Evidence for the role of PO4 deficiency in antihypertensive action of a high-Ca diet

1984 ◽  
Vol 246 (3) ◽  
pp. H324-H331 ◽  
Author(s):  
K. Lau ◽  
S. Chen ◽  
B. Eby
Keyword(s):  
Group Iv ◽  
Hypertensive Rats ◽  
Group Vi ◽  
Group V ◽  
Intact Group ◽  
Volume Contraction ◽  
Antihypertensive Action ◽  
Group I ◽  
Salutary Effect

Previous studies indicated a salutary effect of a high-Ca diet on high blood pressure (BP). The mechanism, however, is obscure. With balance and clearance techniques, the role of parathyroid hormone (PTH), volume contraction, hypercalcemia, and PO4 deficiency was evaluated in female spontaneous hypertensive rats (SHR). The antihypertensive effects of a high (4.3%) Ca diet in intact animals (groups I and II) could be reproduced in both 9- and 22-wk-old chronic stable parathyroidectomized (PTX) rats (groups III and IV), when compared with a low (0.22%) or normal (1.2%) CA diet. In both short (7 days) and long (12 wk) term exposure to the high-Ca diet, evidence for volume contraction could not be documented despite hypercalcemia sustained through the 12th wk (10.8 vs. 9.7 mg/100 ml, group I control, P less than 0.02). When produced by ip injections, chronic hypercalcemia of similar magnitudes as oral Ca supplements failed to reduce BP in either intact (group VI) or PTX (group IV) rats. Rats in group IV fed the high-Ca diet displayed marked hypophosphatemia (3.2 vs. 6.9 mg/100 ml), hypophosphaturia (0.15 vs. 15 mg/day), hypermagnesiuria (11 vs. 7.7 mg/day), and drastically reduced net intestinal PO4 absorption (13.3 +/- 7.5 vs. 66.8 +/- 7.5 mg/day) compared with rats fed 1.2% Ca diet. To test the PO4-deficiency hypothesis, additional SHR (group V) were fed either 1.2% Ca diet and injected ip with NaCl or fed 4.3% Ca diet, with half of these animals injected with neutral NaPO4 and half with NaCl.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Effect of a Diet Composed of Genetically Modified Feed Components on the Selected Immune Parameters in Pigs, Cattle, and Poultry

2013 ◽  
Vol 57 (2) ◽  
pp. 209-217 ◽  
Author(s):  
Dariusz Bednarek ◽  
Katarzyna Dudek ◽  
Krzysztof Kwiatek ◽  
Małgorzata Świątkiewicz ◽  
Sylwester Świątkiewicz ◽  
...  
Keyword(s):  
Soybean Meal ◽  
Genetically Modified ◽  
Group Iv ◽  
Group Vi ◽  
Group V ◽  
Group Iii ◽  
Immune Parameters ◽  
Group I ◽  
Toxin Protein ◽  
Gm Soybean

Abstract The aim of the study was to evaluate the immune effects of genetically modified (GM), insect resistant corn (MON810) expressing toxin protein of Bacillus thuringiensis, and glyphosate-tolerant soybean meal (Roundup Ready MON-40-30-2), which are used as the feed mixture components in domestic animals. The study was conducted on 60 pigs (36 fatteners and 24 sows), 20 calves, 40 broilers, and 40 laying hens. Each species was divided into four basic nutritional groups: group I (control) - conventional feed, group II - feed consisted of GM soybean meal and non-modified corn, group III - non-modified soybean meal and GM corn, group IV - GM soybean meal and GM corn. Moreover, in the experiment on fatteners two additional groups were formed: group V - animals fed both conventional soybean meal and bruised grain, and group VI - GM soybean meal and conventional bruised grain. The results of study did not reveal any significant effect of feed mixtures containing GM components on the immune response in all animals regardless of their species and technological producing groups.

scholarly journals Comparative Evaluation of Apical Sealing Ability of Different Obturation Techniques by Confocal Microscopy: An In Vitro Study

2020 ◽  
Vol 8 (02) ◽  
pp. 55-59
Author(s):  
Reetu Arora ◽  
Yogesh Kumar ◽  
Neetu Jindal ◽  
Renu Aggarwal ◽  
Kavneet Takhar
Keyword(s):  
Root Canal ◽  
Negative Control Group ◽  
Positive Control ◽  
Negative Control ◽  
Group Iv ◽  
Control Group ◽  
Group Vi ◽  
Group V ◽  
Group Iii ◽  
Group I

Abstract Introduction The aim of obturation in the root canal is to completely seal the canal space to eliminate all the portals of entry and exit between root canal and periodontal space. Various techniques have been developed to achieve a hermetic seal. Materials and Methods As many as 150 extracted human maxillary central incisors were taken for the study. Biomechanical preparation was done up to F5 protaper file. According to different obturation techniques, samples were divided into six groups, keeping 30 samples in experimental and 15 samples in control groups. Group I–Lateral Condensation, Group II–Thermafil, Group III–Beefill, Group IV–GuttaFlow, Group V–Positive Control group, Group VI–Negative Control group. After obturation, the samples were immersed in 2% Rhodamine-B dye for 24 hours. Each sample was longitudinally sectioned to examine under confocal laser scanning microscope. Statistical Analysis The results were evaluated with ANOVA and posthoc Tukey honest significant difference (HSD) comparison test. Results The mean values of dye penetration of different groups were Group I (Lateral Condensation) 1.51 ± 0.451, Group II (Thermafil) 0.918 ± 0.399, Group III (Beefill) 1.30 ± 0.559. Group IV (GuttaFlow) 0.655 ± 0.396, Group V (Positive Control group) 1.96 ±0.046, Group VI (Negative Control group) 0 ± 0. The lowest mean value of apical microleakage was found in GuttaFlow amongst all experimental groups. Conclusion It can be concluded that the GuttaFlow obturating material exhibited better apical sealing ability with canal walls.

scholarly journals Chemoprevention with green propolis green propolis extracted in L-lysine versus carcinogenesis promotion with L-lysine in N-Butyl-N-[4-hydroxybutyl] nitrosamine (BBN) induced rat bladder cancer

2012 ◽  
Vol 27 (2) ◽  
pp. 185-192 ◽  
Author(s):  
Conceição Aparecida Dornelas ◽  
Francisco Vagnaldo Fechine-Jamacaru ◽  
Irineu Lima Albuquerque ◽  
Hemerson Iury Ferreira Magalhães ◽  
Adjair Jairo Silva de Souza ◽  
...  
Keyword(s):  
Group Iv ◽  
The Other ◽  
Control Group ◽  
Group Viii ◽  
Group Vi ◽  
Group V ◽  
Induction Group ◽  
Rat Bladder ◽  
Bladder Carcinogenesis ◽  
Group I

PURPOSE: To determine the effects of green propolis extracted in L-lysine (WSDP) and of L- lysine for 40 weeks on induced rat bladder carcinogenesis. METHODS: The animals (groups I, II, III, IV, V and VI) received BBN during 14 weeks. Group I was treated with propolis 30 days prior received BBN, and then these animals were treated daily with propolis; Groups II and III was treated with subcutaneous and oral propolis (respectively) concurrently with BBN. The animals of Group IV were treated L-lysine; Group V received water subcutaneous; and Group VI received only to BBN. Among the animals not submitted to carcinogenesis induction, Group VII received propolis, Group VIII received L-lysine and Group IX received water. RESULTS: The carcinoma incidence in Group I was lower than that of control (Group VI). The carcinoma multiplicity in Group IV was greater than in Group VI. All animals treated with L-lysine developed carcinomas, and they were also more invasive in Group IV than in controls. On the other hand, Group VIII showed no bladder lesions. CONCLUSION: The WSDP is chemopreventive against rat bladder carcinogenesis, if administered 30 days prior to BBN , and that L-lysine causes promotion of bladder carcinogenesis.

scholarly journals Estimation of vitamin C human protective dose for acetaminophen toxicity, using acute animal toxicity study

2017 ◽  
Vol 2 (2) ◽  
pp. 101-105 ◽  
Author(s):  
Mudhaffar I. Al-Farras ◽  
Khalid K. Abdul-Razzak ◽  
Mohammed Yacoub ◽  
Wael M. Hananeh
Keyword(s):  
Mortality Rate ◽  
Vitamin C ◽  
Lethal Dose ◽  
Group Iv ◽  
Group Vi ◽  
Group V ◽  
Liver Histopathology ◽  
Toxic Damage ◽  
Group I ◽  
Group Ii

Acetaminophen (APAP) is the main cause of fulminant hepatic failure. Vitamin C is a natural antioxidant with protective potentials against APAP toxic damage. In this animal study, and after an LD50 determination and selection of suitable lethal dose, the investigation was done to select a proper protective dose of vitamin C against lethal APAP dose. All 6 animal groups received a lethal dose of APAP (3250 mg/kg), group II, III and IV received 500, 1000 and 1500 mg/kg vitamin C respectively, group V received 1200 mg/kg N-Acetylcysteine (NAC), and group VI receive 1000 mg/kg vitamin C and 1200 mg/kg NAC. Mortality was recorded and liver histopathology was carried out. The results showed, the mortality rate in the group I was 68.75% and 37.5%, 31.25% in group II and III respectively, while group IV Showed a higher mortality rate and in group V and VI it was 25%. There was also a gradual reduction in the grade of histopathological damage in all groups, ranging from 2.4 ± 0.55 in group I to 0.4 ± 0.55 in group V and VI. In conclusion, vitamin C showed an increasing reduction in mortality and more histopathological protection, and it was more significant at 1000 mg/kg. NAC adds no more protection or reduction in mortality. The estimated protective dose of vitamin C was 700 to1127 mg for each gram of APAP. Incorporation of this dose of vitamin C with APAP preparations may be considered as a promising method for reducing mortality or severity of APAP intoxication.

ВЗАИМОСВЯЗЬ ПРОДУКТИВНЫХ ПОКАЗАТЕЛЕЙ КОРОВ ЧЕРНО-ПЕСТРОЙ ПОРОДЫ С ВОСПРОИЗВОДИТЕЛЬНЫМИ КАЧЕСТВАМИ

2019 ◽  
pp. 39-42
Author(s):  
G.Yu. BEREZKINA ◽  
S.L. VOROBYEVA ◽  
E.M. KISLYAKOVA ◽  
A.A. KOREPANOVA
Keyword(s):  
Experimental Studies ◽  
Live Weight ◽  
Group Iv ◽  
Reproductive Capacity ◽  
Group Vi ◽  
Group V ◽  
Group Iii ◽  
Group I ◽  
The Republic ◽  
Breeding Farms

Изучено влияние возраста и живой массы при первом осеменении на воспроизводительные качества коровпервотелок чернопестрой породы в племенных заводах Удмуртской Республики. Исследования проводились в период с 2015 по 2018 гг. Для проведения исследований были сформированы 6 групп животных в зависимости от возраста первого осеменения. В I группу вошли коровы с возрастом первого осеменения до 13 мес, во II от 13,1 до 15 мес, в III от 15,1 до 17, в IV от 17,1 до 19, в V от 19,1 до 21 и в VI группу от 21 мес и старше. При этом живая масса телок в I группе в среднем составила 349,5 кг, во II 370,9, в III 387,7, в IV 400,2, в V 420,7 и в VI группе 440,2 кг. Анализ возраста первого осеменения в племенных хозяйствах республики показал, что средний возраст плодотворного осеменения в 2018 году составил 17,0 мес. с живой массой 394 кг. По результатам экспериментальных исследований нами получено, что лучшие воспроизводительные показатели и молочная продуктивность выявлена у коровпервотелок, которых осеменяли в возрасте 14,6 мес. В данной группе продолжительность сервиспериода составила 127,3 дня, коэффициент воспроизводительной способности 0,90, выход телят на 100 коров составил более 85,3. Удой за 305 дней лактации, у коровпервотелок второй опытной группы составил 6332,3 кг с массовой долей жира 3,65 и белка 3,15 .The influence of age and live weight at the first insemination on reproductive qualities of cowsborn black and white breed in breeding farms of the Udmurt Republic was studied. The studies were conducted between 2015 and 2018. For the research 6 groups of animals were formed depending on the age of the first insemination. Group I included cows with the age of first insemination up to 13 months, in group II from 13.1 to 15 months, in III group from 15.1 to 17 months, in group IV from 17.1 to 19 months, in group V from 19.1 to 21 months and in VI group from 21 months and more. At the same time, the live weight of heifers in group I averaged 349.5 kg, in group II370.9 kg, in group III 387.7 kg, in group IV 400.2 kg, in group V 420.7 kg and in group VI 440.2 kg. The analysis of the age of the first insemination in breeding farms of the Republic showed that the average age of fruitful insemination in 2018 was 17.0 months with a live weight of 394 kg. According to the results of experimental studies, we obtained that the best reproductive performance and milk productivity was revealed in cows, which were inseminated at the age of 14.6 months. In this group, the duration of the service period was 127.3 days, the coefficient of reproductive capacity 0.90, yield of calves per 100 cows. Milk yield for 305 days of lactation, in cows of the second experimental group was 6332.3 kg with a mass fraction of fat 3.65 and protein 3.15.

scholarly journals The The Influence of Wharton Jelly Mesenchymal Stem Cell toward Matrix Metalloproteinase-13 and RELA Synoviocyte Gene Expression on Osteoarthritis

2019 ◽  
Vol 7 (5) ◽  
pp. 701-706 ◽  
Author(s):  
Vivi Sofia ◽  
Ellyza Nasrul ◽  
Menkher Manjas ◽  
Gusti Revilla
Keyword(s):  
Gene Expression ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Inflammatory Responses ◽  
Group Iv ◽  
Group Vi ◽  
Group V ◽  
Group Iii ◽  
Group I

BACKGROUND: Therapy for osteoarthritis (OA) with satisfactory results has not been found to date. In OA pathogenesis, RELA gene involved in cartilage degradation and MMP-13 in degrade cartilage, as a member family of NF-ĸβ genes, RELA serves to modulate inflammatory responses and activates pro-inflammatory cytokines. AIM: This study aims to identify the influence of Wharton Jelly Mesenchymal Stem Cell (MSC-WJ) on MMP-13 and RELA expression gene in synoviocyte by in vitro. MATERIAL AND METHODS: This research is pure experimental research. The sample used derived from synovial tissue of OA patients who underwent Total Knee Replacement (TKR) surgery. This study was divided into six groups treated with 4 replications. Group I and II (control groups) were synoviocyte of OA incubated for 24 and 48 hours, respectively. Group III and IV were MSC-WJ incubated for 24 and 48 hours, respectively. Group V and VI were Synoviocyte-MSC-WJ co-culture group incubated for 24 and 48 hours, respectively. Identification of MMP-13 and RELA gene expression in each group was performed by using qPCR. RESULT: The results showed that MSC-WJ reduced MMP-13 gene expression after co-culture for 24 and 48 hours in OA synoviocyte. The highest gene expression of MMP-13 was in Group I and II (1.00 ng/μl), followed by Group III (0.41 ng/μl), Group IV (0.24 ng/μl), Group V (0.13 ng/μl), and Group VI (0.04 ng/μl). MSC-WJ administration also decreased RELA gene expression. The highest gene expression of RELA gene was in Group I and II (1.00 ng/μl), Group V (0.67 ng/μl), Group III (0.58 ng/μl), Group IV (0.16 ng/μl), and Group VI (0.16 ng/μl). CONCLUSION: This study concluded that MSC-WJ in OA synoviocyte significantly reduced the expression of MMP-13 and RELA gene (p <0.05).

scholarly journals Treatment of Bothrops alternatus envenomation by Curcuma longa and Calendula officinalis extracts and ar-turmerone

2005 ◽  
Vol 57 (1) ◽  
pp. 7-17 ◽  
Author(s):  
M.M. Melo ◽  
G.G. Habermehl ◽  
N.J.F. Oliveira ◽  
E.F. Nascimento ◽  
M.M.B. Santos ◽  
...  
Keyword(s):  
Curcuma Longa ◽  
Group Iv ◽  
Calendula Officinalis ◽  
Group Vi ◽  
Group V ◽  
Efficient Treatment ◽  
Sterile Saline ◽  
Group Iii ◽  
Group I ◽  
Bothrops Alternatus

It was investigated the efficiency of two extracts of plants and one fraction of their properties against the local effects of bothropic envenomation. Bothrops alternatus venom (1.25µg) diluted in 100µl of sterile saline solution was inoculated (intradermally) into the shaved dorsal back skin of 30 New Zealand rabbits. The animals were divided in six groups receiving the following treatments: group I: subcutaneous application of Curcuma longa extract (1.0ml); group II: topic treatment of Curcuma longa hydroalcoholic extract (1.0ml); group III: topic application of ar-turmerone in vaseline (1.0g); group IV: topic application of Curcuma longa methanolic extract (1.0ml); group V: topic application of Calendula officinalis ointment (1.0g); group VI: topic application of saline (1.0ml). These treatments were done at 30 minutes, and at 2, 4, 24 and 72 hours after venom inoculation. Intensity of local edema, hemorrhagic halo and necrosis were evaluated until 168h after that. Additionally, seven days after the Bothrops venom inoculation, blood was collected from heart with and without EDTA (10%) for hemogram and biochemical parameters (total protein, blood urea nitrogen, creatinine, and fibrinogen) and all the animals were anesthetized, sacrificed by ether inhalation and submitted to necropsy. Fragments of tissues were taken for histopathological evaluation. The most efficient treatment for inhibition of edema, necrosis and local hemorrhage after Bothrops alternatus venom was the topic application of ar-turmerone.

scholarly journals Shear Bond Strength of Orthodontic Brackets Cured with Different Light Sources under Thermocycling

2010 ◽  
Vol 04 (03) ◽  
pp. 257-262 ◽  
Author(s):  
Oral Sokucu ◽  
Seyda Herguner Siso ◽  
Firat Ozturk ◽  
Ruhi Nalcaci
Keyword(s):  
Bond Strength ◽  
Shear Bond Strength ◽  
Group Iv ◽  
Light Sources ◽  
Group Vi ◽  
Group V ◽  
Group Iii ◽  
Group I ◽  
Significant Difference ◽  
Light Curing

Objectives: The aim of this study was to compare the shear bond strength (SBS) of two different light sources under different thermal cycle frequencies.Methods: Ninety human premolar teeth were divided into six groups, in which three groups consisted of halogen groups – Group I was cured with halogen without thermocycle, Group II cured with halogen with 500 thermocycles, and Group III cured with halogen with 10,000 thermocycles. The other three groups consisted of Plasma arc (PAC) group – Group IV was cured with PAC without thermocycle, Group V cured with PAC thermocycled 500 cycles, and Group VI cured with PAC thermocycled 10,000 cycles. Two way ANOVA was used to compare the SBS between the groups, and chi squaretest was used to compare the bond failure of ARI scores among the groups.Results: A significant difference was found for curing lights (P<.001) and thermocycling (P<.01). However, there was no interaction between light curing and thermocycling (P=.177). The halogen groups demonstrated higher mean SBS than the PAC groups. Both groups showed a significant reduction between no cycles and 10,000 cycles (P<.05).Conclusions: Both light sources showed favorable SBS performance without the thermocycle procedure. Thermocycling significantly decreased the SBS values of both groups. (Eur J Dent 2010;4:257- 262)

scholarly journals RESPONSE OF THE NEW SELF-POLLINATED MAIZE LINES ON THE PARAGUAY TYPE OF CMS

2020 ◽  
Vol 4 (24) ◽  
pp. 90-97
Author(s):  
G.Ya. Krivosheev ◽  
Keyword(s):  
Large Scale ◽  
Agricultural Research ◽  
Field Trials ◽  
Group Iv ◽  
F1 Hybrids ◽  
Natural Fertility ◽  
Flowering Pattern ◽  
Group Vi ◽  
Group V ◽  
Group I

It is extremely important to study cytoplasmic male sterility (CMS) in maize since it is impossible to conduct large-scale commercial seed production of hybridized maize without CMS. The purpose of the current study was to identify the response of the new self-pollinated maize lines in a sterile cytoplasm of the Paraguay type, to group the lines according to the composition of fertility restoring genes based on an optimal quantity of the analyzed crossings. The field trials were carried out in 2016–2019 in the State Scientific Establishment “Agricultural research center “Donskoy”” (SSE “ARC “Donskoy”). To obtain hybrid combinations, the method of full top-crosses, namely eight testers and ten lines, was used. The new early-ripening and mid-ripening self-pollinated maize lines (I6), developed in the ARC “Donskoy”, were grouped according to the composition of the alleles of fertility restoring genes of the Paraguay (“C”) type of CMS based on the flowering pattern of the test cross F1 hybrids. The first group included the line SP 207 (genotype rf4rf4 rf5rf5 rf6rf6); the second group included the line SP 209 (genotype rf4rf4 rf5rf5 Rf6Rf6); the third group included the line SP 194 (genotype rf4rf4 Rf5Rf5 rf6rf6); the fourth group included the line SP 198 (genotype Rf4Rf4 rf5rf5 rf6rf6); the fifth group included the lines SP 203 and SP 195 (genotype rf4rf4 Rf5Rf5 Rf6Rf6); the sixth group included the line SP 206 (genotype Rf4Rf4 rf5rf5 Rf6Rf6); the seventh group included the line SP 180 (genotype Rf4Rf4 Rf5Rf5 rf6rf6); the eighth group included the lines SP 210 and SP 197 (genotype Rf4Rf4 Rf5Rf5 Rf6Rf6). The lines SP 207, SP 210 and SP 197 were of the greatest practical value when converting maize hybrids to a sterile base: the line SP 207 was a complete sterility fixer; the lines SP 210 and SP 197 were constant natural fertility restorers. In order to optimize the quantity of the analyzed crossings for grouping the maize lines according to the composition of the alleles of fertility restoring genes of the Paraguay (“C”) type of CMS, it was necessary to use such sterile sources as KR 21C (group IV), WF9C (group V), LC (group VI), W401C (group VII). The minimum quantity of analyzers to determine the response of the lines on the Paraguay type of CMS should be at least two. However, it was necessary to use sterile sources of certain classes, such as KR 21C (group IV) and Gb834 C (group I).

The Transcriptome of Multiple Myeloma (MM) Defines Disease Subgroups with Distinct Genetic and Clinical Features.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 76-76
Author(s):  
Fenghuang Zhan ◽  
Bart Barlogie ◽  
Yongsheng Huang ◽  
Eric Rasmussen ◽  
Jeffrey Sawyer ◽  
...  
Keyword(s):  
Cluster Analysis ◽  
Risk Groups ◽  
Group Iv ◽  
Published Data ◽  
Training Set ◽  
Group Vi ◽  
Group V ◽  
Cytogenetic Abnormalities ◽  
Kaplan Meier ◽  
Group I

Abstract This study updates our previous molecular classification of myeloma (MM) using gene expression profiling (GEP) of plasma cells from 351 newly diagnosed MM cases and a microarray containing ~33,000 genes. After normalization of expression values, 2,800 genes exhibited a high degree of variation (SD >0.6) across a training set of 177 cases. Unsupervised hierarchical cluster analysis identified seven distinct subgroups with strong correlations to known translocations and cytogenetic abnormalities. The sample dendrogram created two major branches. Cases with normal karyotypes (Group I, n=38) and hyperdiploid karyotypes (Group II, n=36) were located on one branch. On the second branch CCND1 spikes defined Group III (n=30). Group IV (n=16) was defined by proliferation-associated genes and contained an even distribution of hyperdiploid and hypodiploid karyotypes. MAF and MAFB spikes clustered together and defined Group V (n=10). Group VI (n=21), not defined by any of the above parameters, was characterized by elevated expression of CST6. MMSET spikes defined Group VII (n=26). Statistically significant characteristics were as follows. MM cases with an IgA isotype were predominant in Groups V, VI, and VII (P=.009). B2M levels were significantly elevated in Group IV (mean 7.66 mg/L) and Group V (mean 9.09 mg/L) (P=.003). Creatinine (≥2.0 mg/dL) (P=.005) and LDH (UI/L) (P=.003) were significantly elevated in Group IV. Cytogenetic abnormalities predominated in Groups IV and VII (P=.0002). When abnormal karyotypes were present, Groups II and IV tended to have hyperdiploidy (P=.001) and Groups IV and VII hypodiploidy (P=.002). Group VI had fewer MRI lesions (P=.001). Finally, FISH detectable 14q32 translocations predominated in Groups III, V, and VII (P<.0001). SAM and Chi-square analyses were used to identify 50 genes whose expression uniquely defined each subgroup. Using these 350 genes (7′50), we performed PAM analysis on the 177 training set to determine the degree of correlation with the original unsupervised cluster analysis, which revealed 91% accuracy between the two tests. We then applied the 350 gene PAM model to a test group of 174 cases. Resulting cluster designations were highly correlated with a common distribution of cytogenetic and clinical parameters in the training and test sets. Kaplan-Meier test of event-free survival (EFS) and overall survival (OS) among the seven groups resulted only in a marginal separation. Based on data trends and previously published data, groups were separated into low risk (Groups I, II, III, VI) and high risk (Groups IV, V, VII) and Kaplan-Meier tests performed. Significant differences were found in both the training set (EFS, P<.0002; OS, P=.0033) and the test set (EFS, P=.021; OS, P=.0015). Data presented here suggest that MM is broad descriptor of multiple discrete molecular and clinical entities with unique mechanisms of transformation. This classification schema should provide a novel framework for the application of current therapies and may facilitate development of subgroup-specific treatment strategies.

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