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The results of a joint university–industry collaborative project for control loop reconfiguration using closed loop experimental data from a fuel gas pressure control system are described in this paper. The fuel gas pressure was being regulated using a butane stream. For economic reasons, it was necessary to switch control to the ethane stream. Previous attempts at effecting this changeover had proved unsuccessful. In this study, a powerful system identification technique namely Canonical Variate Analysis (CVA) was employed to obtain the empirical plant models. A PI controller was then designed using the direct synthesis method. Acceptable closed loop behavior was obtained with little online tuning.

Process systems with material and/or energy recycles are ubiquitous in the chemical industry. In this paper we address the following problem: Given a manipulated variable and a controlled variable for a process unit which is part of a larger integrated system, how does one proceed with system identification, control structure selection and controller design? While empirical modelling and control design can be easier for stand-alone process units, it can be a very challenging task for units with recycle. The purpose of this paper is to highlight the issues, concepts and challenges using several industrial case studies.

Transgenic mice expressing mutant alpha 1(IX) collagen were produced and found to develop progressive joint degeneration with age, as well as accelerated intervertebral disc degeneration. Radiological and histological studies showed that cervical and lumbar disc degeneration was more advanced in the transgenic mice than in control litter-mates. The changes included shrinkage or disappearance of the nucleus pulposus, and fissures in the annulus fibrosus which sometimes lead to herniation of disc material and slight osteophyte formation. These findings suggest that mutations of the type IX collagen may cause certain forms of degenerative disease in the spine as well as in joints.

This study was conducted to observe the differences between the adsorption of Streptococcus sanguis by saliva-coated and non-saliva-coated cells (plain cells) to the surfaces of saliva-coated, bovine serum albumin-coated or buffer-washed hydroxyapatite beads. Saliva treatment of bacterial cells altered the manner of saturation due to changes of affinity and/or the maximal number of adsorption sites on the hydroxyapatite beads. This result indicates that saliva treatment of bacterial cells might be a necessary step in testing bacterial adsorption to saliva-coated hydroxyapatite beads or saliva-coated teeth.

We have measured the azimuthal correlation of hadrons produced in e(+)e(-) annihilations at root s=58 GeV. In perturbative QCD these correlations are sensitive to the interference between soft gluons emitted at large angles with respect to the event axis. However, Monte Carlo calculations incorporating QCD-inspired hadronization models in which the correlation of interjet particles is treated in a phenomenological manner describe the data well. We also observe that angular ordering of the parton showering in the LUND Monte Carlo program improves the agreement with the data.

The complete exon-intron organization of the human aggrecan gene has been defined, and the exon organization has been compared with the individual domains of the protein core. A yeast artificial chromosome containing the aggrecan gene was selected from the Centre d'Etude du Polymorphisme Humaine yeast artificial chromosome library. A cosmid sulibrary was created from this, and direct sequencing of individual cosmids was used to provide the exon-intron organization. The human aggrecan gene was found to be composed of 19 exons ranging in size from 77 to 4224 bp. Exon 1 is non-coding, whereas exons 2-19 code for a protein core of 2454 amino acids with a calculated mass of 254379 Da. Intron 1 of the gene is at least 13 kb. Overall, the sizes of the 18 introns range from 0.5 to greater than 13 kb. Each intron begins with a GT and ends with an AG, thus obeying the GT/AG rule of splice-junction sequences. The entire coding region is contained in 39.4 kb of the gene. The organization of exons is strongly related to the specific domains of the protein core. The A loop of G1 and the interglobular domain are encoded by exons 3 and 7 respectively. The B and B' loops of G1 are encoded by exons 4-6, and those of G2 are encoded by exons 8-10. These sets of exons, coding for the B and B' loops, are identical in size and organization. This is supported by the intron classes associated with these exons. Exon 11 codes for the 5′ half of the keratan sulphate-rich region, and exon 12 codes for the 3′ half of the keratan sulphate-rich region as well as the entire chondroitin sulphate-rich region. G3 is encoded by exons 13-18, including the alternatively spliced epidermal growth factor-like and complement regulatory protein-like domains. The correspondence between the exon organization and the protein domains argues strongly for modular assembly of the aggrecan gene.

Using e+e− annihilation events accumulated with the AMY detector at the TRISTAN collider, we have studied the Bose-Einstein correlations in the distributions of like-sign charged tracks. As reference samples we used the opposite-sign charged track pairs and mixed pairs, which are like-sign pairs synthesized from tracks belonging to different events. The results of the different reference samples give approximately 0.45 for the correlation strength and approximately 0.65 fm for the source size. Previous measurements of these parameters in e+e− annihilation at energies from CESR to LEP show remarkably flat dependence on s . Our results conform well with this picture.

We present a study of differential two jet ratios in multi-hadronic final states produced by e(+)e(-) annihilation in the AMY detector at TRISTAN. The data are compared to the predictions of the next-to-leading logarithm parton-shower (NLL PS) Monte Carlo and the O(alpha(s)(2)) matrix element QCD models. We determine the strong coupling strength alpha(s)(57.3 GeV) = 0.130 +/- 0.006.

The photon structure function F 2 γ has been measured at average Q 2 values of 73 and 390 GeV 2 using data collected by the AMY detector at the TRISTAN e + e − collider. F 2 γ is observed to be increasing as ln Q 2 . The x -dependence of F 2 γ , where x is the momentum fraction carried by the parton inside the photon, is also measured. The measurements are compared with several parton density models.

With data corresponding to 142 pb−1 accumulated at s = 57.8 GeV by the AMY detector at TRISTAN we measure the cross section of the reactions e+e− → μ+μ− and e+e− → τ+τ− and the symmetry in the angular distributions. For the lowest order cross section we obtain σμμ = 27.54 ± 0.65 ± 0.95 pb and σττ = 28.27 ± 0.87 ± 0.69 pb, and for the forward-backward asymmetry, Aμμ = 0.303 ± 0.027 ± 0.008 and Aττ = −0.291 ± 0.040 ± 0.019. These measurements agree with the standard model. Assuming e−μ−τ univrsality we extract the vector and axial coupling constants | gν| = 0.00 ± 0.09 and |gA| = 0.476 ± 0.024. A fit of data to composite models places lower bounds (95% confidence level) on the compositeness scale of 2–4 TeV.

Using 773 muons found in hadronic events from 142 pb-1 of data at a c.m. energy of 57.8 GeV, we extract the cross section and forward-backward charge asymmetry for the e+e- --> bbBAR process, and the heavy quark fragmentation function parameters for the Peterson model. For the analysis of the e+e- --> bbBAR process, we use a method in which the behavior of the c quark and lighter quarks is assumed, with only that of the b quark left indeterminate. The cross section and asymmetry for e+e- --> bbBAR are found to be R(b) = 0.57 +/- 0.06(stat) +/- 0.08(syst) and A(b) = -0.59 +/- 0.09 +/- 0.09, respectively. They are consistent with the standard model predictions. For the study of the fragmentation function we use the variable [x(e)], the fraction of the beam energy carried by the heavy hadrons. We obtain [x(E)]c = 0.56(-0.05-0.03)+0.04+0.03 and [x(E)]b = 0.65(-0.04-0.06)+0.06+0.05, respectively. These are in good agreement with previously measured values.

We report on a measurement of the forward-backward charge asymmetry in e+e- --> qqBAR at KEK TRISTAN, where. the asymmetry is near maximum. We sum over all flavors and measure the asymmetry by determining the charge of the quark jets. In addition we exploit flavor dependencies in the jet charge determination to enhance the contributions of certain flavors. This provides a check on the asymmetries of individual flavors. The measurement agrees with the standard model expectations.

We present cross section measurements for inclusive jet production in almost-real photon-photon interactions at TRISTAN using the AMY detector. The results are compared with leading-order QCD calculations for different parameterizations of the parton density in the photon.

We present a study of the third moment of the inclusive momentum distribution of particles within jets produced by e+e- annihilation at TRISTAN. In this analysis, the QCD coupling strength alpha(s) is determined by fits to the prediction of the Next-to-Leading Logarithm Parton-Shower model. The measured value of alpha(s) (57.9 GeV) = 0.134(-0.005)+0.006.

We report on measurements of the total cross section for e+e- --> 2-Gamma for center-of-mass energies between 57.4 and 59.5 GeV, using the AMY detector at the TRISTAN collider. We set new limits on the production of a possible new s-channel resonance decaying into photon pairs.

Pacinian corpuscles in the cat urinary bladder were studied using the hematoxylin and eosin staining, formaldehyde-induced fluorescence histochemistry, immunohistochemistry for tyrosine hydroxylase (TH) and immunoelectron microscopy. The existence of catecholaminergic nerve fibers penetrating into the corpuscles was clarified. (1) About 10 Pacinian corpuscles which were mainly located in the subserosa were found in the lower one-third portion of each urinary bladder. (2) One or two corpuscles containing blue-green fluorescent fibers were detected in each bladder. These fibers were equivalent to TH-immunopositive varicose fibers using the avidin-biotin-peroxidase complex method. (3) Thin nerve fibers containing dense-cored vesicles were found in the corpuscle by immunoelectron microscopy. These fibers spirally encompassed a swollen sensory terminal at a distance in the inner core. According to the above findings, we discuss a modulatory function of the catecholaminergic fibers in this mechanoreceptor.

The distribution of oxytocin (OXT) and vasopressin (VP) neurons in the diencephalon of the hibernating Japanese horseshoe bat, Rhinolophus ferrum-equinum, was immunohistochemically investigated by the avidin-biotin complex method. Magnocellular OXT and VP neurons were localized mainly in the para-ventricular nucleus and the supraoptic nucleus. In addition to these main nuclei, both kinds of magnocellular neurons were also found in the periventricular nucleus, perifornical area and lateral hypothalamic area. Extensively distributed parvocellular neurons containing only VP were observed in the rostral and middle portions of the suprachiasmatic nucleus. The size of OXT and VP magnocellular neurons was almost equal in the paraventricular and ventromedial supraoptic nuclei, whereas VP neurons were significantly larger than OXT neurons in the dorsolateral supraoptic nucleus. The OXT and VP cells in the ventral supraoptic nucleus showed a distinctive elliptical shape. Both OXT and VP fibers were distributed in the lateral habenular nucleus, stria medullaris thalami, lateral preoptic area, stria terminalis, and medial and supracapsular part of the bed nucleus of the stria terminalis. Moreover, OXT fibers were found in the substantia nigra, and VP fibers were noted in the nucleus reuniens and the paraventricular nucleus of the thalamus.

Using Propionibacterium freudenreichii and 32P-ATP, batches of 32P-labelled cobalamin (Cbl) were biosynthesized with a maximum specific activity of 61 microCi/mg, i.e. about 100 times higher than previously reported. Pharmacological doses mixed with 57Co-Cbl were injected subcutaneously in the form of hydroxo-Cbl into rats subsequently killed 5-20 days later. The two labelled Cbls were distributed in approximately the same way, the highest concentration being found in kidney (typical for rats) and about one-fifth of that in liver. These findings tallied with previous observations with radioactive cyano-Cbl and microbiological assay. In all injected rats, the 57Co/32P ratio was lower in liver than in kidney. Drugs eradicating the intestinal flora had no influence. In rats receiving the vitamin orally, the ratio was higher in liver than in kidney. All of our findings could be due to formation of a cobinamide-like compound lacking phosphorus. It is concluded that we have produced radiophosphorus-labelled Cbl that enables studies in vivo.

Caveolin-1, a structural component of caveolae, is overexpressed in metastatic and androgen-resistant prostate cancer and highly expressed in tumor-associated endothelial cells. The mouse cav-1 promoter was cloned and placed upstream of the HSV-tk gene in an adenoviral vector (Adcav-1tk) and compared with a cytomegalovirus (CMV) or Rous sarcoma virus (RSV) promoter-driven HSV-tk, AdCMVtk and AdRSVtk vectors, respectively. Mouse and human prostate cancer cells and mouse endothelial cells were infected with Adcav-1tk, AdCMVtk or control vectors without the HSV-tk gene (Adcav-1 and AdCMV) and subsequently treated with ganciclovir (GCV). GCV-mediated in vitro cytotoxicity induced by the Adcav-1tk vector was comparable to that for AdCMVtk in multiple mouse and human prostate cancer cell lines. To evaluate the activity of Adcav-1tk in vivo, orthotopic mouse prostate cancer tumors were generated with RM-9 cells and injected in situ with Adcav-1tk, AdCMVtk, AdRSVtk, or AdCMVbetagal (control) and treated with GCV. All three HSV-tk transducing vectors produced statistically significant reductions in wet weight and increased apoptotic indices compared with the control vector. However, only Adcav-1tk produced significant necrosis, and only Adcav-1tk and AdRSVtk caused significant decreases in microvessel density. In conclusion, Adcav-1tk demonstrated efficacy in vitro and in vivo in preclinical models of prostate cancer. Our results suggest that the cav-1 promoter may have unique benefits in targeting gene therapy to prostate cancer and its associated vasculature.

Previously, we demonstrated that up-regulation of caveolin-1 (cav-1) was associated with prostate cancer metastasis, biochemical recurrence after radical prostatectomy, and androgen insensitivity. The objective of this study was to characterize the regulation of cav-1 by testosterone (T) and to test the effects of cav-1 on prostate cancer cell survival/clonal growth and metastatic activities. Our results demonstrated that T up-regulated cav-1 protein levels in part through transcriptional regulation and significantly enhanced survival of prostate cancer cell lines ABAC3 and LNCaP after serum starvation (40% and60% increased viability, respectively) and in an extended clonogenic assay (approximately 4-fold and 6-fold increase in colonies, respectively). Importantly, antisense cav-1 inhibited the survival effects of T in these assay systems. Modest but not high levels of adenoviral vector-mediated cav-1 expression alone also significantly increased viability (40%) and clonal growth (10-fold increase in colonies) after serum starvation. Analysis of spontaneous metastasis in stably transfected antisense cav-1 mouse prostate cancer cell clones demonstrated reduction of spontaneous lymph node metastasis incidence (13%), spontaneous lymph node metastasis volume (46%), and experimental lung metastasis incidence (40%) compared with vector control cell clones. Surgical castration further reduced spontaneous lymph node metastasis incidence and volume (18% and 28%, respectively) in antisense cancer cell clones, but not in vector control clones. Our studies demonstrate that cav-1 is a downstream effector of T-mediated prostate cancer cell survival/clonal growth and that modest levels of cav-1 can independently promote prostate cancer cell survival/clonal growth and metastatic activities.

Caveolin-1 is an integral protein of caveolae, known to play important roles in signal transduction and lipid transport. We demonstrate that caveolin-1 expression is significantly increased in primary and metastatic human prostate cancer after androgen ablation therapy. We also show that caveolin-1 is secreted by androgen-insensitive prostate cancer cells, and that this secretion is regulated by steroid hormones. Significantly, caveolin-1 was detected in the MDL(3) fraction of serum specimens from patients with advanced prostate cancer and to a lesser extent in normal subjects. Conditioned media from high passage caveolin-1 secreting, androgen-insensitive, LNCaP cells stimulated increased viability and clonal growth of low passage, caveolin-1-negative, androgen-sensitive, LNCaP cells in vitro, and this effect was blocked by treating the media with caveolin-1 antibody. i.p. injections of caveolin-1 antibody suppressed the orthotopic growth and spontaneous metastasis of highly metastatic, androgen-insensitive caveolin-1-secreting mouse prostate cancer. Overall, our results establish caveolin-1 as an autocrine/paracrine factor that is associated with androgen-insensitive prostate cancer. We demonstrate the potential for caveolin-1 as a therapeutic target for this important malignancy.

Tumor-associated macrophages (TAMs) are highly active immune effector cells that may either positively or negatively regulate the growth of various malignant cells, depending on the biological context. However, the role of TAMs in human prostate cancer progression is unclear. TAMs were immunohistochemically labeled using a monoclonal (CD68) antibody in radical prostatectomy specimens derived from 81 prostate cancer patients. CD68-positive cells were counted with the aid of a microscope and expressed as macrophage index (MphiI), including TAMs/mm2 total tumor tissue (MphiItotal), TAMs/mm2 tumor stroma (MphiIstroma), and TAMs/mm2 cancer cell area (MphiIcancer). MphiIs were analyzed in association with patients' clinical and pathological stage, recurrence status, and histological grade of the cancer. There were significant inverse relationships between MphiItotal and MphiIstroma and clinical stage (P = 0.016 and P = 0.006, respectively). Reduced MphiItotal was also associated with the presence of positive lymph nodes (P = 0.010). Interestingly, although all of the MphiIs differed between Gleason score groups, only MphiIcancer was positively associated with Gleason score. Univariate analysis of MphiItotal and multivariate analysis of MphiItotal with specific pathological markers revealed that MphiItotal was an independent predictor for disease-free survival after surgery (Cox proportional hazard model, P = 0.044 and P = 0.007, respectively). For patients with high MphiItotal (or = 185.8, the mean MphiItotal value), the disease-free probability 5 years after surgery was 0.75, which was significantly higher than for those with low MphiItotal (0.31, P = 0.0008). Additional immunohistochemical studies that evaluated cytotoxicity-related biomarkers in stroma-associated mononuclear cells suggested reduced functional activities in highly aggressive prostate cancer compared with less aggressive disease. Our results indicate that reduced MphiItotal is a novel prognostic marker for prostate cancer.

We have documented previously that adenovirus-mediated interleukin 12 (IL-12) gene therapy is effective for orthotopic tumor control and suppression of pre-established metastases in a preclinical prostate cancer model (Y. Nasu et al., Gene Ther., 6: 338-349, 1999). In this report, we directly compare the effectiveness of an adenovirus that expresses both IL-12 and the costimulatory molecule B7-1 (AdmIL12/B7) with one that expresses IL-12 alone (AdmIL-12) using the poorly immunogenic RM-9 orthotopic murine model of prostate cancer. We document AdmIL-12/B7-mediated secretion of IL-12 and increased surface expression of B7-1 in infected RM-9 tumor cells. A significant reduction in orthotopic tumor size and increased survival was demonstrated in mice treated with a single orthotopic injection of AdmIL-12/B7 compared with AdmIL-12 or controls. Six of 19 animals treated with AdmIL-12/B7 survived long term with apparent eradication of the primary tumor in contrast to one of 38 animals in the AdmIL-12-treated group. Orthotopic treatment of tumors with both vectors led to an infiltration of both CD4+ and CD8+ immunoreactive cells, with AdmIL-12/B7 treatment having a more prolonged infiltration of CD8+ cells. AdmIL-12/B7 was also more effective than AdmIL-12 or controls at suppression of pre-established metastases. We further developed a vaccine model based on s.c. injection of infected, irradiated RM-9 cells and found that both AdmIL-12 and AdmIL-12/B7 are effective at suppressing the development and growth of challenge orthotopic tumors using this protocol.

Osteopenia is frequently observed in patients with Turner's syndrome. By contrast, there is no report concerning bone metabolism in patients with Noonan's syndrome which comprises Turner's phenotypic characteristics without any sex chromosome abnormalities. In the present investigation, we determined bone mineral density (BMD) as well as serum and urine indices of bone turnover in two male patients with Noonan's syndrome. Both patients showed remarkably decreased BMD, measured at two sites on the lumbar spine (L2-L4) and the distal end of the radius using dual energy X-ray absorptiometry (DXA). Urinary pyridinoline (PYD) and deoxypyridinoline (DPD) concentrations were significantly elevated in both patients, and serum osteocalcin and carboxyterminal propeptide of type I procollagen (PICP) concentrations were elevated in one patient. Surprisingly, both patients had a low level of serum 17beta-estradiol compared with control males, whereas they had normal levels of serum testosterone and dihydrotestosterone. Conjugated estrogens (Premarin 0.625 mg/day) were continued to be administered to these patients, followed up for 12 months. Urinary PYD and DPD concentrations gradually decreased, followed by an increase in their BMD. This is the first report that male patients with Noonan's syndrome showed osteopenia associated with increased bone resorption. Our data indicate that hypoestrogenism plays a potentially significant role in the abnormal bone metabolism in these patients.

We have reviewed the cervical spine radiographs of 180 patients with athetoid cerebral palsy and compared them with those of 417 control subjects. Disc degeneration occurred earlier and progressed more rapidly in the patients, with advanced disc degeneration in 51%, eight times the frequency in normal subjects. At the C3/4 and C4/5 levels, there was listhetic instability in 17% and 27% of the patients, respectively, again six and eight times more frequently than in the control subjects. Angular instability was seen, particularly at the C3/4, C4/5 and C5/6 levels. We found a significantly higher incidence of narrowing of the cervical canal in the patients, notably at the C4 and C5 levels, where the average was 14.4 mm in the patients and 16.4 mm in normal subjects. The combination of disc degeneration and listhetic instability with a narrow canal predisposes these patients to relatively rapid progression to a devastating neurological deficit.

A comparative study was performed in patients with cervical radiculomyelopathy due to soft disc herniation to compare surgical results of laminoplasty with anterior discectomy and arthrodesis.To determine whether posterior decompression without discectomy can be selected for cervical myelopathy due to cervical soft disc herniation.Anterior cervical discectomy and arthrodesis has had acceptable surgical results, but a significant number of complications have been reported, especially those related to bone grafting.Sixteen patients who received expansive laminoplasty and 17 patients who received anterior arthrodesis were studied. The mean value of the anteroposterior diameter of the spinal canal was 12.4 mm in the former and 12.9 mm in the latter. The mean follow-up was 3.1 years in the laminoplasty group, and 8.8 years in the anterior arthrodesis group. There was no statistical difference between the two groups in prognostic factors believed to affect surgical results. Neurologic results were evaluated with postoperative scores and recovery rates by methods previously described, and assessed by the Japanese Orthopaedic Association scoring system.The difference between the two groups in the recovery rate and final Japanese Orthopaedic Association score was not statistically significant. Surgical complications were more frequent in the anterior arthrodesis group than in the laminoplasty group. Additional surgeries were performed in three cases (18%) in the anterior arthrodesis group: posterior wiring for delayed union and kyphotic deformity in two cases, and laminoplasty for deterioration of myelopathy in one case. Regression of herniated cervical disc after laminoplasty was confirmed by computed tomography or magnetic resonance imaging in six of eight cases (75%).When the incidence of complications and the possibility of regression of herniated disc are taken into consideration, expansive laminoplasty can be selected for radiculomyelopathy due to cervical disc herniation.

Transgenic mice expressing mutant alpha 1(IX) collagen were produced and found to develop progressive joint degeneration with age, as well as accelerated intervertebral disc degeneration. Radiological and histological studies showed that cervical and lumbar disc degeneration was more advanced in the transgenic mice than in control litter-mates. The changes included shrinkage or disappearance of the nucleus pulposus, and fissures in the annulus fibrosus which sometimes lead to herniation of disc material and slight osteophyte formation. These findings suggest that mutations of the type IX collagen may cause certain forms of degenerative disease in the spine as well as in joints.

Spinal metastases result in severe spinal pain, neurologic deficits, or both. These symptoms usually are caused by spinal instability, in which conservative therapy can have no effect, and surgical treatment is required to restabilize the destroyed spinal segments. Surgical indications are instability of the spine, pain and/or paresis resistant to radiation therapy, acute progressing paresis, and unknown histologic diagnosis. There are 2 surgical approaches for vertebral metastases: prosthetic replacement and posterior stabilization. Single or 2 consecutive diseased vertebrae should be treated with replacement surgery. In this series, excellent surgical outcome was attained with this procedure, and surgical benefit was maintained until the terminal stage of each patient. Multiple vertebral metastases are treated with posterior stabilization using various instrumentation systems that provide rigid stabilization. To choose the most appropriate procedure for each patient, the local condition of the lesion and general status of the patient, including prediction of life expectancy, should be evaluated fully. Spinal metastases develop early and are not terminal events. Therefore, not only palliative treatment but also surgical intervention should be considered for spinal metastases when indicated.

The distribution of central nerve fibers in the rat pineal complex was studied by means of fluorescence- and immunohistochemistry and electron microscopy. At 7 days after bilateral superior cervical ganglionectomy (SCG-X), blue-green fluorescent (catecholaminergic) fibers and tyrosine hydroxylase- and serotonin-immunoreactive fibers originating from the brainstem were detected in the deep pineal and the pineal stalk. These fibers were not observed in the superficial pineal. In some animals, a few oxytocin-immunopositive fibers were found in the proximal portion of the superficial pineal. The nerve fibers were submicroscopically counted in transverse sections at 6 levels with an interval of about 200 microns each in the pineal stalk. The number of nerve fibers showed 3 peaks, at the proximal-most, the intermediate and the distal-most levels. On the other hand, various types of synapses, axo-dendritic, axo-axonic and axo-pinealocytic, and many free terminals, were observed in the stalk. In these synapses, the majority of presynaptic swellings contained only clear vesicles, but some of them possessed aminergic (5-hydroxydopamine- or 5,6-dihidroxytriptamine-positive) vesicles or elementary granules. The reduction in the number of nerve fibers was most conspicuous in the distal-most level after the SCG-X. Based on these results, it is supposed that the proximal peak is formed by the central fibers going further to the stalk and turning back to the brain, the intermediate peak is formed by the terminal arborizations of the central fibers, and the distal peak shows penetration of the sympathetic fibers.(ABSTRACT TRUNCATED AT 250 WORDS)

In this study, the detailed distribution of peptidergic nerve fibers in the sinus hair follicle was immunohistochemically investigated by the avidin biotin-complex method using antibodies against calcitonin gene-related peptide (CGRP), substance P (SP), vasoactive intestinal polypeptide (VIP) and neuropeptide Y (NPY) in the cat, dog, hamster, rat, mouse and guinea pig. The peptide-immunoreactive (IR) nerve fibers presented a fine varicose appearance. They entered the sinus hair follicle after penetrating the capsule (Cap) at various levels. Peptide-IR fibers in the sinus hair were classified into the 3 types described below based on their course of entry and terminal distribution. Type A: these fibers arrive at the orifice of the sinus hair follicle from superficial dermis and innervate the upper portion of the follicle. Most of them form a network around the vibrissal shaft (VS) in the outer and inner conical body (OCB and ICB, respectively), and some are distributed around the rete ridge collar (RRC) and the sebaceous gland (SG). Type B: these fibers enter the lower third of the sinus hair follicle after forming a nerve bundle together with myelinated fibers, or accompany an artery. After distribution in the trabeculae (Trab) of the cavernous sinus (CS), they form a dense plexus in the connective tissue follicle (CTF) at the level of the CS. Some ascend through the CTF and terminate at the level of the ring sinus (RS). Type C: these fibers enter the sinus hair follicle at its base. They innervate the hair papilla (HP) and the CTF of the hair bulb. CGRP and SP were detected in all types of nerve fibers in all species investigated. These peptidergic nerve fibers showed the same distribution pattern, but CGRP fibers were more numerous than SP fibers. They were distributed at high density in the OCB, ICB, CTF, ringwulst (Rw), the Trab of the CS and the HP. A moderate number of VIP- and NPY-IR fibers, mainly types B and C, were detected in these portions in the cat, dog and hamster, but few fibers were observed in other portions or in other species. Although the basic structures of the sinus hair follicle presented almost the same features as in the mammalian species, the connective tissue of the HP extended to the level of the RS in the cat, rat, hamster, and guinea pig. In these species, CGRP-, SP- and/or VIP-IR fibers extended to the top of the papillary connective tissue, and in the cat, were especially well developed.(ABSTRACT TRUNCATED AT 400 WORDS)

The distribution of oxytocin (OXT) and vasopressin (VP) neurons in the diencephalon of the hibernating Japanese horseshoe bat, Rhinolophus ferrumequinum, was immunohistochemically investigated by the avidin-biotin complex method. Magnocellular OXT and VP neurons were localized mainly in the paraventricular nucleus and the supraoptic nucleus. In addition to these main nuclei, both kinds of magnocellular neurons were also found in the periventricular nucleus, perifornical area and lateral hypothalamic area. Extensively distributed parvocellular neurons containing only VP were observed in the rostral and middle portions of the suprachiasmatic nucleus. The size of OXT and VP magnocellular neurons was almost equal in the paraventricular and ventromedial supraoptic nuclei, whereas VP neurons were significantly larger than OXT neurons in the dorsolateral supraoptic nucleus. The OXT and VP cells in the ventral supraoptic nucleus showed a distinctive elliptical shape. Both OXT and VP fibers were distributed in the lateral habenular nucleus, stria medullaris thalami, lateral preoptic area, stria terminalis, and medial and supracapsular part of the bed nucleus of the stria terminalis. Moreover, OXT fibers were found in the substantia nigra, and VP fibers were noted in the nucleus reunions and the paraventricular nucleus of the thalamus.

We investigated the relationship between the severity of acute injury and the rapidity of mucosal repair in stomachs of anesthetized rats, and examined the influence of prostaglandins (PGs) on the process of restoration. Different degrees of mucosal damage were produced using ethanol and by varying the concentration (5-100%) and the exposure period (1-60 min). Exposure of the stomach for 10 min to ethanol induced hemorrhagic lesions and a reduction in the transmucosal potential difference (PD); its severity and its magnitude were increased in a concentration-related manner. After removal of ethanol, the reduced PD recovered quickly in the case of 5-25% ethanol, but it normalized slowly or did not show any recovery in the case of 50 or 100% ethanol, respectively. Histologically, ethanol at 5-25% produced various degrees of damage in the superficial epithelial cells, while the damage was deeper into the mucosa beyond the basal lamina after exposure to ethanol at 50% or greater. Similar phenomena were observed after exposure to 50% ethanol for various periods; the rapidity of PD recovery and mucosal restoration was faster when the exposure period was less than 2 min, and these parameters became slower as it was increased. Moreover, the PD recovery was significantly expedited or delayed, respectively, by 16,16-dimethyl PGE2 (30 micrograms/kg) or indomethacin (5 mg/kg), and the former counteracted the inhibitory effect of indomethacin. These results suggest that the process of mucosal regeneration may largely depend on the severity of damage initially formed, and probably involves factors sensitive to endogenous PGs.