Rapid identification and antimicrobial susceptibility testing of Gram-negative rod on positive blood cultures using MicroScan panels.

Shortening the turnaround time of antimicrobial susceptibility testing (AST) of bacteria permits a significant reduction of patient morbidity, mortality, and cost. Conventional blood culture methods are the gold standard diagnostic test to guide management of patient with sepsis, but the conventional process requires at least 12 to 24 h after the blood culture has been flagged as positive due to requirement for pure colonies. We describe a simple and inexpensive method to obtain faster AST with MicroScan system (Beckman Coulter) directly from positive blood cultures. Conventional and direct identification and AST were performed simultaneously by both methods in 1070 blood cultures, and 9106 MICs were determinated. About 96.5% were correctly identified with the direct method. Overall, categorical agreement was 92.86%. We found 46 very major errors, but globally the results showed a good correlation with the standard method, particularly favorable for E. coli and K. pneumoniae, except amoxicillin-clavulanate and piperacillin-tazobactam. For P. mirabilis, betalactams antibiotics (except second- and third-generation cephalosporines) showed a good correlation, and also a good correlation was found for ciprofloxacine and gentamicine in P. aeruginosa and amoxicillin-clavulanate, ciprofloxacine, gentamicine, and cotrimoxazole in E. cloacae. This method has the main advantage of providing reliable results 1 day earlier, being a simple, fast, and cheap method for identification and antimicrobial susceptibility testing results from positive blood cultures.

Intra- and inter-observer variability in intracranial aneurysm segmentation: comparison between CT angiography (semi-automated segmentation software stroke VCAR) and digital subtraction angiography (3D rotational angiography).

PURPOSE: To compare size and morphologic features of three-dimensional aneurysm models, obtained with a semi-automated segmentation software (Stroke VCAR, GE, USA) from cerebral CT angiography (CTA) data, to three-dimensional aneurysm models obtained with digital subtraction angiography (DSA, with 3D rotational angiography acquisition-3DRA), considered as the reference standard. METHODS: In this retrospective study, we reviewed 132 patients, with a total number of 137 intracranial aneurysm, who underwent CTA and subsequent DSA examination, supplemented with 3DRA. We compared neck length, short axis and long axis measured on 3DRA model to the same variables measured on 3D-CTA model by two blinded readers and to the automatic software dimensions. Therefore, statistics analysis assessed intra-observer and inter-observer variability and differences between patients with or without subarachnoid hemorrhage (SAH). RESULTS: There were no significant differences in short-axis and long-axis measurements between 3D angiographic and 3D-CTA models, while comparison of neck lengths revealed a statistically significant difference, which tended to be greater for smaller neck lengths (partial volume effect and "kissing vessels" artifact). There were significant differences between manual and automatic data measured for the same three variables, and the presence of SAH did not affect aneurysm 3D reconstruction. Inter-observer agreement resulted moderate for neck length and substantial for short axis and long axis. CONCLUSION: The examined 3D-CTA segmentation system is a reproducible procedure for aneurysm morphologic characterization and, in particular, for assessment of aneurysm sac dimensions, but considerable carefulness is required in neck length interpretation.

Brain morphometry of preschool age children affected by autism spectrum disorder: Correlation with clinical findings.

The aim of our study was to use a combined imaging and clinical approach to identify possible patterns of clinical and imaging findings in a cohort of preschool age autism spectrum disorder (ASD) patients. In order to identify imaging patterns that could be related to specific clinical features, a selected group of ASD patients (age range 3-6 years) without dysmorphic features, epilepsy or other major neurological signs, malformations or other lesions at MRI was subjected to brain volumetric analysis using semiautomatic brain segmentation. An age-matched group of typically developing children was subjected to the same analysis. Our results were consistent with previous literature: Total gray matter volume, total cortical gray matter volume and amygdalar volumes were significantly greater in the ASD group than the control group. When we divided the study group into subgroups on the basis of clinical findings such as high- or low-functioning, or verbal and nonverbal, the only significant difference between verbal and nonverbal subjects was in cerebellar hemispheric size. In conclusions, our results confirm that newer brain MRI techniques using semiautomatic brain segmentation can provide information useful for defining the differences between ASD patients and controls, particularly if they form part of an integrated approach between MRI and cognitive-behavioral and genetic data. Clin. Anat. 32:143-150, 2019. © 2018 Wiley Periodicals, Inc. HIGHLIGHTS: Combined imaging and clinical approach in autism spectrum disorders Semiautomatic brain segmentation in a selected preschool age ASD group Reduced total cerebellar white matter volume in non-verbal ASD patients.

Outcome of radiosurgery treatment with a linear accelerator in patients with trigeminal neuralgia. / Resultados de la aplicación de radiocirugía con acelerador lineal en pacientes con neuralgia del trigémino.

INTRODUCTION: An overview of the effectiveness of radiosurgery in patients diagnosed with trigeminal neuralgia with an analysis of potential predictors of good outcome. METHODS: All patients treated with linear accelerator radiosurgery between 2004 and 2011 were analysed. A dose of 60Gy dose was administered 1 to 2mm from the root entry zone with a maximum isodose of 20% delivered to the brainstem. Clinical results for pain control and any side effects were analysed at 12 and 36 months (BNI score). RESULTS: The study included 71 patients (mean follow-up 50.5 months). Pain improvement at 12 months was observed in 68.11% of the total (28.98% with BNI score i-ii; 39.12% with BNI score iii) and at 36 months in 58.21% (23.88% BNI score i-ii; 34.32% BNI score iii). Average recovery time was 3.69 months and the relapse rate was 44.68%. Patients with typical pain displayed statistically significant differences in improvement rates at 12 and at 36 months (P<047 and P<.002). Onset of improvement was analysed using Kaplan-Meyer plots. Statistically significant differences were observed between patients with typical and atypical pain at 36 months (P<.012) in Kaplan-Meyer plots. Side effects were recorded in 15 patients (20.89%), including 9 cases of facial numbness (13.43%); only 2 cases were clinically relevant (2.98%). CONCLUSION: According to our results, radiosurgery is an effective treatment for trigeminal neuralgia, with few side effects. Typical pain seems to be a good predictor of pain relief.

Obesity and female sexual dysfunctions: A systematic review of prevalence with meta-analysis.

Obesity represents a major global health challenge. Female sexual dysfunctions have a negative impact on quality of life and overall health balance. A higher rate of female sexual dysfunctions in obese women has been suggested. This systematic review summarized the literature on female sexual dysfunction prevalence in obese women. The review was registered (Open Science Framework OSF.IO/7CG95) and a literature search without language restrictions was conducted in PubMed, Embase and Web of Science, from January 1990 to December 2021. Cross-sectional and intervention studies were included, the latter if they provided female sexual dysfunction rate data in obese women prior to the intervention. For inclusion, studies should have used the female sexual function index or its simplified version. Study quality was assessed to evaluate if female sexual function index was properly applied using six items. Rates of female sexual dysfunctions examining for differences between obese vs class III obese and high vs low quality subgroups were summarized. Random effects meta-analysis was performed, calculating 95% confidence intervals (CI) and examining heterogeneity with I2 statistic. Publication bias was evaluated with funnel plot. There were 15 relevant studies (1720 women participants in total with 153 obese and 1567 class III obese women). Of these, 8 (53.3%) studies complied with >4 quality items. Overall prevalence of female sexual dysfunctions was 62% (95% CI 55-68%; I2 85.5%). Among obese women the prevalence was 69% (95% CI 55-80%; I2 73.8%) vs 59% (95% CI 52-66%; I2 87.5%) among those class III obese (subgroup difference p=0.15). Among high quality studies the prevalence was 54% (95% CI 50-60%; I2 46.8%) vs 72% (95% CI 61-81%; I2 88.0%) among low quality studies (subgroup difference p=0.002). There was no funnel asymmetry. We interpreted that the rate of sexual dysfunctions is high in obese and class III obese women. Obesity should be regarded as a risk factor for female sexual dysfunctions.

Definition of T cell idiotypes using anti-idiotypic antisera produced by immunization with T cell clones.

Alloreactive T cell clones with distinct specificities were used to raise anti-idiotypic antisera via an F1 anti-(parent anti-F1) protocol. Antisera were raised that could stimulate the proliferation of the appropriate T cell clone, but not other clones. The active fraction of the antisera for T cell proliferation was immunoglobulin. In addition to proliferation, an anti-idiotypic antiserum could induce the appropriate T cell clone to secrete substantial amounts of interleukin 2 (IL-2). Production of IL-2 appeared independent of the involvement of accessory cells. These accessory cells may be unnecessary for IL-2 production in our assay, or their effect may be produced by anti-idiotype. Thus, anti-idiotype may provide two or more specific T cell signals.

T cell clones reactive with sperm whale myoglobin. Isolation of clones with specificity for individual determinants on myoglobin.

We have been able to isolate clones of sperm whale muscle myoglobin (Mb)-reactive T cells from (C57BL/6 x A/J)F1 [(B6A)F1] mice. Four types of clones were isolated, distinguished by their patterns of recognition of Mb cyanogen bromide (CNBr) fragments and antigen presenting cell (APC) requirements. Individual T cell clones proliferated in response to one of three CNBr fragments of Mb. Dose-response curves of all clones were identical for native Mb and the appropriate fragment. T cell clones reactive to fragment 1-55 did not proliferate in response to peptide 15-22 (a peptide that binds to serum antibody directed against 1-55). These data support previous findings suggesting differences between antigen recognition by T and B cells, i.e., T cells may not recognize antigen in its native conformation and/or T and B cells may recognize distinct epitopes on the same antigen. Using T cell clones to analyze genetic control of responsiveness to Mb, we found that certain (B6A)F1 T cells recognize Mb presented by low responder strain APC. Thus, genetically determined low responsiveness in this case is probably not due to failure of APC function. We also found that responsiveness to certain Mb epitopes mapped to the I-A subregion whereas others mapped, via gene complementation, to the I-A and I-E subregions. We found no examples of responsiveness mapping to the I-C subregion and suggest an alternative explanation for previous reports mapping genetic control of responsiveness to certain Mb determinants to I-C.

Multiple functional sites on a single Ia molecule defined using T cell clones and antibodies with chain-determined specificity.

Monoclonal antibodies (mAb) were used to inhibit the proliferation of antigen-reactive (C57BL6/J X A/J)F1 restricted T cell clones. We have been able to subdivide these F1 restricted T cell clones into two groups: one of which recognizes the A alpha k A beta b molecule and the other group which recognizes the A alpha b A beta k molecule. Using clones with defined reactivities, we could assign the reactivities of monoclonals to the A alpha or A beta chains. By immunoprecipitation and two-dimensional analysis of Ia molecules from F1 spleen cells, we could independently map the reactivities of the mAb as being determined by the A alpha or A beta chain. To date, these two methods of chain localization of the antibody reactivity have agreed. Further, the differential blocking of the A alpha k A beta b restricted T cell clones suggests that there exists more than one restriction site per Ia molecule. Increasing the number of possible functional Ia restriction sites, either through combinatorial association of alpha and beta chains or by using more than one site per molecule, should increase the number of ways Ia molecules can function in antigen presentation.

T cell clones specific for hybrid I-A molecules. Discrimination with monoclonal anti-I-Ak antibodies.

Alloreactive and soluble antigen-reactive, I-A-restricted T cell clones were examined for their ability to recognize hybrid I-A antigens. Several clones that recognized hybrid I-A(b)/I-A(k) molecules on (C57BL/6 x A/J)F(1) [(B6A)F(1)] spleen cells were studied. We were able to distinguish clones that recognized hybrid I-A molecules of the A(b)(a)A(k)(beta) type from those that recognized A(k)(a)A(b)(beta) molecules. We reached this conclusion by considering data from three independent types of experiments. (a) Monoclonal antibodies were used to inhibit T cell stimulation. Antibodies 10.2.16 and H116.32 distinguished two mutually exclusive "families" of T cell clones. One group of clones was inhibited by 10-2.16 and not H116.32, the other group exhibited reciprocal inhibition. (b) T cell proliferation was assayed using antigen-presenting cells from B6.C-H-2(bml2) (bml2) and [bml2 x B10.A(4R)]F(1) mice. Because the bml2 strain has a mutation that results in an altered A(b)(beta) polypeptide chain (A(bm12)(beta)), we reasoned that clones that could recognize the [bm12 x B 10.A(4R)]F(1) cells were recognizing A(b)(a)A(k)(beta) molecules. Alternatively, clones not recognizing [bml2 x B10.A(4R)]F(1) cells had specificity for A(k)(a)A(b)(beta) molecules. (c) I-A molecules immunoprecipitated from radiolabeled (B6A)F(1) splenocyte extracts were analyzed by two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis. These experiments confirmed an earlier report that antibody 10.2.16 recognized determinants on the A(k)(beta) chain (12). Antibody H116.32 immunoprecipitated products consistent with recognition of A(k)(a) determinants. Taken together, these three types of results offer conclusive evidence that T cell clones recognizing "hybrid" I-A molecules use either A(b(k)A(k)(beta) or A(k)(a)A(b)(beta) molecules as recognition or restriction sites. Clones whose proliferation was supported by [bm 12 x B10.A(4R)]F(1) cells and blocked by anti-I-A(k) antibody 10-2.16 recognized A(b)(a)A(k)(beta) B molecules. Clones that were blocked by antibody H116.32 and did not recognize [bml2 X B10.A(4R)]F(1) cells use a recognition site(s) on A(b)(a)A(k)(beta) molecules. Thus, we can demonstrate both functionally and biochemically that hybrid F(1) I-A molecules of the structure A(k)(a)A(b)(beta) and A(b)(a)A(k)(beta) both exist on (B6A)F(1) splenocytes and that both configurations are used in immune recognition phenomena.

Major histocompatibility complex-restricted antigen presentation to antigen-reactive T cells by B lymphocyte tumor cells.

Previous reports have demonstrated that accessory cells function to present soluble protein antigens in association with gene products encoded within the I region of the major histocompatibility complex (MHC) to antigen-reactive T helper cells. The biochemical events that occur during antigen presentation are, however, not well-documented primarily because of the difficulties involved in purifying sufficient numbers of homogeneous antigen-presenting cells. In this paper, a number of Ia-positive B lymphocyte tumor lines are shown to be capable of presenting soluble protein antigens to antigen-reactive continuous T cell lines in an MHC-restricted fashion. The characterization of the antigen presentation function of these tumor cells indicates that the tumor cells have many of the functional antigen-presenting characteristics previously thought to be limited to macrophages. These tumor cells should provide a useful model system for determining the biochemical events that occur in antigen uptake and processing as well as for determining the potential interactions between processed antigen and Ia molecules on the plasma membrane of these antigen-presenting cells.

[Design and validation of the second edition of the Women's Sexual Function Questionnaire, FSM-2]. / Diseño y validación de la segunda edición del Cuestionario de Función Sexual de la Mujer, FSM-2.

OBJECTIVE: To design and validate the second edition of the Female Sexual Function questionnaire (FSF-2). MATERIAL AND METHODS: A cross-sectional and multicentre study was conducted on 187 women (18-70 years) who completed a test (preliminary questionnaire FSF-2), and then answered a structured anamnesis on female sexual function. Four weeks later they completed a retest, which was equal to the test but with an additional question about possible influence of recent events in their sex life. RESULTS: The mean age of the women was 43.51 years. Internal consistency of the questionnaire: Cronbach's α of the 0.919 test, of structured anamnesis 0.921, of the 0.920 retest. Test-retest reliability: mean test scores 30.53 ± 8.605, retest 30.05 ± 8.770, without significant differences. Correlation between total test and retest scores (intraclass correlation coefficient) 0.960, significant (P<.01); between total test scores and structured anamnesis 0.977, significant (P<.01). Concordance between test questions and structured anamnesis (kappa index), minimum 0.706, maximum 0.915; between test and retest questions, minimum 0.630, maximum 0.802. Content validity by expert consensus. Criteria validity: specificity of the questionnaire exceeding 90% for all items/domains, sensitivity greater than 80%, except for items 5, 6, 9 (70-80%). Validity of the construct through factor analysis, grouping of items into 2 components (they explain 66.586% of variance). CONCLUSIONS: The FSF-2 questionnaire is reliable and valid. It evaluates the sexual response of women, describing important aspects of their sexual activity as a couple: anticipatory anxiety, initiative, confidence to communicate, preferences and events that may influence. It can detect sexual dysfunction in the couple.

Complete covalent structure of a human IgA1 immunoglobulin.

The complete covalent structure has been determined for a human myeloma IgA1 immunoglobulin. This protein has unique features in the amino acid sequence and disulfide bridge structure of the variable (V) and constant (C) regions of both the alpha heavy and the lambda light chains, and in the number and loci of oligosaccharides. Whereas C region domains of heavy chains have evolved independently over eons, recent isotypic variations have occured in lambda light chains and possibly in alpha heavy chains.

Brain DSC MR Perfusion in Children: A Clinical Feasibility Study Using Different Technical Standards of Contrast Administration.

BACKGROUND AND PURPOSE: Dynamic susceptibility contrast MR perfusion imaging has limited results in children due to difficulties in reproducing technical standards derived from adults. This prospective, multicenter study aimed to determine DSC feasibility and quality in children using custom administration of a standard dose of gadolinium. MATERIALS AND METHODS: Eighty-three consecutive children with brain tumors underwent DSC perfusion with a standard dose of gadobutrol administered by an automated power injector. The location and size of intravenous catheters and gadobutrol volume and flow rates were reported, and local and/or systemic adverse effects were recorded. DSC was qualitatively evaluated by CBV maps and signal intensity-time curves and quantitatively by the percentage of signal drop and full width at half-maximum, and the data were compared with the standards reported for adults. Quantitative data were grouped by flow rate, and differences among groups were assessed by analysis of covariance and tested for statistical significance with a t test. RESULTS: No local or systemic adverse events were recorded independent of catheter location (63 arm, 14 hand, 6 foot), size (24-18 ga), and flow rates (1-5 mL/s). High-quality CBV maps and signal intensity-time curves were achieved in all patients, and quantitative evaluations were equal or superior to those reported for adults. No significant differences (P ≥ .05) were identified among the higher-flow-rate groups in the quantitative data. CONCLUSIONS: A custom administration of a standard dose of gadobutrol allows safe and high-quality DSC MR perfusion imaging in children.

Usefulness of automated breast volume scanner (ABVS) for monitoring tumor response to neoadjuvant treatment in breast cancer patients: preliminary results.

OBJECTIVE: We investigated the accuracy of Automated Breast Volume Scanner (ABVS) compared to handheld ultrasound (HHUS) for monitoring tumor response to neoadjuvant treatment (NAT) in breast cancer (BC). PATIENTS AND METHODS: All the patients submitted to biopsy in our Institution, from January 2017 to May 2017, proven invasive BC and eligible for NAT, were enrolled in this prospective study. The participants underwent ABVS, HHUS, dynamic contrast-enhanced Magnetic Resonance Imaging (DCE-MRI) and mammography at the beginning of NAT and ABVS, HHUS and DCE-MRI at the halfway point of therapy and before the surgery. DCE-MRI was considered the standard of reference. Two breast radiologists (R1, R2), with fifteen and five years of experience in breast imaging, independently assigned a visibility score (ordinal 5-point scale) to ABVS, HHUS, and DCE-MRI. Diagnostic performance of ABVS and HHUS as measured by sensitivity, specificity, positive and negative predictive values (PPV and NPV) was calculated. Correlations between ABVS and MRI, and between HHUS and MRI were analyzed using Pearson's correlation test. RESULTS: A total of 21 patients were enrolled. 189 examinations were performed. The comparison between ABVS and DCE-MRI was similar for the both readers: ABVS had a sensitivity of 63,16%, specificity of 83,58%, PPV of 76,60%, NPV of 72,73%, accuracy of 74,19% (R1) and a sensitivity of 54.54%, specificity of 85.51%, PPV of 75%, NPV of 70,24%, accuracy of 71.77% (R2). The comparison between HHUS and DCE-MRI showed that HHUS had a sensitivity of 63,16 %, specificity of 83,58%, PPV of 76,60%, NPV of 72,73%, accuracy of 74,19% (R1) and a sensitivity of 36.84%, specificity of 85.07%, PPV of 67.74%, NPV of 61.29%, accuracy of 62.90% (R2). The calculated Pearson's correlation coefficient r values were 7.8 for HHUS vs. DCE-MRI and 28.5 for ABVS vs. DCE-MRI (R1) and 7.8 for HHUS vs. DCE-MRI and 22.4 for ABVS vs. DCE-MRI (R2). Statistical significance of ABVS and HHUS was p < 0.0001 and 0.005 < p < 0.01, respectively (R1, R2). CONCLUSIONS: DCE-MRI is recommended for the tumor response assessment. ABVS, a product of the biotechnology development, providing reproducible images, in addition to DCE-MRI, can be a potentially useful tool for the monitoring of response to NAT.

Critical analysis of major and ancillary features of LI-RADS v2018 in the differentiation of small (≤ 2 cm) hepatocellular carcinoma from dysplastic nodules with gadobenate dimeglumine-enhanced magnetic resonance imaging.

OBJECTIVE: To evaluate the performance of major features, ancillary features, and categories of Liver Imaging Reporting and Data System (LI-RADS) version 2018 at magnetic resonance (MR) imaging in the differentiation of small hepatocellular carcinoma (HCC) from dysplastic nodules (DNs). PATIENTS AND METHODS: This retrospective study included cirrhotic patients with pathologically proven untreated HCCs and DNs (≤ 2 cm) and liver MR imaging performed with gadobenate dimeglumine contrast agent within 3 months before pathological analysis, between 2015 and 2018. 37 patients with 43 observations (17 HCCs and 26 DNs) met the inclusion criteria. Two radiologists assessed major and ancillary imaging features for each liver observation and assigned a LI-RADS v2018 category in consensus. Estimates of diagnostic performance of major features, ancillary features, and LI-RADS categories were assessed based on their sensitivity, specificity, positive (PPV), and negative predictive values (NPV). RESULTS: Major features (nonrim arterial phase hyperenhancement, nonperipheral "washout", and enhancing "capsule") had a sensitivity of 94.1%, 88.2%, and 41.2%, and a specificity of 57.7%, 42.3%, and 88.5% for HCC, respectively. Ancillary features (hepatobiliary phase hypointensity, mild-moderate T2 hyperintensity, restricted diffusion, and fat in the lesion more than adjacent liver) had a sensitivity of 94.1%, 64.7%, 58.8%, and 11.8%, and a specificity of 26.9%, 61.5%, 65.4%, and 76.9% for HCC, respectively. The LR-5 category (determined by using major features only vs. the combination of major and ancillary features) had a sensitivity of 88.2% at both evaluations and a specificity of 76.9% and 80.8% for HCC, respectively. The combination of LR-4, LR-5 categories (determined by using major features only vs. the combination of major and ancillary features) had a sensitivity of 94.1% at both interpretations and a specificity of 65.4% and 26.9% for HCC, respectively. The use of ancillary features modified LI-RADS category in 25.6% of observations (11/43), predominantly upgraded from LR-3 to LR4 (10/11), increasing the proportion of low-grade DNs and high-grade DNs categorized as LR-4 (from 15.4% to 61.5% and from 7.7% to 46.1%, respectively). CONCLUSIONS: The added value of ancillary features in combination with major features is limited for the non-invasive diagnosis of small HCC; however, their use modifies the final category in a substantial proportion of observations from LR-3 to LR-4, thus allowing possible changes in the management of patients at risk for HCC.

Transferrin synthesis by inducer T lymphocytes.

Transferrin (Tf) is a growth factor that transports iron in plasma. It is essential for proliferation of activated T lymphocytes. Previous studies have suggested that peripheral blood cells are capable of synthesizing Tf. Using in situ hybridization techniques and human Tf complementary DNAs as probes, peripheral blood cells have been examined for sites of Tf messenger RNA (mRNA) transcription. The studies described here demonstrate that Tf is synthesized by a specific subset of T lymphocytes, the T4+ inducer subset. T lymphocyte proliferation is dependent upon the presence of both interleukin 2 (IL-2) and Tf, even though resting cells do not possess receptors for either. The present studies indicate that during T cell activation, induction of IL-2 mRNA transcription and IL-2 receptor expression precede the transcription of Tf mRNA and expression of Tf receptors, respectively. These events in turn precede the initiation of DNA synthesis. Transferrin and its receptor appear to be involved in an autocrine pathway which is functionally linked to the IL-2/IL-2 receptor autocrine loop.

Individual regulation of the accumulation of H1 mRNA and core histone mRNAs in sea urchin embryos.

The relative cytoplasmic accumulation of the individual histone mRNAs in sea urchins was determined by gel analysis of 3H-labeled cytoplasmic RNA isolated from embryos of the early cleavage through the mesenchyme blastula stages. A number of separate determinations showed that H1 mRNA accumulates at a molar ratio of 0.5 or less compared with each of the H2 or H3 core histone mRNAs through approximately the first 12 h of embryonic development. After this time, the accumulation of H1 mRNA increases relative to the core histone mRNAs, and approximately equimolar amounts of the histone mRNAs are produced by about the 14-h stage. The equimolar synthesis of H1 mRNA appears to be transient, returning to 0.5-molar levels several hours later. The increase in H1 mRNA accumulation, relative to the core histone RNAs, is coincident with the transition from expression of the early (alpha) sea urchin histone gene set to the late histone genes. Since all five of the early histone genes occur in a 1:1 ratio within repeating units, the data suggest that the genes within a single repeat, or their immediate products, are individually regulated. Gel analysis of the proteins synthesized in vivo by embryos demonstrates that the pattern of synthesis of the histone proteins reflects the changing ratios of the histone mRNAs.