Interrelationship of depression, stress and inflammation in cancer patients: a preliminary study.

OBJECTIVE: Depression is common in cancer patients and detrimentally affects patients' quality of life. Both depression and stress are associated with raised inflammatory marker levels. This prospective study of cancer patients focuses on childhood trauma, recent life events and inflammatory marker levels as risk factors for high post-surgery depressive symptoms. METHODS: Ninety cancer patients (56 head and neck, 34 colorectal) completed the Hospital Anxiety and Depression Scale, pre-surgery and six, 12 and 24 weeks post-surgery. Recent life events and childhood trauma were assessed at six and 12 weeks respectively. Blood samples were taken pre- and one and six weeks post-surgery to measure C-reactive protein (CRP) and pro-inflammatory cytokine levels. RESULTS: Childhood trauma and recent life events were risk factors for higher depressive symptom levels. In colorectal cancer patients, baseline CRP levels were associated with depressive symptom levels at six (p=0.008) and 12 weeks (p=0.038). Baseline and six week Tumour Necrosis Factor-alpha (TNFα) levels were significantly associated with higher depressive symptoms at later time points after adjusting for cancer-related variables. Childhood trauma was positively associated with TNFα and CRP levels in colorectal cancer patients. The associations between inflammatory markers and depressive symptoms were not significant after adjusting for childhood trauma. LIMITATIONS: Small sample size. CONCLUSIONS: Raised inflammatory mediator levels may be risk factors for depressive symptoms in colorectal cancer patients and thus worth considering as a potential therapeutic target. These pilot data support recent findings demonstrating long-term effects of childhood adversity on adult health.

Seasonal luteal cyclicity of pubertal and adult red deer (Cervus elaphus).

Reproductive failure of rising-two-year-old (R(2)) hinds and seasonal misalignment between calving and pastoral feed production are two factors limiting reproductive productivity of farmed red deer hinds in New Zealand. This study aimed to better understand processes around female puberty and breeding seasonality by describing the potential breeding season (i.e., oestrous cyclicity) of three red deer genotypes. A total of 27 hinds born in December 2005, representing Eastern European (Cervus elaphus hippelaphus), Western European (C.e. scoticus) and F1 crossbred (C.e. hippelaphus×scoticus) red deer, were blood sampled thrice-weekly for 7-8 months (February-September/October) across two years spanning the potential breeding seasons as R(2)'s in 2007 (i.e., puberty) and as adults in 2008. Plasma progesterone profiles were used to construct breeding cycle histories for each hind. Four R(2) hinds failed to initiate oestrous cycles (i.e., puberty failure). The remaining R(2) hinds, including all F1 hinds, exhibited between two and seven oestrous cycles. F1 hinds were significantly earlier to initiate, and later to terminate, cyclic activity, resulting in a longer mean pubertal breeding season (139 days) than for Eastern (86 days) and Western hinds (86 days). However, the data for R(2) hinds are confounded by live-weight, with the F1 hinds being significantly heavier than other genotypes. There were significant correlations between live-weight and seasonality parameters in 2007. All hinds were cyclic as adults in 2008, exhibiting between four and nine oestrous cycles, and a mean breeding season duration of between 132 (Western) and 137 (F1) days. For adult hinds there were no significant genotype differences in cyclic onset and cessation timing, and no observable relationships between live-weight and any reproductive parameter. However, the mean dates for the onset of the breeding season for all genotypes in 2008 were 2-3 weeks later than normally expected for adult hinds in New Zealand. The reasons for this are unclear but may relate to chronic stress of frequent animal handling. The study has demonstrated that puberty in red deer hinds is associated with a shorter potential breeding season than for adult hinds, and that perturbation of breeding activity appears to be quite common, leading to incidences of puberty failure and possibly other aberrant cyclic events. Live-weight×genotype interactions may influence puberty but do not appear to be strongly expressed in adults. However, the relatively late onset of oestrous cyclicity in the adult hinds may be an artefact of the study that has masked genetic influences on seasonal breeding patterns.

Effect of melatonin implants on the incidence and timing of puberty in female red deer (Cervus elaphus).

A study was conducted to test the hypotheses that exogenous melatonin treatment of 11-13 month-old red deer hinds: (1) advances the timing of first ovulation, (2) increases the proportion of individuals attaining puberty at ∼16 months of age, and (3) reduces the live-weight threshold for attainment of first pregnancy. A total of 3901 rising-2-year-old (R2) hinds within two herds (A and B) across two years either received single melatonin implants on two occasions in summer (n=1399) or were untreated controls (n=2502). Hinds were joined with stags from mid January to mid May, and were subjected to real-time rectal ultrasonography in early June to assess pregnancy status (proxy for puberty attainment) and foetal age for conception date assignment. Live-weights were recorded for each hind in January (12 months of age) as a proxy for weight at puberty. Melatonin treatment of hinds was associated with a significant advancement in mean conception dates in both herds in both years (P<0.05), with a cohort difference in mean dates between treated and control hinds ranging from 9 to 17 days. Analysis of the temporal distribution of conception dates for each cohort revealed bi-modal or tri-modal patterns of conception indicative of conceptions to first or subsequent ovulations (oestrous cycles). Across all cohorts, melatonin treatment was associated with higher conception rates to first ovulation (P<0.05) resulting in greater overall synchrony of conceptions. Regression analysis demonstrated a significant negative slope for conception date against live-weight (P<0.001), but there was no evidence that this slope varied with treatment, herd or year (P>0.05); for every 10kg increase in live-weight conception date was advanced by an average of 1.3 days. In Herd A, melatonin treatment was associated with significantly higher pregnancy rates in both years (90.3% vs. 78.0% in Year 1 and 84.4% vs. 57.1% in Year 2; P<0.05). The principle effect of melatonin treatment was to increase the pregnancy rate of hinds of low body-mass. In Year 1, at 60kg live-weight a logit regression model indicated a pregnancy rate of 52% for untreated hinds and 83% for treated hinds. At 105kg the rate for both cohorts was 90%. In Herd B, melatonin treatment was associated with higher conception rates in both years but these differences were not significant following correction for slight differences in mean live-weight (P>0.05). The study has demonstrated that factors influencing puberty attainment in R2 red deer hinds can vary between populations. In Herd A, in which body mass of hinds immediately prior to their first potential breeding season may have been the principle limiting factor, melatonin treatment appears to have instigated the pubertal process in hinds that would otherwise be of insufficient body mass.

Evaluation of management variables to advance conception and calving date of red deer (Cervus elaphus) in New Zealand venison production systems.

The ability to shift the supply of New Zealand chilled venison from farmed yearling red deer stags to obtain premium prices in seasonal European markets necessitates early calving of hinds combined with high growth rates of their calves. Two studies over a three-year period evaluated three management variables that offer potential to advance calving date. Under the conditions of the studies there was no consistent evidence that the management practices of early stag introduction, early weaning and enhanced hind nutrition prior to conception (lactation) and pre-calving (third trimester of pregnancy) advanced conception date and calving date in red deer hinds. However, the nutrition effect was diminished by the difficultly in achieving the dietary contrast necessary for the targeted 5kg differentiation in hind live weight at strategic times of the year. Across all hinds there was a significant pre-mating (mid-March) live weight effect on conception day in the one year in which a 5kg difference between nutritional regimens was achieved, but the driver was live weight and not nutrition. There were significant effects of nutrition on calf growth, with the growth rates of calves weaned in mid-March significantly higher when their dams grazed a high plane of nutrition pre-conception. There were significant and consistent inverse relationships between conception day and calving date that implied variation around gestation length, with early- and late-conceiving hinds exhibiting longer and shorter gestation lengths, respectively. Across all treatments, calving date was predicted to advance by approximately 5 days for every 10-day advance in conception date. However, there was a significant carry-over effect of nutrition pre-conception on calving date, with hinds on a high plane of nutrition pre-conception exhibiting shorter (2-4 days) gestation lengths. There were also indications that hinds may manipulate gestation length in response to live weight gain pre-calving. These findings suggest that fetal growth trajectory may be the principle driver of gestation length and calving date. Although there were no direct effects of hind nutrition pre-mating on conception dates, nutrition remains an important component of the management of hinds and their calves in venison production systems. The outcomes of the 3-year program suggest that there are limited opportunities to manipulate calving date through manipulation of management variables.

The effect of conception date on gestation length of red deer (Cervus elaphus).

Recent studies have demonstrated that gestation length of red deer (Cervus elaphus) is highly variable and influenced by various environmental factors, and this may confer survival advantages for neonates. The current study investigated the relationship between conception date and gestation length to test the hypothesis that within-herd synchrony of red deer births is facilitated by a 'push/pull' control over gestation length, such that hinds conceiving early and late in the breeding season have longer and shorter gestation periods, respectively. In Study 1, data on conception and calving dates were obtained for 393 naturally cycling hinds across two herds. In Study 2, conception and calving dates were obtained from 91 hinds in which oestrus/conception were artificially synchronised across a 4-week range of dates spanning the natural rut. Gestation length for each population was analysed by linear regression, fitting conception day followed by terms for the fixed effect which included hind age (pubertal vs. adult), hind genotype (Cervus elaphus scoticus vs. Cervus elaphus hippelaphus and their crossbreds), calf sex, sire genotype (Study 1 only), birth weight and year. In Study 1, both populations of naturally cycling hinds exhibited highly significant (P<0.001) negative slopes (-0.36, -0.49) for the regression of gestation length against conception date, with indications of a significant hind genotype effect favouring shorter overall gestation lengths for crossbred hinds. Other effects for hind age, calf sex, birth weight, sire genotype and year were not significant. In Study 2, in which conception dates were artificially induced, there was a highly significant negative slope (-0.19), with a notable but non-significant effect of hind age favouring shorter overall gestation length for primiparous (pubertal) hinds (P>0.05). Other effects for hind live weight, calf sex and calf birth weight were not significant. All data sets support the hypothesis, and indicate that for every 10 days difference in conception date there was a change in gestation length of 1.9-4.9 days. This hints at the adaptive importance of optimisation of birth date in wild populations of red deer but the precise physiological mechanisms remain to be resolved. It is postulated that variation in fetal age during the latter stages of pregnancy, when feed quality and voluntary feed intake cycles are in a state of flux, may drive differential growth trajectories for early and late conceived fetuses, leading to nutritional control over fetal maturation and induction of parturition. However, consideration is also given to a putative direct effect of prevailing photoperiod on control of parturition processes in red deer.

Reproductive performance of pubertal red deer (Cervus elaphus) hinds: effects of genetic introgression of wapiti subspecies on pregnancy rates at 18 months of age.

Low reproductive productivity of young red deer (Cervus elaphus) hinds on New Zealand deer farms appears to reflect high incidences of puberty failure at 16 months of age. This is despite the general attainment of average liveweights 15-25 kg in excess of the accepted minimum threshold for puberty in subspecies of western European origin (scoticus, elaphus and hippelaphus) that form the basis of the national herd. The present study tests the hypotheses that introgression of the larger North American wapiti subspecies (nelsoni, manitobensis and roosevelti) into breeding herds (1) can be assessed from morphological features of individuals, (2) that there is a relationship between the level of wapiti parentage and non-pregnancy rate at 18 months of age (a proxy for puberty failure) and (3) that minimum liveweight thresholds for puberty increase with increasing levels of wapiti parentage. A total of 4329 18-month-old hinds across four "red" deer farms in southern New Zealand were scanned for pregnancy status. Each hind was assigned a wapiti score (WS) as a subjective assessment of the obviousness of wapiti features. Various body measurements were additionally recorded for each hind. A hair sample was collected for DNA analysis (14 markers) to objectively assign subspecies pedigree (i.e. "Elkmeter") on a subset of 1258 individuals. A total of 506 (11.7%) hinds were not pregnant at 18 months of age with rates varying between 4.1 and 37.3% between farms and years. Mean WS differed significantly between farms and reflected the genetic management policy of each farm. WS was positively correlated to Elkmeter for each farm/year (<0.05) although regression slopes varied significantly. WS was able to be adjusted for these differences to assign a corrected WS (CWS) for all 4329 individuals that estimated the proportion wapiti parentage. Discriminant analysis of morphological variables relative to Elkmeter supported the first hypothesis and showed that shoulder height and body length were good indicators of the degree of wapiti parentage within individuals. This enabled the development of an objective estimate of wapiti parentage (EWP). The actual level of such parentage within herds ranged from <5 to >55%. There was a significant negative association between wapiti parentage and pregnancy, which was strongly influenced by liveweight, supporting the second and third hypotheses. This was manifest as marked displacement of pregnancy probability curves in relation to liveweight between genotype groups, particularly for those groups with >20% wapiti parentage. For example, predicted threshold liveweights required to achieve a 90% pregnancy rate for EWP values that represent 0, 10, 20, 30, 40 and 50% wapiti parentage were 81, 81, 85, 106, 127 and approximately 137 kg, respectively. Within the study herds, the majority of hinds of 0-20% wapiti parentage exceeded the predicted 90% threshold liveweights for their genotype cohort. However, hinds with higher levels of wapiti parentage generally fell below the predicted threshold for their genotype group. The data strongly suggest that under liveweight performance levels measured for red deer, hinds with >20% wapiti parentage are at high risk of puberty failure.

Genetic and phenotypic variance and covariance components for feed intake, feed efficiency, and other postweaning traits in Angus cattle.

Records on 1,180 young Angus bulls and heifers involved in performance tests were used to estimate genetic and phenotypic parameters for feed intake, feed efficiency, and other postweaning traits. The mean age was 268 d at the start of the performance test, which comprised 21-d adjustment and 70-d test periods. Traits studied included 200-d weight, 400-d weight, scrotal circumference, ultrasonic measurements of rib and rump fat depths and longissimus muscle area, ADG, metabolic weight, daily feed intake, feed conversion ratio, and residual feed intake. For all traits except the last five, additional data from the Angus Society ofAustralia pedigree and performance database were included, which increased the number of animals to 27,229. Genetic (co)variances were estimated by REML using animal models. Direct heritability estimates for 200-d weight, 400-d weight, rib fat depth, ADG, feed conversion,and residual feed intake were 0.17 +/- 0.03, 0.27 +/- 0.03, 0.35 +/- 0.04, 0.28 +/- 0.04, 0.29 +/- 0.04, and 0.39 +/- 0.03, respectively. Feed conversion ratio was genetically (r(g) = 0.66 ) and phenotypically (r(p) = 0.53) correlated with residual feed intake. Feed conversion ratio was correlated (r(g) = -0.62, r(p) = -0.74) with ADG, whereas residual feed intake was not (rg = -0.04, r(p) = -0.06). Genetically, both residual feed intake and feed conversion ratio were negatively correlated with direct effects of 200-d weight (r(g) = -0.45 and -0.21) and 400-d weight (r(g) = -0.26 and -0.09). The correlations between the remaining traits and the feed efficiency traits were near zero, except between feed intake and feed conversion ratio (r(g) = 0.31, r(p) = 0.23), feed intake and residual feed intake (r(g) = 0.69, r(p) = 0.72), and rib fat depth and residual feed intake (r(g) = 0.17, r(p) = 0.14). These results indicate that genetic improvement in feed efficiency can be achieved through selection and, in general, correlated responses in growth and the other postweaning traits will be minimal.

Molecular characterisation of a Rhodococcus ohp operon.

The ohp operon of Rhodococcus strain V49 consists of five genes, ohpR, ohpA, ohpB, ohpC and ohpD which encode putative regulator and transport proteins and confirmed monooxygenase, hydroxymuconic semialdehyde hydrolase and catechol 2,3-dioxygenase enzymes, respectively. These enzymes catalyse the conversion of 3-(2-hydroxyphenyl)propionic acid to the corresponding linear product via a meta-cleavage pathway. Confirmation that the ohp gene cluster formed an operon was provided by gene disruption during which expression of Bacillus levansucrase was confirmed in Rhodococcus. Following biochemical assays of cell-free extracts from recombinant Escherichia coli expressing ohpB (monooxygenase), ohpC (hydroxymuconic-semialdehyde hydrolase) and ohpD (catechol 2,3-dioxygenase), the ortho-hydroxyphenylpropionic acid catabolic pathway in Rhodococcus strain V49 (ATCC 19070) has been predicted.

Optimum postweaning test for measurement of growth rate, feed intake, and feed efficiency in British breed cattle.

The optimum duration of test for measurement of growth rate, feed intake, feed conversion, and residual feed intake was examined using postweaning feed intake and weight data from 760 Angus, Hereford, Polled Hereford, and Shorthorn heifer and Angus bull progeny from 78 sires. Variance components, heritability, phenotypic and genetic correlations, and the efficiency of selection using shortened tests compared with a 199-d test were used as criteria to assess the optimum test length. The results indicated that a 35-d test was sufficient for measurement of feed intake, whereas a 70-d test was required to measure growth rate, feed conversion, and residual feed intake without compromising the accuracy of measurement. When a 70-d test is used to measure growth rate, feed conversion, and residual feed intake there is minimal loss in accuracy when weights are collected every 2 wk instead of weekly, but a further increase in the interval between weights to 5 wk caused a decline in the accuracy of the test. Therefore a 70-d test with cattle weighed every 2 wk seems to be optimal for measuring these traits in British breed cattle.

The DNA sequence and minimal replicon of the Corynebacterium glutamicum plasmid pSR1: evidence of a common ancestry with plasmids from C. diphtheriae.

The complete nucleotide sequence of pSR1, a 3 kb multicopy cryptic plasmid from Corynebacterium glutamicum ATCC 19223 has been determined. pSR1 is unrelated to the 4.4 kb Brevibacterium lactofermentum plasmid pBL1 and shows no DNA sequence conservation with plasmids from Staphylococcus. Transposon insertion and deletion mutants located the minimal replicon to within a 2.1 kb NcoI-BclI restriction fragment. This region contains a single large open reading frame, ORF2, flanked at the 5' end by a series of inverted repeat sequences which may modulate its expression, and at the 3' end by a region which may contain a replication origin. ORF2 (position 1633-2636) with a maximum coding potential of 36 kDa is essential for pSR1 replication and was designated the rep gene. The predicted ORF2 protein product exhibits 47% identity over a length of 343 amino acids with a replication-associated ORF in the C. diphtheriae plasmid pNG2, many of the changes being in the third base position. This observation suggests that pSR1 and pNG2, which are two plasmids from environmentally separated Corynebacterium species, may share a common ancestral rep gene.

A C-terminal deletion in Corynebacterium glutamicum homoserine dehydrogenase abolishes allosteric inhibition by L-threonine.

In Escherichia coli, Bacillus subtilis and Corynebacterium glutamicum, homoserine dehydrogenase (HD), the enzyme after the branch point of the threonine/methionine and lysine biosynthetic pathways, is allosterically inhibited by L-threonine. To investigate the regulation of the C. glutamicum HD enzyme by L-threonine, the structural gene, hom, was mutated by UV irradiation of whole cells to obtain a deregulated allele, homdr. L-Threonine inhibits the wild-type (wt) enzyme with a Ki of 0.16 mM. The deregulated enzyme remains 80% active in the presence of 50 mM L-threonine. The homdr gene mutant was isolated and cloned in E. coli. In a C. glutamicum wt host background, but not in E. coli, the cloned homdr gene is genetically unstable. The cloned homdr gene is overexpressed tenfold in C. glutamicum and is active in the presence of over 60 mM L-threonine. Sequence analysis revealed that the homdr mutation is a single nucleotide (G1964) deletion in codon 429 within the hom reading frame. The resulting frame-shift mutation radically alters the structure of the C terminus, resulting in ten amino acid (aa) changes and a deletion of the last 7 aa relative to the wt protein. These observations suggest that the C terminus may be associated with the L-threonine allosteric response. The homdr mutation is unstable and probably deleterious to the cell. This may explain why only one mutation was obtained despite repeated mutagenesis.

Nucleotide sequence and organization of the upstream region of the Corynebacterium glutamicum lysA gene.

Maximum expression of the Corynebacterium glutamicum lysA gene is dependent upon the presence of a 2.3 kb region immediately 5' of the lysA reading frame. Subcloning and functional analysis of the upstream region implied that this region contained the lysA promoter. Sequence determination of the upstream region revealed a single open reading frame, orfX, in the same orientation as lysA. The orfX coding sequence exhibited all the sequence characteristics of a gene with the potential for a 550-amino-acid polypeptide product. Expression of lysA is coupled to that of orfX via a common promoter located immediately 5' of orfX. The RNA start site has been determined by S1 nuclease mapping. Both the orfX and the lysA gene are expressed as a single 3.0 kb RNA transcript. These data indicate that orfX and lysA are genes within a two-gene operon. Expression of the lysA gene is not subject to regulation by lysine. The orfX gene product was shown not to be directly linked to the lysine biosynthetic pathway, nor is it the enzyme incorporating DAP into the peptidoglycan precursor.

The molecular structure of the Corynebacterium glutamicum threonine synthase gene.

The minimal region encoding the Corynebacterium glutamicum threonine synthase structural gene and its promoter was mapped by deletion analysis and complementation of the C. glutamicum thrC allele to a 1.6 kb region of the recombinant plasmid pFS80. The nucleotide sequence of this and flanking DNA was determined. The transcription and translation start points were identified by S1 mapping analysis and amino-terminal protein sequencing, respectively. The thrC gene encodes a 54481-Dalton polypeptide product. Translation of the thrC mRNA initiates only six nucleotides downstream from transcription. The length of the mRNA transcript is consistent with a single gene transcription unit. The C. glutamicum thrC gene is expressed independently of the other threonine-specific genes hom and thrB.

Characterization of the ColE1 mobilization region and its protein products.

A third of the 6.6 kb genome of ColE1 is devoted to mobilization (mob) genes necessary to promote its specific transfer in the presence of conjugative plasmids. The mob region is genetically complex: two mob genes are entirely overlapped by a third. Oligonucleotide-directed mutagenesis was used to insert an amber codon into one of the overlapped genes and make possible a full complementation analysis of mob. Four mob genes essential for mobilization by R64drd11 were thus identified. Fragments of mob were subcloned under control of the Ptac promoter in a suitable vector, overexpressed in minicells and the mobilization proteins visualized. A comprehensive alignment of the mob region of ColE1 with those of its close relatives ColK and ColA demonstrating that the four essential mob genes are conserved is also presented.

Nucleotide sequence and fine structural analysis of the Corynebacterium glutamicum hom-thrB operon.

The complete nucleotide sequence of the Corynebacterium glutamicum hom-thrB operon has been determined and the structural genes and promoter region mapped. A polypeptide of Mr 46,136 is encoded by hom and a polypeptide of Mr 32,618 is encoded by thrB. Both predicted protein sequences show amino acid sequence homology to their counterparts in Escherichia coli and Bacillus subtilis. The promoter region has been mapped by S1-nuclease and deletion analysis. Located between -88, RNA start site and -219 (smallest deletion clone with complete activity) are sequence elements similar to those found in E. coli and B. subtilis promoters. Although there are no obvious attenuator-like structures in the 5'-untranslated region, there is a dyad-symmetry element, which may act as an operator.

Blood pressure and urinary sodium in black American adolescents.

For 56 black American adolescents ranging in age from 13 to 19 years, 24-hour urinary sodium excretion was compared with blood pressure. The volunteers came from families of middle to low economic levels. Their body weight varied from 70 to 129 percent of ideal body weight. The average systolic pressure of all the subjects was 112.1 mmHg with a standard deviation of 9.5 mmHg; mean diastolic pressure was 69.6 mmHg with a SD of 8 mmHg. The average 24-hour urinary sodium excretion of the total population was 131.5 mEq/24 h with a SD of 59 mEq. For the 29 male subjects, the mean value was 137 mEq/24 h (range, 30 to 309 mEq) and for 27 female subjects, 126.3 mEq/24 h (range, 40 to 197 mEq). The average urinary excretion among these groups was not significantly different (P > .05) and the urinary Na/K ratio of the total group was 4.3 with a SD of 2.0. This ratio among various age and sex subgroups was not significantly different (P > .05). Urinary sodium excretion values were taken as a reflection of dietary salt intake among these volunteers. The data suggest that the black adolescents studied do not consume excess sodium and contradict the belief that blacks eat excess sodium. Further, these baseline data must be considered among the factors responsible for the development of hypertension.

Virus-induced diabetes in autoimmune New Zealand mice.

Infection of autoimmune New Zealand mice with the D variant of encephalomyocarditis (EMC) virus results in beta-cell damage and clinical diabetes. The induction of diabetes in parental NZB and NZW strains was independent of sex. However, the susceptibility to virus-induced diabetes in their F1 offspring was sex dependent. This susceptibility was significantly higher in male (NZB X NZW) F1 mice as compared with female F1 mice. Castration of male F1 mice significantly reduced the susceptibility to diabetes. These results suggest that parental NZB and NZW strains have recessive genes at different loci which do not allow sex hormones to influence the susceptibility to diabetes. It is concluded that both the genetic background of the host and sex hormones influence the development of virus-induced diabetes in autoimmune New Zealand mice.

Virilizing lipid cell tumor of the ovary: light and electron microscopic studies.

Lipid cell tumor of the ovary is among the rarest tumors belonging to the virilizing group of ovarian neoplasms. A lipid cell tumor of the ovary is described in an 18-year-old woman with secondary amenorrhea, hirsutism, and frank virilization. Current diagnostic features, preoperative and postoperative androgen determinations, and histomorphological and ultrastructural studies are presented. Prompt diagnosis and treatment are emphasized in this potentially malignant and disfiguring androgenic tumor that is readily amenable to surgery.

Insulin binding and degradation by human erythrocytes at physiological temperature.

When evaluated at 15 C, insulin binding to human erythrocytes is similar to that of human adipocytes fibroblasts, monocytes and placental membranes. At 37 C, however, both insulin binding and degradation by human erythrocytes have a unique character. At this temperature, by the end of the first 30 minutes, erythrocyte specific insulin binding is 3 to 4% of the total available insulin. This percentage of binding remains until the end of the first hour, then for the next four hours, increases linearly to 24%. Intact erythrocytes had negligible degradation of the free 125I-insulin but 56% of the 125I-insulin associated with the erythrocytes was degraded after five hours of incubation at 37 C. The degradation of the bound insulin was determined to be an intracellular property of erythrocytes. This degradation may be the mass action driving force responsible for the increased association of 125I-insulin observed after one hour of incubation. On the other hand, erythrocyte ghosts reached a steady state with 2% of the 125I-insulin bound after 1.5 hours of incubation at 37 C. More than 94% of the bound and free insulins were intact after 5 hours of incubation. These observations indicate, for the first time, that erythrocyte insulin degrading activity is localized inside the cells, not in their membranes, and that the human erythrocyte with its insulin receptors may be one of the important cell types in the metabolism of insulin.