bluuebunny/crossref_metadata_2025 huggingface dataset:
Down‐regulation of claudin‐2 in breast carcinomas is associated with advanced disease
Authors: Kim T H , Huh J H , Lee S , Kang H , Kim G I , An H J
Published: May 2008

Aims:  Claudin 2 (CLDN2) is a family of integral membrane tight junctions. The aim was to determine the influence of CLDN2 expression on tumour behaviour and its role in breast carcinogenesis.

Method and results:  Thirty‐seven invasive breast carcinomas and corresponding normal breast tissues were examined for CLDN2 protein and mRNA expression using Western blotting and semiquantitative reverse transcriptase‐polymerase chain reaction. The expression of CLDN2 protein in 118 cases of breast carcinoma was further studied with immunohistochemistry and related to various clinicopathological parameters. CLDN2 protein expression was significantly down‐regulated (0.4‐fold) in tumours compared with corresponding normal breast tissue (P < 0.0001). Down‐regulation of CLDN2 was significantly associated with lymph node metastasis (P = 0.047) by Western blot analysis, and with high clinical stage (P = 0.040) by immunohistochemistry. The expression levels of CLDN2 mRNA in high clinical stages (stages II and III) were lower than those in low clinical stage (stage I) and normal tissue, but not statistically significantly so.

Conclusions:  These results suggest that CLDN2 is implicated in the progression as well as the development of breast carcinoma, indicating that CLDN2 is a possible tumour suppressor gene product.
A preliminary study on the technical feasibility and outcome of retrograde root canal treatment
Authors: Jonasson P. , Reit C. , Kvist T.
Published: May 2008

Aim  To investigate the technical feasibility and outcome of retrograde root canal treatment.

Summary  Endodontic access cavity preparation in abutment teeth may jeopardize the retention of the coronal restoration leading to prosthodontic failure. In such cases leaving the crown intact and performing retrograde root canal treatment might be an alternative approach. The potential to promote healing with retrograde endodontic treatment, and the technical feasibility to shape, clean and fill the canal was evaluated retrospectively. The study consisted of 21 incisors, canines and premolar teeth followed‐up clinically and radiographically from 6 to 48 months. In 14 teeth the canals were completely negotiated. These cases were all judged as completely healed. In five cases no canal could be explored by files and a conventional ultrasonic root‐end preparation and filling was performed. Two of these were classified as completely healed and three as ‘uncertain’. In 2 two‐rooted premolars a combination was performed with complete instrumentation of the buccal canal and the ultrasonic root‐end preparation of the palatal root. One case was judged as a failure and the other was classified as completely healed. The results from this preliminary evaluation of retrograde root canal treatment are promising and merit a randomized clinical trial.

Key learning points • Abutment teeth with vital pulps may develop pulp necrosis and apical periodontitis in 10% of cases.

• Endodontic access preparation through an artificial crown may weaken its retention and jeopardize the longevity of a bridgework.

• Retrograde root canal treatment is often feasible in maxillary teeth.

• Results from this preliminary study suggest that treatment outcome for retrograde and orthograde root canal treatment is similar.
Mandibular bone necrosis caused by use of arsenic paste during endodontic treatment: two case reports
Authors: Yavuz M. S. , Şimşek Kaya G. , Yalçın E. , Aras M. H.
Published: May 2008

Aim  To report that arsenical pastes are still employed in endodontics and to highlight the potentially serious consequences of their use.

Summary  Chemotherapeutic agents such as arsenic trioxide and paraformaldehyde were once commonly employed as pulp‐necrotizing agents. Their cytotoxic effects are well recognized, and leakage from teeth has been associated with widespread necrosis of periodontal tissues and bone. This report describes two cases of severe bone necrosis affecting the mandible following the use of an arsenical paste.

Key learning points • Pulp‐necrotizing agents such as arsenic trioxide can cause severe bone necrosis.

• Arsenical pastes have no place in contemporary dental practice.

• Dentists should employ appropriate local anaesthetic techniques for pulp extirpation instead of relying on toxic necrotizing agents.
Characterization of human dental pulp‐derived cell lines
Authors: Suguro H. , Asano M. , Kaneko Y. , Omagari D. , Ogiso B. , Moro I. , Komiyama K.
Published: May 2008

Aim  To establish and characterize different types of fibroblastic cell lines derived from dental pulp tissue.

Methodology  Human dental pulp tissue‐derived cells were transfected with SV40 large T antigen by Lipofectamine transfection method. Geneticin (G418)‐resistant cells were selected and different cell lines were established by a limiting dilution method. To characterize the lineages of cells, each clone was immunofluorescently stained by anti‐fibroblast, anti‐vimentin, anti‐collagen type I and type III antibodies. Total RNA was extracted from each clone and subjected to a differential display experiment.

Results  By transfecting SV40 large T antigen, nine different cell clones were obtained. All these cell clones were positively stained by anti‐fibroblast, anti‐vimentin, anti‐collagen type I and type III antibodies. With differential display experiment, eight different genes, the expression levels of these genes were varied amongst each cell clone, were detected. After sequencing and database search, one gene was revealed to be identical to T‐cell marker, Thy‐1. Thy‐1 expression in dental pulp tissue was confirmed by immunohistochemical staining.

Conclusion  Fibroblastic cell lines derived from human dental pulp tissue possessed different gene expression profiles suggesting the existence of subpopulations.
Euthanasia and assisted suicide in Dutch hospitals: the role of nurses
Authors: Van Bruchem‐van de Scheur GG , Van Der Arend Arie JG , Huijer Abu‐Saad Huda , Van Wijmen Frans CB , Spreeuwenberg Cor , Ter Meulen Ruud HJ
Published: May 2008

Aim.  To report a study on the role of nurses in euthanasia and physician‐assisted suicide in hospitals, conducted as part of a wider study on the role of nurses in medical end‐of‐life decisions.

Background.  Issues concerning legislation and regulation with respect to the role of nurses in euthanasia and physician‐assisted suicide gave the Dutch Minister for Health reason to commission a study on the role of nurses in medical end‐of‐life decisions in hospitals, homecare and nursing homes.

Method.  A questionnaire was sent in 2003 to 692 nurses employed in 73 hospital locations. The response suitable for analysis was from 532 (76·9%) nurses. Data were quantitatively analysed using spss version 11.5 for Windows.

Results.  In almost half of the cases (45·1%), the nurse was the first with whom patients discussed their request for euthanasia or physician‐assisted suicide. Consultations between physicians and nurses quite often took place (78·8%). In several cases (15·4%), nurses themselves administered the euthanatics with or without a physician. It is not self‐evident that hospitals have guidelines concerning euthanasia/physician‐assisted suicide.

Conclusions.  In the decision‐making process, the consultation between the physician and the nurse needs improvement. In administering the euthanatics, physicians should take responsibility and should not leave these actions to nurses. Guidelines may play an important role to improve the collaboration between physicians and nurses and to prevent procedural, ethical and legal misunderstandings.

Relevance to clinical practice.  Nurses in clinical practice are often closely involved in the last stage of a person's life. Consequently, they are often confronted with caring for patients requesting euthanasia or physician‐assisted suicide. The results provide relevant information and may help nurses in defining their role in euthanasia and physician‐assisted suicide, especially in case these practices should become legalised.
What do mentors find difficult?
Authors: Moseley Laurence G , Davies Moira
Published: May 2008

Aims.  (i) To assess whether mentors had a positive or negative attitude towards their role; and (ii) to discover what aspects of the role they found easy or difficult.

Background.  The fact that mentorship is an important element in nurse training was recognized by Sir Leonard Peach, the United Kingdom Central Council for Nursing, Midwifery and Health Visiting and the Nursing and Midwifery Council which has recently published new standards to support learning and assessment in practice, which include standards for the preparation of Mentors, to be implemented by September 2007. There are many anecdotal reports of the problems which face mentors, but little firm evidence.

Method.  This paper reports a study of those problems. It used a Thurstone scale to assess role satisfaction among mentors (n = 86, response rate 89%) and two Likert scales to assess where problems, if any, lay.

Results.  Unlike anecdotal reports, the Thurstone scale found that, overall, mentors regarded the role positively. In addition, a principal components analysis of responses to the Likert scales showed that there were two clearly delineated factors. The first (interpersonal/organisational factors) had been widely discussed in the literature. The second (cognitive/intellectual factors) has been rarely discussed and could with profit be more strongly stressed in mentor training.

Conclusions.  (i) Mentors had a positive attitude towards their role and enjoyed it. (ii) When looking at what caused mentors difficulty, in addition to the commonly discussed dimensions of organisational constraints (workload, skill mix) and interpersonal factors, there was clearly an additional cognitive one. Knowledge, not just personality, mattered.

Implications for clinical practice.  Mentors and those who train them could with profit pay more attention to cognitive components of the role, even if that meant laying a lesser stress on the interpersonal ones.
Pressure ulcers: e‐learning to improve classification by nurses and nursing students
Authors: Beeckman Dimitri , Schoonhoven Lisette , Boucqué Hilde , Van Maele Georges , Defloor Tom
Published: May 2008

Aims and objectives.  To detect problems when classifying pressure ulcers and to examine whether an e‐learning program is able to increase the classification skills of qualified nurses and nursing students.

Background.  Both the distinction between pressure ulcer grades and the differentiation between moisture lesions is difficult. Misclassification and incorrect identification of the lesions results in inadequate preventive and therapeutic measures. Education and training are important for spreading evidence‐based insights about this topic.

Design.  Repeated measure design, consisting of one pretest and three posttests.

Methods.  The experimental intervention consisted of a one‐hour session during which the participants independently went over an e‐learning program. The control intervention consisted of a one‐hour lecture. Both interventions had the same learning contents. A convenience sample of 212 qualified nurses and 214 final‐year nursing students was randomly assigned to an experimental‐and a control group.

Results.  In the pretest, the classification skills were low. After the intervention, these skills improved significantly in both groups. The nursing students achieved better results when using the e‐learning program. Among the qualified nurses, there was no difference between the learning methods. Although the classification skills decreased in the posttests, they did not drop under the level of the pretest.

Conclusion.  The actual classification system does not provide the necessary information about the severity of a pressure ulcer. The differential diagnosis between a moisture lesion was complicated. The classification skills of the qualified nurses and nursing students increased by both learning methods. Repetition remains, however, necessary.

Relevance to clinical practice.  Both instruction methods are adequate to acquire the knowledge about the differences between moisture lesions and pressure ulcers. E‐learning allows studying in one's own time and place, and could therefore be very suitable for repetition of the training. How to organise this training could be a subject for further research.
Being there: parenting the child with acute lymphoblastic leukaemia
Authors: Kars Marijke C , Duijnstee Mia SH , Pool Aart , Van Delden Johannes JM , Grypdonck Mieke HF
Published: May 2008

Aims and objectives.  To gain insight into the lived experience of parenting a child with leukaemia during treatment.

Background.  Diagnosis of leukaemia in children leads to an existential shock for parents and a reversal of normal family life. Today, in the Netherlands, after diagnosis, children stay at home most of the time. Therefore, their parents face considerable responsibilities for administering home‐based treatment and for the support of their child during illness and treatment.

Methods.  A grounded theory study was undertaken at a Dutch University Hospital and involved one‐time individual in‐depth interviews with 12 mothers and 11 fathers (n = 23) of 12 children.

Findings.  ‘Being there’, was identified as the core concept. It means: ‘I’ll be there for you; I will never let you down’. ‘Being there’ is described as a parental response to the perceived vulnerability of the child and the parental need to give meaning to parenthood. It serves two purposes: protection and preservation. Protection means guarding the child against the negative aspects of illness and treatment. Preservation refers to the way parents influence the child’s perception of his/her life, thus contributing to his/her coping and willingness to undergo treatment, to maximise the chances for survival. Six aspects were identified: a trusting relationship, presence, emotional support, advocacy, routines and rituals and effacing oneself.

Conclusions.  The concept provides a theoretical frame for parenting the child with cancer. It clarifies the actions and reactions of parents and increases insight into the underlying force that enables parents to provide continuing care despite their personal burden.

Relevance to clinical practice.  The concept offers an essential insight into parenting the child with acute lymphoblastic leukaemia and has relevance for nursing practice and education. Understanding of the concept would improve the ability to understand, communicate and work pro‐actively in partnership with parents.
A systematic review of the effectiveness of in‐home community nurse led interventions for the mental health of older persons
Authors: Thompson Penelope , Lang Lyn , Annells Merilyn
Published: May 2008

Aims and objectives.  The aim was to systematically review evidence about the effectiveness of in‐home community nurse‐led interventions for older persons with, or at risk of, mental health disorders, to inform best practice nursing care with this focus. The primary review question was ‘How effective are in‐home community nurse‐led interventions for older persons with or at risk of mental health disorders for improving mental health?’ The outcome indices of interest were nursing actions to determine incidence or prevalence of mental health disorders, any change in a patient’s attitude towards their mental health condition, any change in objective measurement of mental health, or a change in diagnostic status.

Background.  The rising incidence of mental health disorders in older persons is a major concern for community nurses in developed countries. Effectively facilitating improved mental health for older persons is necessary in this era of ageing populations with increased demands on health funding. Disseminating systematically reviewed evidence for in‐home community nursing that positively impacts on the mental health of older persons is crucial to ensure effective care is provided to this vulnerable patient group.

Results.  This review reveals that there is evidence to support the superiority of applying validated screening tools for mental health disorders over relying on community nurses’ opinions and non‐validated tools about this matter.

Design.  Systematic review.

Methods.  Search of electronic databases.

Conclusion.  A clear need for replication and multi‐centre trials of reviewed pertinent studies is identified.

Relevance to clinical practice.  Community nurses should consider using validated screening tools for this focus. Until such time as higher quality evidence is available about other nursing interventions, the reviewers suggest that the prime nursing action should be the identification of whether older persons receiving community nursing care might have a mental health disorder and, if so, then collaborative referral is made to appropriate services.
Lay food and health worker involvement in community nutrition and dietetics in England: definitions from the field
Authors: Kennedy L. A. , Milton B. , Bundred P.
Published: May 2008

Background  Community‐based food initiatives have developed in recent years with the aim of engaging previously ‘hard to reach’ groups. Lay workers engaged in community nutrition activities are promoted as a cost‐effective mechanism for reaching underserved groups. The primary objective of the study was to explore perceptions and definitions of lay helping within the context of National Health Service (NHS) community nutrition and dietetic services to identify existing terms and definitions and propose an overarching term.

Methods  Interpretive qualitative inquiry; semi‐structured interviews with lay food and health worker (LFHW) and NHS professionals employed by community‐based programmes, serving ‘hard‐to‐reach’ neighbourhoods, across England.

Results  In total, 29 professionals and 53 LFHWs were interviewed across 15 of the 18 projects identified. Across all the projects, there was a preference for the use of one of two terms, either Community Food Worker or Community Nutrition Assistant, in reference to lay workers. There was no consensus in terms of a unifying term or definition for this new role.

Conclusions  Current variation in the terms and definitions used for this role is problematic and is hindering development and effective utilization of lay helping within the broad remit of community food and health and dietetics. The umbrella term ‘Lay Food and Health Worker’ is proposed based upon definitions and interpretations from the field.
Lay food and health worker involvement in community nutrition and dietetics in England: roles, responsibilities and relationship with professionals
Authors: Kennedy L. A. , Milton B. , Bundred P.
Published: May 2008

Background  Community‐based food initiatives have developed in recent years with the aim of engaging previously ‘hard to reach’ groups. Lay workers engaged in community nutrition activities are promoted as a cost‐effective mechanism for reaching underserved groups. The main objective of the study was to explore perceptions and definitions of lay food and health worker (LFHW) helping roles within the context of National Health Service (NHS) community nutrition and dietetic services in order to define the conceptual and practical elements of this new role and examine the interface with professional roles.

Methods  Interpretive qualitative inquiry; semi‐structured interviews with LFHW and NHS professionals employed by community‐based programmes, serving ‘hard‐to‐reach’ neighbourhoods, across England. A total sampling framework was used to capture all existing and ‘fully operational’ lay food initiatives in England at the commencement of fieldwork (January 2002).

Findings  In total, 29 professionals and 53 LFHWs were interviewed across 15 of the 18 projects identified. Although all 15 projects shared a universal goal, to promote healthy eating, this was achieved through a limited range of approaches, characterized by a narrow, individualistic focus. Lay roles spanned three broad areas: nutrition education; health promotion; and administration and personal development. Narratives from both professionals and LFHWs indicated that the primary role for LFHWs was to encourage dietary change by translating complex messages into credible and culturally appropriate advice.

Conclusions  This research confirms the emerging discipline involving lay helping within the NHS and community dietetics. The primary role of LFHWs in the 15 projects involved was to support existing NHS services to promote healthy eating amongst ‘hard to reach’ communities. The activities undertaken by LFHWs are strongly influenced by professionals and the NHS. Inherent to this is a fairly narrow interpretation of health, resulting in a limited range of practice.
NF‐κB in inflammatory bowel disease
Authors: Atreya I. , Atreya R. , Neurath M. F.
Published: May 2008

Apart from genetic and environmental factors, the mucosal immune system of the gut plays a central role in the pathogenesis of inflammatory bowel disease (IBD). In the healthy gut, the mucosal immune system ensures the balance between pro‐ and anti‐inflammatory mediators and thereby allows an effective defence against luminal pathogens but at the same time prevents an overwhelming immune reaction directed against the huge amount of harmless luminal antigens (for example, components of food or nonpathological bacteria). In both entities of IBD (Crohn’s disease and ulcerative colitis) this immunological balance is severely impaired and shifted towards the pro‐inflammatory side. The chronic mucosal inflammation in IBD is caused by hyperactivation of effector immune cells, which produce high levels of pro‐inflammatory cytokines like tumour necrosis factor‐α, interleukin‐6 and interferon‐γ, resulting in colonic tissue damage. The nuclear transcription factor kappaB (NF‐κB) was identified as one of the key regulators in this immunological setting. Its activation is markedly induced in IBD patients and through its ability to promote the expression of various pro‐inflammatory genes, NF‐κB strongly influences the course of mucosal inflammation. Considering the different cell‐type specific effects which are mediated by NF‐κB, this review aims at describing the complex role of NF‐κB in IBD and discusses existing pharmacological attempts to block the activation of NF‐κB to develop new therapeutic strategies in IBD.
Interplay of commensal and pathogenic bacteria, genetic mutations, and immunoregulatory defects in the pathogenesis of inflammatory bowel diseases
Authors: Packey C. D. , Sartor R. B.
Published: May 2008

Enteric microbiota can contribute to Crohn’s disease and ulcerative colitis in several ways. Pathogenic or functionally altered commensal bacteria with increased mucosal adherence, invasion and intracellular persistence can activate pathogenic T cells and chronic intestinal inflammation. Compositional changes in intestinal microbiota can lead to decreased protective and increased aggressive species. Genetic polymorphisms resulting in increased mucosal permeability, decreased microbial killing, ineffective clearance of bacteria, biased TH1 and TH17 immune responses and loss of immunological tolerance are probably key contributors to IBD. Future therapies for these heterogeneous diseases should be individualized based on the patient‐specific subset.
ULTRASTRUCTURAL CHANGES IN THE DORSAL ROOT AND TRIGEMINAL GANGLIA OF RATS POISONED WITH METHYL MERCURY
Authors: JACOBS JEAN M. , CARMICHAEL N. , CAVANAGH J. B.
Published: May 2008

Ultrastructural changes in the dorsal root and trigeminal ganglia of rats poisoned with methyl mercury

Rats have been dosed with methyl mercury chloride (7.5 mg/kg/day) for 8 days. The dorsal root and trigeminal ganglion cells have been studied by light and electron microscopy from 24 hours after the first dose to the 10th day. Earliest changes were found certainly at day 2 and possibly at day 1 and were confined to focal areas in the periphery of certain Type A cells in which ribosomes were lost from the rough endoplasmic reticulum (RER). Accumulations of dispersed granular material accompanied these earliest changes. After 4 days, changes in nuclear and perinuclear structures occurred just before or at the onset of axon degeneration, and may not be reactive to this event. These findings can be correlated with the defect in amino acid incorporation that occurs before axon degeneration.
CELL DEATH IN THE GERMINAL LAYERS OF THE POSTNATAL RAT BRAIN
Authors: LEWIS P. D.
Published: May 2008

In normal rats aged up to 21 days, between 0.2% and 06% of the cells in the sub‐ependymal and external granular layers show nuclear pyknosis and fragmentation. These cells are postmitotic. In control animals, an estimated 3.2% or less of newly acquired neurones and glia are lost by cell death. In undernourished rats, more pyknotic nuclei are found in the germinal layers of the brain at 12 days, when loss of newly acquired cells may be 3.7–7.8%.
MUSCLE TRANSPLANTATION BETWEEN NORMAL AND DYSTROPHIC MICE. 2. HISTOCHEMICAL STUDIES
Authors: NEERUNJUN J. S. , DUBOWITZ V.
Published: May 2008

Innervated and denervated auto‐ and crosstransplants, ranging in age from 1 hour to over 300 days, of normal and dystrophic tibialis anterior muscles in 129 ReJ mice have been examined histochemically for oxidative and glycolytic enzymes, ATPase, acetylcholinesterase, glycogen and nucleic acids. All transplants were devoid of glycogen and phosphorylase activity within 12 hours of transplantation. Fibre types were distinguished in the central areas of 2 day old transplants with NADH‐TR and ATPase reactions, but at the periphery, where fibres were at a rnore advanced stage of degeneration, fibre typing was not evident and NADH‐TR and ATPase reaction products were clumped. By 3 to 4 days most implanted fibres had broken down, but NADH‐TR and ATPase activity were still evident. “yotubes were observed in areas of 3 day old transplants where muscle fibres had completely degenerated and these stained uniformly for RNA, NADH‐TR and ATPase. Phosphorylase activity and glycogen were first observed in myotubes of 8 day old transplants. When examined before 12 days, myotubes of all transplants showed uniform NADH‐TR, ATPase, phosphorylase and RNA. Subsequently NADH‐TR, ATPase and PAS reactions showed progressive differentiation of type 1 and 2 fibres in innervated normal and dystrophic transplants in normal mice. All transplants in normal and in dystrophic mice, denervated at the time of transplantation, failed to show fibre type differentiation. Despite substantial regeneration before 25 days, all transplants in dystrophic mice subsequently underwent progressive degeneration. A similar pattern was observed in denervated transplants in normal mice. The few fibres that remained in these transplants showed uniform NADH‐TR and ATPase activity, whilst phosphorylase and glycogen were absent. Innervated normal and dystrophic transplants in normal mice showed maintenance of differentiated type 1 and 2 fibres even after 300 days, thus resembling intact normal rather than intact dystrophic muscles. This study supports the view that murine muscular dystrophy may have a neural basis for its pathogenesis.
THE HORMONE DEPENDENCE OF EXPERIMENTALLY INDUCED GLIOMAS IN THE RAT
Authors: HOPEWELL J. W.
Published: May 2008

Pellets of 3,4‐benzpyrene were implanted into the brains of groups of male and female rats. Animals from each of these groups were castrated or ovariectomized, and of these animals half the males and half the females received subcutaneous implants of testosterone. The position of the carcinogenic pellet in the brain was carefully controlled so that it impinged on the subependymal plate of the left lateral ventricle. A high proportion of glial tumours were produced in normal animals and it was found that deaths from cerebral tumour occurred earlier in males. Castration significantly reduced the time‐related tumour incidence, and this was not reversed by testosterone. In ovariectomized females tuinour incidence was unmodified by testosterone and deaths from glioma apparently occurred later than in hormonally normal females. The implications from these results are that glial tumours are not dependent on testosterone as previously suggested. Alternative mechanisms for the sex differentiation incidence are discussed.
THE EFFECTS OF MITOMYCIN C ON THE PROCESS OF REMYELINATION IN THE MAMMALIAN PERIPHERAL NERVOUS SYSTEM
Authors: HALL SUSAN M. , GREGSON N. A.
Published: May 2008

Schwann cell proliferation is a prominent feature of the normal response of a peripheral nerve fibre bundle to injurious stimuli. In this report we have attempted to analyse: (1) the pattern of division of cells in the endoneurium following demyelination induced by lysophosphatidyl choline (LPC), and (2) the consequence of inhibiting this response using mitomycin C. The nuclear uptake of 3H‐thymidine was examined in post‐LPC nerves with or without pretreatment with mitomycin C by means of light microscope autoradiography and by liquid scintillation counting. It was found that mitomycin C pretreatment inhibited the Schwann cell division that follows LPC injection into the nerve and that the fibires demyelinated thereby remained unmyelinated and surrounded by debris‐filled axon‐associated Schwann cells, for at least 1 month after injection of LPC. Remyelination was well established in control fibres by the second week after LPC injection. The nature of the stimuli which might initiate mitotic activity in mature Schwann cells and the possible function of this are discussed.
VARIATIONS IN THE HUMAN PURKINJE CELL POPULATION ACCORDING TO AGE AND SEX
Authors: HALL T. C. , MILLER A. K. H. , CORSELLIS J. A. N.
Published: May 2008

Systematic measurements and Purkinje cell counts have been made on ninety ‘normal’ cerebella. Forty‐eight were male, forty‐two were female. Both hemispheres were sampled in thirty‐eight cases, giving a total of 128 hemispheres. The fresh volume of the cerebellum was measured in each specimen and corrections were made for changes in size during fixation and processing. The methods used and their rationale are described and discussed in detail. A mean of 6318 nucleolated Purkinje cells was counted in each of the 128 hemispheres. The mean length of the Purkinje cell line along which they lay was 1–5 m. Twenty‐seven binucleated Purkinje cells were seen out of the 811769 cells that were counted (about 1 per 30000); they appeared to be unrelated to age, sex or disease.

The number of Purkinje cells per unit length of the Purkinje cell line and the number per unit area of the Purkinje cell sheet were found to be similar at all ages in the two sexes. Since, however, the male cerebellum tends to be larger than the female, the total number of Purkinje cells in the male is 6–8% higher than in the female. Wide individual variations were found in the same sex at all ages but a mean reduction of 2.5% per decade or of 25% over 100 years was identified. The figures suggested, however, that the reduction was curvilinear with the fall first becoming apparent at about the sixtieth year. No evidence was found that the drop was related to vascular degeneration or to any other identifiable pathological process.
THE EFFECT OF CHRONIC DOSING WITH MERCURIC CHLORIDE ON DORSAL ROOT AND TRIGEMINAL GANGLIA OF RATS
Authors: JACOBS JEAN M. , CAVANAGH J. B. , CARMICHAEL N.
Published: May 2008

Rats have been dosed repeatedly with 1.08 mg/kg of HgCl2 for up to 70 days and studied ultrastructurally. After two weeks, focal areas of disruption of endoplasmic reticulum (ER) occur in the neurons of the spinal ganglia; other features are present that are found also in methyl mercury intoxication in this species. At 1 month and longer on this dosing schedule a constant finding is loss of ribosomes from the rough ER of some neurons which persisted throughout the study. Occasional axon degeneration was found in the sciatic nerves of those animals having received the largest doses of HgCl2. Alterations in vascular endothelial cells and enlargement and other abnormalities in mitochondria of the neurones of spinal ganglia were also found. Because of similarities in the ultrastructural changes in the early phases of methyl mercury intoxication and those in chronic HgCl2 intoxication, it is suggested that degraded inorganic mercury may be important in the pathogenesis of the intracellular disturbances in methyl mercury poisoning. It is suggested that the excessive neurotoxicity of methyl mercury compounds may reside in the lipid solubility of these compounds and hence their ready capacity to enter cells.
INCREASE IN INOSINE‐5‐DIPHOSPHATASE ACTIVITY OF GLIAL CELLS IN EXPERIMENTALLY INFECTED MICE
Authors: FARKAS‐BARGETON EDITH , KRISTENSSON K. , LYCKE E. , SOURANDER P.
Published: May 2008

A study was made of inosine‐5‐diphosphatase activity of glial cells after intracerebral inoculation with various viral and non‐viral infectious agents. A generalized and non‐specific increase of the enzymatic activity was observed in cortical glial cells beyond the limits of the morphological lesions normally visible with the light microscope. A similar generalized enzymatic reaction of glial cells was also seen after intracerebral injection with non‐infectious tissue damaging agents such as incomplete Freund's adjuvant and calf serum. The possible role of oedema in the genesis of the changes is discussed.
FURTHER OBSERVATIONS ON THE EXPERIMENTAL TRANSMISSION OF CREUTZFELDT‐JAKOB DISEASE FROM MAN TO SQUIRREL AND SPIDER MONKEYS
Authors: ZLOTNIK I. , GRANT D. P. , DAYAN A. D. , EARL C. J. , ILLIS L. S. , WELLER R. O.
Published: May 2008

Inoculation of brain material from three female patients with Creutzfeldt‐Jakob disease into squirrel and spider monkeys produced an experimental neurological disease similar to Creutzfeldt‐Jakob disease in all the inoculated animals. The incubation period in squirrel monkeys varied from 17 to 29 months, but in the spider monkeys all the animals developed the disease between 19 and 22 months following inoculation. The early clinical signs were more readily recognized in squirrel monkeys than in spider monkeys. Itch and rubbing was a characteristic feature in all but one squirrel monkey, but it was absent in spider monkeys. The pathological change, in the form of widespread status spongiosus in the brain, as a rule was of greater severity in spider than in squirrel monkeys.
HEXACHLOROPHENE‐INDUCED LESIONS IN THE DEVELOPING PERIPHERAL NERVOUS SYSTEM OF MICE
Authors: PERSSON L. , WINGREN U. , KRISTENSSON K.
Published: May 2008

Hexachlorophene‐induced lesions in the developing peripheral nervous system of mice

Hexachlorophene (HCP) locally applied to the sciatic nerve of mice less than 2 weeks old caused a marked sponginess of the myelin. Ultrastructurally, this was due to a splitting of the minor dense lines of the myelin lamellae with the formation of vacuoles. The changes were reversed after discontinuing the treatment. Unexpectedly, this sponginess in the peripheral nerves was much less and failed almost completely to occur when the HCP application was continued after the second week of life. HCP treatment given to mice older than two weeks caused no sponginess of peripheral nerves, but status spongiosus instead developed in the white matter of the central nervous system. The only change in the peripheral nervous system (PNS) in the older mice was a Wallerian type of degeneration of nerve fibres at and distal to the site of HCP injection. It is therefore concluded that the response of the myelin of mouse PNS to HCP is age dependent and differs from the responses of CNS myelin.
EXPERIMENTAL LEAD ENCEPHALOPATHY OF CALVES. HISTOLOGICAL OBSERVATIONS ON THE NATURE AND DISTRIBUTION OF THE LESIONS
Authors: WELLS G. A. H. , HOWELL J. MCC. , GOPINATH C.
Published: May 2008

Experimental lead encephalopathy of calves. Histological observations on the nature and distribution of the lesions

Neurological signs were induced in four calves by the daily administration of 20 mg/kg body weight lead acetate. The time of onset and duration of symptoms varied, and the severity progressed to an acute neurological episode in three calves. Histological lesions in the brains of three calves consisted of focal vacuolation of the neuropil, neuronal necrosis and changes in capillary walls. These changes occurred in the cerebral cortex and in certain grey centres of the brain stem. The encephalopathy was associated with elevated blood and tissue lead levels, but could not be correlated with pathological effects in other organs. The nature of the lesions suggests a basic change in transport mechanisms between the blood and brain.
DEFICIENT VASCULAR INNERVATION IN FAMILIAL DYSAUTONOMIA, AN EXPLANATION FOR VASOMOTOR INSTABILITY
Authors: GROVER‐JOHNSON NICOLA , PEARSON J.
Published: May 2008

Deficient vascular innervation in familial dysautonomia, an explanation for vasomotor instability

An ultrastructural study of peripheral blood vessels in familial dysautonomia demonstrates the absence of autonomic nerve terminals. In control subjects both sympathetic terminals containing dense‐cored vesicles and presumptive cholinergic terminals containing agranular vesicles are readily shown. Lack of autonomic innervation of blood vessels in familial dysautonomia accounts for postural hypotension and other abnormalities of vasomotor reflexes. It also explains exaggerated responses to sympathomimetic and parasympathomimetic agents in terms of denervation hypersensitivity. Ultrastructural analysis of vascular nerve terminals may be of general value in the study of many diseases which show vasomotor instability.
AN ELECTRON MICROSCOPIC STUDY OF CELL DEGENERATION IN CHICK EMBRYO SPINAL GANGLIA
Authors: PANNESE E.
Published: May 2008

An electron microscopic study of cell degeneration in chick embryo spinal ganglia

Cell degeneration which normally occurs during development was studied under the electron microscope in thoracic spinal ganglia of chicken embryos. Cells undergoing degeneration were often identified as primitive neuroblasts or transitional cells between the primitive and intermediate neuroblast, and sometimes as intermediate neuroblasts. Degeneration seems to begin with nuclear alterations (chromatin condensation and segregation of the nucleolar components) and ribosomal changes (polysomal disaggregation, and displacement of many membrane‐associated ribosomes). Soon the Golgi complex is no longer recognizable. Successively, large masses of finely granular material become prominent in the nucleus, the nuclear envelope breaks down, many mitochondria appear altered, many vacuoles with clear contents become evident, and ribosome crystals appear. At the end of the process the degenerated cell appears as a shrunken mass of granular debris and membrane fragments. Some neuroblastic processes contain clumped filaments and microtubules and/or polymorphic dense bodies. These structural changes are not unique to this degenerative process, but closely resemble those following other types of injuries of the nerve cell. A drastic reduction in the nuclear synthesis of RNA, and a profound impairment in protein synthesis are probably the main biochemical events which occur in these degenerating cells. Degeneration, which probably affects the neuroblasts which fail to establish appropriate connections with the periphery, seems to be one of the major factors controlling cell number in the spinal ganglia.
THE EFFECTS OF CARBON MONOXIDE ON NEURONS OF THE CEREBELLUM*
Authors: CHAN‐PALAY VICTORIA , MCCROSKEY L.
Published: May 2008

The effects of carbon monoxide on neurons of the cerebellum

Acute CO exposure in rats produces multifocal edema and neuroglial swelling in cerebellar cortex and nuclei. Chronic multiple daily exposures to CO produce degenerative changes in neurons–shrinkage of cell somata and dendrites, enlargement of nuclei and nucleoli, vacuolation in neuronal cytoplasm, pyknosis and ultimate engulfment by microglia. Focal areas of Purkinje cell loss are typical; individual basket cells and their axons, stellate cells and the deep nuclear neurons are severely affected. Counts of Purkinje cells and their dendritic thorns show reductions of 30% and 31% respectively in affected regions. In foci of severe Purkinje cell loss, dendritic thorns of the neighboring cells which remain assume a greater number of synapses with unusual presynaptic partners, e. g. both parallel fibers and climbing fibers in a single thorn. An increase of 4.2% more synapses per thorn was measured when compared to the normal. Thus, the stress of chronic CO exposure stimulates synaptic plasticity or a compensatory remodelling of neuronal elements in the central nervous system. A scheme is proposed to summarize these changing relationships caused by the loss of some dendritic thorns and the migration of the presynaptic partners to other surviving thorns.
SUBCUTANEOUS C‐1300 MURINE NEUROBLASTOMA. A LIGHT AND ULTRASTRUCTURAL STUDY
Authors: GRAHAM D. I. , GONATAS N. K.
Published: May 2008

A light and electron microscopic study has been carried out on the subcutaneous C‐1300 murine neuroblastoma and compared with the morphology of the same tumour grown in both suspension (‘undifferentiated’) and monolayer (‘differentiated’) tissue culture. Two principal cell types, as in tissue culture, were seen in the solid tumour, (a) ‘undifferentiated’ round cells characterized by short microvilli, dispersed ribosomes, scanty neurofilaments and neurotubules and a high mitotic figure rate, and (b) ‘differentiated’ cells characterized by long processes (neurites), aggregation of ribosomes into polysomes, an extensive network of neurofilaments and neurotubules and an occasional dense‐core vesicle. An occasional point of contact between adjacent cells was seen but never synapse formation. These appearances therefore suggest that the subcutaneous tumour cells express some of the differentiated features of the normal cell type from which they are derived. The majority of the cells both in culture and the subcutaneous tumour contained multiple virus‐like A‐type particles. In addition, and possibly of greater significance, was the finding of occasional budding of C‐type particles at the cell surface and the presence of extracellular C‐type particles in the subcutaneous tumour, features which we never saw in the tissue culture material from which the solid neuroblastoma was derived. Possible reasons for this apparent discrepancy are discussed.
MUSCLE FIBRE SPLITTING AND REGENERATION IN DISEASED HUMAN MUSCLE
Authors: SCHMALBRUCH H.
Published: May 2008

In soleus muscle of rat, necrosis of muscle fibres within a grossly intact endomysium was produced by 60–70°C Ringer's solution injected into the space around the muscle. After 2 weeks regenerated fibres appeared to be fragments of ‘split’ fibres. In split fibres of patients with myopathy all stages of myogenesis were seen in electron micrographs. Hence splitting of muscle fibres is thought to indicate regeneration rather than degeneration. Based on the morphology of the clefts through split fibres and of normal fetal myogenesis a hypothetical mechanism for splitting of muscle fibres is proposed. Myoblasts, myotubes and myofibres occur within a common basement membrane separated only by plasma membranes and a 20 nm wide gap. In light microscopy they appear as a single fibre. Many meshes of the endomysial framework remain empty and condense around regenerating fibres. Myotubes and young myofibres fuse laterally or become detached and appear by light microscopy to be fragments of a longitudinally split fibre. Though encircled by thick endomysial sheaths, connective tissue between them is sparse. The site of fusion may be marked by a strand of mitochondria or by internal nuclei. Incomplete fusion results in branched fibres or short longitudinal clefts or cavities. The prerequisite of this hypothesis is that regeneration is focal and takes place in a grossly intact endomysium. Repeated death of muscle fibres and focal regeneration in human myopathic muscle lead to dissociation of parenchyma and connective tissue. The mechanism is similar to the formation of pseudolobuli in cirrhosis of the liver.
THE PATHOLOGY OF EXPERIMENTAL OBSTRUCTIVE HYDROCEPHALUS
Authors: TORVIK A. , BHATIA R. , NYBERG‐HANSEN R.
Published: May 2008

Acute hydrocephalus was produced in newborn rabbits by the injection of kaolin into the cisterna magna. The light microscopic changes which occurred in the ependyma and periventricular brain tissue were studied. Some animals also received intraventricular injection of Evans blue albumin (EBA) at various times after the kaolin injection to study the permeability of the ependymal lining. There was a progressive dilatation of the lateral ventricles from the second day after the kaolin injection. Marked hydrocephalus was seen after 2 weeks. The white matter of the cerebral hemispheres showed increasing reduction in volume with the degree of hydrocephalus. No destruction of brain tissue, macrophage response, or inflammation were seen. The ependyma adapted remarkably well to the increased intraventricular pressure by extensive flattening and stretching. Apart from occasional and inconstant ruptures at the sites of the ventricular coarctations, no convincing breaks or defects of the ependymal lining were seen. There was a patchy spongy zone beneath the ependyma, possibly indicating oedema of the periventricular white matter due to transventricular movement of cerebrospinal fluid (CSF). Denudation of the ependymal lining is not necessary for the concept of transventricular flow of CSF. No difference was seen in the penetration of EBA into the periventricular tissue between hydrocephalic and control animals. The reduction of the cerebral mantle thickness was probably caused by simple pressure atrophy. This indicates that the changes may to a large extent be reversible if the hydrocephalus is treated within reasonable time.
EFFECTS OF HYPERTONIC SOLUTIONS AND OF MERCURIC CHLORIDE ON THE UPTAKE OF [14C]GLUCOSE ANALOGUES BY RABBIT BRAIN
Authors: SPATZ MARIA , RAP Z. M. , RAPOPORT S. I. , KLATZO I.
Published: May 2008

Intracarotid perfusion of hypertonic solutions of urea, NaCl or acetamide increased the brain uptake index (BUI) of glucose analogues by rabbit brain, while isotonic urea was without effect. Lactamide, whether isotonic or hypertonic, decreased the BUI of glucose analogues. The increased BUI produced by the other hypertonic solutions could be inhibited by unlabeled substrate, unlabeled glucose or by phloridzin, and may reflect stimulated carrier‐mediated transport of monosaccharides into brain. Although the increases could also have been due to altered cerebral blood flow, radioautography showed no gross evidence of such alterations. The BUI of 2‐2‐deoxy‐D‐[1‐14C]glucose was decreased by intracarotid injection of 0.01mM HgCl2, to the same level seen following maximal inhibition with unlabeled 2‐deoxy‐D‐glucose, while 0.08mM HgCl2 gave BUI's above this level. The lower concentration of HgCl2 probably inhibited carrier‐mediated monosaccharide transfer, while the higher concentration appeared to increase passive diffusion into the brain as well.
EFFECT OF BCG ON THE GROWTH OF A TRANSPLANTABLE ETHYLNITROSOUREA‐INDUCED SCHWANNOMA
Authors: RIDLEY A. , RAINBIRD SUSAN
Published: May 2008

The effect of BCG on the growth of a transplantable ethylnitrosourea‐induced schwannoma was studied in pure‐line BD‐IX rats. The tumour was grown at two sites (the foot and the flank) and the BCG was injected locally at these sites, and was injected before, at the same time as, or after the injection of tumour cells. Significant slowing of tumour growth occurred if the BCG was given before or at the same time as the tumour cells. Injection of BCG after tumour growth was established was much less effective, although there was some retardation.