum cholesterol, especially LDL-cholesterol, leads atherosclerosis and causes the narrowing or occlusion of coronary artery which introduces acute myocardial infarction or angina pectoris in the heart. In the brain, it is a risk factor for cerebral thrombosis. On the other hand, a lower level, 160 mg/dl or less of total serum cholesterol relates with the higher incidence of cerebral hemorrhage or subarachnoid hemorrhage, but still with the lower incidence of ischemic heart disease. It is concluded that the higher the total serum cholesterol level and the longer the period of continuous elevation is, the higher the incidence of ischemic heart disease. And there is a U-shape relationship between the level of serum cholesterol and cerebrovascular disease as a whole with a nadir around 160 to 200 mg/dl which means an optimal range of total serum cholesterol. A subject with total serum cholesterol over the optimal level may need some sort of modification in his daily life, in eating or physical exercise but not necessarily requires any pharmacological therapy.     

Association of HLA alleles with response (especially biochemical response) to interferon therapy in Japanese patients with chronic hepatitis C.

The response of chronic hepatitis C to interferon (IFN) treatment is classified as complete response (CR), biochemical response (BR), or no response (NR). Several studies have found no difference in prevention of hepatocellular carcinoma by IFN therapy between patients with CR and those with BR. We investigated whether specific human leukocyte antigen (HLA) alleles were associated with response to IFN, especially BR, in 138 patients with chronic hepatitis C. Comparing patients with and without CR, male, a low viral titer, genotype 2a or 2b, HLA-B55, and HLA-DRB1-0803 were more common in the group with CR. Multivariate analysis showed that age (adjusted odds ratio [OR], 0.95 by every year [95% confidence interval [CI] 0.90 - 0.99], p = 0.028), genotype 2a or 2b (5.21 [95% CI 1.63 - 16.6], p = 0.005), and low viral titer (8.58 (2.66 - 27.7), p < 0.001) were associated with CR. Comparing patients with BR and NR, the pretreatment alanine aminotransferase (ALT) level was lower in the BR group (p < 0.001). Both HLA-B7 and HLA-DRB1-0101 were more common in this group (p = 0.002). As the alleles HLA-B7 and HLA-DRB1-0101 were in linkage disequilibrium, the HLA-B7-DRB1-0101 haplotype may be associated with BR. Multivariate analysis indicated that a low ALT level (0.98 by every 1 IU/L [95% CI 0.98 - 0.99], p = 0.001) and HLA-B7-DRB1-0101 haplotype (32.3 [95% CI 1.50 - 693.1], p = 0.026) contributed significantly to BR. This study suggested that host HLA expression, but not viral factors, can influence BR.     

Serum Cytokines in Patients with Legionella Pneumonia: Relative Predominance of Th1-Type Cytokines

Serum samples from 14 patients with Legionella pneumonia were examined for the presence of cytokines. In spite of high levels of serum C-reactive protein in all patients during the acute phase in only four cases (one involving interleukin-1β [IL-1β], three involving IL-6, and none involving tumor necrosis factor alpha) was the concentration of cytokines more than 100 pg/ml. Th2 cytokines IL-4 and IL-10 were detected in only one patient each. In contrast, significant increases of serum gamma interferon (IFN-γ) and IL-12 levels were observed during the acute phase in 6 and 11 cases, respectively. Interestingly, although serum IFN-γ levels diminished thereafter, in seven cases IL-12 levels remained high or increased further during the convalescent phase. In an additional 22 cases clinically suspected to be but not diagnosed as Legionella pneumonia, increases of serum IL-12 levels were observed in 16 cases, whereas the remaining 6 cases showed no detectable IL-12. Our results demonstrate the relative predominance of Th1 cytokine production in Legionella pneumonia. Although the role and significance of prolonged increases in IL-12 levels in Legionella disease are unknown, our results should prompt further investigation of the host immune response in terms of Th1 and Th2 balance in legionellosis.     

Epithelial inclusion cyst (epidermoid cyst) formation with epithelioid cell granuloma in an intrapancreatic accessory spleen

The histologic characteristics of a case of epidermoid cyst formation with an epithelioid cell granuloma that developed in intrapancreatic accessory spleen were investigated, with the aim of clarifying its origin as well as etiologic factors. The patient, a 48-year-old male, was found to have a cystic lesion in the tail of the pancreas and renal cell carcinoma (clear cell carcinoma) during a medical check up. The pancreatic mass appeared to be a so-called "mucinous tumor" on imaging, and combined resection of the body and tail of the pancreas and the spleen was performed together with a left nephrectomy. The lesion in the tail of the pancreas was then demonstrated to have accessory splenic tissue with cyst formation in its central region. The cystic wall was covered with stratified squamous epithelium and ductal epithelium with squamous metaplasia, and pancreatic islet cells were evident at various sites within the accessory spleen. Formation of epithelioid cell granuloma tissue was observed around the cysts. The epithelium of the cyst was positive for CA19-9 and negative for antibodies against mesothelial cells, whereas the pancreatic island cells were positive for insulin. These results suggested that cystic epithelium in the accessory spleen could be derived from pancreatic duct epithelium. Frequent recurrence of chronic inflammation and epitheloid cell granuloma formation may have resulted from an aberration of the ectopic remaining pancreatic tissue in the spleen.     

Oesophageal squamous cell carcinoma with lymphoid stroma

Summary We treated a 70-year-old Japanese man with squamous cell carcinoma of the oesophagus with evidence of lymphoid stroma. The tumour consisted of a main lesion invading the muscular layer of the oesophagus, in association with wide areas of carcinoma in situ. The tumour stroma of the lesion was nondesmoplastic and was uniformly infiltrated mainly by abundant lymphocytes and plasma cells. Immunohistochemically, the lymphocytes consisted of a large number of T lymphocytes and a small number of B lymphocytes. S-100 protein positive cells were marked in the tumour cell nests and necrotic change of tumour cells was frequent. Abundant infiltration of lymphocytes and plasma cells was also wide-spread beneath the carcinoma in situ, together with the lymphoid follicles. Carcinoma with lymphoid stroma can occur not only in the breast, uterine cervix, nasopharynx and stomach but also in the oesophagus.     

In situ localization of S-phase-specific histone (H3) mRNA in Bowen's disease

PCNA and Ki-67 immunohistochemistry has been used to assess cell proliferation in place of tritiated thymidine or BrdU labeling of S-phase cells. Recently, it has been possible to reliably demonstrate histone H3 mRNA by in situ hybridization in formalin-fixed and paraffin-embedded tissue sections. We have compared this new proliferation marker with Ki-67 and PCNA with regard to distribution of positive cells and labeling indices (LI%) for 22 cases of Bowen's disease. In normal skin, Ki-67-IHC positive cells and histone mRNA positive cells were observed in the basal and suprabasal layers of the epidermis. In Bowen's disease, positive cells with each marker were more frequent in upper neoplastic epidermis than in suprabasal layers, and the average LI%s were markedly elevated with all markers, the scores decreasing in the following order: PCNA-IHC, Ki-67-IHC and H3mRNA-ISH. However, the results of double staining demonstrated that S-phase cells do not necessarily show exactly the same distributions as with PCNA and Ki-67-IHC labeling. H3mRNA-ISH showed three different degrees of reaction with significantly different LI%s, whereas PCNA and Ki-67 LI% did not vary essentially in the same areas. These results strongly suggest that Bowen's disease, which is well known as a low-grade neoplastic state with malignant potential, also demonstrates clear intratumoral heterogeneity of S-phase cells using the H3mRNA-ISH method.     

Heats of dilution of poly[styrene-ran-(butyl methacrylate)] solutions measured with an automatic flow microcalorimeter

In order to obtain information about the thermodynamic behaviour of copolymers in solution, we built an automatic flow microcalorimeter equipped with a computer that satisfies the requirements of accuracy, reliability, and rapidity for the measurement of heats of dilution of copolymer solutions. By using this apparatus, the heats of dilution of the random copolymer, poly[styrene-ran-(butyl methacrylate)] in ethyl methyl ketone solutions were measured at 298 K. Furthermore, light scattering of the copolymer and its constituent homopolymer solutions was measured at 298 K. From the combination of the heat of dilution and the light scattering results, thermodynamic and intramolecular interaction parameters of the copolymer chain were determined.     

THE BEHAVIOUR OF LYMPHOGENEOUSLY GIVEN ANTIGEN IN THE LYMPH NODE THE LOCALIZATION OF GIVEN ANTIGEN and NEWLY FORMED ANTIBODY

The vascular structures in the lymph node and their relation to fluid exchange have been reported in previous communications and it was considered that the morphological changes of the vascular structures were closely correlated with the functional development of lymph nodes as an antibody forming organ. In order to clarify the localization of the given antigen and newly formed antibody in relation to the morphological structure of lymph nodes, the popliteal lymph nodes of rabbits were studied by immuno-fluorescent techniques.
The antibody was found in the pavement arrangement (solid) of reticulum tissue which was formed by the expel of lymphocytes in the cortical mass and by the morphofunctional alterations of the reticulum cells. The given antigen and newly formed antibody were never detected in the follicles throughout the period of this experiment. ACTA PATH. JAP. 22:427–440, 1972.     

Intra-bone marrow-bone marrow transplantation facilitates hemopoietic recovery including dendritic cells

In this report, we provide evidence using a serial bone marrow transplantation (BMT) protocol that intra-bone marrow (IBM)-BMT (IBM-BMT) can efficiently reconstitute the hemopoietic system with cells of donor origin, in contrast to conventional intravenous (IV)-BMT (IV-BMT). Furthermore, the hematolymphoid system of secondary recipients that had received bone marrow cells (BMCs) from primary recipients treated with IBM-BMT recovered earlier than that of the secondary recipients of BMCs from primary recipients treated with IV-BMT. This was the case when the Lin-/c-kit+ progenitor cells of the secondary and tertiary recipients were examined. These findings indicate that IBM-BMT can facilitate the development of not only cells of various lineages but also the effective generation and, more importantly, the maintenance of the progenitor cells. Furthermore, we show that IBM-BMT can reconstitute the dendritic cell (DC) subsets (myeloid and lymphoid DCs), which are critical for the initiation of both adaptive and innate immune responses. The frequency of both myeloid and lymphoid DC subsets was approximately equal to that of normal age-matched untreated controls and, after second and third BMT, this ratio was close to that observed in the normal controls. However, the lymphoid DCs were clearly reduced in the secondary and tertiary recipients of BMCs from mice that had received IV-BMT. Therefore, the development of DC subsets is also normally maintained in the IBM-BMT group.