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A flow system designed by computer-controlled discrete commutation devices is proposed for the multidetermination of metallic ions with a single chromogenic reagent. Intermittent addition of masking agents and changes of the reaction pH were exploited to implement selective determination of four species. Multidetection with an optical-fiber CCD-array spectrophotometer enabled simultaneous measurements at different wavelengths for multidetermination. The proposed system was applied to the determination of iron, copper, nickel and zinc in alloys and pharmaceutical preparations, yielding results in agreement with those obtained by flame atomic absorption spectrophotometry at the 95% confidence level. The sampling rate was estimated to be 80 determinations per hour. Coefficients of variation lower than 2% (n = 20) were achieved for all species.

Most investigations of coordinated gene expression have focused on identifying correlated expression patterns between genes by examining their normalized static expression levels. In this study, we focus on the dynamics of gene expression by seeking to identify correlated patterns of changes in genetic expression level. In doing so, we build upon methods developed in clinical informatics to detect temporal trends of laboratory and other clinical data. We construct relevance networks from Saccharomyces cerevisiae gene-expression dynamics data and find genes with related functional annotations grouped together. While some of these associations are also found using a standard expression level analysis, many are identified exclusively through the dynamic analysis. These results strongly suggest that the analysis of gene expression dynamics is a necessary and important tool for studying regulatory and other functional relationships among genes. The source code developed for this investigation is freely available to all non-commercial investigators by contacting the authors.

According to a popular hypothesis, short-term memories are stored as persistent neural activity maintained by synaptic feedback loops. This hypothesis has been formulated mathematically in a number of recurrent network models. Here we study an abstraction of these models, a single neuron with a synapse onto itself, or autapse. This abstraction cannot simulate the way in which persistent activity patterns are distributed over neural populations in the brain. However, with proper tuning of parameters, it does reproduce the continuously graded, or analog, nature of many examples of persistent activity. The conditions for tuning are derived for the dynamics of a conductance-based model neuron with a slow excitatory autapse. The derivation uses the method of averaging to approximate the spiking model with a nonspiking, reduced model. Short-term analog memory storage is possible if the reduced model is approximately linear and if its feedforward bias and autapse strength are precisely tuned.

Objective: A prospective, double-blind, randomized, controlled trial was conducted to evaluate the growth and nutritional status of preterm infants receiving preterm human milk supplemented with a newly formulated powdered human milk fortifier (HMF), study fortifier (SF), or a powdered commercial HMF (CF)., Methods: Infants (n = 144) with a birth weight

Purpose: To evaluate interleukin-6 (IL-6) levels in the conjunctival epithelium of patients with moderate to severe dry eye disease before and after treatment with cyclosporin A ophthalmic emulsion (CsA) or its vehicle., Methods: Conjunctival cytology specimens were obtained from a subset of patients enrolled in a 6-month randomized, double-masked clinical trial of the efficacy and safety of topical CsA at baseline and after 3 and 6 months of B.I.D. treatment with 0.05% cyclosporine emulsion (n = 13), 0.1% cyclosporine emulsion (n = 8), or vehicle (n = 10). RNA was extracted and a competitive reverse transcriptase polymerase chain reaction (RT-PCR) was used to evaluate the levels of mRNA encoding the inflammatory cytokine IL-6 and a housekeeping gene, G3PDH. Levels of IL-6 and G3PDH were measured and compared., Results: There was no change from baseline in the level of G3PDH after 3 or 6 months in any group. IL-6 normalized for G3PDH (IL-6/G3PDH ratio) was not different from baseline at 3 months but showed a significant decrease from baseline in the group treated with 0.05% CsA (p = 0.048) at 6 months. No significant between-group differences were noted and no correlation was observed between the change in IL-6/G3PDH and corneal fluorescein staining., Conclusions: This preliminary, small-cohort study showed a decrease in IL-6 in the conjunctival epithelium of moderate to severe dry eye patients treated with 0.05% CsA for 6 months. The observed decrease suggests that dry eye disease involves immune-mediated inflammatory processes that may be decreased by treatment with topical ophthalmic cyclosporine.

Objective: To evaluate the validity and reliability of the Ocular Surface Disease Index (OSDI) questionnaire., Methods: Participants (109 patients with dry eye and 30 normal controls) completed the OSDI, the National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25), the McMonnies Dry Eye Questionnaire, the Short Form-12 (SF-12) Health Status Questionnaire, and an ophthalmic examination including Schirmer tests, tear breakup time, and fluorescein and lissamine green staining., Results: Factor analysis identified 3 subscales of the OSDI: vision-related function, ocular symptoms, and environmental triggers. Reliability (measured by Cronbach alpha) ranged from good to excellent for the overall instrument and each subscale, and test-retest reliability was good to excellent. The OSDI was valid, effectively discriminating between normal, mild to moderate, and severe dry eye disease as defined by both physician's assessment and a composite disease severity score. The OSDI also correlated significantly with the McMonnies questionnaire, the National Eye Institute Visual Functioning Questionnaire, the physical component summary score of the Short Form-12, patient perception of symptoms, and artificial tear usage., Conclusions: The OSDI is a valid and reliable instrument for measuring the severity of dry eye disease, and it possesses the necessary psychometric properties to be used as an end point in clinical trials.

Studies of the neural correlates of short-term memory in a wide variety of brain areas have found that transient inputs can cause persistent changes in rates of action potential firing, through a mechanism that remains unknown. In a premotor area that is responsible for holding the eyes still during fixation, persistent neural firing encodes the angular position of the eyes in a characteristic manner: below a threshold position the neuron is silent, and above it the firing rate is linearly related to position. Both the threshold and linear slope vary from neuron to neuron. We have reproduced this behavior in a biophysically plausible network model. Persistence depends on precise tuning of the strength of synaptic feedback, and a relatively long synaptic time constant improves the robustness to mistuning.

Background: Wegener's granulomatosis is a systemic inflammatory disease of unknown etiology. Many studies suggest that autoimmune reactions are involved, and there is good evidence for the participation of immunocompetent cells. In that context, we examined the activation of polymorphonuclear neutrophils (PMNs) of patients with Wegener's granulomatosis., Methods: In a prospective study, the expression on the surface of PMNs of CD64 and of the major histocompatibility class II (MHC II) antigen was measured by cytofluorometry in whole blood. The expression of those antigens was correlated to disease activity., Results: Up to 15% of the peripheral PMNs of patients with active disease expressed MHC II. Follow-up studies showed that expression correlated closely with disease activity and that it decreased rapidly under immunosuppressive therapy. Expression of CD64 was seen in approximately 50% of the patients, regardless of disease activity., Conclusion: MHC II expression on PMNs might serve as a novel diagnostic marker for active disease and appears to be suitable for monitoring immunotherapy. Moreover, our data provide evidence that PMNs, which are normally MHC II negative, acquire MHC II antigens in the course of disease and may be an unrecognized function within the afferent limb of the immune response.

Background: Enhanced synthesis of extracellular matrix proteins including fibronectin (FN) is associated with the development of sclerosis. In this context we studied FN synthesis by tubular epithelial cells in response to transforming growth factor-beta (TGF-beta) and platelet-derived growth factor (PDGF)., Methods: FN protein synthesis by human tubular epithelial cells in culture (TEC) was measured by biosynthetic labeling and ELISA. Splicing of FN was assessed by RT-PCR and by Northern blotting., Results: Cultivated TEC synthesized and released FN, the majority of which was deposited as an unsoluble protein and a minor portion (10 to 15%) was released into the supernatant. TGF-beta and, to a lesser degree, PDGF, up-regulated FN synthesis. All three FN splice variants (EDA, EDB, and IIICS) were produced. PDGF did not influence the splicing. TGF-beta preferentially up-regulated the EDA splice variant, but had no effect on the splicing of the other domains., Conclusions: PDGF and TGF-beta both up-regulate FN synthesis of TEC. TGF-beta, but not PDGF, also changed the quality of the de novo synthesized FN, and thus has a different role in the development of sclerosis.

Purpose: To determine which subjective assessments and objective tests have clinical utility as diagnostic tools in ocular irritation associated with Sjögren's syndrome-related aqueous tear deficiency (ATD), non-Sjögren ATD, inflammatory meibomian gland disease (MGD) associated with rosacea, and atrophic MGD., Methods: Forty adults with ocular irritation and 10 with normal ocular surfaces were enrolled in a nonrandomized, nonblinded clinical trial. Symptoms were evaluated. Tests included biomicroscopy; evaluation of tear-film integrity, production, and clearance; fluorescein and rose bengal staining; and serum autoantibody screening., Results: Symptoms were similar among groups and most severe in the Sjögren's group. Fluorescein tear break-up time was significantly faster in the ATD and MGD groups than that in controls. Schirmer scores were significantly lower in the ATD group than those in MGD and control groups. Tear clearance was delayed in the ATD and atrophic MGD groups. Xeroscope grid distortion was noted only with ATD. The Sjögren's group had greater loss of naso-lacrimal reflex, slower fluorescein clearance, and greater ocular-surface fluorescein and rose bengal staining than did the others. More MGD subjects had meibomian gland orifice metaplasia and acinar dropout than did those with Sjögren-related ATD and controls. Schirmer scores correlated inversely with rose bengal staining, corneal fluorescein staining, and grid distortion. Rose bengal staining correlated with grid distortion and loss of nasal-lacrimal reflex, but not with MGD., Conclusion: Subjective assessments and objective diagnostic tests have clinical utility as diagnostic tools in tear-film disorders. ATD is correlated with ocular-surface disease. An algorithm summarizing the diagnostic utility of these tests is included.

Purpose: This study was designed to compare goblet cell densities and mucosal epithelial membrane mucin (MEM) expression in impression cytology specimens obtained from control subjects and patients with one of the following clinically defined diseases: aqueous tear deficiency (ATD) associated with Sjögren syndrome, ATD not associated with Sjögren syndrome, inflammatory Meibomian gland disease associated with rosacea, and Meibomian gland atrophy. These data were correlated with ocular surface rose Bengal staining scores, Schirmer scores, and HLA-DR antigen staining of conjunctival epithelial cells., Methods: Goblet cell density and MEM expression were studied by impression imprints with immunohistochemical staining using an anti-mucosal epithelial membrane mucin antibody in the temporal and inferior bulbar and inferior tarsal conjunctiva of study subjects., Results: Goblet cell density adjacent to the temporal limbus was significantly reduced at 3 mm posterior to the temporal limbus in both aqueous tear deficiency groups compared with the other groups and in patients with Sjögren syndrome compared with all other groups. In the inferior tarsus, goblet cell density was significantly reduced in patients with non-Sjögren syndrome ATD as compared with all other groups, except those with inflammatory Meibomian gland disease. Mucosal epithelial membrane mucin expression in the bulbar and tarsal conjunctiva was absent in a greater percentage of patients with Sjögren syndrome compared with all other groups. Total ocular surface rose Bengal staining scores were significantly higher in patients with Sjögren syndrome as compared with all other groups and in patients with non-Sjögren syndrome ATD as compared with control groups. Rose Bengal staining scores and Schirmer I test results (without anesthesia) were inversely correlated with bulbar, but not tarsal, conjunctival goblet cell densities, and with the absence of bulbar conjunctival MEM expression., Conclusions: These results suggest that reduced goblet cell density and mucosal epithelial cell mucin expression could explain increased rose Bengal staining in patients with aqueous tear deficiency. In addition, MEM may be regarded as a marker for normal differentiation of ocular surface epithelia, with its absence signifying the development of squamous metaplasia.

Structural analysis of the US-segment of a viable temperature sensitive human cytomegalovirus mutant (ts9) by the use of restriction enzymes, specific amplifications by the polymerase chain reaction and DNA sequencing, revealed deletions of open reading frames (orf) US14 and part of US15 in addition to that concerning US1 through US13 as reported previously [9]. It was further verified that the Hind III H-fragment and a major portion of the Hind III W-fragment were duplicated in inverted orientation. By the use of a monospecific antibody prepared against a procaryotic recombinant US11-specific product it was shown that the ts9 mutant was in fact deficient in a 30 kDa polypeptide, the gene product of orf US11.

A preconcentration procedure was established for sulphate determination in rain waters at the mg/l level, employing a small column packed with the AG1-X8 (200-400 mesh) anionic resin inserted into a flow injection system. Sulphate determination was performed by using the turbidimetric method based on reaction with barium. For concentrations within 0.10 and 2.0 MgSO(2-)(4)/l, a throughput of 50 determinations/hr was achieved, and the relative standard deviation of results was better than 2%.

The author suggests a developmental psychoanalytic frame from which to understand the clinical phenomenology of multiple personality disorder (MPD). Annihilation anxiety and fears of nonbeing are understood as central; they are seen as resulting from actual early traumatic impingements at key developmental periods. Alter "personalities" are conceptualized as functional delusional processes that serve to maintain self-cohesion. The alters are brought about through the subject's lack of capacity for illusion. Some therapeutic implications regarding a psychoanalytic stance are discussed.

We have investigated by electron microscopy the envelopment of progeny human cytomegalovirus particles and vaccinia virus particles. As host cells we used primary human foreskin fibroblasts, in which both viruses replicate, and also AtT20 cells in which vaccinia virus, but not human cytomegalovirus, replicates. As we show here, primary human foreskin fibroblasts contain tubular early endosomes like those in AtT20 cells and many other cells in culture. Our aim was to ascertain whether or not the cisternae which wrap the maturing progeny viral particles are related to tubular endosomes. When infected cells were incubated with the fluid phase endocytic tracer horseradish peroxidase (HRP) at appropriate times after infection (5-8 h post vaccinia infection and 72 h or 96 h post cytomegalovirus infection), we found that many of the partially or fully enveloped vaccinia and human cytomegalovirus particles in the cytoplasm had HRP reaction product in the lumen of their cisternal envelope. Examination of single and serial sections indicated that the cisternal envelopes of the progeny virions were derived from tubular endosomes. Pulse-chase experiments with HRP showed that the viral particles with envelopes derived from tubular endosomes were not directed to late endosomes and autophagic digestion but were released from the cells. Experiments with Brefeldin A established that the envelopment of viral particles by endosomal cisternae proceeded for at least 2 h in the absence of a Golgi apparatus. Our data indicate that vaccinia virus and human cytomegalovirus (and presumably other pox and herpes viruses) have evolved to utilize early endocytic compartments to achieve their egress from host cells. We also found that in cells infected by vaccinia virus the delivery of the endocytic tracer to the Golgi apparatus is greatly enhanced over that in controls or cells infected with human cytomegalovirus. The cytopathic effects of vaccinia virus therefore include perturbation of membrane traffic between endocytic and exocytic compartments.

We report a clinical case of a woman, 56 years old, with a history of duodenal ulcer and esophagitis, under medication with H2 receptors blockers during 3 years. Plasma basal gastrin was near normal levels. A stimulation test with secretin was compatible with gastrinoma. CT scan and selective angiography didn't localize the tumor. At laparotomy we found a pyloric nodule that prove to be the gastrinoma. Eighteen months after surgery the patient is asymptomatic and with a normal endoscopic examination and secretin stimulation test.

Objectives of this study were to quantitate metabolite fluxes in ruminant liver and to delineate effects of recombinant bST on patterns of nutrient metabolism by liver. Nineteen multiparous cows ranging in previous lactational performance from 6400 to 13,500 kg per 305-d lactation were treated with either placebo or bST (40 mg/d) from wk 11 to 18 of lactation. Liver tissue was collected at slaughter. Tissue slices were incubated with various 14C-labeled substrates, and rates of conversion of label to CO2 and metabolites were measured. In vivo recombinant bST treatment increased in vitro conversion of [1-14C]propionate and [2-14C]acetate to glucose more than twofold. At 2.5 mM propionate, bST-treated cows converted propionate to glucose at 90% efficiency. Recombinant bST increased [14C]bicarbonate incorporation into glucose five-fold. Overall, bST treatment resulted in greater C flow from propionate and acetate through the TCA cycle. Acetate had only small effects on propionate metabolism and no effects on lactate plus pyruvate metabolism. Unexpectedly, propionate decreased acetate conversion to ketone bodies. Suggested mechanisms for this observation include depletion of coenzyme A and allosteric regulation of carnitine palmitoyltransferase I by methylmalonyl-coenzyme A formed from propionate. In summary, bST treatment resulted in increased rates of gluconeogenesis and oxidation in liver in support of lactation.

Infected cell proteins immunoprecipitated from human cytomegalovirus (HCMV)-infected fibroblasts with glycoprotein H (gH)-specific conformation-dependent monoclonal antibody (mab 14-4 b) were found to consist of three components of 86 kDa, 89 kDa, and 125 kDa (gp 86, 89, and 125). Affinity purified antibodies from human convalescent serum reactive with an NH2-terminal epitope of gH recognized three polypeptides of comparable size in immunoblots, suggesting antigenic relatedness of these three components of the gH-complex. Using subcellular fractions for immunoblotting, gp 86 was identified as an endoglycosidase H (endo H)-sensitive gH-form present in the nuclear fraction whereas gp 89 and gp 125 were endo H-resistant and present in the membrane fraction or in virions. Incomplete endo H-digestion suggested that four of six predicted N-glycosylation sites of the gH molecule were occupied by carbohydrate side chains. Analysis under nonreducing conditions revealed that the compartmentalized as well as virion-associated gH analogs form high molecular weight complexes. The relation of the recognized gH analogs to the processing pathway of gH is discussed.

Studies of mammary arteriovenous difference were conducted on multiparous lactating Holstein cows (n = 21) on d 35, 70, 105, and 126 of lactation to examine kinetic relationships between arterial concentration and mammary gland extraction of AA. Additionally, these cows were paired by previous lactational performance and assigned to bST-treated or control groups to examine the effect of bST treatment on AA concentration and extraction by lactating mammary glands. Treated cows were injected daily with 40 mg of recombinant bST from d 71 through 126 of lactation. Arterial concentrations of Asp, Ser, Asn, Gly, beta-aminoisobutyrate, and Met were increased. Concentrations of Val, Ile, Leu, Phe, Orn, and Lys were decreased in bST-treated cows compared with controls. Increased extractions of Asp and Met by mammary glands in treated versus control cows were correlated positively with treatment-induced changes in arterial concentrations of these AA. However, increased mammary extractions of Arg, cystathionine, Leu, and Lys by bST-treated compared with control cows were not correlated with bST-induced changes in arterial concentrations of these AA. Extractions of Asn, His, Thr, Arg, Tyr, Met, cystathionine, cystine, Ile, Phe, Orn, Glu, Gly, Tau, Cit, Leu, and Val were correlated linearly with arterial concentrations (r2 greater than .15) of each AA. Extractions of Asp, Glu, Ser, Asn, Gly, Gln, Tau, His, Cit, Thr, Pro, Tyr, Val, cystine, Ile, Leu, Trp, Orn, and Lys also were correlated with arteriovenous differences of Met.

Twenty-one multiparous lactating dairy cows with previous 305-d milk production records varying from 5900 to 13,600 kg were used to investigate effects of bST administration and stage of lactation on nutrient plasma arterial concentrations and arterial-venous differences across the mammary glands (uptake). On d 71 and continuing until d 126 of lactation, cows were injected with 40 mg of sometribove (bST group) or bicarbonate buffer (placebo group). Arterial and venous blood plasma samples were collected over a 12-h period on d 35, 70, 105, and 126 of lactation. Plasma concentration of glucose was 7% higher in midlactation compared with early lactation cows. Plasma concentration of acetate decreased from 2.11 to 1.87 mM in placebo versus bST-treated cows. Plasma arterial concentration and uptake of D-beta-hydroxybutyrate were .52 and .18 mM higher, respectively, in early versus midlactation cows. Concentration and uptake of NEFA were elevated in both early lactation and bST-treated cows. Triacylglyceride concentrations were 24 and 19% lower in early lactation and bST-treated cows compared with midlactation cows receiving placebo. Likewise, uptake of triacylglyceride was reduced in early lactation and with bST treatment compared with midlactation. The mediation of nutrient delivery and uptake by the mammary gland appears to be markedly similar between early lactation and bST-treated cows, suggesting a similarity between these physiological states and the homeostatic and homeorhetic mechanisms regulating nutrient partitioning in the lactating dairy cow. In early compared with midlactation cows receiving placebo, uptakes of D-beta-hydroxybutyrate and NEFA were reduced, and triacylglyceride uptake increased.

Twenty-one multiparous lactating dairy cows with previous 305-d milk production records varying from 5900 to 13,600 kg were used to examine patterns of nutrient uptake by the mammary glands. On d 71 and continuing until d 126 of lactation, animals were injected daily with 40 mg of sometribove (bST group) or bicarbonate buffer (control group). Arterial and venous blood plasma samples were collected over a 12-h period on d 35, 70, 105, and 126 of lactation. Regression equations developed to evaluate linear effects of plasma arterial concentrations on net arterial-venous difference across the mammary glands demonstrated that, for acetate, NEFA, and D-beta-hydroxybutyrate, plasma arterial concentration accounted for over 50% of variation in uptake by the mammary glands. Additionally, a sigmoidal equation fitted the relationship between D-beta-hydroxybutyrate plasma arterial concentration and mammary gland uptake (r2 = .70). Triacylglyceride concentration was less effective in predicting uptake (r2 = .25). Administration of bST did not alter patterns of nutrient uptake, but a fourfold increase in NEFA uptake was predicted for bST-treated cows from this study, using NEFA concentrations from the literature. These observations indicate that plasma concentrations of acetate, NEFA, D-beta-hydroxybutyrate, and triacylglyceride are major determinants of uptake by the mammary glands. Factors other than plasma concentration, such as mammary gland biosynthetic capacity, availability of other nutrients, and blood flow, determine uptakes of glucose, lactate, and total and free cholesterol (r2 less than or equal to .03).

The objective of the experiment was to determine the contribution of red blood cells to transport of individual amino acids to lactating bovine mammary glands. Blood samples were collected from coccygeal and subcutaneous abdominal veins of 21 lactating Holstein cows on d 35, 70, 105, and 126 of lactation. Samples were collected every 20 min for 12 h. Subsamples of whole blood and plasma were pooled by hour and day. Hourly plasma samples and daily whole blood and plasma samples were analyzed for amino acid concentration. Plasma glutamate concentration was stable throughout the 12-h collection period, indicating that sample collection did not perturb amino acid homeostasis. Therefore, data from pooled daily samples were used for subsequent comparisons. Whole blood arteriovenous differences of phosphoserine, aspartate, glutamate, hydroxyproline, phosphoethanolamine, serine, asparagine, glycine, glutamine, taurine, histidine, citrulline, threonine, alanine, beta-aminoisobutyrate, carnosine, arginine, proline, alpha-aminobutyrate, tyrosine, valine, methionine, cystine, isoleucine, leucine, phenylalanine, tryptophan, ornithine, and lysine differed significantly from plasma arteriovenous differences. Uptakes of individual amino acids from plasma were poorly correlated with uptake from whole blood. These data clearly indicate that uptake data derived from plasma do not adequately represent whole blood amino acid uptake.

We have demonstrated that the zinc (Zn) concentration of mouse milk declines significantly over the lactation period. Pups radiolabeled in utero with 65Zn were forward-fostered (FF) to nonradiolabeled dams at a later stage of lactation to study the effects of early milk deprivation. Other groups of radiolabeled pups were back-fostered at 5, 10 and 15 days of age to a nonradiolabeled dam who had just given birth; this provided additional colostrum during the suckling period. Litters fostered at birth to an unlabeled dam at d 0 of lactation were used as controls. Weight gain of FF litters decreased and signs of Zn deficiency increased as the foster dam's days of lactation increased. The Zn concentration of kidney, brain and plasma tended to decrease with increasing lactation days of the foster dam. Tibia Zn concentration declined progressively as the lactation days of the foster dam increased, and the concentration of calcium also was lower in all three groups of FF litters than in controls, indicating that bone calcification may have been impaired. Kinetic data proved to be a more sensitive index of Zn status than tissue Zn concentration. The biological half-life of whole-body 65Zn for FF suckling mice increased in a linear fashion with increasing lactation days of the foster dam; whole-body retention of 65Zn for back-fostered litters did not differ from that for controls. Brain, small intestine, kidney muscle, plasma and tibia of pups FF to late-lactating dams seemed to have greater retention of Zn than did controls. Thus, deprivation of early milk impaired growth and development of the mouse neonate despite some ability to conserve Zn.

We studied changes in the mineral composition of milk of lactating Swiss-Webster mice and the relationship of those changes to mineral metabolism of suckling mouse pups. Concentrations of Zn, Cu, Mg and Ca were analyzed in maternal and neonatal tissues and in milk; Zn metabolism was studied using 65Zn. Although Cu, Ca and Mg concentrations in milk declined during the first 2 d of lactation, only the concentration of Zn decreased progressively throughout 30 d. Various pup tissues were characterized by developmental changes in concentrations of some elements. Turnover of Zn in neonatal tissues was studied by radiolabeling litters in utero and fostering them at birth to nonradiolabeled lactating dams. The turnover of whole-body 65Zn in suckling mice decreased during development, and, at 20 d of age, the biological half-life of 65Zn in the neonate was approximately the same as for a nonpregnant, nonlactating adult female (20 d). The decreased turnover of 65Zn in lactating dams that characterized progressive lactation and was reflected in the Zn concentration of milk is in agreement with changes in whole-body 65Zn turnover observed for the suckling mouse. These findings demonstrate that the metabolism of the suckling neonate is directly related to longitudinal changes in the composition of maternal milk.

Since large volumes of nutrient rich amniotic fluid are swallowed by the fetus, it has been suggested that intestinal digestion and absorption contribute significantly to fetal nutrition. To see if nutrients are being gained across the intestine, we measured blood flow and intestinal arteriovenous concentration differences of glucose, alpha-amino nitrogen, lactate, fructose and oxygen in eleven third trimester fetal sheep with chronically implanted vascular catheters. We found that in fetal blood circulating through the intestine nutrient concentration decreased significantly with arterio-venous concentration differences for glucose of 0.78 +/- 0.21 (SEM) mg/dl (P < 0.002), for alpha-amino nitrogen of 0.52 +/- 0.15 mg/dl (P < 0.005), for lactate of 0.68 +/- 0.24 mg/dl (P < 0.05) and for oxygen of 1.50 +/- 0.08 ml/dl (P < 0.001). Fructose concentration did not change. Blood flow to the fetal intestine averaged 89.92 +/- 7.16 ml/min and the intestine consumed 0.74 +/- 0.24 mg of glucose, 0.43 +/- 0.17 mg of alpha-amino nitrogen, 0.83 +/- 0.28 mg of lactate and 1.37 +/- 0.14 ml of oxygen per minute. Compared to previously published values for the umbilical uptake of nutrients the fetal intestine metabolizes about 4% of the glucose, 6% of the alpha-amino nitrogen, 13% of the lactate and 6% of the oxygen obtained across the umbilical circulation. Intestinal absorption does not appear to serve as a source of simple nutrients for the rest of the fetus, in fact intestinal metabolism extracts significant amounts of nutrients from fetal blood.

A previous study resulted in the discovery of a unique, undesignated strain of mice, referred to as SM (Super Mouse), whose progeny exhibited a resistance to dietary zinc deficiency when pups from the strain suckled dams fed a zinc-deficient diet. Examination of the zinc metabolism in these mice demonstrated in the study reported here that SM mice accumulated significantly more zinc during in utero development than do mice of other strains. Adult mice of the SM strain contained significantly more bone zinc than did mice of other strains. Adult SM mice excreted significantly less 65Zn than did mice of other strains when the mice were fed a zinc-deficient diet. These observations suggest that SM mice are able to resist periods of zinc-deficiency as a result of the development of highly efficient systems for storing and reabsorbing zinc.

The turnover of 65Zn was examined in mice. During pregnancy, lactation, and growth, the loss of 65Zn from the body was twice as great as that observed in mature, nonpregnant animals. The results of this study emphasize the need for consideration of zinc losses in the formulation of the minimum daily requirement for zinc in humans and other mammalian species.

Zinc metabolism of adult female C57BL/6J mice varying in age and reproductive status was studied using 65Zn. Animals were injected intraperitoneally with isotope, and whole-body and tissue turnover of 65Zn was measured. Biological half-life of whole-body 65Zn for pregnant females was 129% of that for nonpregnant, nonlactating females of similar age (25.7 and 20.0 d, respectively). Conversely, the half-life of zinc was less for lactating (11.1 d) and aged (15.3 d) females than for either pregnant or nonpregnant, nonlactating young adult females. Retention of 65Zn was generally lower for all tissues of pregnant and lactating dams than for nonpregnant, nonlactating females except for brain and tibia. In aged females, specific activity at 20 d postinjection did not differ from that of nonpregnant, nonlactating young adult females for any tissue except bone. While specific activity of tibia increased during pregnancy and lactation, it was lower in aged females than in nonpregnant, nonlactating young adult females. Increased organ content of zinc resulted from changes in zinc concentration or in organ mass or both, and was supported by increased food intake. Thus, greater food intake for these groups than for young adult females contributed to the higher turnover of tissue 65Zn. Differences in concentrations of Cu, Ca and Mg were also observed among groups for some tissues; the significance of these differences and their relationship to zinc metabolism are not clear.