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Deletion of chromosome 1p36 is the most commonly observed terminal deletion in humans with a frequency of 1 in 5,000 in the general population. In contrast, 22q13 duplications are rare and only a few cases have been reported. Unbalanced translocations resulting in monosomy 1p36 and a trisomy of 22q13.3 are, thus far, unreported in the literature. Here we present the clinical data and the results of array CGH and FISH analysis of four patients with unbalanced translocations t1;22p36;q13 inherited from unrelated balanced translocation carrier parents. The sizes of the imbalances ranged from 0.12 Mb to nearly 10 Mb. One balanced translocation carrier parent had disruption of the period homolog 3 PER3 gene and reported sleep disturbances. Overall, patients tended to have more features consistent with deletion of 1p36 than duplication of 22q. © 2008 WileyLiss, Inc.

We report the clinical, laboratory, and pathological findings in a series of 52 consecutive patients with adult celiac sprue observed over a 20-year period. The frequency of that diagnosis increased from an average of 0.7 case/year during the period 1966–1975 to 5.8 cases/year during the period 1981 −1985. Apart from two patients with dermatitis herpetiformis, nonclassical clinical presentations were observed in 16 of 50 (32) patients overall and in 13 of 28 (46) patients diagnosed since 1981. Diarrhea was the most common complaint leading to the diagnosis; since 1981, hematologic abnormalities warranted investigation in 38 of the patients. Decreased iron stores (88), decreased red cell folate (82), or both (74), and abnormal radiographic studies of the small bowel (83) were the most sensitive tests in the diagnostic investigation. We conclude that atypical or nonclassical presentations of adult celiac sprue, mostly with hematologic abnormalities, are not uncommon.

The present study compares the stratum corneum of human skin and human reconstructed epidermis by histological examination as well as by estimation of water permeability. Measurement of the percutaneous absorption of benzoic acid, testosterone, and hydrocortisone revealed that under the same experimental conditions the reconstructed epidermis on de-epidermized dermis exhibits a barrier function with qualitative properties similar to that of normal skin: water and benzoic acid penetrate more rapidly than testosterone and hydrocortisone. Quantitatively, however, reconstructed epidermis is more permeable than normal human skin. This points to an impaired barrier function of the epidermis reconstructed in vitro.

The Pseudomonas aeruginosa mutant Z61 has been shown to be highly supersusceptible to a wide range of antibiotics, including beta-lactams, aminoglycosides, rifampin, tetracycline, and chloramphenicol (W. Zimmerman, Int. J. Clin. Pharmacol. Biopharm. 17:131-134, 1979). Spontaneous revertants were isolated, using gentamicin or carbenicillin as selective agents, and shown to have two patterns of susceptibility to a group of 12 antibiotics. Partial revertants had 2- to 10-fold greater resistance to these antibiotics than mutant Z61, whereas full revertants had antibiotic susceptibilities indistinguishable from those of the wild-type strain K799, from which mutant Z61 had been derived. Uptake of a chromogenic beta-lactam nitrocefin was studied in both uninduced and induced cells of all strains by measuring the steady-state rate of nitrocefin hydrolysis by the inducible, periplasmic beta-lactamase in both whole and broken cells. This demonstrated that outer membrane permeability decreased as antibiotic resistance increased in the series mutant Z61, partial revertants, wild type, and full revertants. The data were consistent with the idea of low outer membrane permeability being caused by a low proportion of open functional porins in the outer membrane as the reason for the high natural antibiotic resistance of wild-type P, aeruginosa strains. In addition, it was observed that levels of benzylpenicillin below the minimal inhibitory concentration for mutant Z61 failed to induce beta-lactamase production. The possibility that this was related to the observed increase in outer membrane permeability is discussed. Preliminary evidence is presented that the pore-forming outer membrane porin protein F is not altered in mutant Z61.

Stable hybridomas generated by fusion of spleen cells from hyperimmunized mice and mouse myeloma cells were cloned to prepare monoclonal antibodies to alpha 2u-globulin, an androgen-dependent urinary protein of hepatic origin. One of these monoclonal antibodies was used as a probe for immunocytofluorometric analysis of alpha 2u-globulin producing hepatocytes during androgenic induction and aging through fluorescence-activated cell sorting (FACS). FACS patterns of hepatocytes from mature male rats that produce high levels of alpha 2u-globulin showed tow distinct peaks, arbitrarily designated as peak I (weakly fluorescent) and peak II (brightly fluorescent). In the mature male rat, peak II represented about 40% of the total hepatocytes, and the fluorescence intensity of this subpopulation decreased in direct correspondence with the gradual decline of alpha 2u-globulin synthesis during aging. Similarly the androgenic induction of this protein in ovariectomized female rats was associated with an increase in the fluorescence intensity of the hepatocyte subpopulation under peak II rather than an increase in the relative number of these cells. From these results we conclude that the androgen-dependent synthesis of alpha 2u-globulin and its alteration during aging are confined to a specific subpopulation of hepatocytes within the liver.

Seed production on male‐sterile soybeans [Glycine max(L.) Merr.] in cages with honeybees (Apis melliferaL.) and alfalfa leafcutting bees [Megachile rotundata(F.)] was compared with plants exposed to native insect populations in open‐caged plots and with plants grown in closed cages. All plots consisted of alternate rows of ߢWilliamsߣ male‐sterile plants (ms2, ms2) and ‘Calland’ which were covered by cages after flowering commenced. Significant differences were found between treatments for the number of seeds/plant, pods/plant, and seeds/pod. A significant increase in seed production of over 477% was observed on plants in cages containing the bees compared with plants in open or closed cages. No significant differences in seed production were observed between open or closed cages or between the use of honey or alfalfa leafcutting bees as the pollen vector. Honeybees were efficient pollen vectors, but were inconvenient to handle. Leafcutting bees seem to be preferable for mass pollination of male‐sterile soybeans in caged studies because of their temperament and ease of handling.

Background: Adapalene (Differin(R) gel) is a new naphthoic acid derivative developed for the topical treatment of acne vulgaris. Objective: We assessed, in healthy volunteers, the skin irritancy potential of three combinations, each including adapalene 0.1% gel and one topical marketed antiacne product. Methods: Twenty-five healthy volunteers were enrolled in a 21-day cumulative irritancy study performed in a double-blind, randomized, controlled, intraindividual design. Five days a week, the three materials (benzoyl peroxide, clindamycin phosphate, and erythromycin) were applied in a nonocclusive manner either alone or in combination with adapalene gel on seven cutaneous sites on the upper back. Adapalene was applied in the evening whereas the three other materials were applied in the morning. Irritation was evaluated and scored daily except on weekends. Results: All materials were well-tolerated when tested alone. The combinations of adapalene 0.1% gel and either benzoyl peroxide, clindamycin phosphate, or erythromycin were also well-tolerated. The mean cumulative irritancy indices indicated that all three combinations were nonirritating. Conclusion: Under the conditions of the study, all tested treatments alone or in combination appeared nonirritating. (J Am Acad Dermatol 1997;36:S113-5.)

Background: Adapalene is a new naphthoic acid derivative developed for the topical treatment of acne vulgaris. Objective: We compared the skin tolerance of adapalene 0.1% gel with tretinoin 0.025% gel in subjects with acne. Methods: Fifteen acne patient volunteers were enrolled in this investigator-masked, left-right comparison, randomized, controlled, intraindividual study. Adapalene 0.1% gel and tretinoin 0.025% gel were applied once a day to one half-face by the volunteers for 14 consecutive days. Clinical signs (erythema, desquamation, papules, vesicles, edema) and subjective symptoms (tightness, pruritus, burning) were evaluated and scored daily except on weekends. Results: Adapalene 0.1% gel was better tolerated than tretinoin 0.025% gel. The overall mean score calculated from all features combined was significantly higher with tretinoin gel than with adapalene gel ( p = 0.002). Conclusion: Adapalene 0.1% gel was significantly less irritating than tretinoin 0.025% gel when tested in acne patients. (J Am Acad Dermatol 1997;36:S110-2.)

Patients with t(11;19) leukemias have one of two different translocations resulting in gene rearrangement with the MLL gene on 11q23. The ELL (eleven-nineteen lysine-rich leukemia) gene at 19p13.1, is rearranged in individuals with t(11;19) and acute myeloid leukemia, while the ENL (eleven-nineteen leukemia) gene at 19p13.3, is rearranged most frequently in those patients with t(11;19) and B-cell acute lymphoid leukemia. However, AML and rare T-cell ALL patients have been reported with the ENL gene rearrangement. At the cytogenetic level of resolution, it is not always possible to distinguish which of the two genes is involved in these translocations and precise molecular classification may be necessary for appropriate chemotherapy regimens to be devised and administered. We therefore developed a dual-color FISH (fluorescent in situ hybridization) assay using BACs (bacterial artificial chromosomes) for ELL and ENL. ELL is directly labeled in spectrum orange and ENL is directly labeled in spectrum green and the probes are co-hybridized. The strategy for the assay is to assess the interphase nuclei of patients for gain of an orange signal, indicating an ELL gene rearrangement (3O2G signal pattern), or gain of a green signal, indicating an ENL gene rearrangement (3G2O signal pattern). The gain of signal is due to splitting of the respective locus during the translocation of distal 19p to 11q23. As constructed, the probes showed a 100% specificity for the respective translocations, based on metaphase and interphase analysis of ELL and ENL t(11;19) positive patients; all of the patients were diagnosed with myeloid leukemia. In addition, further comparative validation was performed using the commercially available dual-color breakapart MLL probe (Vysis). Analysis of the ELL positive AML patients with the MLL probe showed the expected abnormal interphase signal pattern (1O1G1Fusion), confirming MLL gene rearrangement. However, the MLL pattern for the single patient with an ENL gene rearrangement and AML showed an alternate interphase pattern, indicating an alternate MLL breakpoint. Analysis of additional patients is required to determine if those with AML and ENL gene rearrangements routinely have a different MLL breakpoint; this difference could potentially contribute to a myeloid disease presentation. In order to establish clinically valid cut-offs for residual disease analysis, interphase validation was performed. Probe specificity was 100%, with a sensitivity of greater than 97% for both loci. This results in a normal cut-off (plus 2 S.D.) of 0.9/200 abnormal cells for ENL gene rearrangement and 2.18/200 abnormal cells for ELL gene rearrangement. In this laboratory’s use, the probe set is slightly more sensitive for disease detection than the commercially available MLL gene probe (Vysis), which has a sensitivity of 96% and a normal cut-off of 1.84/200 cells. This probe set allows quick distinction between ELL and ENL gene rearrangements in patients with acute leukemia.

Patients with t(11;19) leukemias have one of two different translocations resulting in gene rearrangement with the MLL gene on 11q23. The ELL (eleven-nineteen lysine-rich leukemia) gene at 19p13.1, is rearranged in individuals with t(11;19) and acute myeloid leukemia, while the ENL (eleven-nineteen leukemia) gene at 19p13.3, is rearranged most frequently in those patients with t(11;19) and B-cell acute lymphoid leukemia. However, AML and rare T-cell ALL patients have been reported with the ENL gene rearrangement. At the cytogenetic level of resolution, it is not always possible to distinguish which of the two genes is involved in these translocations and precise molecular classification may be necessary for appropriate chemotherapy regimens to be devised and administered. We therefore developed a dual-color FISH (fluorescent in situ hybridization) assay using BACs (bacterial artificial chromosomes) for ELL and ENL. ELL is directly labeled in spectrum orange and ENL is directly labeled in spectrum green and the probes are co-hybridized. The strategy for the assay is to assess the interphase nuclei of patients for gain of an orange signal, indicating an ELL gene rearrangement (3O2G signal pattern), or gain of a green signal, indicating an ENL gene rearrangement (3G2O signal pattern). The gain of signal is due to splitting of the respective locus during the translocation of distal 19p to 11q23. As constructed, the probes showed a 100% specificity for the respective translocations, based on metaphase and interphase analysis of ELL and ENL t(11;19) positive patients; all of the patients were diagnosed with myeloid leukemia. In addition, further comparative validation was performed using the commercially available dual-color breakapart MLL probe (Vysis). Analysis of the ELL positive AML patients with the MLL probe showed the expected abnormal interphase signal pattern (1O1G1Fusion), confirming MLL gene rearrangement. However, the MLL pattern for the single patient with an ENL gene rearrangement and AML showed an alternate interphase pattern, indicating an alternate MLL breakpoint. Analysis of additional patients is required to determine if those with AML and ENL gene rearrangements routinely have a different MLL breakpoint; this difference could potentially contribute to a myeloid disease presentation. In order to establish clinically valid cut-offs for residual disease analysis, interphase validation was performed. Probe specificity was 100%, with a sensitivity of greater than 97% for both loci. This results in a normal cut-off (plus 2 S.D.) of 0.9/200 abnormal cells for ENL gene rearrangement and 2.18/200 abnormal cells for ELL gene rearrangement. In this laboratory's use, the probe set is slightly more sensitive for disease detection than the commercially available MLL gene probe (Vysis), which has a sensitivity of 96% and a normal cut-off of 1.84/200 cells. This probe set allows quick distinction between ELL and ENL gene rearrangements in patients with acute leukemia.