A multidimensional model of memory complaints in older individuals and the associated hub regions.

Memory complaints are highly prevalent among middle-aged and older adults, and they are frequently reported in individuals experiencing subjective cognitive decline (SCD). SCD has received increasing attention due to its implications for the early detection of dementia. This study aims to advance our comprehension of individuals with SCD by elucidating potential cognitive/psychologic-contributing factors and characterizing cerebral hubs within the brain network. To identify these potential contributing factors, a structural equation modeling approach was employed to investigate the relationships between various factors, such as metacognitive beliefs, personality, anxiety, depression, self-esteem, and resilience, and memory complaints. Our findings revealed that self-esteem and conscientiousness significantly influenced memory complaints. At the cerebral level, analysis of delta and theta electroencephalographic frequency bands recorded during rest was conducted to identify hub regions using a local centrality metric known as betweenness centrality. Notably, our study demonstrated that certain brain regions undergo changes in their hub roles in response to the pathology of SCD. Specifically, the inferior temporal gyrus and the left orbitofrontal area transition into hubs, while the dorsolateral prefrontal cortex and the middle temporal gyrus lose their hub function in the presence of SCD. This rewiring of the neural network may be interpreted as a compensatory response employed by the brain in response to SCD, wherein functional connectivity is maintained or restored by reallocating resources to other regions.

Protein complexes in transport vesicle targeting.

The transport of material between membrane-bounded organelles in eukaryotic cells requires the accurate delivery of different classes of carrier vesicles to specific target compartments. Recent studies indicate that different targeting reactions involve distinct protein complexes that act to mark the target organelle for incoming vesicles. This review focuses on the proteins and protein complexes that have been implicated in various targeting reactions.

TRAPP stimulates guanine nucleotide exchange on Ypt1p.

TRAPP, a novel complex that resides on early Golgi, mediates the targeting of ER-to-Golgi vesicles to the Golgi apparatus. Previous studies have shown that YPT1, which encodes the small GTP-binding protein that regulates membrane traffic at this stage of the secretory pathway, interacts genetically with BET3 and BET5. Bet3p and Bet5p are 2 of the 10 identified subunits of TRAPP. Here we show that TRAPP preferentially binds to the nucleotide-free form of Ypt1p. Mutants with defects in several TRAPP subunits are temperature-sensitive in their ability to displace GDP from Ypt1p. Furthermore, the purified TRAPP complex accelerates nucleotide exchange on Ypt1p. Our findings imply that Ypt1p, which is present on ER-to-Golgi transport vesicles, is activated at the Golgi once it interacts with TRAPP.

Bet1p activates the v-SNARE Bos1p.

Bet1p is a type II membrane protein that is required for vesicular transport between the endoplasmic reticulum and Golgi complex in the yeast Saccharomyces cerevisiae. A domain of Bet1p, that shows potential to be involved in a coiled-coil interaction, is homologous to a region of the neuronal protein SNAP-25. Here, we used in vitro binding studies to demonstrate that Bet1p plays a role in potentiating soluble NSF attachment protein receptor (SNARE) interactions. Mutational analysis points to the coiled-coil region as necessary for Bet1p function, and circular dichroism experiments support this theory. In vitro binding studies were also used to demonstrate that a direct interaction between Bet1p and Bos1p is required for the efficient interaction of the vesicle SNARE with its SNARE target. Genetic studies suggest that the interactions of Bet1p with Bos1p are regulated by the small GTP-binding protein Ypt1p.

High-copy suppressor analysis reveals a physical interaction between Sec34p and Sec35p, a protein implicated in vesicle docking.

A temperature-sensitive mutant, sec34-2, is defective in the late stages of endoplasmic reticulum (ER)-to-Golgi transport. A high-copy suppressor screen that uses the sec34-2 mutant has resulted in the identification of the SEC34 structural gene and a novel gene called GRP1. GRP1 encodes a previously unidentified hydrophilic yeast protein related to the mammalian Golgi protein golgin-160. Although GRP1 is not essential for growth, the grp1Delta mutation displays synthetic lethal interactions with several mutations that result in ER accumulation and a block in the late stages of ER-to-Golgi transport, but not with those that block the budding of vesicles from the ER. Our findings suggest that Grp1p may facilitate membrane traffic indirectly, possibly by maintaining Golgi function. In an effort to identify genes whose products physically interact with Sec34p, we also tested the ability of overexpressed SEC34 to suppress known secretory mutations that block vesicular traffic between the ER and the Golgi. This screen revealed that SEC34 specifically suppresses sec35-1. SEC34 encodes a hydrophilic protein of approximately 100 kDa. Like Sec35p, which has been implicated in the tethering of ER-derived vesicles to the Golgi, Sec34p is predominantly soluble. Sec34p and Sec35p stably associate with each other to form a multiprotein complex of approximately 480 kDa. These data indicate that Sec34p acts in conjunction with Sec35p to mediate a common step in vesicular traffic.

Identification and characterization of five new subunits of TRAPP.

TRAPP (transport protein particle), a multiprotein complex containing ten subunits, plays a key role in the late stages of endoplasmic reticulum to Golgi traffic in the yeast Saccharomyces cerevisiae. We previously described the identification of five TRAPP subunits (Bet5p, Trs20p, Bet3p, Trs23p and Trs33p). Now we report the identification of the remaining five subunits (Trs31p, Trs65p, Trs85p, Trs120p and Trs130p) as well as an initial characterization of the yeast complex and its human homologue. We find that three of the subunits are dispensable for growth and a novel sequence motif is found in Bet3p, Trs31p and Trs33p. Furthermore, biochemical characterization of both yeast and human TRAPP suggests that this complex is anchored to a Triton X-100 resistant fraction of the Golgi. Differences between yeast and human TRAPP as well as the relationship of TRAPP subunits to other docking/tethering factors are discussed.

Gated radionuclide angiocardiography in the noninvasive evaluation of a partially reversible alcoholic cardiomyopathy.

Serial gated radionuclide angiocardiography was used to demonstrate partial reversal of alcoholic cardiomyopathy, following abstention from alcohol. Six months subsequent to total abstention, the resting ejection fraction, which is a sensitive index of left ventricular function, increased from 19 percent to 42 percent. Thirteen months following total abstention, the resting ejection fraction was preserved at 40 percent. During stress, the ejection fraction increased to 53 percent. The clinical implication of this case report is that gated radionuclide angiocardiography may be used to noninvasively evaluate accurately the subsequent course of reversible alcoholic cardiomyopathy.

Avid uptake of technetium-99m-HMPAO by an intracranial plasmacytoma during carotid balloon test occlusion.

A 56-yr-old woman was evaluated for removal of a tumor at the base of the skull. A test to determine the risk of carotid artery sacrifice was performed prior to surgery using carotid balloon occlusion of the left internal carotid artery and 99mTc-HMPAO perfusion scintigraphy during the occlusion. An unusual intense focus of increased uptake was seen at the site of the primary tumor in the left cavernous sinus. The tumor, found to be plasmacytoma at surgery, demonstrated only mild washout from 30 min to 2 hr after administration of 99mTc-HMPAO, with a tumor-to-cerebellum ratio of 1.6 and 1.5, respectively, and a tumor-to-contralateral cranial ratio of 2.5 and 2.4, respectively. Intracranial plasmacytoma shows good response to radiation therapy, and the differentiation of this tumor from other neoplasms is pertinent to the mode of treatment and surgical approach. Technetium-99m-HMPAO SPECT imaging may be a useful tool in distinguishing these tumors from other neoplasms at the base of the skull.

Rapid differential diagnosis of cerebral toxoplasmosis and primary central nervous system lymphoma by thallium-201 SPECT.

UNLABELLED: This study sought to assess whether 201Tl brain SPECT can significantly reduce the time required for the differential diagnosis of primary central nervous system (CNS) lymphoma and cerebral toxoplasmosis in patients with AIDS. METHODS: Eighteen patients who presented with focal lesions on CT or MRI, or both, underwent 201Tl brain SPECT shortly after admission and before a CT-guided stereotactic brain biopsy. Early and delayed 201Tl uptake ratios were obtained for patients with positive 201Tl study results, and the retention index of 201Tl was calculated. RESULTS: Ten patients had 11 foci of significantly increased 201Tl uptake in regions of corresponding CT/MRI lesions. Five of these patients had biopsy-proven lymphomas, one of them in two separate foci. Another patient was found to have metastatic adenocarcinoma. Three patients had a clinical course and response to radiation therapy consistent with lymphoma, and study results in another patient were considered falsely positive. Of nine patients with no 201Tl uptake in regions of CT/MRI lesions, two had biopsy findings consistent with a benign etiology, and the other seven improved clinically on antitoxoplasmosis medications alone. The overall sensitivity of 201Tl brain SPECT was 100%, and specificity was 90%. The 201Tl retention index in patients with lymphomas was significantly higher than that in patients with adenocarcinomas and nonmalignant lesions (1.35 +/- 0.16 versus 0.24 and 0.56, respectively). CONCLUSION: Thallium-201 brain SPECT is a sensitive and specific method for rapid differential diagnosis of CNS lymphoma and toxoplasmosis in patients with AIDS. The 201Tl retention index is useful in differentiating CNS lymphomas from other malignant and nonmalignant pathologies.

Thallium-201 retention in focal intracranial lesions for differential diagnosis of primary lymphoma and nonmalignant lesions in AIDS patients.

UNLABELLED: The purpose of this study was to determine whether 201Tl retention in focal intracranial lesions can help distinguish central nervous system (CNS) lymphoma from toxoplasmosis and other nonmalignant CNS lesions in patients with acquired immunodeficiency syndrome. METHODS: Forty-nine patients who presented with focal lesions on CT and/or MRI had 201Tl brain SPECT studies (early and delayed image sets) performed shortly after admission. Early and delayed 201Tl uptake ratios were obtained for the positive studies, and the retention index of thallium was calculated (delayed/early target-to-background mean count ratio). RESULTS: Twenty-nine patients had foci of significantly increased 201Tl uptake on the early images in regions of corresponding CT/MRI lesions. Ten of these patients had biopsy-proven lymphomas. Another patient was found to have metastatic adenocarcinoma. Twelve additional patients had a response to radiation therapy or a clinical course consistent with lymphoma and six patients had a false-positive SPECT study. The early uptake ratio could not separate malignant from nonmalignant lesions. The 201Tl retention index in patients with lymphomas (1.18 +/- 0.16) was significantly higher than the retention index in adenocarcinoma (0.24) and in the six nonmalignant lesions (0.62 +/- 0.07). The lowest retention index in patients with lymphoma was 1.07, and the highest retention index in nonmalignant lesions was 0.70. Twenty patients showed no 201Tl uptake in the regions of CT/MRI lesions. Three of them had biopsies consistent with a benign etiology, and one patient was diagnosed with tuberculosis. Fifteen patients improved clinically on antitoxoplasmosis medications alone, and one patient had CNS lymphoma. The overall sensitivity of 201Tl brain SPECT was 96%. The specificity was 76% by counting all studies with abnormal 201Tl uptake, but it increased to 100% when the retention index was also considered. CONCLUSION: The retention index increases the specificity of 201Tl brain SPECT in human immunodeficiency virus patients. In the presence of abnormal early 201Tl uptake, it is essential to perform delayed imaging and calculate the retention index to distinguish nonmalignant lesions from lymphoma. The absence of 201Tl uptake on early images at the site of a CT/MRI abnormality excludes the diagnosis of lymphoma with a high degree of confidence and delayed imaging is unnecessary.

Brain perfusion imaging during preoperative temporary balloon occlusion of the internal carotid artery.

UNLABELLED: The main objective of this study was to assess whether 99mTc-HMPAO brain SPECT imaging can identify patients at high risk of developing an infarct following permanent carotid occlusion in the course of brain surgery. METHODS: Test balloon occlusion of the internal carotid artery was performed in 44 patients with a variety of head and neck tumors or aneurysms. Technetium-99m-HMPAO was injected intravenously while the balloon was initiated and a SPECT study was obtained 30 min later. Follow-up CT scans were obtained routinely for all patients at 2 wk and 1 mo following surgery, or earlier when necessary. Thirty patients and five normal volunteers had semiquantitative analysis of cerebral perfusion. RESULTS: Twenty-six patients demonstrated ipsilateral perfusion abnormalities during trial occlusion. Eight patients in this group underwent bypass grafting prior to sacrifice of the artery: two resulting in infarcts. Eighteen patients had symmetric cerebral perfusion during occlusion and four of these patients underwent permanent therapeutic carotid occlusion; three patients had subsequent infarcts and the fourth patient had an impending stroke. CONCLUSION: Patients with symmetric cerebral perfusion measured by 99mTc-HMPAO SPECT may still have a high long-term complication rate following carotid sacrifice. The scan findings in these patients were not predictive of the outcome. Patients with asymmetric cerebral perfusion had alternative therapeutic approach to carotid sacrifice and most of them had good surgical outcomes.

Outpatient dobutamine therapy: the rhyme and the riddle.

Advances in critical care medicine have increased survival for victims of myocardial infarction and other acute cardiac events so that increasingly patients are receiving long-term, labor-intensive, and costly medical care. Innovations in drug delivery systems and skyrocketing health care costs have fostered the growth of home health care which has blossomed into a $2.8 billion industry. There is evidence that outpatient dobutamine therapy produces definite physical and possibly psychological improvements of variable degree and duration. Hemodynamic improvements are generally associated with improvement in functional class, and the financial savings are recognizably substantial. However, three major problems confront therapies with beta-adrenergic agonists: tendency for tolerance, ventricular arrhythmias, and increased myocardial oxygen consumption. There is a dire need for establishment of exclusionary patient criteria and for risk stratification, as well as for development of a portable radionuclide nonimaging monitor. Given the current fund of knowledge, outpatient dobutamine therapy should be undertaken cautiously after meticulous patient selection reflecting an awareness of the tremendous complexities and inherent risks. The therapeutic implications are dependent on the nature of the underlying cardiomyopathy and the fact that beta-adrenergic receptor desensitization is unlikely to be overcome by progressive dosage increases. Therapy is initiated with the understanding that treatment will remain blindly empirical and conjectural in the absence of a continuous physiologic monitor and an expanded comprehension of the molecular pathophysiology of the failing ventricle.

Relapsing native-valve enterococcal endocarditis: a unique cure with oral ciprofloxacin combination drug therapy.

Enterococcal endocarditis is the third most common presentation in native valves, and it is the most refractory. Unique among the streptococci, enterococci are relatively resistant to beta-lactam antibiotics requiring a combination aminoglycoside regimen for cure. Relapse is common even after apparently adequate therapy and may be seen in up to 25% of cases that involve streptomycin-resistant strains. This problem is magnified by the recent appearance of beta-lactamase-producing strains of S. faecalis resistant to both ampicillin and gentamicin. Ciprofloxacin is being investigated with a number of antimicrobials in the attempt to identify superior protocols against troublesome pathogens. However, little published data is available concerning the clinical efficacy of this drug in enterococcal endocarditis. In vitro studies and preliminary trials with animal models have generally been disappointing with broth macrodilution time-kill or agar dilution proving the most reliable in vitro methods for predicting in vivo outcomes. The urgent need to identify new combination drug regimens is underscored not only by the development of new resistance patterns, but by the well-documented toxicities of conventional therapies. The authors present a case of relapsing enterococcal endocarditis caused by a non-beta-lactamase-producing strain of S. faecalis, which demonstrated high-level resistance to streptomycin but not to gentamicin. Relapses occurred despite favorable laboratory data and aggressive beta-lactam-gentamicin therapies. Cure was achieved using oral ciprofloxacin in a combination drug regimen, which is reported here for the first time.

Digital angiography of pulsatile masses in the neck.

Twenty-six consecutive patients with pulsatile neck masses were studied with digital subtraction angiography (DSA) by venous injection, computed tomography (CT), and conventional direct angiography. The neck masses proved to be secondary to tortuous and ectatic carotid or subclavian arteries in 13 cases, resulted from subclavian artery aneurysms in three cases, and resulted from tumor in 10 cases. DSA alone was sufficient for diagnosis in 16 of 26 cases. CT was performed in 15 cases and was contributory in 10. It was most useful when a tumor was demonstrated or suspected on DSA. Conventional angiography was performed in six cases. It contributed no useful information when arteriosclerotic vascular changes were the source of the neck mass, and added useful diagnostic information in only two of 10 neck tumors.

"Benign" metastasizing meningiomas.

Less than one in 1000 meningiomas metastasizes. Although the angioblastic and hemangiopericytic tumors are believed by some authors to metastasize with a greater frequency than the other histologic forms of meningioma, most investigators believe that neither the histologic pattern, local aggressiveness, size, nor location of the tumor can be used accurately to predict which tumors will metastasize. Three new cases are presented, bringing the total reported number of metastasizing meningiomas to 113. If the angioblastic meningiomas and hemangiopericytomas are eliminated from this group, 69 reported cases of "benign" metastasizing meningioma remain.

CT evaluation of the greater sciatic foramen in patients with sciatica.

Sciatic and lower extremity neurologic symptoms may be from pathologic involvement of the sacral plexus or sciatic nerve in the region of the greater sciatic foramen. Twenty-five patients were reviewed who presented consecutively over a 4 year period with sciatic symptoms secondary to pathologic changes in the greater sciatic foramen. Malignant neoplasm alone (18 patients) and malignant neoplasm associated with infection (two patients) account for most of these cases. Neurogenic tumors (three patients), both benign and malignant, and infection alone (three patients) were less frequent. Although sciatic symptoms usually derive from spinal abnormalities, the evaluation of sciatic symptoms should not be considered complete without CT scanning of the greater sciatic foramen.

Bilateral extradural hematomas in a thrombocytopenic infant receiving anticoagulants: case report.

A unique case of bilateral extradural hematomas in an infant is reported. Relevant aspects of the patient's history, including the absence of any known trauma and the presence of an underlying coagulopathy are discussed. The radiographic and operative findings of this case are presented, and an explanation of the mechanism of the hematomas is offered.

Acute atraumatic subdural hematoma associated with moyamoya disease in an African-American.

A 57-year-old black woman with an atraumatic subdural hematoma was treated for congestive heart failure and was found to have moyamoya disease. The association of these two lesions is rare and has never been described in an African-American. High cerebral venous pressures and changes in cerebral perfusion caused by congestive heart failure and the loss of cerebrovascular autoregulation in moyamoya disease may explain the spontaneous occurrence of a subdural hematoma. Recommendations for management are discussed.

Spinal Charcot arthropathy.

Charcot joints of the spine are well-documented clinical entities most commonly associated with tabes dorsalis. Spinal neuropathic joints, however, may be produced by other disease processes including syringomyelia. In this review, the authors discuss the cause and treatment of spinal Charcot arthropathy with emphasis on surgical therapy and results.

Isolated central nervous system metastasis from transitional cell carcinoma of the bladder: report of a case and review of the literature.

Although systemic metastases from transitional cell carcinoma of the bladder occur frequently, involvement of the central nervous system is uncommon. We describe a patient with an isolated cerebral metastasis who had previously undergone resection of a Grade III, Stage B2 carcinoma of the bladder. We have been able to find only one previous case report of a solitary intracerebral metastasis from transitional cell carcinoma of the bladder without evidence of primary recurrence or additional sites of spread. Central nervous system metastasis from bladder carcinoma must be considered in the differential diagnosis of solitary intracerebral lesions.