Search PubMed⌕ Search

Biomedical subjects

S Love

Publications and source records attributed to S Love.

At least 127 records · Page 7Linked to original sources

Demonstration of apoptotic cells in tissue sections by in situ hybridization using digoxigenin-labeled poly(A) oligonucleotide probes to detect thymidine-rich DNA sequences.

The recognition of apoptotic cells by morphological appearance alone may be difficult. We have investigated the use of in situ hybridization (ISH) with digoxigenin-labeled poly(A) probes to detect apoptotic cells in tissue sections. This method was compared to conventional morphologic assessment and in situ end-labelling (ISEL) in a range of tissues in which apoptosis is known to occur. ISH with poly(A) probes detected apoptotic nuclei in all tissues in which there was evidence of apoptosis as judged by conventional histology. ISH and, to a lesser extent, ISEL preferentially labeled shrunken but still intact nuclei with margination of chromatin, presumably at an early stage of apoptosis. The poly(A) hybridization was abolished by pretreatment of tissue sections with DNAse. After denaturation of DNA, poly(A) hybridized to nuclei in all cells. No convincing hybridization signal was detected in alcohol-fixed or fresh-frozen sections. Both ISEL and ISH labeled some of the nuclei in ischemic tissues. ISH with poly(A) oligonucleotide probes offers a simple alternative to ISEL for detection of cells in early stages of apoptosis. These probes hybridize to thymidine-rich sequences of DNA in the highly repeated Alu sequences within the nuclear genome. These sequences are believed to become available for hybridization after formalin fixation and paraffin embedding as a result of the apoptosis-related increase in the susceptibility of nuclear DNA to denaturation.

Apoptosis↗

An update on core needle biopsy for radiologically detected breast lesions.

BACKGROUND: Traditionally, radiologically detected lesions of the breast have been evaluated by open surgical biopsy with wire localization. Recently, core needle biopsy has been introduced as an alternative to open surgical biopsy. The authors evaluated their own results with long term follow-up after core needle biopsy and reviewed the experience of other physicians with this new technique. METHODS: Four hundred thirty-one core needle biopsies performed at UCLA were analyzed. The outcome of these cases was determined by either surgery or long term follow-up. Statistical analysis was performed to determine the accuracy of the method. RESULTS: Definitive outcome was obtained in 96% of the core needle biopsy cases, with a median follow-up time of 18 months (range, 6-38 months). The authors achieved a sensitivity of 99% and a specificity of 100%. The false-negative rate was 1.7%. There were no complications in this series. CONCLUSIONS: Core needle biopsy is a highly accurate and safe method for the diagnosis of radiologically detected lesions of the breast.

Biopsy, Needle↗

Assessment of the distribution of mitochondrial ribosomal RNA in melas and in thrombotic cerebral infarcts by in situ hybridization.

In situ hybridization to mitochondrial ribosomal RNA (rRNA) has been used to study the distribution of mitochondria in paraffin-embedded autopsy brain tissue from two patients with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) and other organs from one of the patients. Comparison of in situ hybridization and electron microscopic findings in an antemortem biopsy specimen of pylorus from the latter patient showed a close correspondence between the distribution of hybridization signal on light microscopy and of mitochondria in ultrathin sections. Strong hybridization signal was present over smooth muscle fibres of the muscularis externa, which contained abnormal accumulations of mitochondria on electron microscopy. Hybridization to sections of skeletal muscle confirmed previous reports of 'ragged-red' fibres in this disorder and of mitochondrial accumulations in the walls of intramuscular blood vessels. To try to elucidate the role of vessel wall accumulation of mitochondria in the genesis of the stroke-like lesions, the distribution of mitochondrial rRNA was assessed in sections of brain from both of the cases of MFLAS and several cases of atherothrombotic cerebrovascular disease. Blood vessels in and adjacent to the cerebral lesions of MELAS showed strong hybridization signal with the mitochondrial probes, as was also seen in infarcts of various ages in the control brains. Only weak signal was present in the walls of blood vessels distant from the lesions, in both MELAS and control brains. These findings suggest that mitochondria accumulate in vascular endothelium and tunica media as a normal response to cerebral infarction or ischaemia. The accumulation of mitochondria in the cerebral lesions of MELAS may, at least in part, be a reaction to the destructive effects of the underlying metabolic dysfunction.

Brain↗

No correlation between nigral degeneration and striatal plaques in Alzheimer's disease.

Although Alzheimer's disease may involve both the substantia nigra and the striatum, there is little information concerning the relationship between the resulting abnormalities in these reciprocally interconnected regions of the brain. We have examined the correlation between plaque density in the striatum and counts of neurons and neurofibrillary tangles in the pars compacta of the substantia nigra, in 12 cases of "pure" Alzheimer's disease (i.e. without clinical or neuropathological evidence of Parkinson's or cortical Lewy body disease) and 11 normal controls. Diffuse plaques in the striatum and neurofibrillary tangles in the substantia nigra were consistent findings in all of the Alzheimer brains. However, quantitation did not reveal a statistically significant correlation between the density of striatal plaques and the numbers of either neurofibrillary tangles or neurons in the substantia nigra. Although the mean number of neurons in the substantia nigra of Alzheimer brains was lower than that in controls, the difference did not reach statistical significance. We suggest that previous assessments of substantial loss of nigral neurons in Alzheimer's disease may have been skewed by the inclusion of cases with coexistent cortical Lewy bodies.

Aged↗

Sequence analysis and immunolocalisation of phosphatidylethanolamine binding protein (PBP) in human brain tissue.

We have cloned and sequenced cDNA corresponding to human brain phosphatidylethanolamine binding protein (PBP) and have used the resultant data to generate PBP-specific anti-peptide antisera for immunohistochemical studies. The distribution of PBP was assessed immunohistochemically in sections from multiple regions of neonatal brain and spinal cord, including spinal nerve roots. Strong PBP immunoreactivity was present in the cytoplasm of oligodendrocytes in the white matter and Schwann cells in the nerve roots. There was only weak immunostaining within the neurones and neuropil. The findings are in keeping with a role for PBP in the organisation of phospholipids in the myelin sheath.

Base Sequence↗

Neuropsychometric evaluation of long-term survivors of adult brain tumours: relationship with tumour and treatment parameters.

BACKGROUND: Cognitive deficits are the hallmark of dose limiting late radiation morbidity in the CNS. Little is known about the neuropsychometric morbidity of treatment in adults with primary brain tumours. We set out to evaluate systematically the neuropsychometric function of all long-term survivors in order to document the frequency and severity of impairment and study its relationship with tumour and treatment related parameters. MATERIALS AND METHODS: 30 patients surviving in clinical and radiological remission for > 4 years following irradiation were recalled for clinical examination, CT/MRI scan and neuropsychometric testing. The 14 males, 16 females, (mean age 42.5 years), represented all but one long term survivors treated with radiotherapy in the Department of Clinical Oncology between 1971 and 1990. Twenty-five patients had a histological diagnosis of glioma. Patients treated before 1987 (n = 16) received whole brain irradiation (WBI); focused irradiation (FI) has been used since (n = 14). RESULTS: The two groups were similar were in age, initial tumour type and surgical treatment, but the WBI group showed more evidence of neuropsychometric impairment than the FI group with significantly lower group median scores in tests of visuospatial organisation (WAIS Block Design, P = 0.01), visual memory (Rey Complex figure, P = 0.003) and complex information processing (Trails A, P = 0.003; Trails B, P = 0.002). Pre-morbid IQ estimated from sociodemographic variables, was comparable in the 2 groups which were not significantly different in their emotional state as assessed by the HADS. On univariate analysis radiation volume (P = 0.05) and time from treatment (P = 0.02) were the main factors associated with neuropsychometric deficit. Multivariate analysis by logistic regression confirmed WBI as the only independent predictor of neuropsychometric impairment (WBI vs. FI, odds ratio = 7.1, 95% C.I. 1.2-42.3, P = 0.03). CONCLUSIONS: Neuropsychometric deficits are common and can be related to time from treatment and radiation technique. Neuropsychometric testing can be a useful tool in the evaluation of different treatment strategies.

Adult↗

The prognostic value of epidermal growth factor receptor mRNA expression in primary ovarian cancer.

The expression of mRNA for the epidermal growth factor (EGF) receptor, EGF and transforming growth factor alpha (TGF-alpha) was determined in 76 malignant, six borderline and 15 benign primary ovarian tumours using the reverse transcriptase-polymerase chain reaction and related to clinical and pathological parameters. Of the malignant tumours, 70% (53/76) expressed EGF receptor mRNA, 31% (23/75) expressed EGF mRNA and 35% (26/75) expressed TGF-alpha mRNA. For the borderline tumours, four of six (67%) expressed EGF receptor mRNA, 1/6 (17%) expressed TGF-alpha mRNA and none expressed EGF mRNA. Finally, 33% (5/15) of the benign tumours expressed EGF receptor mRNA, whereas 40% (6/15) expressed EGF mRNA and 7% (1/15) expressed TGF-alpha mRNA. The presence of the EGF receptor in malignant tumours was associated with that of TGF-alpha (P = 0.0015) but not with EGF (P = 1.00), whereas there was no relationship between the presence of EGF and TGF-alpha (P = 1.00). EGF receptor mRNA expression was significantly and positively associated with serous histology (P = 0.006) but not with stage or grade. Neither EGF nor TGF-alpha showed any link with histological subtype or stage. The survival of patients with malignant tumours possessing EGF receptor mRNA was significantly reduced compared with that of patients whose tumours were negative (P = 0.030 for all malignant tumours; P = 0.007 for malignant epithelial tumours only). In contrast, neither the expression of TGF-alpha nor EGF was related to survival. These data suggest that the presence of EGF receptor mRNA is associated with poor prognosis in primary ovarian cancer.

Base Sequence↗

Colorectal polyp counts and cancer risk in familial adenomatous polyposis.

BACKGROUND & AIMS: In familial adenomatous polyposis, colorectal cancer prevention is by prophylactic colectomy, but dietary or chemopreventative strategies have been recently proposed in low-risk individuals. The aim of this study was to define predictive risk factors for colorectal cancer in familial adenomatous polyposis. METHODS: Between 1918 and 1993, 317 patients underwent colectomy. A multivariate analysis was performed to assess the relationship between colorectal cancer risk and polyp count, sex, and age at colectomy. RESULTS: The median polyp count was 842 (range, 78-7500), and cancer was found in 22% of patients. Polyp count and age, but not sex, predicted cancer risk. Patients with >1000 polyps had 2.3 times greater risk of cancer than those with <1000 polyps (P=0.006). Synchronous cancers increased with poly count (P<0.05). Each 10-year age group had a 2.4-fold difference in cancer risk (95% confidence interval, 1.9-3.2; P<0.001). Four cases of cancer occurred in patients at low risk (younger than 30 years of age, <1000 polyps; 3.3%). CONCLUSIONS: More adenomas and older age are associated with a higher risk of colorectal cancer. However, cancer does occur in low-risk individuals and may be missed by surveillance, making alternatives to prophylactic surgery inadvisable.

Adenomatous Polyposis Coli↗

Herpes simplex virus type 1 encephalitis in acquired immunodeficiency syndrome.

Herpes simplex (HSV) infection of the central nervous system is uncommon in AIDS and usually has an atypical topography. This review is centred around the case of a 49-year-old homosexual patient with AIDS who died from diffuse encephalopathy. Neuropathological examination revealed necrotic and haemorrhagic changes involving both temporal lobes, insulae and cingulate gyri. Cowdry type A intranuclear inclusion bodies were abundant but inflammation was minimal. Electron microscopy confirmed characteristic herpes virus particles. Immunocyto-chemistry was positive for HSV type 1 and 2. In situ hybridization and PCR, however, were positive for HSV type 1 but excluded HSV type 2. There was associated cytomegalovirus ventriculitis but clearly separated from HSV encephalitis. There were no histological features of HIV encephalitis and HIV could not be demonstrated by immunocytochemistry or by PCR to demonstrate proviral DNA. Apoptotic neurons were numerous in areas with a severe macrophage reaction. Only two pathological cases with characteristic limbic distribution and necrotic haemorrhagic histologic have been reported previously. The rarity of these reports suggests that in advanced AIDS, the immune reaction causing a typical necrotizing encephalitis cannot be mounted. Distinction between HSV type 1 and 2 infection may be difficult by immunocytochemistry and usually requires in situ hybridization, tissue culture or PCR. In AIDS patients, HSV-1 has been identified as responsible for encephalitis whereas HSV-2 has been more responsible for myelitis. Associated productive HIV infection of the CNS was found in none of the cases. In contrast, cytomegalovirus encephalitis was found in nine of 11 cases of AIDS-associated HSV encephalitis.

Acquired Immunodeficiency Syndrome↗

Hypertrophic osteopathy (Marie's disease) in Equidae: a review of twenty-four cases.

The case records of 23 horses and one donkey affected by hypertrophic osteopathy (HO) (Marie's disease) were reviewed. All affected animals presented with limb swellings, which were bilaterally symmetrical and usually involved both fore- and hindlimbs. Associated signs included stiffness/lameness and weight loss. Radiological features included periosteal new bone formation over the diaphyses and metaphyses of affected bones. The metacarpal and metatarsal bones were most frequently affected. Articular surfaces remained free of disease. Seventeen animals were destroyed on humane grounds, 3 horses recovered after successful treatment of the primary disease, 3 horses recovered after symptomatic treatment and one horse was lost to follow-up. Significant primary diseases that were believed to predispose to HO were identified (pre- or post mortem) in 14 cases. In each of these cases, an intrathoracic disease was identified, although co-existing extrathoracic disease was present in 3 cases. Granulomatous inflammatory lesions were present in 9 of these 14 cases. In 4 horses, which underwent necropsy examination, no significant underlying disease was identified.

Animals↗

Intracranial ependymomas: analysis of prognostic factors in a population-based series.

A retrospective study of 31 children presenting in the period 1976-1993 with intracranial ependymomas in the south-west region of the UK was performed. The diagnosis was confirmed by histological review and several histological variables recorded, including pleomorphism, cellularity, numbers of mitotic figures and extent of necrosis. Histological features, presentation and treatment were correlated with outcome. Eleven patients had supratentorial primaries and 20 infratentorial primaries. Seven patients had macroscopically complete resections of which 5 had supratentorial primaries. Eight patients had no other therapy apart from surgery. Six patients received craniospinal irradiation, 11 had involved-field irradiation and 14 did not have radical radiotherapy. Twelve patients received chemotherapy. Eleven patients are relapse-free at a median of 43 months. Of the 20 relapses, 19 were local and only 1 metastatic. The grade of the tumor assigned at presentation had no correlation with outcome. On histological review, the only feature that had a significant correlation (p = 0.05) with survival was tumor cellularity. There was a survival advantage for a supratentorial primary site (p = 0.04). The event-free survival was significantly longer for patients diagnosed after 1986 than before (p = 0.006). Survival was not significantly affected by radiotherapy or chemotherapy. Children who had had a macroscopically complete excision of the tumor had a 5-year survival of 69% as opposed to 47% for those who had incomplete surgery, but this difference is not significant (p = 0.13). The data suggest that: (1) the event-free survival rate has improved significantly with time; (2) there is little correlation between a variety of pathological features and outcome, and (3) failure at the primary site is the major obstacle to improved cure rates. The role of complete resection, including second-look surgery, needs further evaluation.

Adolescent↗

Role of image-guided core-needle biopsy in the management of patients with lymphoma.

PURPOSE: The results of 106 radiologically guided core needle biopsies in 96 patients were analyzed retrospectively to evaluate the accuracy, safety, and role of this technique in the management of patients with lymphoma and to determine factors predictive of success. PATIENTS AND METHODS: Biopsies were performed in 51 patients with low-grade non-Hodgkin's lymphoma (NHL), 24 with high-grade NHL, 16 with previously diagnosed Hodgkin's disease (HD), and 15 with no previous history of lymphoma. Disease was infradiaphragmatic in 92 patients and supradiaphragmatic in 14. Computed tomography (CT) guidance was used in 98 biopsies and ultrasonography (US) in eight. RESULTS: The biopsy was diagnostic and yielded information on the basis of which treatment was started in 88 of 106 patients. The procedure was well tolerated and there were no major complications. Small size of the sample or inappropriate tissue sampled were the main causes of failure. The technique was equally successful in the diagnosis of HD and both high-grade and low-grade NHL as in nonlymphoproliferative disorders. The procedure was equally successful at diagnosis as at suspected recurrence or progression. In 33 of 80 cases in which the biopsy was performed at the time of recurrence or progression, the histology had changed; in 31 of 33, this influenced treatment. The technique was efficient at diagnosing transformation of follicular NHL in 16 of 18 patients, which allowed early adjustment of treatment at recurrence. CONCLUSION: At St Bartholomew's Hospital (SBH), image-guided core-needle biopsy has proven to be a quick, safe, and efficient alternative to excisional biopsy in the evaluation of lymphoproliferative disorders at presentation, recurrence, or progression. It should become the procedure of choice for histologic sampling in the absence of peripheral lymphadenopathy.

Adolescent↗