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PubMedDate not supplied

Modulation of mammalian sperm function by fertilization promoting peptide (FPP).

Fertilization promoting peptide (FPP; pGlu-Glu-ProNH2) is produced by the prostate gland and secreted into seminal plasma. When added to uncapacitated mouse and human sperm suspensions, it stimulates capacitation as demonstrated by both cytological changes and increased fertilizing ability in vitro. When added to capacitated suspensions, FPP inhibits spontaneous acrosome loss but cells retain high fertility in vitro. Adenosine elicits similar responses to FPP in both uncapacitated and capacitated cells and FPP + adenosine has a greater effect on uncapacitated cells than either used individually. We have proposed that these two molecules modulate the same pathway (adenylate cyclase/cAMP) but act via different receptors. The structure of FPP is crucial for bioactivity: loss of the terminal amide group abolishes activity and substitution of the central glutamic acid can markedly alter activity. Most recently we have found that stimulation of TCP-11, the product of the mouse t-complex gene Tcp-11, elicits responses indistinguishable from those obtained with FPP and we have hypothesized that the protein TCP-11 is the receptor for FPP. The existence of a human homologue for Tcp-11 suggests that the gene product, in conjunction with FPP, could play an important role in human fertility.

Animals↗
PubMedDate not supplied

Radiological appearance of pancreatic calculi in tropical versus alcoholic chronic pancreatitis.

Tropical and alcoholic forms of chronic pancreatitis differ in their clinical, aetiological and epidemiological features. We compared the radiological appearances of pancreatic calculi seen on plain roentgenogram of the abdomen of 89 patients with tropical calcific pancreatitis (TCP) and 32 patients with alcoholic calcific pancreatitis (ACP) seen in Madras, Southern India. While TCP was characterized by the frequent occurrence of large, discrete, dense calculi, patients with ACP had typically small, speckled calculi with irregular, hazy margins. The calculi in TCP resembled those described for hereditary pancreatitis. This is the first report comparing the radiological appearances of TCP and ACP patients seen at the same centre.

Adult↗
PubMed1999

Obtaining resources for evidence-based public health initiatives at the local level: insights from the Central Sydney Tobacco Control Plan.

OBJECTIVE: In response to inquiries regarding the processes of developing a Tobacco Control Plan (TCP) for the Central Sydney Area Health Service (which in 1997 allocated dedicated funding of $ 800,000 over 2 1/2 years to implement the plan), this article describes the strengths and weaknesses of the TCP and outlines the process which contributed to its funding. CONCLUSIONS: Consistent with national and state priorities, the TCP recommended strategies based on best available evidence in the four action areas: reducing sales of cigarettes to minors, marketing, passive smoking and smoking cessation. Funding of this amount for a single public health issue at a local level represents a unique achievement in the application of an evidence-based approach to population health. IMPLICATIONS: Key elements of our advocacy methods included the involvement of all key primary health care and clinical stakeholders; comprehensive background research to identify evidence-based strategies; careful attention to budget options; strategic lobbying of senior staff and decision makers; the proposal for a multidisciplinary management structure for the TCP and specifications for funding allocation and evaluation. Early achievements and other reflections are discussed.

Adolescent↗
PubMed1988

Solubilization of rat brain phencyclidine receptors in an active binding form that is sensitive to N-methyl-D-aspartate receptor ligands.

Phencyclidine (PCP) receptors were successfully solubilized from rat forebrain membranes with 1% sodium cholate. Approximately 58% of the initial protein and 20-30% of the high-affinity PCP binding sites were solubilized. The high affinity toward PCP-like drugs, the stereo-selectivity of the sites, and the sensitivity to N-methyl-D-aspartate (NMDA) receptor ligands were preserved. Binding of the potent PCP receptor ligand N-[3H][1-(2-thienyl)cyclohexyl] piperidine ([3H]TCP) to the soluble receptors was saturable (KD = 35 nM), and PCP-like drugs inhibited [3H]TCP binding in a rank order of potency close to that observed for the membrane-bound receptors; the most potent inhibitors were TCP (Ki = 31 nM) and the anticonvulsant MK-801 (Ki = 50 nM). The NMDA receptor antagonist 2-amino-5-phosphonovaleric acid inhibited binding of [3H]TCP to the soluble receptors; glutamate or NMDA diminished this inhibition in a dose-dependent manner. Taken together, the results indicate that the soluble PCP receptor preparation contains the glutamate recognition sites and may represent a single receptor complex for PCP and NMDA, as suggested by electrophysiological data. The successful solubilization of the PCP receptors in an active binding form should now facilitate their purification.

2-Amino-5-phosphonovalerate↗
PubMed1990

The glycine site of the N-methyl-D-aspartate receptor channel: differences between the binding of HA-966 and of 7-chlorokynurenic acid.

The mechanisms of action of three different glycine-site antagonists of the N-methyl-D-aspartate (NMDA)-receptor channel were analyzed employing [3H]glycine direct binding assays, as well as functional glycine- and glutamate-induced uncompetitive blocker binding assays. The latter assays measure apparent channel opening. All three antagonists tested, viz., 7-chlorokynurenic acid (7-Cl-KYNA), kynurenic acid (KYNA), and 1-hydroxy-3-aminopyrrolidone-2 (HA-966), inhibited the binding of [3H]glycine to the NMDA receptor in a dose-dependent manner. These antagonists also inhibited the glycine-induced increase in accessibility of the uncompetitive blocker [3H]N-[1-(2-thienyl)cyclohexyl]-piperidine ([3H]TCP) to the channel. 7-Cl-KYNA and KYNA, but not HA-966, completely blocked the glutamate-induced binding of [3H]TCP, in a manner similar to the non-competitive manner in which the selective NMDA antagonist D-(-)-2-amino-5-phosphonovaleric acid (AP-5) inhibited glycine-induced [3H]TCP binding. The inhibitory effects of HA-966 and of AP-5 on glutamate-induced [3H]TCP binding were overcome when glutamate concentrations were increased. Of the three antagonists, 7-Cl-KYNA appears to be the most potent (Ki = 0.4-1.0 microM) and the most selective glycine antagonist. KYNA was found to act at both the glycine (Ki = 40-50 microM) and the glutamate sites. In contrast, HA-966 (Ki = 6-17 microM) appears to act either on a domain distinct from the glutamate and the glycine sites, but tightly associated with the latter, or at the glycine site, but according to a mechanism distinct from that of 7-Cl-KYNA.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Prehospital transcutaneous cardiac pacing for symptomatic bradycardia.

We studied patients with symptomatic bradycardia to determine the importance of presenting hemodynamic status and prehospital transcutaneous cardiac pacing (TCP) upon patient survival. Of 51 patients with witnessed cardiovascular decompensation and initial bradycardia, 27 (53%) received TCP. There were no significant differences between the paced patients and those without TCP for mean times from collapse until cardiopulmonary resuscitation, paramedic arrival and a paceable rhythm, or from paramedic arrival until a paceable rhythm. Overall, emergency department arrival with a palpable pulse (26% in paced vs 13% in nonpaced group; P = 0.20) and survival to hospital discharge (15% in paced vs 0% nonpaced group; P = 0.07) tended to be better for the paced group. No patient without a palpable pulse on paramedic arrival survived to leave the hospital. Of patients with a palpable pulse upon paramedic arrival, survival to hospital discharge was greater for the paced group (80% in paced vs 0% in nonpaced group; P = 0.024). TCP appears to be most beneficial in those patients with bradycardia who have a palpable pulse when first seen.

Aged↗
PubMed2004

Effects of tricalcium phosphate bone graft materials on primary cultures of osteoblast cells in vitro.

The aim of this study was to evaluate beta-tricalcium phosphate (beta-TCP Cerasorb Curasan-Germany) graft materials on specific parameters of rat osteoblast activity in vitro. Primary culture osteoblastic cells were isolated from neonatal rat calvaria by sequential collagenase digestion. To analyze the effect of biomaterials on cell proliferation, cell numbers and viability of the cells were cultured on the graft material for 24, 48 or 96 h. Osteoblast cells cultured in DMEF-12 media supplemented with 10% fetal calf serum were used as the control group. [3H]thymidine was added during the last 2 h of the incubation. The cell numbers of each well were counted. Cell viability was estimated by counting the number of cells, which excluded trypan blue solution. Scanning electron microscopy was used to observe for visualizing the interactions between osteoblastic cells and TCP graft material. The proportion of cells undergoing DNA synthesis, estimated by thymidine uptake, was significantly (P<0.05) greater on the control group after the 24- and 48-h incubations. Regarding the cell numbers the difference was not statistically significant for the three time points. The number of viable cells recovered was similar for the two groups. No morphological differences were observed in cell morphology on TCP graft material and the control group. The results demonstrate that TCP graft material has no adverse effect on cell count, viability and morphology, and this material provides a matrix that favors limited cell proliferation.

Alkaline Phosphatase↗
PubMed1989

Ultrastructural and histochemical study of beta-tricalcium phosphate resorbing cells in periodontium of dogs.

beta-TCP was implanted in surgically prepared alveolar bone defects on the mesial side of the upper canine. The dogs that we used were sacrificed after 5 weeks, fixed by perfusion, and the beta-TCP resorbing cells were examined ultrastructurally and histochemically, with the following results: (1) beta-TCP was resorbed by macrophages and multinucleated giant cells. (2) Mitochondria, vacuoles and Golgi apparatus were abundant in beta-TCP-resorbing multinucleated giant cells that possessed neither ruffled borders nor clear zones. (3) The addition of tartric acid inhibited acid phosphatase activity in the cytoplasm of the multinucleated giant cells and macrophages.

Acid Phosphatase↗
PubMed1995

Transforming growth factor-beta 1 coated beta-tricalcium phosphate pellets stimulate healing of experimental bone defects of rat calvariae.

OBJECTIVE: TGF-beta 1-coated beta-TCP pellets were grafted in experimental defects of rat calvariae to study the effects on new bone formation. MATERIALS AND METHODS: The grafted sites were evaluated by light microscopy using hematoxylin-eosin (H-E) staining for histology and detection of alkaline phosphatase (ALPase) and tartrate-resistant acid phosphatase (TRACPase) activities to demonstrate osteoblastic and osteoclastic cells. Confocal laser scanning microscopy (CLSM) was performed for morphometry of newly formed bone. RESULTS: H-E sections showed more new bone formation in sites grafted with TGF-beta 1-coated beta-TCP pellets (experimental sites) than those with beta-TCP pellets only (control sites). TRACPase-positive and ALPase-positive cells at experimental sites were more frequent than at control sites. The bone formation rate calculated by computerized CLSM pixel image analysis showed more new bone formation at the experimental sites than at control sites (3.4 +/- 0.8% vs 9.3 +/- 1.7% on week 2 and 11.8 +/- 2.1% vs 39.8 +/- 10.9% on week 4). CONCLUSION: TGF-beta 1-coated beta-TCP pellets promote new bone formation and may be a useful modality in synthetic bone grafting.

Acid Phosphatase↗
PubMed2004

Atypical Ca2+-induced Ca2+ release from a sarco-endoplasmic reticulum Ca2+-ATPase 3-dependent Ca2+ pool in mouse pancreatic beta-cells.

The contribution of Ca(2+) release from intracellular stores to the rise in the free cytosolic Ca(2+) concentration ([Ca(2+)](c)) triggered by Ca(2+) influx was investigated in mouse pancreatic beta-cells. Depolarization of beta-cells by 45 mm K(+) (in the presence of 15 mm glucose and 0.1 mm diazoxide) evoked two types of [Ca(2+)](c) responses: a monotonic and sustained elevation; or a sustained elevation superimposed by a transient [Ca(2+)](c) peak (TCP) (40-120 s after the onset of depolarization). Simultaneous measurements of [Ca(2+)](c) and voltage-dependent Ca(2+) current established that the TCP did not result from a larger Ca(2+) current. Abolition of the TCP by thapsigargin and its absence in sarco-endoplasmic reticulum Ca(2+)-ATPase 3 (SERCA3) knockout mice show that it is caused by Ca(2+) mobilization from the endoplasmic reticulum. A TCP could not be evoked by the sole depolarization of beta-cells but required a rise in [Ca(2+)](c) pointing to a Ca(2+)-induced Ca(2+) release (CICR). This CICR did not involve inositol 1,4,5-trisphosphate (IP(3)) receptors (IP(3)Rs) because it was resistant to heparin. Nor did it involve ryanodine receptors (RyRs) because it persisted after blockade of RyRs with ryanodine, and was not mimicked by caffeine, a RyR agonist. Moreover, RyR1 and RyR2 mRNA were not found and RyR3 mRNA was only slightly expressed in purified beta-cells. A CICR could also be detected in a limited number of cells in response to glucose. Our data demonstrate, for the first time in living cells, the existence of an atypical CICR that is independent from the IP(3)R and the RyR. This CICR is prominent in response to a supraphysiological stimulation with high K(+), but plays little role in response to glucose in non-obese mouse pancreatic beta-cells.

Animals↗
PubMed2003

Investigating the effect of cell repopulation on the tumor response to fractionated external radiotherapy.

In this work we study the descriptive power of the main tumor control probability (TCP) models based on the linear quadratic (LQ) mechanism of cell damage with cell recovery. The Poisson, binomial, and a dynamic TCP model, developed recently by Zaider and Minerbo are considered. The Zaider-Minerbo model takes cell repopulation into account. It is shown that the Poisson approximation incorporating cell repopulation is conceptually incorrect. Based on the Zaider-Minerbo model, an expression for the TCP for fractionated treatments with varying intervals between two consecutive fractions and with cell survival probability that changes from fraction to fraction is derived. The models are fitted to an experimental data set consisting of dose response curves that correspond to different fractionation regimes. The binomial TCP model based on the LQ mechanism of cell damage solely was unable to fit the fractionated response data. It was found that the Zaider-Minerbo model, which takes tumor cell repopulation into account, best fits the data.

Cell Proliferation↗
PubMed2004

Relationship between the generalized equivalent uniform dose formulation and the Poisson statistics-based tumor control probability model.

The generalized equivalent uniform dose (GEUD) model uses a power-law formalism, where the outcome is related to the dose via a power law. We herein investigate the mathematical compatibility between this GEUD model and the Poisson statistics based tumor control probability (TCP) model. The GEUD and TCP formulations are combined and subjected to a compatibility constraint equation. This compatibility constraint equates tumor control probability from the original heterogeneous target dose distribution to that from the homogeneous dose from the GEUD formalism. It is shown that this constraint equation possesses a unique, analytical closed-form solution which relates radiation dose to the tumor cell survival fraction. It is further demonstrated that, when there is no positive threshold or finite critical dose in the tumor response to radiation, this relationship is not bounded within the realistic cell survival limits of 0%-100%. Thus, the GEUD and TCP formalisms are, in general, mathematically inconsistent. However, when a threshold dose or finite critical dose exists in the tumor response to radiation, there is a unique mathematical solution for the tumor cell survival fraction that allows the GEUD and TCP formalisms to coexist, provided that all portions of the tumor are confined within certain specific dose ranges.

Algorithms↗
PubMed2004

The impact of daily shifts on prostate IMRT dose distributions.

It is becoming common clinical practice to shift prostate patients daily based on transabdominal ultrasound (US) or imaging of implanted fiducial markers. This paper investigates the dosimetric impact of these shifts by looking at five patients shifted using an optically guided 3D US localization system and treated with IMRT. Treatment plans were generated for each patient for the following 3 cases: (1) the initial preplan, which represents the ideal case in which no shifts are necessary; (2) a postplan incorporating each day's actual shifts; and (3) a postplan in which no shifts were made but the internal organs move by the amounts indicated by daily US imaging. Results show that when daily shifts are made, doses to the target, rectal wall, and bladder wall are nearly identical to those in the preplan. Equivalent uniform dose (EUD) and tumor control probability (TCP) for these plans were also the same as for the preplans. When no shifts were made, however, the dose distributions were degraded, and the computed target EUD and TCP were lower for all five patients. The magnitude of these differences varied: for three patients, the TCP was only 1%-2% lower than for the preplan. For the other two patients, however, the EUD was reduced by more than 10%, resulting in TCP reductions of 6% and 11%. These results indicate that for a symmetric beam arrangement and properly chosenmargins, shifting the patient each day and treating without recalculating the dose is unlikely toaffect local control or the sparing of normal tissues.

Humans↗
PubMed2005

Image-guided adaptive radiation therapy (IGART): Radiobiological and dose escalation considerations for localized carcinoma of the prostate.

The goal of this work was to evaluate the efficacy of various image-guided adaptive radiation therapy (IGART) techniques to deliver and escalate dose to the prostate in the presence of geometric uncertainties. Five prostate patients with 15-16 treatment CT studies each were retrospectively analyzed. All patients were planned with an 18 MV, six-field conformal technique with a 10 mm margin size and an initial prescription of 70 Gy in 35 fractions. The adaptive strategy employed in this work for patient-specific dose escalation was to increase the prescription dose in 2 Gy-per-fraction increments until the rectum normal tissue complication probability (NTCP) reached a level equal to that of the nominal plan NTCP (i.e., iso-NTCP dose escalation). The various target localization techniques simulated were: (1) daily laser-guided alignment to skin tattoo marks that represents treatment without image-guidance, (2) alignment to bony landmarks with daily portal images, and (3) alignment to the clinical target volume (CTV) with daily CT images. Techniques (1) and (3) were resimulated with a reduced margin size of 5 mm to investigate further dose escalation. When delivering the original clinical prescription dose of 70 Gy in 35 fractions, the "CTV registration" technique yielded the highest tumor control probability (TCP) most frequently, followed by the "bone registration" and "tattoo registration" techniques. However, the differences in TCP among the three techniques were minor when the margin size was 10 mm (< or = 1.1 %). Reducing the margin size to 5 mm significantly degraded the TCP values of the "tattoo registration" technique in two of the five patients, where a large difference was found compared to the other techniques (< or = 11.8 %). The "CTV registration" technique, however, did maintain similar TCP values compared to their 10 mm margin counterpart. In terms of normal tissue sparing, the technique producing the lowest NTCP varied from patient to patient. Reducing the margin size seemed the only sure way to reduce the NTCP significantly, irrespective of the IGART technique employed. In escalating the dose with the iso-NTCP constraint, the largest average gain in dose was observed with the "tattoo registration" technique, followed by the "CTV registration" and "bone registration" techniques. This is attributed to the fact that in three of the five patients, the "tattoo registration" technique yielded the lowest NTCP, hence a greater window of opportunity to escalate the dose was possible with this technique. However, the variation among the five patients was also largest with the "tattoo registration" technique where, in the case of one patient, the required dose actually needed to be below the original prescription dose of 70 Gy to satisfy the iso-NTCP constraint. This was not the case with the "CTV registration" technique where positive and similar dose escalation was allowed on all five patients. Based on these data, an attractive dose escalation strategy may be to implement the "CTV registration" technique (for consistent dosimetric coverage) for daily target localization in combination with a margin reduction (for increased normal tissue sparing).

Dose Fractionation, Radiation↗
PubMed2002

Amphetamine inhibits the N-methyl-D-aspartate receptor-mediated responses by directly interacting with the receptor/channel complex.

Amphetamine (AMPH) induces behavioral sensitization and neurotoxicity primarily by enhancing the dopamine-mediated neurotransmission. However, the involvement of the N-methyl-D-aspartate (NMDA) receptor in AMPH-induced neuropathology is also known. Recent investigation has found that high concentration of dopamine could inhibit NMDA receptor-mediated responses by blocking the NMDA receptor channel. By virtue of the structure similarity between dopamine and AMPH, we determined whether d-AMPH and its analogs, l-AMPH and methamphetamine (MAMH), could affect the NMDA receptor-mediated [3H]N-[1-(2-thienyl)cyclohexyl] piperidine ([3H]TCP) binding in rat cortical membrane preparations and intracellular 45Ca2+ accumulation and cell death in the rat primary cortical cell cultures. AMPH concentration-dependently inhibited NMDA- and glycine-stimulated [3H]TCP binding and intracellular 45Ca2+ accumulation with two distinct potencies; a minor inhibition with high potency and a major inhibition with low potency. [3H]TCP binding suggested that the high-potency inhibition was produced by decreasing agonist-induced activation of the NMDA receptor channel. On the other hand, the low-potency inhibition was produced by competing with [3H]TCP binding in the NMDA receptor channel, like the action of noncompetitive antagonist of the NMDA receptor. However, AMPH analogs were less potent in inhibiting NMDA- and glycine-induced cultured cell death. Thus, this result indicates that AMPH could antagonize the NMDA receptor-mediated responses in vitro by two different mechanisms, probably, through directly interacting with two distinct sites on this receptor/channel complex.

Amphetamines↗
PubMed1975

Effect of surfactants on antibiotic resistance.

The effectiveness of surfactants as potentiators of antibiotic activity on several resistant strains of bacteria, selected from clinical sources and laboratory collections, was studied using a tube dilution assay. Bacterial strains included members of the Enterobacteriaceae and staphylococci. Cetyltrimethylammonium bromide (CTAB), Tween 80 (Tw80), a mixture of n-alkyldimethyl betaines (L14), and alpha-(2,4,5-trichlorophenoxy) propionic acid (TCP) were tested in combination with pencillin G (PenG), methicillin (Met), streptomycin (Sm), polymyxin B (PmB), and chlortetracycline (CTC). Growth response to the drug combinations was compared with the response to each drug alone. CTAB and L14 but not Tw80 or TCP were found to potentiate the activity of CTC on strains of Escherichia coli, Proteus mirabilis, and Klebsiella pneumoniae. Studies on the inhibition of protein synthesis by CTC in cells of a strain of E. coli suggested that the surfactants increased the uptake of antibiotic into the cells. CTAB and L14 almost completely sensitized strains of P. mirabilis, Serratia marcescens, K. pneumoniae, and E. coli to PmB. With the exception of K. pneumoniae, TCP was also effective in potentiating the activity of PmB on the above strains whereas Tw80 showed potentiation only with a strain of E. coli. CTAB and L14 but not TCP or Tw80 potentiated the activity of PenG but not Met on strains of staphylococci. Studies of penicillinase in the cells suggested that the surfactants inhibited the formation of this enzyme possibly at the level of induction. None of the surfactants were found to potentiate the activity of Sm.

Anti-Bacterial Agents↗
PubMed1994

Nucleotide sequence and functional analysis of the genes encoding 2,4,5-trichlorophenoxyacetic acid oxygenase in Pseudomonas cepacia AC1100.

Pseudomonas cepacia AC1100 is able to use the chlorinated aromatic compound 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) as the sole source of carbon and energy. One of the early steps in this pathway is the conversion of 2,4,5-T to 2,4,5-trichlorophenol (2,4,5-TCP). 2,4,5-TCP accumulates in the culture medium when AC1100 is grown in the presence of 2,4,5-T. A DNA region from the AC1100 genome has been subcloned as a 2.7-kb SstI-XbaI DNA fragment, which on transfer to Pseudomonas aeruginosa PAO1 allows the conversion of 2,4,5-T to 2,4,5-TCP. We have determined the directions of transcription of these genes as well as the complete nucleotide sequences of the genes and the number and sizes of the polypeptides synthesized by pulse-labeling experiments. This 2.7-kb DNA fragment encodes two polypeptides with calculated molecular masses of 51 and 18 kDa. Proteins of similar sizes were seen in the T7 pulse-labeling experiment in Escherichia coli. We have designated the genes for these proteins tftA1 (which encodes the 51-kDa protein) and tftA2 (which encodes the 18-kDa protein). TftA1 and TftA2 have strong amino acid sequence homology to BenA and BenB from the benzoate 1,2-dioxygenase system of Acinetobacter calcoaceticus, as well as to XylX and XylY from the toluate 1,2-dioxygenase system of Pseudomonas putida. The Pseudomonas aeruginosa PAO1 strain containing the 2.7-kb SstI-XbaI fragment was able to convert not only 2,4,5-T to 2,4,5-TCP but also 2,4-dichlorophenoxyacetic acid to 2,4-dichlorophenol and phenoxyacetate to phenol.

Amino Acid Sequence↗
PubMed1999

Lysogenic conversion of environmental Vibrio mimicus strains by CTXPhi.

The filamentous bacteriophage CTXPhi, which encodes cholera toxin (CT) in toxigenic Vibrio cholerae, is known to propagate by infecting susceptible strains of V. cholerae by using the toxin coregulated pilus (TCP) as its receptor and thereby causing the origination of new strains of toxigenic V. cholerae from nontoxigenic progenitors. Besides V. cholerae, Vibrio mimicus strains which are normally TCP negative have also been shown to occasionally produce CT and cause diarrhea in humans. We analyzed nontoxigenic V. mimicus strains isolated from surface waters in Bangladesh for susceptibility and lysogenic conversion by CTXPhi and studied the expression of CT in the lysogens by using genetically marked derivatives of the phage. Of 27 V. mimicus strains analyzed, which were all negative for genes encoding TCP but positive for the regulatory gene toxR, 2 strains (7.4%) were infected by CTX-KmPhi, derived from strain SM44(P27459 ctx::km), and the phage genome integrated into the host chromosome, forming stable lysogens. The lysogens spontaneously produced infectious phage particles in the supernatant fluids of the culture, and high titers of the phage could be achieved when the lysogens were induced with mitomycin C. This is the first demonstration of lysogenic conversion of V. mimicus strains by CTXPhi. When a genetically marked derivative of the replicative form of the CTXPhi genome carrying a functional ctxAB operon, pMSF9.2, was introduced into nontoxigenic V. mimicus strains, the plasmid integrated into the host genome and the strains produced CT both in vitro and inside the intestines of adult rabbits and caused mild-to-severe diarrhea in rabbits. This suggested that in the natural habitat infection of nontoxigenic V. mimicus strains by wild-type CTXPhi may lead to the origination of toxigenic V. mimicus strains which are capable of producing biologically active CT. The results of this study also supported the existence of a TCP-independent mechanism for infection by CTXPhi and showed that at least one species of Vibrio other than V. cholerae may contribute to the propagation of the phage.

Animals↗