Cytomegalovirus infection after acute rejection therapy in seropositive kidney transplant recipients.

BACKGROUND: Acute rejection (AR) after solid organ transplantation has been known to be a risk factor for cytomegalovirus (CMV) infection. However, data regarding the risk for CMV infection during and after anti-rejection therapy are limited. This study investigated whether the risk of CMV infection and disease within 6 months of kidney transplantation (KT) increases in CMV-seropositive KT recipients who develop AR. METHODS: A total of 992 seropositive KT recipients, including 75 patients (8%) who developed AR within 6 months after KT and 917 patients (92%) who did not, were recruited between May 2007 and April 2012. RESULTS: No significant difference was found in the incidence of CMV infection between the groups (AR group, 13% [10/75] vs. non-AR group, 10% [92/917], P = 0.37). The number of KT recipients in each group receiving preemptive therapy for CMV was similar (5% [4/75] vs. 6% [53/917], P > 0.99). While the incidence of CMV syndrome was comparable (0% [0/75] vs. 1% [12/917], P > 0.99), the incidence of tissue-invasive CMV disease (8% [6/75] vs. 3% [27/917], P = 0.04), particularly gastrointestinal CMV disease, was significantly greater in patients who experienced AR. No CMV-related mortality occurred in either group. AR (odds ratio, 2.81; 95% confidence interval, 1.08-7.29; P = 0.03) was an independent risk factor for tissue-invasive CMV disease within 6 months of KT. CONCLUSIONS: A high index of suspicion and active evaluation for tissue-invasive CMV disease in KT recipients suffering AR may be necessary to ensure appropriate treatment.

Wildtype Kras2 can inhibit lung carcinogenesis in mice.

Although the ras genes have long been established as proto-oncogenes, the dominant role of activated ras in cell transformation has been questioned. Previous studies have shown frequent loss of the wildtype Kras2 allele in both mouse and human lung adenocarcinomas. To address the possible tumor suppressor role of wildtype Kras2 in lung tumorigenesis, we have carried out a lung tumor bioassay in heterozygous Kras2-deficient mice. Mice with a heterozygous Kras2 deficiency were highly susceptible to the chemical induction of lung tumors when compared to wildtype mice. Activating Kras2 mutations were detected in all chemically induced lung tumors obtained from both wildtype and heterozygous Kras2-deficient mice. Furthermore, wildtype Kras2 inhibited colony formation and tumor development by transformed NIH/3T3 cells and a mouse lung tumor cell line containing an activated Kras2 allele. Allelic loss of wildtype Kras2 was found in 67% to 100% of chemically induced mouse lung adenocarcinomas that harbor a mutant Kras2 allele. Finally, an inverse correlation between the level of wildtype Kras2 expression and extracellular signal-regulated kinase (ERK) activity was observed in these cells. These data strongly suggest that wildtype Kras2 has tumor suppressor activity and is frequently lost during lung tumor progression.

Emerging fluoroquinolone resistance in Streptococcus agalactiae in South Korea.

The goal of this study was to determine the prevalence of fluoroquinolone resistance in Streptococcus agalactiae and the serotype distribution of this resistant bacterium. S. agalactiae strains collected from 221 asymptomatic pregnant women (35-37 weeks of gestation) and 838 patients with S. agalactiae infection in Korea, from 2006 to 2008, were tested for susceptibility to four fluoroquinolones. Rates of resistance of S. agalactiae to ciprofloxacin, levofloxacin, and moxifloxacin were 9.3 %, 9.5 %, and 0.8 %, respectively; greater than 94 % of S. agalactiae strains were resistant to norfloxacin. Resistance to ciprofloxacin and levofloxacin increased between 2006 and 2008. All strains were susceptible to penicillin. Resistance to ciprofloxacin and levofloxacin was higher in the clinical strains of S. agalactiae isolated from infections than in colonizing strains isolated from pregnant women. Mutations in the quinolone resistance-determining regions of gyrase and topoisomerase genes were detected in strains resistant to ciprofloxacin, levofloxacin, and moxifloxacin; no such mutations were found in strains resistant only to norfloxacin. There was a strong correlation between the minimum inhibitory concentrations and the presence of mutations in gyrase and topoisomerase genes. In conclusion, the prevalence of fluoroquinolone resistance was unexpectedly high. Strain serotypes were not associated with susceptibility to fluoroquinolones.

[Retrospective analysis of 35 burn patients in different stages of pregnancy].

Objective: To summarize the clinical outcomes of burn patients in different stages of pregnancy and explore a rational therapeutic scheme for burns during pregnancy. Methods: A retrospective observational study was conducted. From June 2010 to June 2020, 21 patients who met the inclusion criteria were admitted to the Department of Burns of Wuhan Third Hospital and 14 patients who met the inclusion criteria were admitted to the Department of Burns of the First Affiliated Hospital of Nanchang University. Based on the pregnancy period when patients suffered burns, the 35 patients were divided into early pregnancy group with 18 patients (aged (26±4) years, with 8 (4, 11) weeks of gestation), middle pregnancy group with 10 patients (aged (26±3) years, with 21 (14, 27) weeks of gestation), and late pregnancy group with 7 patients (aged (30±5) years, with 32 (29, 35) weeks of gestation). All the patients received treatment including fluid resuscitation, anti-infection, wound treatment, and multidisciplinary comprehensive managements. The burn-related complications during the treatment, maternal outcomes, fetal outcomes, fetal delivery mode, gestational weeks at delivery, and newborn weight of patients in the 3 groups were recorded. Data were statistically analyzed with one-way analysis of variance, Kruskal-Wallis test, and Fisher's exact probability test. Results: During the treatment, there were 4, 4, and 2 patients who suffered wound infections and 1, 3, and 2 patients who developed shock symptoms, respectively, in early pregnancy group, middle pregnancy group, and late pregnancy group. There were no statistically significant differences in them among the 3 groups (P>0.05). One patient in late pregnancy group developed into multiple organ dysfunction syndrome after debridement. At last, all the pregnant women survived, and no statistically significant difference existed among the 3 groups (P>0.05). In early pregnancy group, middle pregnancy group, and late pregnancy group, the survived fetus cases were 9, 8, and 6, respectively, and the differences between them were not statistically significant (P>0.05). Variables including stillbirth and full-term birth were close in patients in the 3 groups (P>0.05), while the preterm birth and miscarriage in patients in the 3 groups were statistically different (P<0.05 or P<0.01), with the early pregnancy group having the most miscarriage cases and the fewest preterm birth cases. There were no statistically significant differences in fetal delivery mode, gestational weeks at delivery, and newborn weight among the patients with survived fetus in 3 groups (P>0.05). Conclusions: For patients suffering burns during early, middle, and late pregnancy, superior rates of maternal and fetal survival can be achieved after timely and adequate treatments including fluid resuscitation, anti-infection, wound treatment, and multidisciplinary comprehensive managements.

LncRNA PAPAS aggravates the progression of gastric cancer through regulating miRNA-188-5p.

Since this paper presents several inaccuracies and mistakes, the article "LncRNA PAPAS aggravates the progression of gastric cancer through regulating miRNA-188-5p, by X. Shi, X. You, W.-C. Zeng, Y.-J. Deng, H.-L. Hong, O.-X. Huang, M.-F. Wang, published in Eur Rev Med Pharmacol Sci 2019; 23 (24): 10761-10768-DOI: 10.26355/eurrev_201912_19778-PMID: 31858543" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/19778.

LncRNA PAPAS aggravates the progression of gastric cancer through regulating miRNA-188-5p.

OBJECTIVE: To uncover the biological effect of long non-coding RNA (lncRNA) PAPAS on the progression of gastric cancer (GC) by mediating microRNA-188-5p (miRNA-188-5p) level. PATIENTS AND METHODS: The relative level of PAPAS was determined in GC tissues and cell lines by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The Kaplan-Meier method was introduced to assess the prognostic potential of PAPAS in the overall survival of GC patients. Regulatory effects of PAPAS on proliferative, migratory, and invasive abilities of HGC-27 and AGS cells were detected by cell counting kit-8 (CCK-8), transwell, and wound closure assay, respectively. Subsequently, the binding relation between PAPAS and miRNA-188-5p was verified by the Dual-luciferase reporter gene assay. Correlation between expression levels of PAPAS and miRNA-188-5p in GC tissues was explored. Finally, rescue experiments were conducted to uncover the role of PAPAS/miRNA-188-5p axis in the progression of GC. RESULTS: PAPAS was upregulated in GC tissues and cell lines compared to controls. GC patients expressing a high level of PAPAS suffered worse prognosis relative to those with low level. The silence of PAPAS remarkably attenuated proliferative, migratory, and invasive abilities of HGC-27 cells. Overexpression of PAPAS in AGS cells obtained the opposite trends. MiRNA-188-5p was the direct target of PAPAS, which was negatively regulated by PAPAS. MiRNA-188-5p was able to reverse the regulatory effects of PA-PAS on proliferative, migratory, and invasive abilities of GC cells. CONCLUSIONS: LncRNA PAPAS is upregulated in GC and closely related to lymphatic metastasis, distant metastasis, and poor prognosis of GC patients. PAPAS aggravate the malignant progression of GC by negatively regulating the miRNA-188-5p level.

Knockdown of LINC00461 inhibits cell proliferation and induces apoptosis in gastric cancer by targeting LSD1.

OBJECTIVE: To uncover the function of LINC00461 in regulating cellular behaviors of gastric cancer (GC) via targeting LSD1. PATIENTS AND METHODS: LINC00461 level in GC tissues with different tumor node metastasis (TNM) staging and lymphatic metastasis statues was determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). In vitro influences of LINC00461 on proliferative and apoptotic rates were evaluated in AGS and SGC-7901 cells. The interaction between LINC00461 and LSD1 was explored by RNA immunoprecipitation (RIP) assay and qRT-PCR. Finally, the potential role of LSD1 in the proliferative ability of GC cells mediated by LINC00461 was assessed. RESULTS: LINC00461 level was higher in GC tissues relative to matched control ones. It was positively correlated to TNM staging and lymphatic metastasis of GC. Knockdown of LINC00461 markedly attenuated viability and the proliferative ability of AGS and SGC-7901 cells, but induced apoptosis. RIP assay demonstrated the interaction between LINC00461 and LSD1. Moreover, LSD1 could reverse the regulatory effect of LINC00461 on the proliferative ability of GC cells. CONCLUSIONS: LINC00461 is upregulated in GC, which is positively related to TNM staging and lymphatic metastasis. LINC00461 mediates proliferation and apoptosis of GC cells, thereafter aggravating the progression of GC.

Carcinogenic activity of pentabrominated diphenyl ether mixture (DE-71) in rats and mice.

Pentabrominated diphenyl ether (PBDE) flame retardants have been phased out in Europe and in the United States, but these lipid soluble chemicals persist in the environment and are found human and animal tissues. PBDEs have limited genotoxic activity. However, in a 2-year cancer study of a PBDE mixture (DE-71) (0, 3, 15, or 50 mg/kg (rats); 0, 3, 30, or 100 mg/kg (mice)) there were treatment-related liver tumors in male and female Wistar Han rats [Crl:WI(Han) after in utero/postnatal/adult exposure, and in male and female B6C3F1 mice, after adult exposure. In addition, there was evidence for a treatment-related carcinogenic effect in the thyroid and pituitary gland tumor in male rats, and in the uterus (stromal polyps/stromal sarcomas) in female rats. The treatment-related liver tumors in female rats were unrelated to the AhR genotype status, and occurred in animals with wild, mutant, or heterozygous Ah receptor. The liver tumors in rats and mice had treatment-related Hras and Ctnnb mutations, respectively. The PBDE carcinogenic activity could be related to oxidative damage, disruption of hormone homeostasis, and molecular and epigenetic changes in target tissue. Further work is needed to compare the PBDE toxic effects in rodents and humans.

Ganciclovir and Foscarnet Therapy of Cytomegalovirus-Associated Meningoencephalitis in a Hemodialysis Patient With Liver Transplantation: Case Report.

Cytomegalovirus (CMV) infection in patients with liver transplantation (LT) remains a highly prevalent complication with a significant increase in morbidity and mortality. However, CMV-associated meningoencephalitis is rarely diagnosed, and treatment is very difficult. The aim of the present report is to review the experience of successful treatment with combined ganciclovir and foscarnet of CMV-associated meningoencephalitis refractory to ganciclovir alone in a hemodialysis (HD) patient after LT. A 54-year-old woman with end-stage renal disease on HD developed a seizure with loss of consciousness. She had received a liver transplant 4 months before. Blood CMV polymerase chain reaction was positive, and cerebrospinal fluid (CSF) analysis was compatible with viral meningitis. Brain magnetic resonance imaging (MRI) showed extensive dural thickening with enhancement and a round ring-like enhancement in the left centrum semiovale. She was diagnosed with CMV-associated meningoencephalitis. At that time, ganciclovir was started intravenously. After that, there were no improvements in mental state, CSF analysis, or brain MRI. Intravenous foscarnet at reduced dose was added to ganciclovir therapy. With combined ganciclovir and foscarnet, there was a slight improvement in her mental state and brain MRI.

Myelotoxicity induced in female B6C3F1 mice by inhalation of methyl isocyanate.

The effects of a 4-day inhalation exposure (6 hr/day) to 0, 1, and 3 ppm methyl isocyanate (MIC) on bone marrow parameters in female mice were examined at 5, 8, and 21 days following exposure. The MIC exposure was associated with myelotoxicity as evidenced by hypocellularity, suppression of pluripotent stem cells (CFU-S), granulocyte-macrophage progenitors (CFU-GM) and erythroid precursors (CFU-E) in both dose groups. Hematopoietic parameters returned to normal by 21 days in the 1 ppm dose group, but not in the 3 ppm dose group. This indicates that the alterations in the bone marrow parameters persist for a relatively long period at dose levels where there are little or no changes in body weight, clinical pathology, or immunological parameters, suggesting that the bone marrow may be a sensitive endpoint for MIC exposure in mice. MIC is a highly reactive chemical that appears to exert its effect directly on the lining epithelium of the nasal cavity and major airways; there was no histological evidence of a systemic effect. The pathogenesis of the bone marrow depression is unknown; however, there were chronic bronchitis and bronchial fibrosis in the 3 ppm dose group. One possible explanation is that the cell injury induced in the lung is associated with the release of inhibitory factors for hematopoiesis, as the rodent lung is a potent source of both stimulatory and inhibitory growth factors for bone marrow progenitor cells. A second possibility is that the thymic atrophy found in MIC-exposed mice might be related to myelotoxicity. The pathogenesis of myelotoxicity in MIC exposure and its relationship with pulmonary injury require further study.

Microbial keratitis--a late complication of penetrating keratoplasty.

A retrospective review of 323 penetrating keratoplasties performed in Taiwan between January 1993 and December 1997 revealed that late microbial keratitis developed in 39 eyes of 36 patients (12.1%). All patients were operated on by the same surgeon, and all were followed for at least 1 year. The mean interval between the corneal transplantation and the onset of graft infection was 8.6 +/- 8.8 months (range 3 weeks-47 months). Predisposing risk factors for keratitis included chronic blepharitis with poor lid hygiene (43.6%), suture-related problems (38.5%), dry eyes (28.2%), epithelial defects (25.6%), and use of contact lenses (5.1%). Infectious keratitis was diagnosed within 6 months after keratoplasty in 59% of cases. Positive cultures were obtained in 100% of the ulcers; Pseudomonas aeruginosa and Staphylococcus aureus were the most common pathogens. In the final visual outcome assessment, 30.8% of cases had clear grafts, 20.5% had graft failures, and 10.3% had corneal perforations.

Demonstration of residual bone marrow effect in mice exposed to ethylene glycol monomethyl ether.

Ethylene glycol monomethyl ether (EGMME) has been reported to cause hematopoietic abnormalities in man. We have shown that mice exposed to EGMME post-natally have suppressed bone marrow cellularity and progenitor cells 8 weeks post-exposure which returns to normal values by 16 weeks. Studies were designed to determine whether EGMME exposed mice that recovered had evidence of residual marrow stem cell injury. B6C3F1 mice were injected subcutaneously with EGMME on days 1-5 after birth at doses of 0, 100, 200 and 400 mg/kg per day, allowed to recover, and stressed with 200 rads whole body irradiation at 15 and 21 weeks post-exposure. Bone marrow functions were examined during the recovery period. Mice that had been exposed to EGMME were more sensitive to irradiation and recovery of marrow cellularity and progenitor cell numbers occurred more slowly than in unexposed controls. This indicates that EGMME can cause persistent residual damage of bone marrow progenitor cells in mice, an effect that would not be apparent with routine hematological techniques.

Point mutations of K-ras and H-ras genes in forestomach neoplasms from control B6C3F1 mice and following exposure to 1,3-butadiene, isoprene or chloroprene for up to 2-years.

1,3 Butadiene (BD), isoprene (IP) and chloroprene (CP) are structural analogs. There were significantly increased incidences of forestomach neoplasms in B6C3F1 mice exposed to BD, IP or CP by inhalation for up to 2-years. The present study was designed to characterize genetic alterations in K- and H-ras proto-oncogenes in a total of 52 spontaneous and chemically induced forestomach neoplasms. ras mutations were identified by restriction fragment length polymorphism, single strand conformational polymorphism analysis, and cycle sequencing of PCR-amplified DNA isolated from paraffin-embedded forestomach neoplasms. A higher frequency of K- and H-ras mutations was identified in BD-, IP- and CP-induced forestomach neoplasms (83, 70 and 57%, respectively, or combined 31/41, 76%) when compared to spontaneous forestomach neoplasms (4/11, 36%). Also a high frequency of H-ras codon 61 CAA-->CTA transversions (10/41, 24%) was detected in chemically induced forestomach neoplasms, but none were present in the spontaneous forestomach neoplasms examined. Furthermore, an increased frequency (treated 13/41, 32% versus untreated 1/11, 9%) of GGC-->CGC transversion at K-ras codon 13 was seen in BD-, and IP-induced forestomach neoplasms, similar to the predominant K-ras mutation pattern observed in BD-induced mouse lung neoplasms. These data suggest that the epoxide intermediates of the structurally related chemicals (BD, IP, and CP) may cause DNA damage in K-ras and H-ras proto-oncogenes of B6C3F1 mice following inhalation exposure and that mutational activation of these genes may be critical events in the pathogenesis of forestomach neoplasms induced in the B6C3F1 mouse.

Residual damage to hematopoietic system in mice exposed to a mixture of groundwater contaminants.

To assess the potential health effects of chemically contaminated groundwater, we initiated a toxicological program on a mixture of 25 frequently-detected groundwater contaminants derived from hazardous waste disposal sites. As part of this program, myelotoxicity studies were conducted. Bone marrow parameters were examined in mice exposed to 0, 1, 5 or 10% of a simulated chemical mixture stock solution of groundwater contaminants in drinking water for 108 days. Mice treated with 5 or 10% of chemical mixture stock solution for 108 days showed suppressed marrow granulocyte macrophage progenitors (CFU-GM); however, this suppression disappeared in 10 weeks following the cessation of treatment. The possible toxicological interaction of groundwater contaminants and radiation on hematopoiesis was investigated by using the number of bone marrow CFU-GM as an index. When mice were exposed to 200 rads whole body irradiation at 2 and 9 weeks during this 10-week recovery period, the combined treatment (i.e., chemical mixture followed by irradiation) group showed a significantly slower recovery of bone marrow progenitors as compared with the control group (i.e., radiation but without prior chemical mixture treatment). This study showed that even 10 weeks after the cessation of chemical mixture treatment when all hematological parameters were normal, a residual effect of the chemical mixture may still be demonstrated as lower progenitor cell numbers following irradiation. Thus, residual damage of hematopoiesis in mice exposed to groundwater contaminants for 108 days renders the mice more sensitive to subsequent irradiation-induced injury.

Toxicology of chemical mixtures: experimental approaches, underlying concepts, and some results.

The toxicology of chemical mixtures will be the toxicology of the 1990s and beyond. While this branch of toxicology most closely reflects the actual human exposure situation, there is yet no standard protocol or consensus methodology for investigating the toxicology of mixtures. Thus, in this emerging science, experimentation is required just to develop a broadly applicable evaluation system. Several examples are discussed to illustrate the different experimental designs and the concepts behind each. These include the health effects studies of Love Canal soil samples, the Lake Ontario Coho salmon, the water samples repurified from secondary sewage in the city of Denver Potable Water Reuse Demonstration Plant, and the National Toxicology Program (NTP) effort on a mixture of 25 frequently detected groundwater contaminants derived from hazardous waste disposal sites. In the last instance, an extensive research program has been ongoing for the last 2 years at the NTP, encompassing general toxicology, immunotoxicology, developmental and reproductive toxicology, biochemical toxicology, myelotoxicology, genetic toxicology, neurobehavioral toxicology, and hepato- and renal toxicology.

Comparative effects of ethylene glycol and ethylene glycol monomethyl ether exposure on hematopoiesis and histopathology in B6C3F1 mice.

Ethylene Glycol (EG) or Ethylene Glycol Monomethyl Ether (EGMME) was administered by gavage to both sexes of B6C3F1 mice for 4 consecutive days at total doses of 200, 400, and 1000 mg/kg body weight. Bone marrow parameters were examined on days 1, 5, and 14 after the final treatment. Exposure to EG produced hypocellularity and suppression of granulocyte-macrophage progenitor (CFU-C) colony formation in both sexes on days 1 and 5 postexposure. Values returned to normal by day 14 in the female mice but not in the males. Erythropoiesis, as measured by 59Fe incorporation and quantitation of erythroid precursors in culture (CFU-E), revealed no effect in female mice and affected male mice at the high dose only. In contrast, EGMME exposure in female mice resulted in inhibition of erythropoiesis. There was also a pronounced effect on white blood cells with decreased peripheral counts, and decreases in the number of CFU-C's cultured from marrow cells. The effect of EGMME was also seen at the lower dose levels and was sustained through the 14-day evaluation period. In addition, EGMME caused a 20% decrease in testicular weight, which was shown microscopically to be a segmented degeneration of seminiferous tubules, an effect not found with EG. This study demonstrates that EGMME is more myelotoxic in mice than EG and that pancytopenia is more pronounced in males, while erythropoiesis is more affected in females.

Alterations in hematopoietic responses in B6C3F1 mice caused by drinking a mixture of 25 groundwater contaminants.

Myelotoxicity parameters were monitored in female B6C3F1 mice exposed to 0, 1, 5, and 10% of a chemical mixture stock in drinking water for 2.5 to 31.5 weeks. The mixture consisted of 25 groundwater contaminants frequently found near toxic waste dumps, as determined by U.S. Environmental Protection Agency (EPA) surveys. Water consumption, body and organ weights, and hematological and histopathological examinations were conducted. No animals developed overt signs of toxicity after 2.5 weeks of treatment. No significant effect on bone marrow cellularity was observed after 2.5, 15.5, or 31.5 weeks of exposure; however, mice exposed to 5% or higher concentrations of the chemical mixture stock solution for 15.5 weeks showed significant suppression of granulocyte-macrophage progenitor cells (CFU-GM) and erythroid precursors (CFU-E) with no changes in body weight, histopathological or hematological parameters. Decreases occurred in erythrocyte mean corpuscular volume of mice exposed to a 10% solution for 15.5 weeks and to 5 and 10% solutions following 31.5 weeks of treatment. In addition, dose-related decreases were found in body, liver, and thymus weights in the 5 and 10% solutions exposure groups after 31.5 weeks. These results suggest that bone marrow may be a sensitive indicator for long-term, low-level exposure of multiple chemicals in mice. Furthermore, long-term exposure to highly contaminated groundwater may present a subtle risk to the hematopoietic system.

Understanding the Cu-Zn brass alloys using a short-range-order cluster model: significance of specific compositions of industrial alloys.

Metallic alloys show complex chemistries that are not yet understood so far. It has been widely accepted that behind the composition selection lies a short-range-order mechanism for solid solutions. The present paper addresses this fundamental question by examining the face-centered-cubic Cu-Zn α-brasses. A new structural approach, the cluster-plus-glue-atom model, is introduced, which suits specifically for the description of short-range-order structures in disordered systems. Two types of formulas are pointed out, [Zn-Cu12]Zn(1~6) and [Zn-Cu12](Zn,Cu)6, which explain the α-brasses listed in the American Society for Testing and Materials (ASTM) specifications. In these formulas, the bracketed parts represent the 1(st)-neighbor cluster, and each cluster is matched with one to six 2nd-neighbor Zn atoms or with six mixed (Zn,Cu) atoms. Such a cluster-based formulism describes the 1st- and 2nd-neighbor local atomic units where the solute and solvent interactions are ideally satisfied. The Cu-Ni industrial alloys are also explained, thus proving the universality of the cluster-formula approach in understanding the alloy selections. The revelation of the composition formulas for the Cu-(Zn,Ni) industrial alloys points to the common existence of simple composition rules behind seemingly complex chemistries of industrial alloys, thus offering a fundamental and practical method towards composition interpretations of all kinds of alloys.

Effect of cell shape on proteinase secretion by epithelial cells.

Cell proliferation has been found to correlate with increased secretion of proteinases, such as plasminogen activator, in several different cell populations. In addition, the shape of the cell may also play a role in regulating proteinase secretion. However, the relationship between cell proliferation, cell shape and proteinase secretion has not been studied in diploid epithelial (E) cells cultured from porcine periodontal ligament (PL). We have modified PLE cell shape by physical means, such as growth on less-adhesive substrata and mechanical stretching, and by exposure to cholera toxin and 12-O-tetradecanoylphorbol-13-acetate (TPA). Neutral proteinase and plasminogen activator secretion were found to correlate with cell shape, the more round the cells, the greater the amount of proteinase secreted. PLE cells, stimulated to proliferate by cholera toxin or dibutyryl cyclic AMP, were more spread than control cells, but secreted less neutral proteinase and plasminogen activator. TPA stimulated cell proliferation slightly but, in contrast to cholera toxin, increased cell rounding and the secretion of neutral proteinase and plasminogen activator. Thus proteinase secretion was related more to cell shape than to cell proliferation.

Residual myelotoxicity of lindane in mice.

Lindane (gamma-1,2,3,4,5,6-hexachlorocyclohexane), a widely used insecticide, may be found at low concentrations in the human diet. Male B6C3F1 mice given lindane daily at doses of 20 and 40 mg/kg body wt by gavage in corn oil for 3 days had suppressed bone marrow cellularity, erythrocyte precursors, granulocyte-macrophage progenitor cells (CFU-GM), and residual progenitor cell damage, which could be demonstrated by two whole-body irradiations (WBI) at 200 rads. Lindane exposure for 10 consecutive days at doses of 0, 10, or 20 mg/kg did not cause clinical abnormality or changes in body weights, but there were dose-dependent decreases in marrow cellularity, in more pluripotent stem cells and in committed CFU-GMs, which returned to control values by 4 weeks. These mice were then subjected to two 100-rad exposures of WBI at 4 and 9 weeks following cessation of lindane treatment. This level of irradiation caused only a transient drop in number of marrow progenitor cells. Control and lindane-exposed mice were examined at 1 and 6 weeks following the last irradiation, which was 10 and 15 weeks following the final lindane exposure. The lindane-exposed mice had lower progenitor cell numbers and slower recovery from the irradiation. These results indicate that lindane has significant myelotoxicity in mice and short-term lindane exposure can induce residual progenitor cell damage that can be demonstrated by subsequent irradiation.