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Long-term follow-up of thoracoscopic splanchnicectomy for chronic pancreatitis pain.

BACKGROUND: Thoracoscopic splanchnicectomy (SPL) has been reported to give excellent short-term pain relief in chronic pancreatitis. This study prospectively evaluates the long-term efficacy of SPL in pancreatitis patients. METHODS: Chronic pancreatitis patients with severe pain unrelieved by standard therapy completed a standard 10-point analogue pain scale prior to surgery and at postoperative visits. Midline and left-sided pain was treated with left SPL; right-sided pain was treated with right SPL. If pain recurred on the contralateral side, contralateral SPL was done. RESULTS: Fifteen patients underwent SPL. Eleven of them required narcotics preoperatively. Follow-up is complete and ranges from 4.2 to 6.1 years (median, 5.75). All patients had constant pain prior to surgery. Following SPL, it decreased in the short term to a mean of 3.9 attacks a month. At long-term follow-up, the mean number of attacks was 8.6 per month. Preoperatively, the mean score for worst pain within the last 2 months was 9.1. This score decreased to 3.9, but at long-term follow-up it had increased to near preoperative values (8.6). Current severity of pain decreased from 7.2 preoperatively to 2.9 at short-term follow-up, but at long-term follow-up it had increased. The degree of disability decreased from 9.1 preoperatively to 5.1 at short-term follow-up, but in the long term it increased toward preoperative values. Although eight patients were narcotic free at early follow-up, only three remained narcotic free in the long-term. CONCLUSION: Thoracoscopic SPL offers short-term relief of pain from chronic pancreatitis, but the relief is not durable in most cases. Similarly, there are short-term improvements in degree of disability, mood, and freedom from narcotic use that are not sustained in the long-term. Nevertheless, two-thirds of patients stated that they would have the surgery again.

Abdominal Pain↗

Natural anti-chondrocyte cytotoxic activity in the mouse: supportive role of macrophages.

The role of macrophages (M phi) in natural anti-chondrocyte cytotoxic activity of normal murine splenocytes (SPL) and peritoneal cells (PC) was examined by means of an 18-hr 51Cr-release assay. Removal of M phi by either plastic adherence or carbonyl iron and magnet resulted in significant (P less than 0.01) reduction of SPL-mediated lysis of chondrocytes. It, however, did not influence natural anti-YAC-1 leukemia activity. On the contrary, M phi-depleted suspensions of PC retained their anti-chondrocyte activity at the initial level. Neither adherent SPL nor adherent PC exerted significant anti-chondrocyte cytotoxicity. The activity of nonadherent SPL could be, however, restored by reconstitution with the graded numbers of syngeneic adherent spleen- or peritoneal cavity-derived cells. Restoration of anti-chondrocyte activity of nonadherent SPL to the level comparable with that of untreated SPL was achieved with about 10% of adherent cells. On the other hand, reconstitution of nonadherent PC did not result in an increase of chondrocyte lysis. Potentiation of nonadherent SPL activity was seen only with syngeneic M phi, and the latter could not be replaced by conditioned media which were generated in the 18-hr culture of adherent SPL or PC.

Animals↗

Noise exposure induces up-regulation of ecto-nucleoside triphosphate diphosphohydrolases 1 and 2 in rat cochlea.

Extracellular ATP acting via P2 receptors in the inner ear initiates a variety of signaling pathways that may be involved in noise-induced cochlear injury. Nucleoside triphosphate diphosphohydrolase (NTPDase)1/CD39 and NTPDase2/CD39L1 are key elements for regulation of extracellular nucleotide concentrations and P2 receptor signaling in the cochlea. This study characterized the effect of noise exposure on regulation of NTPDase1 and NTPDase2 expression in the cochlea using a combination of real-time RT-PCR, immunohistochemistry and functional studies. Adult Wistar rats were exposed to broad band noise at 90 dB and 110 dB sound pressure level (SPL) for 72 h. Exposure to 90 dB SPL induced a small and temporary change of auditory thresholds (temporary threshold shift), while exposure to 110 dB SPL induced a robust and permanent change of auditory thresholds (permanent threshold shift). NTPDase1 and NTPDase2 mRNA transcripts were upregulated in the cochlea exposed to 110 dB SPL, while mild noise (90 dB SPL) altered only NTPDase1 mRNA expression levels. Changes in NTPDases expression did not correlate with levels of circulating corticosterone, implying that the up-regulation of NTPDases expression was not stress-related. Semi-quantitative immunohistochemistry in the cochlea exposed to 110 dB SPL localized the increased NTPDase1 and NTPDase2 immunostaining in the stria vascularis and up-regulation of NTPDase2 in the intraganglionic spiral bundle. In contrast, NTPDase1 was down-regulated in the cell bodies of the spiral ganglion neurones. Distribution of NTPDases was not altered in the cochlea exposed to 90 dB SPL. Functional studies revealed increased ectonucleotidase activities in the cochlea after exposure to 110 dB SPL, consistent with up-regulation of NTPDases. The changes in NTPDases expression may reflect adaptive response of cochlear tissues to limit ATP signaling during noise exposure.

Acoustic Stimulation↗

Lactic acid bacterium potently induces the production of interleukin-12 and interferon-gamma by mouse splenocytes.

We previously have reported that the lactic acid bacterium, Lactobacillus casei strain Shirota (LcS), shows marked antitumor activities and an ability to modify immune responses. In this study, we examined whether LcS can induce the production of interleukin (IL)-12 and interferon-gamma (IFN-gamma), which are important cytokines for antitumor and antimicrobial immunity, from murine splenocytes in vitro in order to clarify the mechanisms of its immune modification. Stimulation by LcS induced a marked production of IL-12 by X-ray-irradiated splenocytes (X-irr-Spl). The production of IL-12 by X-irr-Spl was independent of the presence of nylon wool column-passed splenocytes (NW-Spl). IFN-gamma was produced by splenocytes by the stimulation with concanavalin A (Con A). LcS showed a synergistic stimulatory effect on the ConA-induced production of IFN-gamma. In addition, X-irr-Spl were required for the IFN-gamma; production by NW-Spl treated with LcS. The IFN-gamma production was reduced by anti-IL-12 antibody treatment. NW-Spl produced IFN-gamma following treatment with recombinant IL-12. Thus, we confirmed that IFN-gamma production by splenocytes was the result of the production of IL-12 from X-irr-Spl stimulated by LcS. Furthermore, in BALB/c mice, the oral administration of viable LcS augmented the production of IFN-gamma but not that of IL-4 or IL-5 by splenocytes. Thus, we suggested that LcS primarily activated X-irr-Spl, probably macrophages, and these cells secreted IL-12. The IL-12 induced by LcS stimulated the production of IFN-gamma.

Animals↗

Functional, life-threatening disorders and splenectomy following liver transplantation.

UNLABELLED: Splenectomy (SPL) in cirrhotic patients undergoing liver transplantation (LTx) may resolve specific problems related to the procedure itself, in case of functional and life-threatening clinical situations often occurring as a result of liver cirrhosis and portal hypertension. METHOD: A single-center experience of ten splenectomies in a series of 180 consecutive adult liver transplant patients over a period of 6 yr is reported. The mean patient age was 46.8 +/- 9.5 yr (range 25 57 yr). Indications for SPL were post-operative massive ascitic fluid loss (n = 3), severe thrombocytopenia (n = 3), acute intra-abdominal hemorrhage (n = 2), infarction of the spleen (n = 1), and multiple splenic artery aneurysms (n = 1). RESULTS: Extreme ascites production due to functional graft congestion disappeared post-SPL, with an improvement of the hepatic and renal functions. SPL was also effective in cases of thrombocytopenia persistence post-LTx, leading to an increase in the platelet count after about 1 wk. Bleeding episodes related to left-sided portal hypertension or trauma were also resolved. The rejection rate during hospitalization was 0%, and no other episodes were recorded in the course of the long-term follow-up. However, sepsis with a fatal outcome occurred in 4 patients, i.e. between 2 and 3 wk post-SPL in three cases and 1 yr after the procedure as a result of pneumococcal infection in the last case. Fatal traumatic cranial injury occurred 3 yr post-LTx in another case. Five patients (50%) are still alive and asymptomatic after a median follow-up period of 36 months. CONCLUSION: The lowering of the portal flow appears to resolve unexplained post-operative ascitic fluid loss as a result of functional graft congestion following LTx. However, because of the enhanced risk of SPL-related sepsis, a partial splenic embolization (PSE) or a spleno-renal shunt could be used as an alternative procedure because it allows us to preserve the immunological function of the spleen. SPL is indicated in case of post-transplant bleeding due to left-sided portal hypertension and trauma, spleen infarction, and to enable prevention of hemorrhage in liver transplant patients with multiple splenic artery aneurysms. Severe and persistent thrombocytopenia could be treated with PSE. Because the occurrence of fatal sepsis post-SPL is a major complication in LTx, functional disorders, such as ascites and thrombocytopenia, should be treated with a more conservative approach.

Acute Disease↗

A tripartite interaction among alleles of Notch, Delta, and Enhancer of split during imaginal development of Drosophila melanogaster.

A dramatic example of a phenotypic interaction that involves neurogenic loci during Drosophila imaginal development is the synergistic impact of split (spl), a recessive allele of the Notch locus, and E(spl)D, a dominant gain-of-function allele of the Enhancer of split locus, on morphogenesis of the compound eye. Screens for mutations that relieve the enhancing effect of E(spl)D on spl have yielded three classes of mutations: intragenic revertants of the E(spl)D allele, extragenic suppressors that are allelic to the neurogenic gene Delta (Dl) and unlinked extragenic modifiers. Analysis of the suppression of the spl-E(spl)D interaction by various Dl alleles indicates that this modification is sensitive to the dosage of the Dl locus. This tripartite interaction illustrates the combinatorial action of N, Dl and E(spl) during imaginal development.

Alleles↗

Normal hearing thresholds for clicks.

This paper evaluates the normal hearing thresholds for clicks and assesses the effects on these thresholds of varying the duration of the listening period and the presentation rate, polarity, and symmetry of the clicks. There were no significant changes in thresholds as the listening period decreased from 2s to 300 mg. There was, however, a 2.5 dB increase in threshold at the listening period decreased from 300 to 100 ms. Increase stimulus presentation rate from 5 to 80/s decreased threshold 4.5 dB per tenfold change in rate. There were no significant differences in threshold between rarefaction and condensation clicks. The average threshold obtained from 40 normal young adults using 100-microseconds square-wave clicks presented through a TDH-49 earphone at 10/s was 36.4-dB peak SPL or 29.9 peak equivalent SPL. Neither peak SPL nor peak equivalent SPL measurements gave consistent thresholds for clicks with different degrees of symmetry. A root-mean-square measure of the pressure over the initial millisecond-SPL(1 ms)-gave a threshold of 25.6 dB. This SPL(1ms) measure of threshold proved to be far more consistent for clicks with different degrees of symmetry than either the peak SPL or the peak equivalent SPL measures.

Adolescent↗

The influence of systematic primary-tone level variation L2-L1 on the acoustic distortion product emission 2f1-f2 in normal human ears.

The purpose of the present study was to determine the effect of primary-tone level variation, L2--L1, on the amplitude of distortion-product otoacoustic emissions (DPOAEs). The DPOAE at the frequency 2f1--f2 (f2 greater than f1) was measured in 20 ears of ten normally hearing subjects. Acoustic distortion products were generated by primaries f1 and f2 with geometric mean frequencies of 1, 2, and 4 kHz. The f2/f1 ratios were 1.25 (1 kHz), 1.23 (2 kHz), and 1.21 (4 kHz). The primary-tone level L1 was kept constant at either 65 or 75 dB SPL while the second primary-tone level L2 was varied between 20 and 90 dB SPL in 5-dB steps. The level differences L2--L1 generating maximal DPOAE amplitudes depended on L1 and on the geometric mean frequency of f1 and f2. There were large interindividual differences. Overall, the L2--L1 evoking maximal mean DPOAE amplitudes was --10 dB for geometric mean frequencies of 1 and 2 kHz with both L1 = 65 dB SPL and L1 = 75 dB SPL. For 4 kHz, L2-L1 was --5 dB with L1 = 65 dB SPL and 0 dB with L1 = 75 dB SPL. The mean slopes of the DPOAE growth functions in the initial linearly increasing portions were steeper at higher stimulus frequencies, increasing from 0.52 at 1 kHz to 0.72 at 4 kHz for L1 = 65 dB SPL and from 0.48 at 1 kHz to 0.72 at 4 kHz for L1 = 75 dB SPL.

Adult↗

Protection against acoustic trauma by forward and backward sound conditioning.

The purpose of the present study was to determine if short-term sound conditioning provides protection when delivered either before (forward sound conditioning) or after (backward sound conditioning) a traumatic exposure in the guinea pig. Two different sound conditioning paradigms were studied (1 kHz, 81 dB SPL, 24 h; 6.3 kHz, 78 dB SPL, 24 h). The 1-kHz forward sound conditioning paradigm (81 dB SPL, 24 h) protected distortion product otoacoustic emissions (DPOAEs) against a short-duration acoustic trauma (2.7 kHz, 103 dB SPL, 5 min) compared to the group exposed to the acoustic trauma alone. The 1-kHz forward sound conditioning paradigm (81 dB SPL, 24 h) also protected both the auditory brainstem response (ABR) thresholds and DPOAEs against a longer-duration acoustic trauma (2.7 kHz, 103 dB SPL, 30 min). The group exposed to the acoustic trauma alone showed ABR threshold shifts between 15 and 24 dB, and DPOAE amplitude shifts between 11 and 24 dB, while the group with 1-kHz forward sound conditioning showed statistically significant protection at all ABR frequencies and at all DPOAE frequencies. The 1-kHz backward sound conditioning paradigm protected against acoustic trauma (2.7 kHz, 103 dB SPL, 30 min). The ABR thresholds were protected at 1, 2 and 4 kHz, and DPOAEs at all frequencies (except 8 kHz) when compared to the group exposed only to the acoustic trauma. The 6.3-kHz forward sound conditioning paradigm protected against acoustic trauma (5.5 kHz, 109 dB SPL, 30 min) at 6.3, 8 and 10 kHz. The 6.3-kHz backward sound conditioning paradigm showed no protection against acoustic trauma at any DPOAE frequency. Taken together, these findings are important for understanding how the auditory system can be modulated by acoustic stimulation and highlights the importance of the acoustic environment during the recovery process of the auditory system.

Acoustic Stimulation↗

Secretory disorders in pituitary thyrotropes of streptozocin-diabetic male rats.

Pituitary cells transport secretory products from deep cytoplasmic portions towards the subplasmalemmal region (SPL) by two mechanisms: (a) the regulated, secretagogue-dependent and (b) the secretagogue-independent constitutive pathway. Since thyrotropin (TSH) secretion is impaired in diabetes, we studied both pathways in the thyrotropes of control and streptozocin (STZ)-treated male rats. By electron microscopy, we measured the nucleus and cytoplasm area and counted the secretory granules. In 4 selected SPL (500 nm deep) areas per cell we also counted the marginated secretory granules and measured their area. Moreover, after TSH indirect immunogold labelling we counted immunogold particles on (a) the secretory granules of the SPL and (b) the intergranular SPL cytoplasm. To check the background staining we also counted immunogold particles on nonthyrotropic cells. In diabetic compared with control thyrotropes we found: (a) cytoplasmic atrophy and increased number of secretory granules per cytoplasm unit area, (b) reduced number of secretory granules in the SPL (blunted regulated secretion), (c) larger secretory granules in the SPL (abnormal secretory granule maturation), (d) decreased immunogold labelling of secretory granules in the SPL (reduced TSH transported by each secretory granule towards the cell membrane) and (e) decreased immunogold labelling of the intergranular SPL cytoplasm (blunted constitutive secretion). Our data suggest reduced regulated and constitutive TSH secretion and may thus contribute to a better understanding of the hypothyroidism in STZ-diabetic rats.

Animals↗

Reduced number and LH content of marginated secretory granules in pituitary gonadotropes of streptozocin-induced diabetic male rats.

The transport of secretory granules towards the subplasmalemmal (SPL) region of the luteinizing-hormone (LH) gonadotrope is controlled by the LH-releasing-hormone-dependent pathway. The SPL granules contain the most readily releasable LH. To test the effect of diabetes on both the number and LH content of marginated granules, we studied by indirect immunogold-labelling pituitaries from control and streptozocin (STZ)-treated male rats. On electron micrographs we measured the areas of the gonadotrope nucleus and cytoplasm, counted all secretory granules, and counted and measured secretory granules in selected SPL regions. Furthermore, we counted gold particles (IG) on (a) the secretory granules of the SPL regions, (b) the intergranular SPL cytoplasm and (c) the region outside the cell. Finally, in order to evaluate possible diabetes-related changes of the pituicyte cytoskeleton, we measured by densitometry actin, tubulin, vimentin, and desmin in immunocytochemically stained pituitary sections. In diabetic compared with control cells of the studied pituitary region, we observed: (a) cytoplasmic atrophy; (b) the number of secretory granules per unit area increased in the total cytoplasm, and decreased in the SPL cytoplasm (lowered regulated secretion); (c) decreased IG labelling in the SPL granules (reduced amount of hormone transported by each granule towards the cell membrane); (d) decreased IG labelling in the integranular SPL cytoplasm (reduced constitutive secretion), and (e) strongly increased actin and desmin, yet unchanged tubulin and vimentin immunoreactivity. Our data indicate that both regulated and constitutive secretion are possibly reduced in gonadotropes of diabetic male rats. The cytoskeletal alterations may also contribute to the reduced regulated secretion.

Actins↗

Healing of carotid stents: a prospective duplex ultrasound study.

PURPOSE: To study the dynamics of carotid stent healing over a 2-year period using duplex ultrasound imaging. METHODS: One hundred twelve patients with 121 successfully stented carotid arteries were examined with color-coded duplex ultrasound the day after the stent procedure and at 1, 3, 6, 12, and 24 months in follow-up. The maximal thickness and echogenicity of the layer between the stent and the perfused lumen (SPL) were evaluated. Echogenicity was classified as echogenic if the SPL layer was clearly detected in B mode and echolucent if the SPL layer was barely visible in B mode, its border defined by assistance of color-coded flow. RESULTS: At day 1, an echolucent SPL layer with a median thickness of 0.7 mm was interpreted as a thrombotic layer, which decreased at 1 month to practically zero (i.e., not detectable). In follow-up, increases in thickness (mainly up to 6 months) and echogenicity (up to 12 months) of the SPL layer were interpreted as neointimal ingrowth. At 3, 6, and 12 months, the median maximal thickness of the SPL layer was 0.5 mm, 0.9 mm, and 1.0 mm, respectively, whereas the percentage of patients with an echogenic SPL layer was 27% (32/119), 56% (66/117), and 95% (105/110), respectively, at the same time intervals. No further change was observed at the 24-month examination. CONCLUSIONS: Three phases of carotid stent incorporation are defined: (1) an early unstable period soon after stent placement with an echolucent (thrombotic) SPL layer, (2) a moderately unstable phase with ingrowing neointima (1-12 months), and (3) a stable phase from the second year on. These data may indicate the need for different intensities of therapy and surveillance intervals.

Aged↗

Sp1 and SF-1 interact and cooperate in the regulation of human steroidogenic acute regulatory protein gene expression.

Steroidogenic acute regulatory (StAR) protein plays a critical role in the movement of cholesterol from the outer to the inner mitochondrial membrane. Steroidogenic factor 1 (SF-1) controls basal and cAMP-stimulated transcription of the StAR gene. The 1.3-kb StAR promoter has three SF-1 binding sites, and two consensus transcription factor Spl binding sequences near the two most distal SF-1 binding sites. Spl mediates cAMP-dependent transcription of steroidogenic P450 enzyme genes, raising the possibility of Sp1 involvement in cAMP regulation of the StAR gene. However, the mechanism of Spl-mediated, cAMP-stimulated responsiveness is not known. In this study, we elucidated the roles of Sp1 and SF-1 in the regulation of the human StAR gene promoter. We found that there was negligible promoter activity in a pGL2 StAR construct (-235 to +39) in which Spl and SF-1 binding sites were mutated in Y-1 adrenal tumor cells. An Sp1 binding site mutation (pGL2Sp1M) did not support promoter activity, suggesting that Spl cooperates with SF-1 in regulating StAR promoter function. In gel shift assays, the SF-1 binding site formed a complex with an SF-1-GST fusion protein and Spl. Coimmunoprecipitation cross-linking experiments indicated that SF-1 physically interacts with Sp1 in vitro. Finally, a mammalian two-hybrid system was employed to demonstrate that Spl and SF-1 associate in vivo. In conclusion, our data indicate that Spl and SF-1 physically interact and cooperate in the regulation of human StAR promoter activity.

Adrenal Cortex Neoplasms↗

Characteristics of transient-evoked otoacoustic emissions (TEOES) in neonates.

Transient-evoked otoacoustic emissions (TEOEs) were measured in 1164 ears from 582 neonates without any risk of hearing impairment in order to define basic characteristics useful in deciding if TEOEs could be considered as "normal" in a screening test. Five neonates had no recordable TEOE and ABR thresholds greater than 30 dBnHL. Technical conditions have been analysed using the intensity of the click stimulation, the time necessary to record TEOEs, and the noise floor in the external ear canal (i.e. A-B magnitude). The TEOE magnitude varied between 6.6 dB SPL and 38 dB SPL (mean = 21.75 dB SPL). Only 5% of the tested neonates had a TEOE magnitude lower than 7.75 dB SPL. The TEOE magnitude for the right ear of a neonate was statistically different from those recorded in the left ear (22.4 dB SPL versus 21 dB SPL). The mean TEOE magnitude for male ears was statistically different from those recorded in female ears (21.4 dB SPL versus 22.1 dB SPL).

Acoustic Stimulation↗

Splenic arterial ligation prevents liver injury after a major hepatectomy by a reduction of surplus portal hypertension in hepatocellular carcinoma patients with cirrhosis.

BACKGROUND/AIMS: In this study, we investigated whether a reduction of surplus portal hypertension after a major hepatectomy by SPL (splenic arterial ligation) prevents a liver injury in cirrhotic patients with hepatocellular carcinoma. METHODOLOGY: Six hepatocellular carcinoma patients (SPL group) with liver cirrhosis (67 +/- 10 years old, ICGR15: 21.0 +/- 9.8%, T.Bil: 1.1 +/- 1.2 mg/dL) underwent major hepatectomy with splenic arterial ligation in order to reduce excessive portal hypertension after hepatectomy from 1998 to 2000, July. The patients (n = 15, 60 +/- 9 years old, ICGR15: 11.5 +/- 5.9%, T.Bil: 0.66 +/- 0.15 mg/dL) who underwent liver resection above subsegmentectomy in the same period (control group) served as the control for SPL group. RESULTS: In the SPL group, the portal pressures before hepatectomy were 26 +/- 7 cm H2O and those after hepatectomy were 29 +/- 6 cm H2O. The portal pressure after splenic arterial ligation decreased to 24.5 +/- 6.3 cm H2O. The splenic tissue blood flows before SPL were 16.8 +/- 5.6 mL/min/100 g, while those after SPL were 7.2 +/- 2.2 mL/min/100 g. The portal pressures before hepatectomy were 17 +/- 2 cm H2O and those after hepatectomy were 19 +/- 2 cm H2O in the six control patients. At the peak levels of liver function after surgery, T.Bil was 2.6 +/- 1.5 mg/dL, GOT was 165 +/- 59 IU/L, and GPT was 107 +/- 49 IU/L. All patients could discharge without complications except for one case with bile leakage in SPL. At the peak levels of liver function in control group, T.Bil was 3.7 +/- 1.9 mg/dL, GOT was 404 +/- 227 IU/L, and GPT was 322 +/- 171 IU/L. At the peak levels of liver function after surgery, T.Bil was 3.4 +/- 1.3 mg/dL, GOT was 398 +/- 289 IU/L, and GPT was 319 +/- 220 IU/L. Conversely, there were 11 episodes of complications (11/15), including two cases of hospital death resulting from liver failure in patients who underwent right lobectomy, in the control patients. CONCLUSIONS: The decompression of surplus portal hypertension by SPL might be effective in the prevention of post hepatectomized liver injury and the improvement of postoperative mortality and morbidity.

Aged↗

Apparent specificity of bovine seminal ribonucleases can depend on the conditions used for the isolation of substrate.

RNAase SPL, a ribonuclease isolated earlier from bovine seminal plasma, was shown to possess the ability to produce large acid-insoluble fragments of Mg(2+)-containing RNA in a limit digest. The factor which could be responsible for this apparent specificity has been identified as polyvinyl sulphate; it has been shown that polyvinyl sulphate inhibits RNAase SPL at much lower concentrations than required for RNAase A. The earlier results are now reinterpreted based on this effect of polyvinyl sulphate, thus providing a plausible explanation for RNAase SPL's apparent specificity. RNAase SPL has been shown to be a mixture of two ribonucleases, RNAase SPL I and RNAase SPL II. RNAase SPL I is like RNAase A in its activity while RNAase SPL II, the major ribonuclease in seminal plasma, appears to be identical to RNAase BS1.

Amino Acid Sequence↗

Essential requirement of I-A region-identical host bone marrow or bone marrow-derived cells for tumor neutralization by primed L3T4+ T cells.

The antitumor activity of Meth A-hyperimmunized BALB/c mouse spleen cells (Meth A-Im-SPL) was assayed by the Winn test in H-2 incompatible bone marrow chimeras in closed colony CD-1 (nu/nu), inbred DDD/1(nu/nu) (H-2s), or inbred BALB/c(nu/nu) (H-2d) mice as recipients. We found that Meth A-Im-SPL suppressed Meth A growth in the chimera nude mice which were reconstituted with bone marrow cells of the H-2d haplotype (i.e., BALB/c, DBA/2 and B10.D2), but not in the chimeras which were reconstituted with bone marrow cells of the H-2a, H-2b, or H-2k haplotype (i.e., B10.A, B10, and B10.BR). These results suggested that H-2 restriction occurred between Meth A-Im-SPL and bone marrow or bone marrow-derived cells in tumor neutralization. Furthermore, Meth A-Im-SPL did not suppress Meth 1 tumors (antigenically distinct from Meth A tumors) in the presence or absence of mitomycin C-treated Meth A in a Winn assay. These results suggested that there is tumor specificity in the "effector phase" as well as in the "induction phase". The phenotype of the effectors in the Meth A-Im-SPL was Thy-1.2+ and L3T4+, because Meth A-Im-SPL lost their antitumor activity with pretreatment with anti-Thy-1.2 monoclonal antibody (mAb) and complement or anti-L3T4 mAb and complement, but not with anti-Lyt-2.2 mAb and complement or complement alone. Positively purified L3T4+ T cells from Meth A-Im-SPL (Meth A-Im-L3T4), obtained by the panning method, suppressed the tumor growth in the chimera nude mice which were reconstituted with bone marrow cells of B10.KEA2 mice (that were I-A region-identical with Meth A-Im-L3T4 cells but not others in H-2) as well as B10.D2 cells (that were fully identical with Meth A-Im-L3T4 cells in H-2). We conclude that Meth A-Im-SPL (L3T4+) neutralized the tumors in collaboration with I-A region-identical host bone marrow or bone marrow-derived cells, and the neutralization was not accompanied by the "bystander effect."

Animals↗

Enkephalin-mediated basal ganglia influences over the optic tectum: immunohistochemistry of the tectum and the lateral spiriform nucleus in pigeon.

By using immunohistochemical techniques with antisera directed against either leucine-enkephalin or methionine-enkephalin (generously supplied by K.-J. Chang), four distinct bands of fibers with enkephalinlike immunoreactivity were demonstrated in the pigeon tectum: (1) a thin band of thick fibers and tightly clustered bulbous swellings in layer 3, (2) a broader band of fibers with less tightly clustered bulbous swellings in layer 5, (3) a broad band of numerous obliquely and radially oriented fibers that spanned layers 8-13, and (4) a band of sinuous fibers in layer 15. In addition, numerous enkephalinergic cell bodies with radially ascending processes were seen in layers 8-10. Since the neurons of the avian lateral spiriform nucleus (SpL) of the pretectum are known to contain enkephalin (Davis et al., '80; De Lanerolle et al., '81) and project to the tectum (Brecha et al., '76; Reiner et al., '82), unilateral electrolytic lesions were made of SpL. In birds with unilateral lesions of SpL, layers 8-13 of the ipsilateral tectum were nearly devoid of enkephalinergic fibers, but no alterations were seen in layers 3, 5, and 15. Since no other neurons in the vicinity of SpL are enkephalinergic and project to the tectum, the loss of enkephalin-immunoreactive fibers in the ipsilateral tectal layers 8-13 is attributable to the destruction of SpL. Although the source of the enkephalinergic fibers in tectal layers 3, 5, and 15 is unclear, part of the enkephalin pattern in layers 3 and 5 may derive from the ascending processes of the enkephalinergic neurons of layer 8-10. The present results indicate that SpL has an enkephalinergic projection to layers 8-13 of the ipsilateral tectum. The avian SpL receives its major input from the ascending processes of the enkephalinergic neurons of layers 8-10, nuclei that themselves receive major basal ganglia inputs (Reiner et al., '82) and projects to the tectal layers 8-13 (Reiner et al., '82), the layers of origin of the major tectal efferent projections (Reiner and Karten, '82). The enkephalinergic fibers in layers 8-13 may, thus, have some influence upon the motor output functions of the avian tectum.

Animals↗