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2.
Neuropathol Appl Neurobiol ; 32(6): 625-34, 2006 Dec.
Article in English | MEDLINE | ID: mdl-17083477

ABSTRACT

Unexplained subdural and retinal haemorrhages in an infant are commonly attributed to 'shaking', the mechanism of which is believed to be traumatic venous rupture. However, the haemorrhagic retinopathy reported as a result of Valsalva manoeuvres and the subdural bleeding that is a rare complication of pertussis together demonstrate that if a sustained rise in intrathoracic pressure is transmitted to cerebral and retinal vessels, it may result in bleeding, similar to that reported in inflicted injury. Such haemorrhages would be expected to occur whenever severe paroxysmal coughing were induced, whatever the cause. This study used a computer modelling approach to investigate feeding accidents as the trigger for bleeding. A dynamic circulatory model of a 3-month-old infant was induced to 'cough', and the response to changes in physiological variables monitored. It showed that coughing causes intracranial pressures to build up exponentially to approach a maximum, proportional to the amount of pressure the musculature of the thorax can produce, as venous return is impeded. They do not have time to become dangerous during individual coughs, as blood quickly returns after the cough is over, reestablishing normal pressures. Paroxysmal coughing, however, does not allow blood to return between coughs, with the result that very high luminal pressures may be generated, sufficient to damage veins. A history of coughing, vomiting or choking is not uncommon in otherwise normal infants with retinal and subdural bleeding. Our findings suggest that paroxysmal coughing could account for such bleeding in some cases.


Subject(s)
Computer Simulation , Cough/complications , Hematoma, Subdural/etiology , Intracranial Hypertension/complications , Models, Neurological , Retinal Hemorrhage/etiology , Brain/blood supply , Humans , Infant
3.
Forensic Sci Int ; 146(2-3): 83-8, 2004 Dec 16.
Article in English | MEDLINE | ID: mdl-15542267

ABSTRACT

There is scant neuropathological information in the child abuse literature; even the best reviews include assumptions based on the findings of a few inadequate early studies. Our recent series of 53 fatal cases (Brain 124 (2001) 1290, 1299 [1,2]) demonstrated age-related patterns of brain injury and showed the substrate of severe encephalopathy in the infants to be hypoxic brain damage, not diffuse traumatic axonal injury ('DAI'), as had previously been thought. About one-third had craniocervical injuries, particularly in the brain stem, suggestive of stretch injury to the neuraxis. Our interpretation was that this finding implied a mechanism of injury--brain stem damage from stretch injury to the neck with resultant apnoea--that could account for the clinical scenario in many cases, and for which violence would not necessarily be required. Since publishing this study we have turned our attention to the subgroup of infants who die without objective signs of injury, such as skull fracture or impact, whose carers are accused of abuse, usually, "violent shaking", on the pathologic findings alone. Given the striking discrepancy that there often is in such cases between the relatively trivial findings in the brain and the accusations of violence, we have been looking at the pathogenesis of the typical intracranial bleeding. A histologic study of dura from 50 paediatric autopsies, none of whom had suffered a head injury, has led us to propose that the subdural and retinal bleeding in such cases may well have a physiological aetiology, rather than being caused directly by trauma.


Subject(s)
Brain/pathology , Dura Mater/pathology , Forensic Pathology , Intracranial Hemorrhages/pathology , Shaken Baby Syndrome/pathology , Brain Edema/pathology , Diagnosis, Differential , Dura Mater/blood supply , Humans , Hypertension/pathology , Hypoxia-Ischemia, Brain/pathology , Infant , Intracranial Hemorrhages/etiology , Intracranial Hypertension/pathology , Microcirculation/pathology , Retinal Hemorrhage/etiology , Retinal Hemorrhage/pathology
4.
Pediatr Rehabil ; 7(4): 261-5, 2004.
Article in English | MEDLINE | ID: mdl-15513769

ABSTRACT

In this article we reply to the recent critique by Punt et al. in Pediatric Rehabilitation. Our hypothesis about the pathogenesis of intracranial bleeding in infants has three important implications. First, in the case of an infant with a swollen brain, subdural and retinal haemorrhage but no objective evidence of trauma, the findings by themselves are not certain evidence of abuse; second, violence is not necessary to produce subdural and retinal haemorrhage; and lastly, non-traumatic events producing apnoea with a catastrophic rise in intracranial pressure could produce a clinical picture identical to that seen in trauma.


Subject(s)
Brain Hemorrhage, Traumatic/diagnosis , Child Abuse , Hematoma, Subdural/physiopathology , Retinal Hemorrhage/physiopathology , Brain Hemorrhage, Traumatic/mortality , Child, Preschool , Female , Hematoma, Subdural/etiology , Hematoma, Subdural/mortality , Humans , Infant , Injury Severity Score , Male , Prognosis , Retinal Hemorrhage/etiology , Retinal Hemorrhage/mortality , Risk Assessment , Shaken Baby Syndrome/diagnosis , Shaken Baby Syndrome/mortality , Survival Rate , Violence
5.
BMJ ; 328(7442): 719-20, 2004 Mar 27.
Article in English | MEDLINE | ID: mdl-15044267
7.
Virchows Arch ; 442(6): 591-6, 2003 Jun.
Article in English | MEDLINE | ID: mdl-12695912

ABSTRACT

A method was developed for detection of influenza genes in formalin-fixed brains of mice that had been experimentally infected with influenza A/NWS/33 (H1N1) virus. Using this technique, messenger ribonucleic acid (mRNA) of the beta-actin gene was detected in eight clinical brain samples from the 1916-1920 outbreak of encephalitis lethargica, showing preservation of particular mRNAs. However, we did not detect influenza nucleotide sequences of M, NP, and NS genes from these same samples. We conclude either that influenza was not the causative agent of encephalitis lethargica or, possibly, that the virus had a hit-and-run mechanism and was no longer present in the brain at the time of death of the patients.


Subject(s)
Brain/pathology , Disease Outbreaks , Influenza, Human/complications , Orthomyxoviridae/isolation & purification , Parkinson Disease, Postencephalitic/etiology , Actins/genetics , Actins/metabolism , Adolescent , Adult , Animals , Brain/virology , Child, Preschool , DNA Primers/chemistry , Female , Formaldehyde , Humans , Infant , Influenza, Human/pathology , Influenza, Human/virology , Male , Mice , Orthomyxoviridae/genetics , Paraffin Embedding , Parkinson Disease, Postencephalitic/pathology , Parkinson Disease, Postencephalitic/virology , RNA, Messenger/metabolism , RNA, Viral/analysis , Reverse Transcriptase Polymerase Chain Reaction , Tissue Fixation
9.
Neuropathol Appl Neurobiol ; 29(1): 14-22, 2003 Feb.
Article in English | MEDLINE | ID: mdl-12581336

ABSTRACT

A histological review of dura mater taken from a post-mortem series of 50 paediatric cases aged up to 5 months revealed fresh bleeding in the dura in 36/50, the bleeding ranging from small perivascular haemorrhages to extensive haemorrhage which had ruptured onto the surface of the dura. Severe hypoxia had been documented clinically in 27 of the 36 cases (75%). In a similar review of three infants presenting with classical 'shaken baby syndrome', intradural haemorrhage was also found, in addition to subdural bleeding, and we believe that our findings may have relevance to the pathogenesis of some infantile subdural haemorrhage. Recent work has shown that, in a proportion of infants with fatal head injury, there is little traumatic brain damage and that the significant finding is craniocervical injury, which causes respiratory abnormalities, severe global hypoxia and brain swelling, with raised intracranial pressure. We propose that, in such infants, a combination of severe hypoxia, brain swelling and raised central venous pressure causes blood to leak from intracranial veins into the subdural space, and that the cause of the subdural bleeding in some cases of infant head injury is therefore not traumatic rupture of bridging veins, but a phenomenon of immaturity. Hypoxia with brain swelling would also account for retinal haemorrhages, and so provide a unified hypothesis for the clinical and neuropathological findings in cases of infant head injury, without impact or considerable force being necessary.


Subject(s)
Dura Mater/pathology , Intracranial Hemorrhages/etiology , Shaken Baby Syndrome/complications , Shaken Baby Syndrome/pathology , Diagnosis, Differential , Dura Mater/blood supply , Humans , Infant , Infant, Newborn , Intracranial Hemorrhages/pathology , Retrospective Studies
10.
Eur J Endocrinol ; 148(2): 203-11, 2003 Feb.
Article in English | MEDLINE | ID: mdl-12590639

ABSTRACT

OBJECTIVE: Pituitary tumour transforming gene (PTTG) is a recently identified protooncogene, ubiquitously expressed in pituitary tumours at levels higher than those detected in normal pituitary. Although the precise function of PTTG protein is unknown, in vitro experiments have shown that it induces angiogenesis. In this study, we have examined the potential relationship between the level of PTTG expression and tumour phenotype, tumour size, in vitro pituitary hormone secretion and release of vascular endothelial growth factor (VEGF), a potent angiogenic factor. METHODS: Pituitary tumours (12 somatotroph, five lactotroph, five corticotroph and 18 non-functioning) were studied by cell culture, measuring the basal secretion of anterior pituitary hormones and VEGF in vitro. Immunocytochemistry was used to confirm the clinical diagnosis and tumour phenotype. PTTG mRNA expression was investigated by comparative RT-PCR. Tumour Volume was quantitated from pre-operative MRI scans. RESULTS: PTTG expression was significantly increased 2.7-fold in somatotroph tumours compared with non-functioning adenomas (P<0.01, ANOVA). A positive correlation was demonstrated between PTTG expression and in vitro GH secretion (r=0.41, P<0.01, Spearman) but no correlations were found for any of the other pituitary hormones. In 16 out of 40 pituitary tumours, we were able to determine the in vitro secretion of VEGF and relate this to PTTG expression. All of the adenomas tested secreted measurable VEGF but there was no correlation between the amount of VEGF secreted and either the tumour phenotype or PTTG expression. Neither PTTG expression nor VEGF secretion correlated with tumour Volume. CONCLUSIONS: Our studies have confirmed the presence of PTTG in pituitary adenomas and demonstrated a higher level of expression in somatotroph tumours and a significant correlation with GH secretion. We failed to demonstrate a relationship between PTTG expression and production of the angiogenic factor, VEGF, or tumour Volume. Thus, although PTTG induces angiogenesis experimentally, it seems unlikely that a VEGF-mediated angiogenic mechanism occurs during pituitary tumour progression.


Subject(s)
Adenoma/metabolism , Endothelial Growth Factors/metabolism , Human Growth Hormone/metabolism , Intercellular Signaling Peptides and Proteins/metabolism , Lymphokines/metabolism , Neoplasm Proteins/metabolism , Pituitary Neoplasms/metabolism , Adenoma/diagnosis , Adenoma/genetics , Gene Expression , Humans , In Vitro Techniques , Magnetic Resonance Imaging , Neoplasm Proteins/genetics , Phenotype , Pituitary Neoplasms/diagnosis , Pituitary Neoplasms/genetics , Securin , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth Factors
13.
J Clin Endocrinol Metab ; 86(6): 2476-83, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11397843

ABSTRACT

The orphan nuclear receptors, steroidogenic factor 1 (SF-1) and DAX-1, are involved in gonadotroph differentiation, and SF-1 has been shown to activate the LH-beta and glycoprotein hormone alpha-subunit (alpha GSU) gene promoters. Pituitary adenomas from 34 patients [13 somatotroph tumors, 4 prolactinomas, and 17 clinically nonfunctioning pituitary adenomas (NFPAs)] were enzymatically dispersed and cultured in vitro for 48 h. Tissue culture medium was collected and assayed for LH, FSH, and alpha GSU; messenger RNA was extracted from adherent cells, and expression of SF-1 and DAX-1 messenger RNA was determined by RT-PCR and verified by direct DNA sequencing. The presence of DAX-1 protein in tumor tissue was confirmed by immunocytochemistry. DAX-1 was demonstrated in all NFPAs, 7 of 13 somatotroph tumors and 0 of 4 prolactinomas. SF-1 expression occurred in 8 of 16 NFPAs, 4 of 12 somatotroph tumors, and 1 of 4 prolactinomas. LH secretion in vitro was greater in NFPAs that were SF-1 positive (P < 0.05). Neither FSH secretion nor alpha GSU secretion in vitro were significantly related to the expression of SF-1 or DAX-1. SF-1-positive somatotroph tumors immunostained positively for LH-beta and/or FSH-beta and secreted gonadotropins in vitro. SF-1 expression is associated with the in vitro secretion of LH by NFPAs. A proportion of somatotroph tumors also express SF-1 and DAX-1 and secrete gonadotropin hormones in vitro.


Subject(s)
Adenoma/metabolism , DNA-Binding Proteins/metabolism , Gonadotropins/metabolism , Pituitary Neoplasms/metabolism , Receptors, Retinoic Acid/metabolism , Repressor Proteins , Transcription Factors/metabolism , Adenoma/pathology , DAX-1 Orphan Nuclear Receptor , Fushi Tarazu Transcription Factors , Homeodomain Proteins , Humans , Immunohistochemistry , Pituitary Neoplasms/pathology , Receptors, Cytoplasmic and Nuclear , Reference Values , Reverse Transcriptase Polymerase Chain Reaction , Steroidogenic Factor 1 , Tumor Cells, Cultured
14.
Brain ; 124(Pt 7): 1290-8, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11408324

ABSTRACT

Fifty-three cases of non-accidental head injury in children were subjected to detailed neuropathological study, which included immunocytochemistry for microscopic damage. Clinical details were available for all the cases. There were 37 infants, age at head injury ranging from 20 days to 9 months, and 16 children (range 13 months to 8 years). The most common injuries were skull fractures (36% of cases), acute subdural bleeding (72%) and retinal haemorrhages (71%); the most usual cause of death was raised intracranial pressure secondary to brain swelling (82%). On microscopy, severe hypoxic brain damage was present in 77% of cases. While vascular axonal damage was found in 21 out of 53 cases, diffuse traumatic axonal injury was present in only three. Eleven additional cases, all of them infants, showed evidence of localized axonal injury to the craniocervical junction or the cervical cord. When the data were analysed by median age at head injury, statistically significant patterns of age-related damage emerged. Our study shows that infants of 2-3 months typically present with a history of apnoea or other breathing abnormalities, show axonal damage at the craniocervical junction, and tend also to have a skull fracture, a thin film of subdural haemorrhage, but lack extracranial injury. Children over 1 year are more likely to suffer severe extracranial, particularly abdominal, injuries. They tend to have larger subdural haemorrhages, and where traumatic axonal injury is present, show patterns of hemispheric white matter damage more akin to those reported in adults. Diffuse axonal injury is an uncommon sequel of inflicted head injury in children.


Subject(s)
Brain/pathology , Child Abuse/diagnosis , Craniocerebral Trauma/pathology , Age Distribution , Apnea/epidemiology , Apnea/pathology , Child , Child, Preschool , Comorbidity , Craniocerebral Trauma/epidemiology , Diffuse Axonal Injury/epidemiology , Diffuse Axonal Injury/pathology , Female , Forensic Medicine , Humans , Infant , Infant, Newborn , Intracranial Hemorrhages/epidemiology , Intracranial Hemorrhages/pathology , Intracranial Hypertension/epidemiology , Intracranial Hypertension/pathology , Male , Organ Size , Retinal Hemorrhage/epidemiology , Retinal Hemorrhage/pathology , Risk , Skull Fractures/epidemiology , Skull Fractures/pathology , United Kingdom/epidemiology
15.
Brain ; 124(Pt 7): 1299-306, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11408325

ABSTRACT

There are very few reports in the literature dealing with the neuropathology of infant head injury, and the question of whether diffuse traumatic brain damage [diffuse axonal injury (DAI)] occurs in such children has not yet been reliably established by detailed neuropathological studies. We report the findings in the brains of a series of 37 infants aged 9 months or less, all of whom died from inflicted head injuries, and 14 control infants who died of other causes. Axonal damage was identified using immunohistochemistry for beta-amyloid precursor protein. Full clinical details were available for each case, the most constant of which in the study cohort was an episode of significant apnoea at presentation, found to have been recorded in 75% of cases. Global hypoxic damage was the most common histological finding. Widespread axonal damage, interpreted as vascular, was present in 13 cases, but widespread traumatic axonal injury was found in only two children, both of whom had severe head injuries with multiple skull fractures. Epidural cervical haemorrhage and focal axonal damage to the brainstem and the spinal nerve roots, found in 11 cases but not in controls, indicate that the craniocervical junction is vulnerable in infant head injury, the neuropathology being that of stretch injury from cervical hyperextension/flexion. Damage to this region could account for the observed apnoea, which could in turn lead to hypoxic damage and brain swelling. The observation that the predominant histological abnormality in cases of inflicted head injury in the very young is diffuse hypoxic brain damage, not DAI, can be explained in one of two ways: either the unmyelinated axon of the immature cerebral hemispheres is relatively resistant to traumatic damage, or in shaking-type injuries the brain is not exposed to the forces necessary to produce DAI.


Subject(s)
Brain/pathology , Child Abuse/diagnosis , Craniocerebral Trauma/pathology , Hypoxia, Brain/pathology , Amyloid beta-Protein Precursor/metabolism , Brain/metabolism , Brain Edema/epidemiology , Brain Edema/pathology , Brain Stem/metabolism , Brain Stem/pathology , Cohort Studies , Comorbidity , Craniocerebral Trauma/epidemiology , Craniocerebral Trauma/metabolism , Diffuse Axonal Injury/epidemiology , Diffuse Axonal Injury/metabolism , Diffuse Axonal Injury/pathology , Female , Forensic Medicine , Humans , Hypoxia, Brain/epidemiology , Immunohistochemistry , Infant , Infant, Newborn , Male , Neck Injuries/epidemiology , Neck Injuries/pathology , Skull Fractures/epidemiology , Skull Fractures/pathology , Spinal Nerve Roots/pathology , United Kingdom/epidemiology
16.
Cancer Res ; 61(10): 4287-93, 2001 May 15.
Article in English | MEDLINE | ID: mdl-11358858

ABSTRACT

JC virus (JCV) is a neurotropic polyomavirus infecting greater than 70% of the human population worldwide during early childhood. Replication of JCV in brains of individuals with impaired immune systems results in the fatal demyelinating disease, progressive multifocal leukoencephalopathy (PML). Furthermore, JCV possesses an oncogenic potential and induces development of various neuroectodermal origin tumors including medulloblastomas and glioblastomas in experimental animals. The oncogenecity of JCV is attributed to the viral early gene product, T-antigen, which has the ability to associate with and functionally inactivate well-studied tumor suppressor proteins including p53 and pRB: The observations from laboratory animal experiments have provided a rationale for examining the presence of the JCV DNA sequence and expression of the viral oncogenic protein in human brain tumors. We have examined 85 clinical specimens from the United Kingdom, Greece, and the United States, representing various human brain tumors including oligodendroglioma, astrocytoma, pilocytic astrocytoma, oligoastrocytoma, anaplastic astrocytoma, anaplastic oligodendroglioma, glioblastoma multiforme, gliomatosis cerebri, gliosarcoma, ependymoma, and subependymoma, for their possible association with JCV. We performed gene amplification techniques using a pair of primers that recognize the JCV DNA sequence, and we demonstrated the presence of the viral early sequence in 49 (69%) of 71 samples. More importantly, our results from immunohistochemistry analysis revealed expression of JCV T-antigen in the nuclei of tumor cells in 28 (32.9%) of 85 tested samples. These observations, along with earlier in vitro and in vivo data on the transforming ability of this human neurotropic virus invite additional studies to re-evaluate the role of JCV in the pathogenesis of human brain tumors.


Subject(s)
Antigens, Polyomavirus Transforming/genetics , Brain Neoplasms/virology , DNA, Viral/genetics , JC Virus/genetics , Animals , Antigens, Polyomavirus Transforming/biosynthesis , Brain Neoplasms/genetics , Brain Neoplasms/immunology , Brain Neoplasms/pathology , Cricetinae , Gene Expression , Humans , Immunohistochemistry , JC Virus/immunology , Mesocricetus , Tumor Suppressor Protein p53/biosynthesis
17.
Br J Neurosurg ; 15(2): 147-50, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11360380

ABSTRACT

Chordoid glioma, a rare tumour of the third ventricle, has distinctive histological appearances. Fewer than 20 cases have been reported in the literature, all but three in females. This paper describes a 54-year-old man with a chordoid glioma and reviews the clinicopathological features of this lesion.


Subject(s)
Cerebral Ventricle Neoplasms/diagnosis , Glioma/diagnosis , Cerebral Ventricle Neoplasms/chemistry , Cerebral Ventricle Neoplasms/surgery , Glial Fibrillary Acidic Protein/analysis , Glioma/chemistry , Glioma/surgery , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Neurosurgical Procedures , S100 Proteins/analysis , Third Ventricle , Tomography, X-Ray Computed , Vimentin/analysis
18.
Arch Pathol Lab Med ; 125(5): 613-24, 2001 May.
Article in English | MEDLINE | ID: mdl-11300931

ABSTRACT

BACKGROUND: The class III beta-tubulin isotype (betaIII) is widely regarded as a neuronal marker in development and neoplasia. In previous work, we have shown that the expression of betaIII in neuronal/neuroblastic tumors is differentiation dependent. In contrast, the aberrant localization of this isotype in certain nonneuronal neoplasms, such as epithelial neuroendocrine lung tumors, is associated with anaplastic potential. OBJECTIVE: To test the generality of this observation, we investigated the immunoreactivity profile of betaIII in astrocytomas. DESIGN: Sixty archival, surgically excised astrocytomas (8 pilocytic astrocytomas, WHO grade 1; 18 diffuse fibrillary astrocytomas, WHO grade 2; 4 anaplastic astrocytomas, WHO grade 3; and 30 glioblastomas, WHO grade 4), were studied by immunohistochemistry using anti-betaIII monoclonal (TuJ1) and polyclonal antibodies. A monoclonal antibody to Ki-67 nuclear antigen (NC-MM1) was used as a marker for cell proliferation. Antibodies to glial fibrillary acidic protein (GFAP) and BM89 synaptic vesicle antigen/synaptophysin were used as glial and neuronal markers, respectively. RESULTS: The betaIII immunoreactivity was significantly greater in high-grade astrocytomas (anaplastic astrocytomas and glioblastomas; median labeling index [MLI], 35%; interquartile range [IQR], 20%-47%) as compared with diffuse fibrillary astrocytomas (MLI, 4%; IQR, 0.2%-21%) (P <.0001) and was rarely detectable in pilocytic astrocytomas (MLI, 0%; IQR, 0%-0.5%) (P <.0001 vs high-grade astrocytomas; P <.01 vs diffuse fibrillary astrocytomas). A highly significant, grade-dependent relationship was observed between betaIII and Ki-67 labeling and malignancy, but this association was stronger for Ki-67 than for betaIII (betaIII, P <.006; Ki-67, P <.0001). There was co-localization of betaIII and GFAP in neoplastic astrocytes, but no BM89 synaptic vesicle antigen/synaptophysin staining was detected. CONCLUSIONS: In the context of astrocytic gliomas, betaIII immunoreactivity is associated with an ascending gradient of malignancy and thus may be a useful ancillary diagnostic marker. However, the significance of betaIII-positive phenotypes in diffuse fibrillary astrocytomas with respect to prognostic and predictive value requires further evaluation. Under certain neoplastic conditions, betaIII expression is not neuron specific, calling for a cautious interpretation of betaIII-positive phenotypes in brain tumors.


Subject(s)
Astrocytoma/chemistry , Astrocytoma/diagnosis , Biomarkers, Tumor/analysis , Brain Neoplasms/chemistry , Brain Neoplasms/diagnosis , Tubulin/analysis , Adolescent , Adult , Aged , Child , Child, Preschool , Glial Fibrillary Acidic Protein/analysis , Humans , Immunoenzyme Techniques , Ki-67 Antigen/analysis , Ki-67 Antigen/immunology , Middle Aged , Synaptophysin/analysis , Tubulin/immunology
19.
J Clin Endocrinol Metab ; 85(7): 2537-42, 2000 Jul.
Article in English | MEDLINE | ID: mdl-10902805

ABSTRACT

We have studied the expression of the pituitary transcription factors Ptx-1 and Prop-1 in a series of 34 pituitary adenomas fully characterized for in vitro hormone secretion and histological staining. In studies involving mammalian cell lines, the pituitary transcription factor Ptx-1 has been shown to be a pituitary hormone panactivator, whereas more recent studies have shown that it plays an important role in alpha-subunit gene expression. Its expression has not been examined previously in human pituitary adenomas characterized by in vitro hormone secretory profiles. Of the 34 pituitary adenomas studied, Ptx-1 expression was reduced by more than 50% compared to that of the housekeeping gene human glyceraldehyde-3-phosphate dehydrogenase in the 6 corticotroph adenomas, which also had significantly reduced alpha-subunit production (all 6 tumors secreting < or =0.5 ng/24 h). Mutations of the pituitary transcription factor Prop-1, which is responsible for the syndrome of Ames dwarfism in mice, are being increasingly recognized as a cause of combined pituitary hormone deficiency in humans, although ACTH deficiency has been described only once. Prop-1 expression was detected in all 34 pituitary adenomas, including 6 corticotroph adenomas and 5 gonadotroph adenomas. The expression of Prop-1 has not been described previously in these cell phenotypes.


Subject(s)
Adenoma/metabolism , Adrenocorticotropic Hormone/biosynthesis , Glycoprotein Hormones, alpha Subunit/biosynthesis , Homeodomain Proteins/biosynthesis , Pituitary Neoplasms/metabolism , Transcription Factors/biosynthesis , Acromegaly , Adrenocorticotropic Hormone/deficiency , Adrenocorticotropic Hormone/genetics , Animals , Glyceraldehyde-3-Phosphate Dehydrogenases/metabolism , Humans , Immunohistochemistry , Mice , Paired Box Transcription Factors , Pituitary Hormones/blood , RNA, Messenger/biosynthesis , Reverse Transcriptase Polymerase Chain Reaction , Tumor Cells, Cultured
20.
Neuropathol Appl Neurobiol ; 26(2): 105-16, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10840273

ABSTRACT

In the 25 years or so after the first clinicopathological descriptions of diffuse axonal injury (DAI), the criterion for diagnosing recent traumatic white matter damage was the identification of swollen axons ('bulbs') on routine or silver stains, in the appropriate clinical setting. In the last decade, however, experimental work has given us greater understanding of the cellular events initiated by trauma to axons, and this in turn has led to the adoption of immunocytochemical methods to detect markers of axonal damage in both routine and experimental work. These methods have shown that traumatic axonal injury (TAI) is much more common than previously realized, and that what was originally described as DAI occupies only the most severe end of a spectrum of diffuse trauma-induced brain injury. They have also revealed a whole field of previously unrecognized white matter pathology, in which axons are diffusely damaged by processes other than head injury; this in turn has led to some terminological confusion in the literature. Neuropathologists are often asked to assess head injuries in a forensic setting: the diagnostic challenge is to sort out whether the axonal damage detected in a brain is indeed traumatic, and if so, to decide what - if anything - can be inferred from it. The lack of correlation between well-documented histories and neuropathological findings means that in the interpretation of assault cases at least, a diagnosis of 'TAI' or 'DAI' is likely to be of limited use for medicolegal purposes.


Subject(s)
Axons/pathology , Craniocerebral Trauma/pathology , Forensic Medicine/methods , Animals , Diagnostic Techniques, Neurological , Humans , Terminology as Topic
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