Exposure to benzene in a pooled analysis of petroleum industry case-control studies.

Cases of lymphohematopoietic cancer from three petroleum industry cohorts, matched to controls from the respective cohort, were pooled into single study. Average benzene exposure was quantitatively estimated in ppm for each job based on measured data from the relevant country, adjusted for the specific time period, site and job exposure characteristics and the certainty of the exposure estimate scored. The probability of dermal exposure and of peak exposure was also assessed. Before risk was examined, an exposure estimate comparison and rationalisation exercise was performed across the studies to ensure accuracy and consistency of approach. This article evaluates the final exposure estimates and their use in the risk assessments. Overall benzene exposure estimates were low: 90% of participants accumulated less than 20 ppm-years. Mean cumulative exposure was estimated as 5.15 ppm-years, mean duration was 22 years, and mean exposure intensity was 0.2 ppm. 46% of participants were allocated a peak exposure (>3 ppm at least weekly). 40% of participants had a high probability of dermal exposure (based on the relative probability of at least weekly exposure). There were differences in mean intensity of exposure, probability of peak, and/or dermal exposure associated with job category, job site, and decade of exposure. Terminal Operators handling benzene-containing products were the most highly exposed group, followed by Tanker Drivers carrying gasoline. Exposures were higher around 1940-1950 and lower in more recent decades. Overall confidence in the exposure estimates was highest for recently held jobs and for white-collar jobs. We used sensitivity analyses, which included and excluded case-sets on the basis of exposure certainty scores, to inform the risk assessment. The above analyses demonstrated that the different patterns of exposure across the three studies are largely attributable to differences in jobs, site types, and time frames rather than study. This provides reassurance that the previous rationalisation of exposures achieved inter-study consistency and that the data could be confidently pooled.

Acute myeloid and chronic lymphoid leukaemias and exposure to low-level benzene among petroleum workers.

BACKGROUND: High benzene exposure causes acute myeloid leukaemia (AML). Three petroleum case-control studies identified 60 cases (241 matched controls) for AML and 80 cases (345 matched controls) for chronic lymphoid leukaemia (CLL). METHODS: Cases were classified and scored regarding uncertainty by two haematologists using available diagnostic information. Blinded quantitative benzene exposure assessment used work histories and exposure measurements adjusted for era-specific circumstances. Statistical analyses included conditional logistic regression and penalised smoothing splines. RESULTS: Benzene exposures were much lower than previous studies. Categorical analyses showed increased ORs for AML with several exposure metrics, although patterns were unclear; neither continuous exposure metrics nor spline analyses gave increased risks. ORs were highest in terminal workers, particularly for Tanker Drivers. No relationship was found between benzene exposure and risk of CLL, although the Australian study showed increased risks in refinery workers. CONCLUSION: Overall, this study does not persuasively demonstrate a risk between benzene and AML. A previously reported strong relationship between myelodysplastic syndrome (MDS) (potentially previously reported as AML) at our study's low benzene levels suggests that MDS may be the more relevant health risk for lower exposure. Higher CLL risks in refinery workers may be due to more diverse exposures than benzene alone.

Hypothalamic suppressor-of-cytokine-signalling 3 mRNA is elevated and pro-opiomelanocortin mRNA is reduced during pregnancy in Brandt's voles (Lasiopodomys brandtii ).

Leptin acts within the hypothalamus to diminish food intake. In Brandt's voles (Lasiopodomys brandtii), both circulating leptin levels and food intake are elevated during pregnancy, suggesting an ineffectiveness of leptin to reduce food intake. Diminished hypothalamic leptin receptors and impaired leptin signal transduction are characteristic of central leptin resistance. The present study aimed to determine whether these characteristic modulations of leptin sensitivity occurred in pregnant Brandt's voles. The mRNA expression of the long form of the leptin receptor (Ob-Rb), suppressor-of-cytokine-signalling 3 (SOCS3), neuropeptide Y (NPY), agouti-related protein (AgRP), pro-opiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) in the hypothalamus were examined on dioestrous, day 5, day 10 and day 18 of pregnancy. Compared to controls, there was no significant change in hypothalamic Ob-Rb mRNA during the pregnancy. SOCS3 mRNA was increased significantly by 68% on day 10% and 93% on day 18 of pregnancy compared to controls. Despite elevated leptin levels, POMC mRNA was decreased significantly by 60% on day 18 of pregnancy, whereas no differences were found in the mRNA expression of NPY, AgRP and CART in pregnant voles compared to controls. The elevation of SOCS3 mRNA together with disrupted leptin regulation of neuropeptides in the hypothalamus suggests that leptin resistance may develop in pregnant Brandt's voles.

Genetic polymorphisms of the urea transporter gene are associated with antihypertensive response to nifedipine GITS.

Nifedipine GITS has diuretic and natriuretic properties, which may enhance its antihypertensive efficacy. We assessed contributions of polymorphisms in the urea transporter-A gene (SLC14A2) to interindividual variations in blood pressure (BP) response to nifedipine treatment. 405 subjects from a single Chinese county received a single oral dose of 30 mg nifedipine GITS (gastrointestinal therapeutic system) daily for 16 days. We genotyped two SNPs in SLC14A2 and found significant associations for the Val227Ile (rs1123617) and Ala357Thr (rs3745009) polymorphisms with BP response to nifedipine treatment. After treatment, subjects with either Ala357/Thr357 or Thr357/Thr357 genotypes had significantly smaller mean changes in systolic BP (SBP) (beta +/- SE = -2.87 +/- 1.24 mmHg, p = 0.020) and diastolic BP (DBP) (beta +/- SE = -1.69 +/- 0.62 mmHg, p = 0.006) compared to those with the Ala357/Ala357 genotype. Subjects with either Val227/Ile227 or Ile227/Ile227 genotypes had significantly larger mean changes in SBP (beta +/- SE = 3.13 +/- 1.19, p = 0.009) and DBP (beta +/- SE = 1.50 +/- 0.60 mmHg, p = 0.013) compared with those with the Val227/Val227 genotype after treatment. Subjects carrying both the Ala357/Ala357 genotype in the Ala357Thr polymorphism and either Val227/Ile227 or Ile227/Ile227 genotypes in the Val227Ile polymorphism had the highest mean change in SBP and DBP. Our study supports the conclusion that polymorphisms in the SLC14A2 gene can predict the antihypertensive efficacy of nifedipine GITS.

The use of midazolam and small-dose ketamine for sedation and analgesia during local anesthesia.

UNLABELLED: Small-dose ketamine in combination with sedative drugs has increasingly been used for sedation and analgesia in local anesthesia. We compared the clinical efficacy of midazolam with two different ketamine infusion regimens during plastic surgery under local anesthesia. Sixty patients undergoing plastic surgery procedures with local anesthesia were randomly assigned to two groups of 30 patients each in a double-blinded fashion. All patients received a bolus of 0.05 mg/kg midazolam, followed by a stepwise infusion: 1.67 microg x kg(-1) x min(-1) for the first 30 min, then reduced to 1.33 microg x kg(-1) x min(-1) for 90 min and subsequently to 1 microg x kg(-1) x min(-1). Two minutes before the infiltration of local anesthetic solution, a bolus of ketamine 0.3 mg/kg IV was administered, followed by a stepwise infusion of ketamine: Group A, 16.67 microg x kg(-1) x min(-1) for 30 min, 13.3 microg x kg(-1) x min(-1) for 90 min, and subsequently 10 microg x kg(-1) x min(-1); Group B, 8.33 microg x kg(-1) x min(-1) for 30 min, 6.67 microg x kg(-1) x min(-1) for 90 min, and then 5 microg x kg(-1) x min(-1). The level of sedation was evaluated by using the modified Observer's Assessment of Alertness/Sedation scale. We observed the effects of the two ketamine infusion regimens on sedation levels, respiratory and cardiovascular variables, and perioperative side effects. In both groups, midazolam and ketamine produced adequate sedation (with Observer's Assessment of Alertness/Sedation scores of 2-4) without significant respiratory and cardiovascular depression during surgery. However, there were fewer disruptive movements and there was less postoperative vomiting in Group B (P < 0.01). In conclusion, ketamine and midazolam provided satisfactory intraoperative sedation, analgesia, and amnesia in both groups. However, side effects associated with ketamine occurred less often in the smaller-dose ketamine group. IMPLICATIONS: Sedation and analgesia are often provided during local anesthesia. This study demonstrates that a small-dose ketamine infusion in combination with midazolam provided satisfactory intraoperative sedation, analgesia, and amnesia in healthy plastic-surgery patients when it was used to supplement local anesthesia.

The use of the Minimum Data Set. Home Care in a case management project in Hong Kong.

130 hospital-discharged elderly patients received our comprehensive assessment by using a Chinese Minimum Data Set-Home Care (MDS-HC). Our case manager developed and implemented care plans with reference to the computer-generated Clients Assessment Protocols. Results showed that the MDS-HC was sensitive to identify elderly persons' holistic needs, and helpful in formulating all-inclusive care plans.

[Separation of catechins and caffeine in tea polyphenol by isocratic elution high performance liquid chromatography].

The catechins, particularly in green tea, have been found to possess anti-mutagenic and anti-tumorigenic properties. As each catechin possesses distinct properties, a simple and rapid method that could be used for analysis of individual catechins in a complex mixture would be necessary. A relatively simple and rapid method for simultaneous separation of five catechins and caffeine in tea polyphenol by isocratic elution high performance liquid chromatography has been developed. The analysis could be finished within 30 min. They were measured using Resolve C18 column (at 43 degrees C) and UV detector (at 280 nm), water-85% phosphoric acid aqueous solution-acetonitrile-dimethyl formamide(DMF) (859:1:120:20, V/V) as mobile phase. There was a good linear relationship between the content of component and its peak area for catechins and caffeine, with the correlation coefficients of 0.9992-0.9999. The average recoveries (n = 5) were 83.33%-104.42%, and the relative standard deviations (n = 6) were 0.74%-1.43%. The effect of concentration of DMF in mobile phase was studied.

Neoadjuvant therapy for organ preservation in head and neck cancer.

OBJECTIVES/HYPOTHESIS: We designed two sequential trials of induction chemotherapy followed by definitive radiation in patients with potentially resectable head and neck cancer to determine whether organ preservation is feasible without apparent compromise of survival Study Design Both trials were Phase II studies. METHODS: Two clinical trials were conducted sequentially at the University of Michigan. Fifty-two patients enrolled in the first study and were treated with a planned three cycles of carboplatin and 5-fluorouracil. Patients who achieved at least 50% reduction in the size of the primary tumor received definitive radiation therapy, to a dose of 6600 to 7380 cGy. Patients with minimal response or progression had immediate salvage surgery. Thirty-seven patients enrolled in the second trial, in which the chemotherapy consisted of carboplatin, 5-fluororuracil, and leukovorin. Responders were treated with accelerated radiation therapy, to a total dose of 7120 cGy delivered in 41 fractions over 5.5 weeks. RESULTS: Toxicity and response were similar in both trials; therefore, the results are reported first separately and then combined for all 89 patients. Tumor sites included: oropharynx, 55 patients; hypopharynx, 34 patients. Eighty-three percent of patients tolerated all three cycles of chemotherapy and toxicity was mild. Response to chemotherapy was: 48% complete response at the primary tumor site, and 34% partial response at the primary tumor site. Initial organ preservation at individual tumor sites was: oropharynx, 58%; hypopharynx, 59%. Median survival was 28 months, and survival at 3 and 5 years was 40% and 24%, respectively. CONCLUSIONS: These two regimens were well tolerated, and survival did not appear to be compromised by organ preservation treatment compared with historical controls. This approach warrants further investigation, particularly in those patients for whom surgery could be functionally debilitating.

[Effect of green and yellow vegetables on serum carotenoid in children].

OBJECTIVE: To assay the effect of green and yellow vegetables on serum carotenoid concentration and its relation to serum retinol level in children. METHODS: A ten-week green and yellow vegetable intervention study was conducted in children aged 5.3 to 6.4 years of two classes in a kindergarten in Tai'an City of Shandong Province in early September 1996, one class of light-colored vegetable supplemented with daily 193 grams of light colored vegetables, such as cabbage, Chinese cabbage, potato, cucumber, cauliflower and turnip, and 56 grams of yellow-green vegetables, such as spinach, Chinese chive, carrots and red yams; and the other one of yellow-green vegetables with daily 238 grams of yellow-green vegetables and 34 grams of light colored vegetables, both without change in regular diet. Venous blood specimens were collected before and after the experiment from each of the subjects. Serum retinol and carotenoid were determined with high performance liquid chromatography. RESULTS: Serum level of carotenoid, including all-trans-beta-carotene, cis-beta-carotene, cryptoxanthin and lutein were significantly higher after intervention in yellow-green vegetable group, as compared to their baseline levels. However, in the light-colored vegetable group, all those components, including all-trans-beta-carotene, 13-cis-beta-carotene and lutein, decreased significantly after intervention, as compared with those at their baseline levels. Serum carotene level correlated significantly with that of retinol, and their coefficient of correlation was greater in the winter than in the autumn. CONCLUSION: Carotenoid nutrition status can be improved by supplementation of green and yellow vegetables.

[Effects of maxillary growth of Wistar rats with bilateral artificial cleft palate after premaxillary orthopedic treatment on expression of proliferating cell nuclear antigen(PCNA)].

OBJECTIVE: Being based on the principle of Latham's appliance, this experiment is designed to detect activity of osteoblasts in the maxillary sutures of Wistar rats with bilateral artificial cleft palate by immunohistochemistry technique, and evaluate the effects of this appliance on the growth and development of the maxilla. METHODS: The animal models of male infant Wistar rats with bilateral cleft palate were made by removing some palatal bones, splitting a "V" gap of 1.5 cm wide at the line between premaxilla and segments of maxilla. A sort of appliances, which could be fixed in the mouth of Wistar rats with bilateral cleft palate for correcting protrusion premaxilla was constructed basing on the principle of Latham's appliance. Then the diferent pathological changes of osteoblast proliferation between the experimental group and the two controlled groups were examined. The jugomaxillary sutrues, temporomalar sutures and sphenoipalatine suture were harvested 7, 14 days after premaxillar orthopedic treatment, followed by 4% paraformaldehyde fixing about 1 hour, demineralization with 15% EDTA and 0.5% paraformaldehyde for 48 hours, distilled water washing for a night, dimethylbenzene transparant dealing, and paraffin wax embeding. Proliferating Osteoblasts in all these sutures were investigated using immunohiostochemical technique with monoclonal antibodies of proliferating cell nuclear antigen (PCNA). RESULTS: Seven days after orthopedic treatment, no significant difference was observed between the experimental group and the two controlled groups. While after fourteen days, obvious PCNA-positive expression were observed in cells of all these sutures of the experimental group. CONCLUSION: The distribution of proliferating cells and the degree of cell proliferation change after premaxillary orthopedic treatment. And significant cell proliferation is observed in the experimental group, but there are no significant differences between the two controlled groups.

[Experimental study on the influence of Gynostemma pentaphyllam Mak upon point mutation of Ha-ras oncogene in blocking leukoplakia from canceration].

OBJECTIVE: To study the influence of Gynostemma pentaphyllam Mak (GP) upon point mutation of Ha-ras oncogene the molecular mechanism of GP in blocking canceration, and the relationship between Ha-ras oncogene and canceration of leukoplakia. METHODS: DMBA induced carcinogeneses of the buccal pouch mucosa of the hamsters were divided into leukoplakia model group(LKG) and GP treated group(GPG). Point mutation (codon 61) of Ha-ras oncogene was detected by PCR-SSCP in both groups. RESULTS: The mutation incidence of LKG was 22.96%, while the mean incidence of GPG was 7.59% (The incidences of C20-OH group, glucoside group and aglucon group were 5.32%, 6.25% and 11.00% respectively). When treated with DMBA for 4 to 8 weeks, the mutation incidence of LKG ranged from 11.10% to 40.00%, while GPG ranged from 0 to 10.70%. CONCLUSIONS: GP has outstanding cancer blocking effect chiefly affected by free C20-OH. Mutation of Ha-ras oncogene plays an important role in leukoplakia canceration.

Effect of transcutaneous electrical nerve stimulation for pain relief on patients undergoing hemorrhoidectomy: prospective, randomized, controlled trial.

PURPOSE: Posthemorrhoidectomy pain control remains a challenging problem. Transcutaneous electrical nerve stimulation is known to be effective in the treatment of many diseases. Our aim was to investigate the effect of transcutaneous electrical nerve stimulation on pain relief in patients undergoing hemorrhoidectomy. METHODS: Sixty patients with symptomatic hemorrhoids were randomly allocated into two groups, the acupoint group (n = 30) and the nonpoint control group (n = 30). Transcutaneous electrical nerve stimulation was applied to those patients who received hemorrhoidectomy, and patient-controlled analgesia was achieved by injection of morphine through ambulatory infusion pumps. The dependent measures in this study were pain score from 0 (no pain) to 10 (agonizing pain), analgesic doses administrated through patient-controlled analgesia, and postoperative complications. RESULTS: The subjective pain scores evaluated 8, 12, 16, and 24 hours after hemorrhoidectomy in the control group and the acupoint group were 5.9 +/- 0.5 and 4.1 +/- 0.5, 5.7 +/- 0.5 and 3.5 +/- 0.4, 4.1 +/- 0.4 and 2.3 +/- 0.3, and 3.2 +/- 0.4 and 1.9 +/- 0.2, respectively (two-way analysis of variance; P < 0.05). There was a significant difference between treatment groups in morphine use, with 11.6 +/- 2.2 mg in the control group and 6.2 +/- 1.3 mg in the acupoint group (P < 0.05). The acupoint group tended to have less postoperative acute urinary retention (Fisher's exact probability test; P = 0.145) and less need for analgesics than the control group (P = 0.112, Fisher's exact test). CONCLUSION: Transcutaneous electrical nerve stimulation is effective for pain relief in patients receiving hemorrhoidectomy. Its efficacy and safety could assist outpatient pain management after hemorrhoidectomy.

Assessment of total body stores of vitamin A in Guatemalan elderly by the deuterated-retinol-dilution method.

BACKGROUND: Deuterated retinol dilution (DRD) gives quantitative estimates of total body stores of vitamin A. OBJECTIVES: In elderly people, we studied 1) the time when an oral dose of deuterated vitamin A equilibrates with body stores, 2) whether serum ratios of deuterated to nondeuterated retinol (D:H) at 3 or 6 d postdosing predicted body stores, and 3) the ability of DRD to detect changes in the size of the body vitamin A pool. DESIGN: A 10-mg oral dose of [2H4]retinyl acetate was administered to 60-81-y-old Guatemalans (n = 47); percentage enrichment of serum retinol with deuterated retinol was determined at 1-3 time points per subject at 3, 6, 7, 14, 20, 21, and 54 d. In subjects from whom blood was obtained at 3 and 21 d (n = 15) and at 6 and 20 d (n = 9), total body stores were calculated by using the formula of Furr et al (Am J Clin Nutr 1989;49:713-6) with 21- or 20-d data and correlated with serum D:H at 3 or 6 d postdosing. Nine subjects received diets containing 982+/-20 microg RE (x+/-SEM) plus 800 microg RE as retinyl acetate supplements for 32 d. DRD, serum retinol, and relative dose response were used to assess vitamin A status before and after the intervention. RESULTS: Deuterated retinol equilibrated with the body pool by 20 d postdosing. Vitamin A supplementation for 32 d increased body stores, although unexplained exaggerated increases were seen in some subjects. An inverse linear relation was found between estimates of body stores and serum D:H at 3 d postdosing (r = -0.75, P = 0.002); at 6 d postdosing, the correlation was weaker. CONCLUSIONS: DRD can detect changes in total body stores of vitamin A, although factors affecting serum D:H need to be elucidated. Serum D:H 3 d postdosing might be used as an early indicator of total body stores of vitamin A, although a predictive equation will need to be developed.

Effects of tea polyphenols on cerebral lipid peroxidation, liver and renal functions in rats after repeated +Gz stress.

OBJECTIVE: To observe the effects of repeated +10 Gz stress on cerebral lipid peroxidation, liver and renal function in rats and the prophylactic effects of antioxidant tea polyphenols (TP). METHOD: Twenty-four male Wistar rats were randomly divided into three groups (n = 8, each): group A (control), group B (+10 Gz), and group C (TP). Group B and C were exposed to repeated +10 Gz stress (each for 30s, onset rate about 0.5 G/s, 3 times/d with +1 Gz 1 min intervals, 3 d/wk, 4 weeks in total), but group A was only submitted to +1 Gz. TP (200 mg/kg) was given orally in group C about 1 h prior to the +Gz experiment, while distilled water was given in group A and B. Lipid peroxidation in the brain, liver and renal functions and serum lipids were determined. RESULTS: As compared with the control, lipid peroxidation in rat cerebral homogenate, mitochondria and cytoplasm was significantly increased (P < 0. 05), and serum creatinine concentration was markedly elevated after repeated +10 Gz stress (P < 0. 01). But, TP had significant inhibitory effect on +10 Gz stress induced peroxidative injury in rat brain and reduced the serum creatinine level. There were no differences of serum triglyceride and total cholesterol concentrations and glutamic-pyruvic transaminase activity among the three groups. CONCLUSION: These results indicated that repeated high +Gz stress could bring about peroxidative injury in brain and harmful effect on renal function, and natural antioxidant TP had significant protective effects.

Effects of tea polyphenols on cardiac function and myocardial ultrastructure in rats after repeated +Gz stress.

Objective. To observe the effects of tea polyphenols (TP) on cardiac function and myocardial ultrastructure in rats after repeated +10 Gz stress. Method. Twenty four male Wistar rats were randomly divided into three groups (n=8 each): group A (control), group B (+10 Gz), group C (+Gz with TP). Group B and C were repeatedly exposed to +10 Gz (each for 30 s, onset rate about 0.5 G/s, 3 times/d with +1 Gz 1 min intervals, 3 d/wk, 4 weeks in total), but group A was only submitted to +1 Gz. TP (200 mg kg-1) was given orally to group C about 1 h prior to the +Gz experiment, and distilled water was given to group A and B. Function of isolated rat working hearts and myocardial ultrastructure were observed. Result. A significant decrease of left ventricular systolic pressure (LVSP) and injury of myocardial structure in rats were demonstrated after repeated +10 Gz stress. But TP could remarkably elevate the LVSP and improve myocardial ultrastructural injury in +10 Gz stressed rats. Conclusion. These results indicated that repeated high G exposure may produce cardiac structural and functional injuries in rats which might be partly related to free radical metabolism; and antioxidant TP had significant protective effects on the hearts of +Gz stressed rats.

[Determination of vitamin D3 in health-care foods fortified with calcium by reversed-phase high performance liquid chromatography].

"Bu Gai Bao" and "Gaoxiao Man Gai" are health-care foods fortified with calcium for people of all ages. This paper describes a method of reversed-phase high performance liquid chromatography for quantitating vitamin D3 in these products. The method is simple, sensitive, and suitable for routine analysis of vitamin D3 in a variety of health-care foods fortified with calcium. Shimadzu LC-4A high performance liquid chromatograph with SPD-2AS UV detector and C-R2AX data processor were used. The vitamin D3 in products was extracted with chloroform and separated with mu-Bondapak C18 column(300 mm x 3.9 mm i.d.) and methanol water(87:13, V/V) mobile phase with detection at UV-264 nm. Regression coefficient of correlation of calibration curves in the range of 10-50 mg/L was 0.9998. Average recoveries of vitamin D3 added to the products was 95.63%. The coefficients of variation of vitamin D3 in both products were 0.24%-0.49%.

[Isolation, purification and determination of the constituents of a toxic protein from plant amenone].

A toxic protein constituent named AME from the stems of plant amenone, have been isolated and purified. Through CM-SFF column chromatography and gel filtration on Sephacryl S-200 column with phosphate saline buffer as mobile phase. All of the operations were performed at 4 degrees C. The pulverized plant amenone material was soaked in phosphate saline buffer, homogenized, left standing overnight and then squeezed through coarse cloth by wringing. The supernatant was applied on the S-SFF column. Then, the column was eluted with the phosphate buffer containing 1 mol/L NaCl. The eluate was collected and dialyzed against water and phosphate buffer. The chromatography of the crude toxin dialyzed was carried out on the CM-SFF column with gradient elution of phosphate buffer containing NaCl. The fourth peak was collected and then applied on a gel filtration Sephacryl S-200 column using neutral phosphate buffer as mobile phase. The protein was further separated on two connected Protein 125 columns with mobile phase of 0.2 mol/L phosphate buffer (pH 6.5), the eluate was monitored at 280 nm on photodiode array detector. The protein presents typical the absorption spectrum of protein in ultraviolet region with the strong absorption at 280 nm and the weak absorption at 260 nm. The purity of peak of the protein was judged from the spectrum. The molecular weight of AME measured by two connected protein columns was approximately 35,000 D. The composition of amino acids was determined with OPA post-column derivatization/fluorescence detection.

Measurement of retinoids and carotenoids in breast adipose tissue and a comparison of concentrations in breast cancer cases and control subjects.

A case-control study of the associations of retinoids and specific carotenoids with breast cancer using concentrations of these nutrients in breast adipose tissue was conducted among women attending a breast clinic in the Boston area in 1989-1992. Breast adipose tissue was collected during breast biopsy. Cases (n = 46) were women whose biopsies revealed invasive or in situ breast cancer; control subjects (n = 63) were women whose biopsies revealed benign disease. We observed inverse associations between breast adipose concentrations of retinoids and carotenoids and risk of breast cancer, although not all were statistically significant. The multivariate-adjusted odds ratio comparing women above the median value of the control group for retinol with those below or equal to the median was 0.71 (95% CI: 0.26, 1.93; NS); corresponding odds ratios were 0.61 (95% CI: 0.23, 1.64; NS) for retinyl palmitate, 0.30 (95% CI: 0.11, 0.85) for beta-carotene, 0.32 (95% CI: 0.11, 0.94) for lycopene, and 0.68 (95% CI: 0.27, 1.73; NS) for lutein/zeaxanthin. There was a nonsignificant positive correlation (r = 0.23, P = 0.15) between breast adipose tissue concentrations of retinol and dietary intake of preformed vitamin A, including supplements measured by using a food-frequency questionnaire. No correlation was found between breast adipose concentrations of carotenoids and intake of dietary carotenoids. These data suggest that higher breast adipose concentrations of retinoids and some carotenoids may be associated with decreased risk of breast cancer and that further examination of these relations is warranted.

Regulation of lysine catabolism through lysine-ketoglutarate reductase and saccharopine dehydrogenase in Arabidopsis.

In plant and mammalian cells, excess lysine is catabolized by a pathway that is initiated by two enzymes, namely, lysine-ketoglutarate reductase and saccharopine dehydrogenase. In this study, we report the cloning of an Arabidopsis cDNA encoding a bifunctional polypeptide that contains both of these enzyme activities linked to each other. RNA gel blot analysis identified two mRNA bands-a large mRNA containing both lysine-ketoglutarate reductase and saccharopine dehydrogenase sequences and a smaller mRNA containing only the saccharopine dehydrogenase sequence. However, DNA gel blot hybridization using either the lysine-ketoglutarate reductase or the saccharopine dehydrogenase cDNA sequence as a probe suggested that the two mRNA populations apparently are encoded by the same gene. To test whether these two mRNAs are functional, protein extracts from Arabidopsis cells were fractionated by anion exchange chromatography. This fractionation revealed two separate peaks-one containing both coeluted lysine-ketoglutarate reductase and saccharopine dehydrogenase activities and the second containing only saccharopine dehydrogenase activity. RNA gel blot analysis and in situ hybridization showed that the gene encoding lysine-ketoglutarate reductase and saccharopine dehydrogenase is significantly upregulated in floral organs and in embryonic tissues of developing seeds. Our results suggest that lysine catabolism is subject to complex developmental and physiological regulation, which may operate at gene expression as well as post-translational levels.