Replacement of lateral line sensory organs during tail regeneration in salamanders: identification of progenitor cells and analysis of leukocyte activity

It has been proposed that supporting cells may be the progenitors of regenerated hair cells that contribute to recovery of hearing in birds, but regeneration is difficult to visualize in the ear, because it occurs deep in the skull. Hair cells and supporting cells that are comparable to those in the ear are present in lateral line neuromasts, and in axolotl salamanders these cells are accessible to microscopic observation in vivo. After amputation of a segment of the tail that contains neuromasts, cells from the posteriormost neuromast on the tail stump divide rapidly and form a migratory regenerative placode. The cells of the regenerative placode represent a lineage that eventually produces both hair cells and supporting cells in replacement neuromasts. We sought to identify the progenitors of the regenerative placode by using differential interference contrast microscopy combined with time-lapse video recording in living axolotl salamanders. In response to amputation, the mantle-type supporting cells at the posteroventral edge of the neuromast that is nearest to the wound increased their frequency of cell division, and gave rise to the first cells of the placode. The increase in mitotic activity of mantle-type supporting cells was accompanied by an unexplained decrease in the frequency of divisions in the same neuromast's population of internal supporting cells. The time-lapse records suggested that the changes in the mitotic activity of supporting cells might have been linked to the presence of phagocytic leukocytes in the vicinity of the neuromast that was nearest to the wound. Leukocytes were evenly distributed around control neuromasts, but during regeneration leukocyte activity increased significantly in the vicinity of the posterior half of the posteriormost neuromast. The redistribution of leukocytes occurred early in the regenerative response, but a causal role for the leukocytes has not been conclusively established. It is possible that the leukocytes could contribute to the formation of the regenerative placode at that location by breaking down the glycocalyx that ensheaths the outermost cells of the neuromast, or through the secretion of mitogenic growth factors.     

Leafbladeless1 is required for dorsoventrality of lateral organs in maize

The maize leafbladeless1 (lbl1) mutant displays a variety of leaf and plant phenotypes. The most extreme manifestation in the leaf is the formation of radially symmetric, abaxialized leaves due to a complete loss of adaxial cell types. Less severe phenotypes, resulting from a partial loss of adaxial cell identity, include the formation of ectopic laminae at the boundary between abaxialized, mutant sectors on the adaxial leaf surface and the bifurcation of leaves. Ectopic laminae and bifurcations arise early in leaf development and result in an altered patterning of the leaf along the proximodistal axis, or in complete duplication of the developing organ. Leaf-like lateral organs of the inflorescences and flowers show similar phenotypes. These observations suggest that Lbl1 is required for the specification of adaxial cell identity within leaves and leaf-like lateral organs. Lbl1 is also required for the lateral propagation of leaf founder cell recruitment, and plays a direct or indirect role in the downregulation of the homeobox gene, knotted1, during leaf development. Our results suggest that adaxial/abaxial asymmetry of lateral organs is specified in the shoot apical meristem, and that formation of this axis is essential for marginal, lateral growth and for the specification of points of proximodistal growth. Parallels between early patterning events during lateral organ development in plants and animals are discussed.     

The PHANTASTICA gene encodes a MYB transcription factor involved in growth and dorsoventrality of lateral organs in Antirrhinum

To study the impact of yeast populations on wine flavour and to better understand yeast growth dynamics, wines were produced by the (i) indigenous microflora, (ii) vigorous yeast starter EC1118 and (iii) slowly fermenting yeast Assmannshausen. Sensory analysis revealed that wines differed depending on the fermentation type. However, these yeast-related differences did not exceed the varietal character. Both added starter cultures clearly dominated the Saccharomyces population from the middle of fermentation onwards. The starter cultures differed in their repression of indigenous non-Saccharomyces yeast. EC1118 limited growth of non-Saccharomyces yeasts more strongly than Assmannshausen. Sulphite addition further repressed growth of non-Saccharomyces yeasts. On completion, more than one Saccharomyces strain was present in each fermentation, with the largest variety in the non-inoculated and the smallest in the EC1118-inoculated fermentation. Results from the two genetic assays, karyotyping, and PCR using delta-primers were not fully equivalent, limiting the usefulness of delta-PCR in studies of native Saccharomyces yeasts.     

Responses of cells of posterior lateral line lobe to activation of electroreceptors in a mormyrid fish

Activity of neurons in the lateral line lobe was studied by intracellular recording of responses to stimulation of the lateral line nerves and of electroreceptors on the skin surface. Two modes of activation occur for cells responding to inputs from medium receptors. There is a direct monosynaptic input mediated by a single fiber. Short latency of response and antidromic spread from cell to afferent fiber indicate that the mediating synapse is electrotonic. The second input is from a number of additional fibers and is relayed, presumably by the granule cells. At shortest latency this input is disynaptic, probably involving at least one electrotonic synapse. A relay is indicated by heterosynaptic facilitation of the PSP and by pronounced depression with repetitive stimulation. The monosynaptic input may be on the axon. Disynaptic inputs are distributed over the dendrites, and impulses can arise in the dendrites. What appear to be spikes restricted to dendritic regions are often recorded as small brief potentials in the cell body. There is a somatotopic projection of the electroreceptors to the lateral line lobe. The monosynaptic input comes from a specific receptor in the periphery. Strong disynaptic inputs come from a group of receptors generally found anterior, but less commonly posterior or lateral, to the receptor giving rise to the monosynaptic input. Additional inputs that are inhibitory come from surrounding receptors. The inhibition only affects responses to the disynaptic input. The different inputs and multiple sites of impulse initiation must modify the cell's response as compared with the input-output relations that would be obtained with inputs acting on a single summation point. Cells responding to activation of large receptors are infrequent. They are characterized by low threshold, little latency change near threshold, and ability to follow high frequencies of stimulation.     

Medicine taking in Southampton: a second look

1. A 1 in 200 sample of the Southampton electorate were sent a postal questionnaire in January 1993. Of the 756 adults surveyed, 400 (52.9%) returned completed questionnaires. One hundred and eighty-eight (47.0%) of the respondents had been prescribed a medicine within the previous month. 2. Compared with a survey 9 years earlier, medicine taking had increased amongst men (44.1% vs 33.7% NS) and drugs acting on the respiratory system were in more widespread use (19 vs 7 patients P < 0.05). 3. Patterns of storage of medicines were almost identical to those found in 1984. However, methods of disposal were significantly different with 34% of the respondents stating that they would return left-over medicines to the Doctor or Pharmacist compared with 17% in the previous study (P < 0.01). 4. Of those taking medicines 120 (63.8%) had received a manufacturers' information leaflet. Medicines used to treat disorders of the respiratory and cardiovascular systems were most likely to be accompanied by such a leaflet (74% and 70% respectively). 5. Those who received a leaflet were almost all satisfied by it. However, patient awareness of potential side effects remained poor with only 30% being aware of any which their medicine might cause. 6. Despite improvements in attitudes towards medicine taking over time patients awareness of potential adverse effects remains limited. Further research is necessary in order to determine how best to educate patients on this topic.     

Variation in HLA-DM expression influences conversion of MHC class II alpha beta:class II-associated invariant chain peptide complexes to mature peptide-bound class II alpha beta dimers in a normal B cell line

The maturation of invariant chain (Ii):MHC class II complexes into peptide-loaded alpha beta dimers occurs by proteolytic removal of Ii chain and binding of antigenic peptides derived from exogenous and endogenous Ags. A fragment of the Ii chain (class II-associated invariant chain peptide (CLIP) remains associated with class II alpha beta and is an intermediate in this process. Conversion of alpha beta:CLIP complexes into alpha beta:peptide complexes is facilitated by HLA-DM. Two unique mAbs, specific for I-Ab bound to human CLIP and I-Ab bound to DR alpha peptide, were used to assess the formation of these peptide:class II complexes in a human B lymphoblastoid cell line (B-LCL) (Swei) transfected with I-A(b). In multiple independent Swei:I-Ab transfectants, the amount of human CLIP (hCLIP):I-Ab expressed was inversely proportional to the amount of DR alpha 52-68:I-Ab; quantitative differences in HLA-DM expression accounted for this phenotype. In the low DM transfectant, a substantial proportion of I-Ab, but not DR molecules, was altered structurally and unable to present native protein Ags. Addition of DM transgenes to the DM-low cells resulted in an increase in DR alpha 52-68:I-Ab coupled with a decrease in hCLIP:I-Ab complexes and restoration of exogenous protein Ag presentation. The DR5 molecules in Swei cells, which have a lower affinity for hCLIP than I-Ab, were not affected by low DM expression, suggesting that the amount of DM required for conversion of CLIP:class II to peptide:class II may depend on the affinity of the class II molecules for CLIP or DM.     

Clinical evaluation of panipenem/betamipron as a second line chemotherapy in severe infections associated with hematological disorders

Thirty three patients with severe infections associated with hematological disorders were treated with panipenem/betamipron as a second line chemotherapy. Of these, 30 patients were evaluated for effectiveness. An excellent response was obtained in 14 patients (46.7%) and a good response in 5 (16.7%), and the overall efficacy rate was 63.3%. Efficacy rates were 3/6 in patients with sepsis, 68.4% (13/19) in patients with fever of undetermined origin, 2/4 in patients with pneumonia. In patients whose peripheral granulocyte count was below 100/microliter at the start of chemotherapy, the efficacy rate was 3/7. Side effects were observed in 5 of 33 patients (15.2%). These results show that PAPM/BP is useful as a second line chemotherapy for the treatment of severe infections in patients with hematological disorders.     

一类二阶多时滞泛函微分方程多个周期解的存在性

利用重合度理论获得了二阶多时滞泛函微分方程xw(t)+f(t,x(t-τ1(t),x(t-τ2(t)))(x'(t))n+f(x(t))·x'(t)+a(t)x2(t-τ3(t))+b(t)x(t-τ3(t))=p(t)(n≥2)多个周期解的存在性,得到了这类方程至少存在2个周期解的结论.     

Transformation of peripheral inputs by the first-order lateral line brainstem nucleus

Extracellular recording techniques were used to record the responses of medial nucleus cells and posterior lateral line nerve fibers in mottled sculpin, Cottus bairdi, and goldfish, Carassius auratus, to a 50-Hz dipole source (vibrating sphere). Responses were characterized in terms of (1) receptive fields that relate responsiveness (spike rate and phase-locking) to the location of the source along the length of the fish, (2) input-output functions that relate responsiveness to vibration amplitude for a fixed source location, and (3) peri-stimulus time histograms that relate responsiveness to time during a sustained period of vibration. Relative to posterior lateral line nerve fibers, medial nucleus cells in both species were similar in showing (1) lower spontaneous and evoked rates of spike activity, (2) greater degrees of adaptation, (3) greater heterogeneity in all response characteristics, and (4) evidence for inhibitory/excitatory interactions. Whereas receptive fields of nerve fibers in both species faithfully reflect both pressure gradient amplitudes (with rate changes) and directions (with phase-angle changes) in the stimulus field, receptive fields of medial nucleus were more difficult to relate to the stimulus field, Some, but not all, receptive fields could be modeled with excitatory center/inhibitory surround and inhibitory center/excitatory surround organizations.     

Amyotrophic lateral sclerosis: a lesson in deficiency diseases

Amyotrophic lateral sclerosis (ALS) is an age-dependent degeneration of motor neurons in the central nervous system. ALS is not caused by faulty nutrition. Recent data suggest that ALS could be an oxidative neurotoxicity induced by a mutation in the SOD1 protein. This finding extends beyond the simple loss of an antioxidant enzyme.     

Fine structure of the medullary lateral line area of Chelon labrosus (order perciformes), a nonelectroreceptive teleost

Changes in serum levels of rat tissue kallikrein (rK1) in venous blood were measured, using a newly developed radioimmunoassay, before and after autonomic nerve stimulations of submandibular salivary secretion. rK1 secreted into saliva under these conditions was measured by radioimmunoassay and by enzymic activity assay, using the fluorogenic peptide substrate D-Val-Leu-Arg-7-amino-4-trifluoromethylcoumarin (AFC). Following an overnight fast, serum rK1 concentration was 30-40 ng ml-1. Unilateral electrical stimulation of the submandibular sympathetic nerve supply (at 50 Hz in bursts of 1 s every 10 s for 60 min) evoked a small flow of saliva with a very high rK1 concentration, resulting in a large output of rK1 of 2104.4 +/- 603.5 micrograms (n = 6). Such stimulation caused a large degranulation of granular duct cells and a corresponding reduction in glandular rK1 content. Unilateral electrical stimulation of the parasympathetic nerve supply (at 5 Hz continuously for 60 min) evoked a copious flow of saliva with a very low rK1 concentration, resulting in a low output of rK1 (18.1 +/- 4.9 micrograms; n = 6). Despite these large differences in salivary outputs of rK1, serum concentrations of rK1 were increased similarly following either sympathetic or parasympathetic stimulation by 48 and 46%, respectively. If the submandibular duct was briefly obstructed during sympathetic stimulation, inducing leakage and glandular oedema, then serum rK1 increased greatly (40-fold); a similar increase to that seen by others in previous studies without deliberate obstruction. Four days after bilateral submandibular-sublingual sialadenectomy serum rK1 concentration was reduced by approximately 50%. The results indicate that submandibular glands normally contribute to circulating levels of rK1 in rats, but this contribution is independent of the amounts of rK1 secreted into saliva by sympathetically induced exocytosis, and is likely to arise from basal vesicular transport. However, if glandular leakage occurs during sympathetic stimulation of submandibular secretion this then causes increases in the circulating levels of rK1 that correlate with the large amounts being secreted into saliva.     

Editorial: Sex and alcohol: a second peek

The effects of alcohol on male sexual function is discussed. Various phenomena affecting sexual function in males have been reported: 1) increased conversion of androgens to estrogens in the liver, 2) interconversion of weak and potent estrogens, 3) increased rate of conversion of adrenocortical steroid precursor to estrogenic substances, 4) decreased plasma levels of luteinizing hormone(LH) and follicle stimulating hormone (FSH), and 5) diminished uptake of androstenedione by the liver and increased peripheral conversion to estrone. It is proposed that the pathogenesis of feminization in alcoholic males may be due partly to the derivative effects of liver damage and to a direct action of alcohol on the testes. Rats fed alcohol have shown atrophy of the gonads and accessory organs, and impaired spermtogenesis. In normal men ingesting alcohol for short periods of time, the frequency and intensity of bursts of testosterone secretion by the testes is dampened, and testosterone concentrations and production rates are increased while the metabolic clearance of testosterone is diminished. Deranged hypothalamic-pituitary function has also been observed. Further research is needed to elucidate the mechanism(s) by which alcohol influences sexual function.     

Environmental factors in cancer of the larynx: a second look

During a retrospective case-control study of recent laryngeal cancer patients, several associated factors were studied to determine possible changes in the epidemiology of laryngeal cancer between 1956 and 1974. The large sex difference noted in the early survey (male: female ratio of 14.9:1) diminished considerably in the present sample (4.6:1) because more women are cigarette smokers in the cancer age group today than was the case 20 years ago. Laryngeal cancer patients tended to be less educated than the controls and included a smaller proportion of Jews and more Catholics than the control group. The risk for developing laryngeal cnacer was considerably lower for exsmokers and long-term (10+ years) filter cigarette smokers as compared with non-filter smokers. At each level of alcohol consumption, the risk increased as exposure to tobacco increased. Occupations associated with wood exposure were found to affect the development of laryngeal cancer, independently of smoking status. Future studies should include an extensive study of nutritional deficiencies associated with alcoholism to determine if a correlation exists between such deficiencies, socioeconomic status, and an increased risk of laryngeal cnacer.     

Eye movement in amyotrophic lateral sclerosis: a longitudinal study

Conservative therapy in cases of severe dysthyroid ophthalmopathy (DO) has not given satisfactory results. Since 1986, 51 patients (99 orbits) with marked DO have been treated by surgical decompression of the orbits. The procedure begins within the upper eyelid. The excision of the excessive skin and subcutaneous tissue is performed and eyelid fat is removed. In order to obtain the correction of the upper eyelid retraction, the levator aponeurosis is divided by 2-3 transverse incisions in its central part and Muller's muscle is sectioned at the level of its tarsal insertion. Through an incision in the lower eyelid, the posterior part of the orbital floor, the lateral orbit wall, as well as the periorbital and intraorbital fat are removed. Through an incision made over the medial margin of the orbit, the ethmoidal part of the medial orbital wall and the retrobulbar fat are removed. The periorbital periosteum should be incised at several sites. After operation all patients showed a significant reduction of exophthalmos (5-11 mm, 7.16 mm on average), significant reduction of intraocular pressure, marked improvement in ocular muscle function, as well as considerable reduction or disappearance of subjective symptoms. There was an improvement in vision in 68% patients who had impaired vision before the operation. There were no cases of subsequent impairment of vision or ocular motility. Mild relapse was recorded in three cases only and only one patient required unilateral reoperation. Strabismus surgery had to be performed in five patients due to unsatisfactory correction of double vision. It can be concluded that this method of orbital decompression gives very good functional and aesthetical long-term results.     

Germinal centers: a second childhood for lymphocytes

Recent observations show that, in the peripheral lymphoid organs known as germinal centers, lymphocytes appear to regain the phenotypic and molecular traits of immature cells; this cellular regression may play an important role in the affinity maturation of immune responses.     

Study of the central representation of the posterior nerve of the lateral line in dwarf sheatfish

Applying the axon-terminal degeneration method, the representation of the lateral line posterior nerve in acustico-lateral area of the dwarf sheatfish medulla oblongata was studied. The connections of the lateral line posterior nerve were demonstrated to be topically organized within the medial nucleus of the acustico-lateral area, however, within the limits of the nucleus the projections were not evenly distributed. The greatest degree of localization of the degenerated terminals was revealed in the dorsolateral area of the medial nucleus on the ipsilateral side, where previously, under adequate stimulation of the organs on the lateral line of the dwarf sheatfish, the greatest amount of responses was registered.