Offender and offense characteristics of a nonrandom sample of mass murderers.

A nonrandom sample (N = 30) of mass murderers in the United States and Canada during the past 50 years was studied. Data suggest that such individuals are single or divorced males in their fourth decade of life with various Axis I paranoid and/or depressive conditions and Axis II personality traits and disorders, usually Clusters A and B. The mass murder is precipitated by a major loss related to employment or relationship. A warrior mentality suffuses the planning and attack behavior of the subject, and greater deaths and higher casualty rates are significantly more likely if the perpetrator is psychotic at the time of the offense. Alcohol plays a very minor role. A large proportion of subjects will convey their central motivation in a psychological abstract, a phrase or sentence yelled with great emotion at the beginning of the mass murder; but in our study sample, only 20 percent directly threatened their victims before the offense. Death by suicide or at the hands of others is the usual outcome for the mass murderer.

Use of 4-heptylumbelliferyl-beta-D-glucoside to identify Gaucher's disease heterozygotes.

Three fluorometric beta-glucosidase assays were compared for their ability to identify Gaucher's disease heterozygotes, using leukocytes as the source of enzyme: the pH 5.5-taurocholate assay of Peters et al.; the conduritol B epoxide dependent variation of that assay; and the newly developed method described herein. While the first two procedures utilize the standard substrate 4-methylumbelliferyl-beta-D-glucopyranoside to estimate beta-glucosidase activity, the new assay uses 4-heptylumbelliferyl-beta-D-glucoside as (C7UGlc) substrate. Use of this substrate enhances the specificity of the method for lysosomal glucocerebrosidase, thereby minimizing the contribution of the nonspecific cytosolic beta-glucosidase to estimates of substrate hydrolysis. Using Student's t test for the three assays examined, the C7UGlc assay procedure was determined to have the lowest p value (p less than 0.001) and highest t value (t = 4.95) for the discrimination between the mean glucocerebrosidase value of control and obligate Gaucher heterozygote samples. The high reliability and simplicity of the C7UGlc assay lends adequate reason to favor this assay for regular clinical diagnosis of Gaucher heterozygotes.

Effects of sublethal irradiation on changes in crypts of the mouse colon during treatment with 1,2-dimethylhydrazine.

The effects of low-dose X-irradiation on the progression of early neoplastic changes induced in the colon by 1,2-dimethylhydrazine (DMH) were assessed. Outbred female Swiss-Webster mice were treated with DMH only, DMH-irradiation, irradiation only, or 0.001 M EDTA. Animals were pulsed with [3H]thymidine for 1 hour, and the distal colon was radioautographed. The number of labeled cells per crypt in animals tested with DMH-irradiation was greater (P less than 0.01) than the number in "DMH-only" animals, but a corresponding increase in the length of the crypts did not occur. After 16 weeks of treatment, the percentage of animals with focal atypia was similar in the DMH-irradiation group (87%), and the DMH-only group (100%), but there were more focal atypias per animal in the DMH-only group. After 20 weeks, 14% of the DMH-irradiation group had visible tumors compared to 63% of the DMH-only group. The results suggest that DMH increased the number of cells at risk for irradiation; thus the surge in proliferation subsequent to cell depletion was amplified. However, the development of precancerous lesions was not promoted.

The effect of the carcinogen, 1,2-dimethylhydrazine, on turnover of 3H-thymidine labeled cells from mucosal glands of mouse colon.

1,2-dimethylhydrazine (DMH), administered weekly to mice for 20 weeks, induces tumors in the distal segment of colon. Tumors are preceded by enlargement of the mucosal glands resulting from increases in the number of total cells and 3H-thymidine labeled cells/crypt. Cells located in the crypt base normally undergo 2-3 division as they migrate toward the lumen, and they become post-mitotic in the upper crypt. It is not known if cells in these enlarged crypts have rates of turnover similar to cells in normal crypts. Groups of w/s female mice were treated with DMH (20 mg/kg body wt) for 3,8, or 16 weeks; controls were given 0.001 M EDTA. After treatment, the animals were injected with 3H-thymidine and killed one hour or 1,2,4,7 or 17 days later. Autoradiographs were prepared from sections of distal colon. The total cells/crypt column in 30 crypts/animals were counted. Crypts were divided into 10 equal segments based on the crypt length and the labeled cells/segment were counted. The relative number of labeled cells and the distribution of these cells within crypts were similar in DMH-treated and control animals after one hour. However, as the cells migrated toward the lumen, the number of labeled cells doubled after 2 days and tripled after 4 days in DMH-treated animals but only doubled during the 4 days in controls. This difference caused by retention of an increased number of dividing cells in the lower 4 segments of the crypts and suggests an increase in those cells that divide twice. In addition, increased numbers of labeled cells were retained in the upper 3 segments of DMH-treated animals after 4 days. These findings indicate that the crypt cells of DMH-treated animals are generally more immature than those of controls and this immaturity contributes to the enlargement of mucosal glands during carcinogenesis.

Changes in crypt cell populations of mouse colon during recovery from treatment with 1,2-dimethylhydrazine.

The induction of adenocarcinomas in distal colons of noninbred female Swiss Webster white mice by 1,2-dimethylhydrazine (DMH) is preceded by the development of hyperplasia of mucosal glands, which includes absolute increases in both the total number of cells and labeled cells per crypt. This experiment was designed to determine if these changes are reversible. Groups of noninbred female Swiss Webster white mice were given weekly injections of DMH, 20 mg/kg body weight, for 1--20 weeks and killed 1--52 weeks after treatment. Animals were pulsed with tritiated thymidine ([3H]dTHd) for 1 hour and autoradiographs were made of sections of distal colon. The total number of cells per crypt and number of [3H]dThd-labeled cells per crypt were significantly elevated in animals killed 1 week after termination of treatment. With increasingly longer periods of recovery, base-line values were reached rapidly in animals given one or two treatments; however, reduction in cells was slower and less complete in animals given eight or more treatments. The latency before tumors developed was inversely related to the number of treatments. Animals that received 20 treatments developed more tumors per tumor-bearing animal than did animals given fewer treatments but allowed by survive for long periods. The findings indicate that once induced changes in the mucosa progress to a threshold level, mucosal glands are irreversibly enlarged and the development of tumors is irrevocable.

Localization of pyruvate kinase isozymes in bovine kidney and comparison of these patterns with those of lactate dehydrogenases and aldolases.

Electrophoretic and immunofluorescence analysis were used to study the distribution of pyruvate kinase isozymes in the bovine kidney. Electrophoretic analysis demonstrated the presence of large amounts of K4 plus small amounts of K-M hybrids in cortical, medullary, and papillary sections cut from the kidney. Nearly all of the K-L hybrids seen in whole kidney extracts were found in cortical sections. Immunofluorescence of frozen sections revealed the presence of type L subunits in the tubules but the complete absence of this subunit type in flomeruli. Glomeruli do contain large quantities of pyruvate kinase isozymes, probably K4 and K-M hybrids, that cross-react with antibodies produced against type M pyruvate kinase. Type L-containing forms of pyruvate kinase and aldolase type B both appear to be found in cell types thought to be capable of catalyzing of gluconeogenesis, while type K pyruvate kinase and type A aldolase are found in predominantly glycolytic cell types of the kidney. Lactate dehydrogenase isozymic patterns appear to be less closely correlated with glycolytic versus gluconeogenic functions of the kidney but may be determined more directly by other metabolic functions.

Early changes in the dynamics of crypt cell populations in mouse colon following administration of 1,2-dimethylhydrazine.

The effects of the carcinogen, 1,2-dimethylhydrazine (DMH), on the proliferative characteristics of the crypt cell population of mouse colon were studied. DMH (20 mg/kg body weight) was injected s.c., weekly, for 2, 8, 16, 20, or 26 weeks. At the end of each treatment period, a group of animals was injected with [3H]thymidine and killed. After 2 weeks of DMH treatment, the crypts appeared normal histologically, but the total number of cells, the number of labeled cells, and the percentage of labeled cells per crypt column had increased. The relative distribution of labeled cells in crypt columns was not changed. DMH treatment did not affect the phases of the cell cycle of epithelial cells and the transit time of these cells through the crypt. None of the indices of crypt dynamics were altered further with the appearance of focal atypias (after 16 weeks of DMH). However, the total number of cells per crypt increased and the percentage of labeled cells decreased as adenocarcinomas developed in adjacent areas of the mucosa (after 20 to 26 weeks of DMH). The exact role of these early mucosal changes in the eventual development of malignant tumor has not been established. However, it appears that DMH carcinogenesis may involve two steps; (a) an initial increase in the number of mitotocally active cells leading to an enlarged cell population; and (b) an eventual transformation of at least some of the crypt cells of the enlarged population.

Pyruvate kinase isozymes in cells isolated from fetal and regenerating rat liver.

There are at least three major mammalian isozymes of pyruvate kinase (ATP : pyruvate 2-O-phosphotransferase, EC 2.7.1.40), designated K4, L4, and M4. Whereas parenchymal cells from adult rat liver contain only the type L isozyme, parenchymal cells isolated from fetal and regenerating liver were found to synthesize both the K4 and L4 isozymes. A small amount of K-M hybrid was seen in regenerating liver, but there were no detectable M-L or K-L hybrids. Thus, it appears that type L pyruvate kinase is not synthesized at the same time in the same liver cell with either of the other two isozymes. The intermediate electrophoretic bands seen with homogenates of whole fetal liver, and in some earlier work attributed to either hybrid isozymes or to the presence of M4, are contributed by nonparenchymal cells which, in the fetus, are largely hemopoietic. These additional bands of pyruvate kinase are electrophoretically and immunologically similar to the pyruvate kinase isozymes found in adult erythrocytes. The results reported here suggest a very rigorous control in the synthesis of K4 and L4 isozymes in parenchymal cells of both fetal and regenerating liver as opposed to developing neurons and glia, where the shift from synthesis of type K to type M subunits appears to occur gradually and results in the production of substantial amounts of hybrid isozymes.