Pathologic Basis of Diseaseby Stanley L. Robbins is really the fourth edition of hisPathology. Appropriate updating and addition enhance the otherwise identical format, sequence, writing, and illustrations. So many medical students have benefited from this source that it may be the best known general book in the field. I recommend it even more now. Like his former texts, this will be enjoyed for its readability. He clearly lays out a great deal of information. When he includes minutiae, the reasons are clear and one feels that all the material is pertinent. Robbins keeps the whole field in perspective—that is, he does not dwell so long or so heavily on pathologic anatomy or pathogenesis as to tempt the reader to overlook clinical presentation or prognosis. A great strength of the subject of pathology is that it bonds strongly with many other medical sciences and specialties and thus occupies the

Pathologic Basis of Disease

The neurodegeneration that occurs in sporadic Alzheimer's disease (AD) is consistently associated with a number of characteristic histopathological, molecular, and biochemical abnormalities, including cell loss, abundant neurofibrillary tangles and dystrophic neurites, amyloid-beta deposits, increased activation of pro-death genes and signaling pathways, impaired energy metabolism/mitochondrial function, and evidence of chronic oxidative stress. The general inability to convincingly link these phenomena has resulted in the emergence and propagation of various heavily debated theories that focus on the role of one particular element in the pathogenesis of all other abnormalities. However, the accumulating evidence that reduced glucose utilization and deficient energy metabolism occur early in the course of disease, suggests a role for impaired insulin signaling in the pathogenesis of AD. The present work demonstrates extensive abnormalities in insulin and insulin-like growth factor type I and II (IGF-I and IGF-II) signaling mechanisms in brains with AD, and shows that while each of the corresponding growth factors is normally made in central nervous system (CNS) neurons, the expression levels are markedly reduced in AD. These abnormalities were associated with reduced levels of insulin receptor substrate (IRS) mRNA, tau mRNA, IRS-associated phosphotidylinositol 3-kinase, and phospho-Akt (activated), and increased glycogen synthase kinase-3beta activity and amyloid precursor protein mRNA expression. The strikingly reduced CNS expression of genes encoding insulin, IGF-I, and IGF-II, as well as the insulin and IGF-I receptors, suggests that AD may represent a neuro-endocrine disorder that resembles, yet is distinct from diabetes mellitus. Therefore, we propose the term, "Type 3 Diabetes" to reflect this newly identified pathogenic mechanism of neurodegeneration.

/pdf/impaired-insulin-and-insulin-like-growth-factor-expression-59boeqzm6c.pdf

Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer's disease--is this type 3 diabetes?

Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer disease-is this type 3 diabetes?

Reduced glucose utilization and energy metabolism occur early in the course of Alzheimer's disease (AD) and correlate with impaired cognition. Glucose utilization and energy metabolism are regulated by insulin and insulin-like growth factor I (IGF-I), and correspondingly, studies have shown that cognitive impairment may be improved by glucose or insulin administration. Recently, we demonstrated significantly reduced levels of insulin and IGF-I polypeptide genes and their corresponding receptors in advanced AD relative to aged control brains. The abnormalities in gene expression were accompanied by impaired survival signaling downstream through PI3 kinase-Akt. The present work characterizes the abnormalities in insulin and IGF gene expression and receptor binding in brains with different Braak stage severities of AD. Realtime quantitative RT-PCR analysis of frontal lobe tissue demonstrated that increasing AD Braak Stage was associated with progressively reduced levels of mRNA corresponding to insulin, IGF-I, and IGF-II polypeptides and their receptors, tau, which is regulated by insulin and IGF-I, and the Hu D neuronal RNA binding protein. In contrast, progressively increased levels of amyloid beta protein precursor (AbetaPP), glial fibrillary acidic protein, and the IBA1/AIF1 microglial mRNA transcripts were detected with increasing AD Braak Stage. Impairments in growth factor and growth factor receptor expression and function were associated with increasing AD Braak stage dependent reductions in insulin, IGF-I, and IGF-II receptor binding, ATP levels, and choline acetyltransferase (ChAT) expression. Further studies demonstrated that: 1) ChAT expression increases with insulin or IGF-I stimulation; 2) ChAT is expressed in insulin and IGF-I receptor-positive cortical neurons; and 3) ChAT co-localization in insulin or IGF-I receptor-positive neurons is reduced in AD. Together, these data provide further evidence that AD represents a neuro-endocrine disorder that resembles a unique form of diabetes mellitus (? Type 3) and progresses with severity of neurodegeneration.

Insulin and insulin-like growth factor expression and function deteriorate with progression of Alzheimer's disease: link to brain reductions in acetylcholine.

Interest in characterizing the role of impaired insulin actions in Alzheimer's disease (AD) and vascular dementia is growing exponentially. This review details what is currently known about insulin, insulin-like growth factor type I (IGF-I) and IGF-II proteins and their corresponding receptors in the brain, and delineates the major controversies pertaining to alterations in the expression and function of these molecules in AD. The various experimental animal models generated by over-expression, mutation, or depletion of genes that are critical to the insulin or IGF signaling cascades are summarized, noting the degrees to which they reproduce the histopathological, biochemical, molecular, or behavioral abnormalities associated with AD. Although no single model was determined to be truly representative of AD, depletion of the neuronal insulin receptor and intracerebroventricular injection of Streptozotocin reproduce a number of important aspects of AD-type neurodegeneration, and therefore provide supportive evidence that AD may be caused in part by neuronal insulin resistance, i.e. brain diabetes. The extant literature did not resolve whether the CNS insulin resistance in AD represents a local disease process, or complication/extension of peripheral insulin resistance, i.e. chronic hyperglycemia, hyperinsulinemia, and Type 2 diabetes mellitus. The available epidemiological data are largely inconclusive with regard to the contribution of Type 2 diabetes mellitus to cognitive impairment and AD-type neurodegeneration. A major conclusion drawn from this review is that there is a genuine need for thorough and comprehensive study of the neuropathological changes associated with diabetes mellitus, in the presence or absence of superimposed AD or vascular dementia. Strategies for intervention may depend entirely upon whether the CNS disease processes are mediated by peripheral, central, or both types of insulin resistance.

/pdf/review-of-insulin-and-insulin-like-growth-factor-expression-16bl2o4iw0.pdf

Review of insulin and insulin-like growth factor expression, signaling, and malfunction in the central nervous system: relevance to Alzheimer's disease.

Melatonin and cortisol levels in psychiatric illness.

The two main forms of somatomedins, termed insulin-like growth factor I and II (IGF-I and IGF-II), have been isolated from human plasma. Pure IGF-I or IGF-II was incubated with foetal rat brain cells and found to be equipotent in stimulating the [3H]thymidine incorporation into DNA, despite the fact that IGF-I not is present during foetal life.

The influence of purified somatomedins and insulin on foetal rat brain DNA synthesis in vitro.

The pineal-hypothalamic-pituitary function was investigated in twelve patients with major depressive illness. The laboratory investigation included analysis of Cortisol, prolactin and melatonin diurnal rhythms as well as the TSH response to TRH and the Cortisol response to dexamethasone administration. The results showed that the patients could be divided into three groups, each containing four patients, according to their Cortisol response to dexamethasone. A correlation between the Cortisol response after dexamethasone and the Cortisol/melatonin ratio at night time before the dexamethasone suppression test was found. Analyses of the diurnal rhythms showed that the patients with no Cortisol-response to dexamethasone administration showed the highest Cortisol and lowest melatonin and prolactin levels. This group of patients did not show any suppression of prolactin after dexamethasone in contrast to the other two groups. Only two patients showed a blunted TSH response to TRH administration, however one of these was receiving thyroxine medication. The serum Cortisol: melatonin ratio at 02 hr was significantly higher in the group of patients showing no Cortisol suppression to dexamethasone compared to the other groups. No gross clinical difference was found between the groups. It is concluded that patients with no Cortisol response to dexamethasone may have an enhanced CRF production secondary to a subfunction of a proposed pineal factor inhibiting CRF.

Pineal-hypothalamic-pituitary function in patients with depressive illness

— Cerebrospinal fluid levels of radioreceptor assayable insulin-like growth factors (RRA-IGFs) and immunoreactive somatomedin B (SMB) (RIA-B) were determined in apparently healthy individuals and in patients with dementia of the Alzheimer type (AD). The CSF levels of RIA-B and RRA-IGFs did not alter from the healthy controls. After being acidified, the CSF from the controls and from the presenile ADs were separated over a G-50 fine Sephardex. The RRA-IGFs activity eluted in three peaks. The results indicate that the major constituent of CSF RRA in both AD patients and controls is an IGF binding protein. The two minor peaks eluted at approximately 9 K and 6 K, corresponding to the elution possitions of “big” IGF-2 and IGF-2.

Insulin-like growth factors and somatomedin B in the cerebrospinal fluid of patients with dementia of the Alzheimer type.

31 The Relationship Between Cortisol and Melatonin Serum Levels in Patients with Affective Disorders and in Healthy Subjects

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

A. Tham

Author Tools

Chat about Author