Biomedical subjects

J Xu

Publications and source records attributed to J Xu.

At least 523 records · Page 29Linked to original sources

PubMed1999

The SPOROCYTELESS gene of Arabidopsis is required for initiation of sporogenesis and encodes a novel nuclear protein.

The formation of haploid spores marks the initiation of the gametophytic phase of the life cycle of all vascular plants ranging from ferns to angiosperms. In angiosperms, this process is initiated by the differentiation of a subset of floral cells into sporocytes, which then undergo meiotic divisions to form microspores and megaspores. Currently, there is little information available regarding the genes and proteins that regulate this key step in plant reproduction. We report here the identification of a mutation, SPOROCYTELESS (SPL), which blocks sporocyte formation in Arabidopsis thaliana. Analysis of the SPL mutation suggests that development of the anther walls and the tapetum and microsporocyte formation are tightly coupled, and that nucellar development may be dependent on megasporocyte formation. Molecular cloning of the SPL gene showed that it encodes a novel nuclear protein related to MADS box transcription factors and that it is expressed during microsporogenesis and megasporogenesis. These data suggest that the SPL gene product is a transcriptional regulator of sporocyte development in Arabidopsis.

Amino Acid Sequence↗

PubMed1999

Sterol regulatory element binding protein-1 expression is suppressed by dietary polyunsaturated fatty acids. A mechanism for the coordinate suppression of lipogenic genes by polyunsaturated fats.

Polyunsaturated fatty acids (PUFA) coordinately suppress the transcription of a wide array of hepatic lipogenic genes including fatty acid synthase (FAS) and acetyl-CoA carboxylase. Interestingly, the over-expression of sterol regulatory element binding protein-1 (SREBP-1) induces the expression of all of the enzymes suppressed by PUFA. This observation led us to hypothesize that PUFA coordinately inhibit lipogenic gene transcription by suppressing the expression of SREBP-1. Our initial studies revealed that the SREBP-1 and FAS mRNA contents of HepG2 cells were reduced by 20:4(n-6) in a dose-dependent manner (i.e. EC(50) approximately 10 microM), whereas 18:1(n-9) had no effect. Similarly, supplementing a fat-free, high glucose diet with oils rich in (n-6) or (n-3) PUFA reduced the hepatic content of precursor and nuclear SREBP-1 60 and 85%, respectively; however, PUFA had no effect on the nuclear content of upstream stimulatory factor (USF)-1. The PUFA-dependent decrease in nuclear content of mature SREBP-1 was paralleled by a 70-90% suppression in FAS gene transcription. In contrast, dietary 18:1(n-9), i.e. triolein, had no inhibitory influence on the expression of SREBP-1 or FAS. The decrease in hepatic expression of SREBP-1 and FAS associated with PUFA ingestion was mimicked by supplementing the fat-free diet with the PPARalpha-activator, WY 14, 643. Interestingly, nuclear run-on assays revealed that changes in SREBP-1 mRNA abundance were not accompanied by changes in SREBP-1 gene transcription. These results support the concept that PUFA coordinately inhibit lipogenic gene transcription by suppressing the expression of SREBP-1 and that the PUFA regulation of SREBP-1 appears to occur at the post-transcriptional level.

CCAAT-Enhancer-Binding Proteins↗

PubMed1999

Structural organization of mammalian lipid phosphate phosphatases: implications for signal transduction.

This article describes the regulation of cell signaling by lipid phosphate phosphatases (LPPs) that control the conversion of bioactive lipid phosphates to their dephosphorylated counterparts. A structural model of the LPPs, that were previously called Type 2 phosphatidate phosphatases, is described. LPPs are characterized by having no Mg(2+) requirement and their insensitivity to inhibition by N-ethylmaleimide. The LPPs have six putative transmembrane domains and three highly conserved domains that define a phosphatase superfamily. The conserved domains are juxtaposed to the proposed membrane spanning domains such that they probably form the active sites of the phosphatases. It is predicted that the active sites of the LPPs are exposed at the cell surface or on the luminal surface of intracellular organelles, such as Golgi or the endoplasmic reticulum, depending where various LPPs are expressed. LPPs could attenuate cell activation by dephosphorylating bioactive lipid phosphate esters such as phosphatidate, lysophosphatidate, sphingosine 1-phosphate and ceramide 1-phosphate. In so doing, the LPPs could generate alternative signals from diacylglycerol, sphingosine and ceramide. The LPPs might help to modulate cell signaling by the phospholipase D pathway. For example, phosphatidate generated within the cell by phospholipase D could be converted by an LPP to diacylglycerol. This should change the relative balance of signaling by these two lipids. Another possible function of the LPPs relates to the secretion of lysophosphatidate and sphingosine 1-phosphate by activated platelets and other cells. These exogenous lipids activate phospholipid growth factor receptors on the surface of cells. LPP activities could attenuate cell activation by lysophosphatidate and sphingosine 1-phosphate through their respective receptors.

Amino Acid Sequence↗

PubMed1999

Brefeldin A increases the quantal size and alters the kinetics of catecholamine release from rat adrenal chromaffin cells.

The fungal metabolite, brefeldin A (BFA), is known to inhibit guanine nucleotide exchange on the ADP-ribosylating factors that are involved in vesicle membrane trafficking. Here, we investigated the action of BFA on Ca2+-regulated exocytosis in single rat adrenal chromaffin cells. Incubation of chromaffin cells with BFA (1 or 10 microM) for 2 h effectively disrupted the Golgi membranes but did not affect the pattern of catecholamine release triggered by high extracellular K+, which was monitored with carbon fiber amperometry along with cytosolic Ca2+ measurement. The BFA treatment, however, increased the mean quantal size of catecholamine-containing vesicles and the occurrence of amperometric events with a "foot" or "stand alone" signal (which reflects sluggish or incomplete dilation of the fusion pore). To examine whether BFA altered the Ca2+-dependence of exocytosis, we employed the whole-cell recording technique in conjunction with the capacitance measurement to measure exocytosis evoked from the entire cell during voltage-gated Ca2+ entry. Our results suggested that BFA treatment did not alter either the initial rate of capacitance increase or the total amount of capacitance increase. Therefore, in chromaffin cells, BFA treatment affects Ca2+-regulated exocytosis predominantly by increasing the quantal size and by slowing the fusion kinetics of some vesicles.

Animals↗

PubMed1999

Keratin filament suspensions show unique micromechanical properties.

All epithelial cells feature a prominent keratin intermediate filament (IF) network in their cytoplasm. Studies in transgenic mice and in patients with inherited epithelial fragility syndromes showed that a major function of keratin IFs is to provide mechanical support to epithelial cell sheets. Yet the micromechanical properties of keratin IFs themselves remain unknown. We used rheological methods to assess the properties of suspensions of epidermal type I and type II keratin IFs and of vimentin, a type III IF polymer. We find that both types of IFs form gels with properties akin to visco-elastic solids. With increasing deformation they display strain hardening and yield relatively rapidly. Remarkably, both types of gels recover their preshear properties upon cessation of the deformation. Repeated imposition of small deformations gives rise to a progressively stiffer gel for keratin but not vimentin IFs. The visco-elastic moduli of both gels show a weak dependence upon the frequency of the input shear stress and the concentration of the polymer, suggesting that both steric and nonsteric interactions between individual polymers contribute to the observed mechanical properties. In support of this, the length of individual polymers contributes only modestly to the properties of IF gels. Collectively these properties render IFs unique among cytoskeletal polymers and have strong implications for their function in vivo.

Animals↗

PubMed1999

Neurotoxic potentiation is related to a metabolic interaction between p-bromophenylacetylurea and phenylmethanesulfonyl fluoride.

This study investigated the neurotoxic potentiation and metabolic interaction between p-bromophenylacetylurea (BPAU) and phenylmethanesulfonyl fluoride (PMSF). The results showed that F344 rats given two successive daily doses of 150 mg/kg BPAU developed a moderate degree of ataxia. When rats were coadministrated a single intraperitoneal dose of 100 mg/kg PMSF either 1 day before, or 4 h or 1 day after the two daily doses of BPAU, the severity of ataxia was significantly increased. No such effect was observed when PMSF was given 4 days after BPAU, although this time point was still prior to the development of the neuropathy. The enhancement or potentiation of neuropathy by PMSF was thus seen only at times when parent BPAU was present in the target tissues. A pharmacokinetic study showed that PMSF increased the concentrations of BPAU and its metabolite, N'-hydroxy-p-bromophenylacetylurea (M1), in tissues and decreased the concentration of the metabolite 4-(4-bromophenyl)-3-oxapyrrolidine-2,5-dione (M2) in serum. This indicated that PMSF inhibited the M2 pathway and more BPAU was metabolized via the M1 pathway. This increased both BPAU and M1 levels in tissues and hence would have increased BPAU-induced neurotoxicity. We conclude that PMSF does not need to act directly on target sites to potentiate BPAU-induced neurotoxicity, since its interference with BPAU metabolism was sufficient to account for the increase in BPAU neurotoxicity. Thus a metabolic interaction underlies the neurotoxic potentiation between these two compounds rather than the target site interaction seen between PMSF and neuropathic organophosphates. This study is the first to demonstrate that interference with the metabolism of BPAU is an important aspect of the potentiation of BPAU-induced neurotoxicity.

Animals↗

PubMed1999

Lipid phosphate phosphohydrolase-1 degrades exogenous glycerolipid and sphingolipid phosphate esters.

Lipid phosphate phosphohydrolase (LPP)-1 cDNA was cloned from a rat liver cDNA library. It codes for a 32-kDa protein that shares 87 and 82% amino acid sequence identities with putative products of murine and human LPP-1 cDNAs, respectively. Membrane fractions of rat2 fibroblasts that stably expressed mouse or rat LPP-1 exhibited 3.1-3. 6-fold higher specific activities for phosphatidate dephosphorylation compared with vector controls. Increases in the dephosphorylation of lysophosphatidate, ceramide 1-phosphate, sphingosine 1-phosphate and diacylglycerol pyrophosphate were similar to those for phosphatidate. Rat2 fibroblasts expressing mouse LPP-1 cDNA showed 1.6-2.3-fold increases in the hydrolysis of exogenous lysophosphatidate, phosphatidate and ceramide 1-phosphate compared with vector control cells. Recombinant LPP-1 was located partially in plasma membranes with its C-terminus on the cytosolic surface. Lysophosphatidate dephosphorylation was inhibited by extracellular Ca2+ and this inhibition was diminished by extracellular Mg2+. Changing intracellular Ca2+ concentrations did not alter exogenous lysophosphatidate dephosphorylation significantly. Permeabilized fibroblasts showed relatively little latency for the dephosphorylation of exogenous lysophosphatidate. LPP-1 expression decreased the activation of mitogen-activated protein kinase and DNA synthesis by exogenous lysophosphatidate. The product of LPP-1 cDNA is concluded to act partly to degrade exogenous lysophosphatidate and thereby regulate its effects on cell signalling.

Animals↗

PubMed1999

Cloning and characterization of KCC3 and KCC4, new members of the cation-chloride cotransporter gene family.

The K+-Cl- cotransporters (KCCs) belong to the gene family of electroneutral cation-chloride cotransporters, which also includes two bumetanide-sensitive Na+-K+-2Cl- cotransporters and a thiazide-sensitive Na+-Cl- cotransporter. We have cloned cDNAs encoding mouse KCC3, human KCC3, and human KCC4, three new members of this gene family. The KCC3 and KCC4 cDNAs predict proteins of 1083 and 1150 amino acids, respectively. The KCC3 and KCC4 proteins are 65-71% identical to the previously characterized transporters KCC1 and KCC2, with which they share a predicted membrane topology. The four KCC proteins differ at amino acid residues within key transmembrane domains and in the distribution of putative phosphorylation sites within the amino- and carboxyl-terminal cytoplasmic domains. The expression of mouse KCC3 in Xenopus laevis oocytes reveals the expected functional characteristics of a K+Cl- cotransporter: Cl--dependent uptake of 86Rb+ which is strongly activated by cell swelling and weakly sensitive to furosemide. A direct functional comparison of mouse KCC3 to rabbit KCC1 indicates that KCC3 has a much greater volume sensitivity. The human KCC3 and KCC4 genes are located on chromosomes 5p15 and 15q14, respectively. Although widely expressed, KCC3 transcripts are the most abundant in heart and kidney, and KCC4 is expressed in muscle, brain, lung, heart, and kidney. The unexpected molecular heterogeneity of K+-Cl- cotransport has implications for the physiology and pathophysiology of a number of tissues.

Amino Acid Sequence↗

PubMed1999

No evidence for a role of BRCA1 or BRCA2 mutations in Ashkenazi Jewish families with hereditary prostate cancer.

BACKGROUND: Two genes responsible for hereditary breast cancer (BRCA1 and BRCA2) have been identified, and predisposing mutations identified. Several studies have provided evidence that germline mutations in BRCA1 and BRCA2 confer an increased risk of prostate cancer. Based on these findings, one might expect to find an increased frequency of mutations in these genes in family clusters of prostate cancer. The Ashkenazi Jewish population is unique in that it has an approximate 2% incidence of specific founder BRCA1 and BRCA2 mutations (i.e., 185delAG and 5382insC in BRCA1, and 6174delT in BRCA2). METHODS: To address the question of whether or not mutations in either of these genes were overrepresented in prostate cancer families, we searched for these mutations in germline DNA samples collected from affected and unaffected members of 18 Ashkenazi Jewish families, each having at least 3 first-degree relatives affected with prostate cancer. RESULTS: No mutations were found in the BRCA1 gene in any of the 47 individuals tested. One individual possessed a BRCA2 mutation (6174delT). This individual was unaffected at the time of analysis, but had an affected paternal uncle, and an affected first cousin, neither of whom harbored the mutant gene. CONCLUSIONS: In this sample of Ashkenazi prostate cancer families, the frequency of founder BRCA1 and BRCA2 mutations was not elevated, suggesting that such mutations will account for only a small, perhaps minimal, fraction of familial prostate cancer.

DNA Primers↗

PubMed1999

A lymphoma growth inhibitor blocks some but not all prolactin-stimulated signaling pathways.

Cytokines and hormones activate a network of intracellular signaling pathways to regulate cell division, survival and differentiation. In parallel, a series of growth inhibitory mechanisms critically restrict cell population sizes. For example, mitogens can be opposed in crowded cell cultures through contact-inhibition or by autocrine release of antiproliferative substances. Here, we characterize a small, heat-stable growth inhibitor secreted by a rat T lymphoma line when cultured at high cell density. Short term incubation (<60 min) of prolactin-responsive Nb2 lymphoma cells at high density selectively blocked prolactin stimulation of p42/p44 mitogen-activated protein kinases and transcription factors Stat1 and Stat3 but not prolactin activation of Stat5 or the tyrosine kinase Jak2. The selective effects of cell density on prolactin signaling were reversible. Furthermore, exposure of cells at low density to conditioned media from cells incubated at high density had the same inhibitory effects on prolactin signaling. This selective inhibition of discrete prolactin signals was mimicked by short term preincubation of cells at low density with staurosporine or genistein but not with bis-indoleyl maleimide, cyclic nucleotide analogs, calcium ionophore A23187, or phorbol 12-myristate 13-acetate. A heat-stable, proteinase K-resistant, low molecular weight factor with these characteristics was recovered from high density culture medium. The partially purified inhibitor suppressed Nb2 cell growth with a sigmoidal concentration response consistent with a saturable, receptor-mediated process.

Animals↗

PubMed1999

Adjusting for measurement error to assess health effects of variability in biomarkers. Multicenter AIDS Cohort Study.

Longitudinal studies of health effects often relate individuals' biomarker levels to disease progression. Repeated measurements also provide an opportunity to assess within-individual biomarker variability, and it is reasonable to postulate that this measure might provide additional information about a particular outcome variable. Given the existing precedent for application of adjustment methods to account for measurement error in subject-specific average levels of a covariate, this concept motivates the application of such methods to incorporate variability as well. In this paper, we investigate the nature of the relationship between the decline of CD4 cell count induced by infection with human immunodeficiency virus, and CD4 level and variability prior to infection. We first describe the distribution of repeated CD4 measurements prior to infection using a model that accounts both for random average levels and random subject-specific variance components. Based on this model, we define true unobservable random variables that correspond to prior level and stability. We perform a linear regression analysis, using these latent variables as covariates, by means of a full maximum likelihood approach. We compare the resulting parameter estimates with those based on regressions employing sample-based estimates of pre-infection levels and variances, and empirical Bayes estimates of these quantities. Although the final inferences are similar to those based on the unadjusted analysis, we find that the magnitude of association with prior level decreases, while that with prior stability increases. Stratified analyses indicate that smoking status affects the relationship between prior CD4 level and initial CD4 decline. We point out advantages associated with the maximum likelihood approach in this particular application.

Biomarkers↗

PubMed1999

A novel pathway for tumor necrosis factor-alpha and ceramide signaling involving sequential activation of tyrosine kinase, p21(ras), and phosphatidylinositol 3-kinase.

Treatment of confluent rat2 fibroblasts with C2-ceramide (N-acetylsphingosine), sphingomyelinase, or tumor necrosis factor-alpha (TNFalpha) increased phosphatidylinositol (PI) 3-kinase activity by 3-6-fold after 10 min. This effect of C2-ceramide depended on tyrosine kinase activity and an increase in Ras-GTP levels. Increased PI 3-kinase activity was also accompanied by its translocation to the membrane fraction, increases in tyrosine phosphorylation of the p85 subunit, and physical association with Ras. Activation of PI 3-kinase by TNFalpha, sphingomyelinase, and C2-ceramide was inhibited by tyrosine kinase inhibitors (genistein and PP1). The stimulation of PI 3-kinase by sphingomyelinase and C2-ceramide was not observed in fibroblasts expressing dominant-negative Ras (N17) and the stimulation by TNFalpha was decreased by 70%. PI 3-kinase activation by C2-ceramide was not modified by inhibitors of acidic and neutral ceramidases, and it was not observed with the relatively inactive analog, dihydro-C2-ceramide. It is proposed that activation of Ras and PI 3-kinase by ceramide can contribute to signaling effects of TNFalpha that occur downstream of sphingomyelinase activation and result in increased fibroblasts proliferation.

Animals↗

PubMed1999

Mice deficient in the steroid receptor co-activator 1 (SRC-1) are resistant to thyroid hormone.

Steroid receptor co-activator 1 (SRC-1) is a transcription co-factor that enhances the hormone-dependent action, mediated by the thyroid hormone (TH) receptor (TR) and other nuclear receptors. In vitro studies have shown that SRC-1 is necessary for the full expression of TH effect. SRC-1 knockout mice (SRC-1(-/-)) provide a model to examine the role of this co-activator on TH action in vivo. At baseline, SRC-1(-/-) mice display resistance to TH (RTH) as evidenced by a 2.5-fold elevation of serum TSH levels, despite a 50% increase in serum free TH levels as compared with wild-type (SRC-1(+/+)) mice. When mice were made hypothyroid, TSH levels increased, obliterating the difference between SRC-1(+/+) and SRC-1(-/-) mice observed at baseline. In contrast, the decline of TSH by treatment with L-triiodothyronine was severely blunted in SRC-1(-/-) mice. These data indicate that SRC-1 is not required for the upregulation of TSH in TH deficiency. However, SRC-1 enhances the sensitivity of TSH downregulation by TH. This is the first demonstration of RTH caused by a deficient co-factor other than TR. It supports the hypothesis that a putative defect in the SRC-1 gene or another co-factor could be the cause of RTH in humans without mutations in the TR genes.

Animals↗

PubMed1999

Reconstitution of the human endothelial cell protein C receptor with thrombomodulin in phosphatidylcholine vesicles enhances protein C activation.

Blocking protein C binding to the endothelial cell protein C receptor (EPCR) on the endothelium is known to reduce protein C activation rates. Now we isolate human EPCR and thrombomodulin (TM) and reconstitute them into phosphatidylcholine vesicles. The EPCR increases protein C activation rates in a concentration-dependent fashion that does not saturate at 14 EPCR molecules/TM. Without EPCR, the protein C concentration dependence fits a single class of sites (Km = 2.17 +/- 0.13 microM). With EPCR, two classes of sites are apparent (Km = 20 +/- 15 nM and Km = 3.2 +/- 1.7 microM). Increasing the EPCR concentration at a constant TM concentration increases the percentage of high affinity sites. Holding the TM:EPCR ratio constant while decreasing the density of these proteins results in a decrease in the EPCR enhancement of protein C activation, suggesting that there is little affinity of the EPCR for TM. Negatively charged phospholipids also enhance protein C activation. EPCR acceleration of protein C activation is blocked by anti-EPCR antibodies, but not by annexin V, whereas the reverse is true with negatively charged phospholipids. Human umbilical cord endothelium expresses approximately 7 times more EPCR than TM. Anti-EPCR antibody reduces protein C activation rates 7-fold over these cells, whereas annexin V is ineffective, indicating that EPCR rather than negatively charged phospholipid provide the surface for protein C activation. EPCR expression varies dramatically among vascular beds. The present results indicate that the EPCR concentration will determine the effectiveness of the protein C activation complex.

Blood Coagulation Factors↗

PubMed1999

Classifying individuals based on predictors of random effects. Multicenter AIDS Cohort Study.

Often one wishes to describe individuals according to whether their average exposure over a period of time is above or below some meaningful threshold. In this article, we treat predictors of random effects as diagnostic tools to aid in such classification, given that the true unobservable mean exposure for each of a set of individuals is defined according to a mixed linear model. Viewing candidate predictors in this light engenders the consideration of a unique set of performance criteria, and invites the use of nomenclature commonly used by epidemiologists and decision analysts to evaluate diagnostic techniques. We describe these criteria analytically and graphically under a random effects analysis of variance model, with the expressed goal of classifying subjects with regard to their true mean. Given knowledge of the model parameters, we compare typical predictors and illustrate the fact that completely new alternatives can arise depending on the particular set of criteria emphasized. We include a brief simulation study in which we also compare prediction methods according to various classification criteria, after incorporating estimates of the unknown model parameters. We provide two examples using data from participants in the Multicenter AIDS Cohort Study. In the first example, we seek to classify HIV seronegative individuals based on their mean diastolic blood pressure. In the second, via a natural extension to a randomized regression model, we classify HIV seropositive individuals according to their CD4+ slope over time.

Analysis of Variance↗

PubMed1999

Effect of capping protein, CapZ, on the length of actin filaments and mechanical properties of actin filament networks.

We report on how physiological concentrations of capping protein shorten actin filaments and on the remarkably fluid nature of solutions of such short filaments even at the high concentrations that exist in cells. We measured the lengths of actin filaments formed by spontaneous polymerization of highly purified actin monomers by fluorescence microscopy after labeling with rhodamine-phalloidin. The length distributions are exponential with a mean of about 7 microm (2600 subunits). As observed previously with less quantitative assays, copolymerization with the actin capping protein, CapZ, reduces the length of the filaments. At cellular concentrations of capping protein, one filament forms for each molecule of capping protein and the population of filaments is uniformly short. Using CapZ to vary the length of actin filaments, we measured how their mechanical properties depend on length. The stiffness (elastic modulus) of actin filament networks depends steeply on the length, with long filaments contributing far out of proportion to their numbers to the stiffness. Even at physiological concentrations (300 microM), networks of filaments limited to lengths observed in cells with a 1 to 500 molar ratio of CapZ are more fluid and much less elastic than lower concentrations of longer actin filaments. Thus the high concentration of short actin filaments in cells must be crosslinked to produce the observed stiffness of the cortex.

Actins↗

PubMed1999

Mass spectral fragmentation of cis- and trans-1a,3-disubstituted 1, 1-dichloro-1a,2,3,4-tetrahydro-1H-azirino[1,2-a] [1, 5]benzodiazepines.

The mass spectrometric behaviour of six cis- and trans-1a, 3-disubstituted 1,1-dichloro-1a,2,3,4-tetrahydro-1H-azirino[1,2-a][1, 5]benzodiazepines has been studied with the aid of mass-analysed ion kinetic energy spectrometry and exact mass measurements under electron impact ionization. All compounds show a tendency to eliminate a neutral propene or styrene molecule from the diazepine ring and to simultaneously eliminate a chlorine atom from the aziridine ring to yield azirino[1,2-b][1,3]benzimidazole ions, and to lose hydrogen chloride plus propene or styrene to give quinoxaline ions. All compounds also show a tendency to eliminate N=CCl(2) or HN=CCl(2) to produce dihydro- or tetrahydroquinoline ions, and to eliminate sequentially hydrogen chloride and a chlorine atom to yield pyrrolo[1,2-a][1, 3]benzimidazole ions.

Aziridines↗

PubMed1999

Electron impact mass spectra of 1a,3-disubstituted 1,1-dichloro-1,1a, 2,3-tetrahydroazirino [2,1-d][1,5]benzothiazepines.

The mass spectrometric behaviour of eight 1a,3-disubstituted 1, 1-dichloro-1,1a,2,3-tetrahydroazirino[2,1-d][1,5]benzothiazepines has been studied with the aid of mass-analyzed ion kinetic energy spectrometry and exact mass measurements under electron impact ionization. All compounds show a tendency to eliminate a chlorine radical from the aziridine ring and then eliminate a neutral propene or substituted/unsubstituted styrene from the thiazepine ring to yield 1,4-benzothiazine ions. They can also lose hydrogen chloride and a chlorine radical, or lose two chlorine atoms, to undergo a ring enlargement rearrangement to produce 1,6-benzothiazocine ions, which can further eliminate propyne or phenylacetylene, or small molecular fragments, to yield some abundant fragment ions.

Aziridines↗