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Biomedical subjects

M Sachs

Publications and source records attributed to M Sachs.

At least 19 recordsLinked to original sources
PubMed2006

Sex differences in baseline neuropsychological function and concussion symptoms of collegiate athletes.

OBJECTIVE: To investigate sex differences in baseline neuropsychological function and concussion symptoms between male and female collegiate athletes. METHODS: A post-test only design was used to examine baseline neuropsychological test scores and concussion symptoms. A total of 1209 NCAA Division I collegiate athletes from five northeastern universities in the USA completed a baseline ImPACT test. ImPACT, a computerised neuropsychological test battery, was administered during an athlete's pre-season. RESULTS: Female athletes performed significantly better than male athletes on baseline verbal memory scores (p = 0.001), while male athletes performed significantly better than female athletes on baseline visual memory scores (p = 0.001). Female athletes endorsed a significant number of mild baseline symptoms as compared to male athletes. CONCLUSIONS: Male and female athletes exhibit differences on baseline neuropsychological test performance and concussion symptoms.

Athletic Injuries↗
PubMed2006

[Utilizing optical coherence tomography (OCT) for visualization of urothelial diseases of the urinary bladder].

PURPOSE: The technique of optical coherence tomography (OCT) has significantly improved over the last few years. This new diagnostic procedure allows imaging of tissue structure of the bladder wall during cystoscopy with high resolution. MATERIALS AND METHODS: The penetration depth of OCT is limited to 2.5 mm. The resolution is approximately 15 microm. Fifty patients with different clinical conditions of the bladder were examined. Altogether 488 OCT images were generated. RESULTS: OCT of normal bladder mucosa clearly shows a differentiation between urothelium, lamina propria, and smooth muscle. Cystitis and metaplasia are characterized by blurring of the laminated structure and thickening of the epithelial layer. In malignant areas there is complete loss of the regular layered tissue structure. CONCLUSION: OCT improves the diagnosis of flat lesions of the urothelium. It has the potential for facilitating intraoperative staging of malignant areas in the bladder.

Aged↗
PubMed2005

Posterior "nutcracker" phenomenon: hemodynamic relevant aorto-retroaortal renal vein fistula leading to fatal right heart failure.

A rare complication of an aneurysm of the abdominal aorta is the so-called "posterior nutcracker phenomenon", which describes compression of a retroaortal renal vein between the abdominal aorta and the vertebral column. The clinical presentation is flank pain and hematuria, which are usually caused by a renal (respectively ureteral) calculus or neoplasia. Another rare differential diagnosis for these very common clinical symptoms is an aorto-left renal vein fistula (ALRVF), which is a spontaneous vascular fistula, usually also associated with an aortic aneurysm, infrequently a result of abdominal trauma.

Aged↗
PubMed2004

[The impact of ALA (5-aminolevulinic acid)-fluorescence detection on the prognosis of superficial bladder cancer].

PURPOSE: Throughout the past years, several studies have shown that fluorescence cystoscopy with ALA (5-aminolevulinic acid) improves the detection rate of superficial bladder tumors by approximately 20 % compared to standard white light cystoscopy. These results suggest a reduced rate of residual/recurrent tumors with the routine use of ALA fluorescence technique prior to bladder tumor resection. The present prospectively randomized study was performed to verify this hypothesis. MATERIALS AND METHODS: A total of 115 bladder tumor patients were randomized for initial resection under white light or ALA fluorescence. After 6 to 8 weeks, a second-look resection was performed in all patients guided by ALA fluorescence. Additional white light cystoscopies were performed after 3, 6 and 12 months. RESULTS: The second-look resection did not find a tumor in 31 of 51 (59 %) patients initially resected under white light guidance compared to 43 of 51 (84 %) patients in the fluorescence group. This difference was statistically significant (p = 0.005). At 12 months, a tumor was not found in 17 of 48 patients from the white light group vs. 25 of 47 patients from the fluorescence group (p = 0.03). Seven patients were lost to follow-up. CONCLUSIONS: By reducing otherwise inevitable re-operations, fluorescence cystoscopy decreases morbidity and lowers treatment costs.

Adult↗
PubMed2004

CYP1A1 alleles in women with focal nodular hyperplasia of the liver (FNH).

OBJECTIVE: Disorders of steroid hormone metabolism might be related to the etiology of focal nodular hyperplasia of the liver (FNH), a benign tumor, especially prevalent in women. The cytochrome P450 1A1 (CYP1A1) enzyme is implicated in the bioactivation of multiple precarcinogens as well as in the metabolism of steroids. Genetic polymorphisms of CYP1A1 have been associated with altered catalytic activity in the hydroxylation of sex hormones and this may account for interindividual variability in exposure to hormone-mediated cell proliferation signals and reactive steroid metabolites. In the study at hand, we aimed to evaluate a possible association between CYP1A1*1, *2A, *2B, and *4 alleles and FNH. METHOD: Genotyping of 26 affected female patients of Caucasian origin was carried out using PCR/RFLP. RESULTS: Allele frequencies for the CYP1A1 variants *2A, *2B and *4 in 26 female patients with FNH were 0.058, 0.019 and 0.058, respectively. Crude odds ratios for the individual alleles were 0.75 (95% CI 0.23-2.44), 0.72 (95% CI 0.10-5.34) and 1.96 (95% CI 0.59-6.50), respectively. There were no significant differences between these values and corresponding allele frequencies obtained in a large German sample of unaffected Caucasian women. CONCLUSION: The present data do not suggest a relevant association between CYP1A1 polymorphisms and focal nodular hyperplasia of the liver in female Caucasians.

Adult↗
PubMed2003

[The prohibition of lithotomy within the Hippocratic Oath: historical and ethical considerations on the history of surgery].

A passage with one of the most contradictory interpretations of the so-called Hippocratic Oath, which was presumably created between 500 and 300 before Christ, is the prohibition of lithotomy. The oldest handwritten traditions of the Hippocratic Oath are dating back to the 11th-12th century. However the section of the prohibition of lithotomy is missing in the oldest preserved tradition (Codex Urbinas gr. 64), which led to some authors interpretation of being added later on. Beyond all doubt the analysis of the texture of the Hippocratic Oath leads to the conclusion that the prohibition of bladder stone lithotomy must have been an integrative part of the oath from the very first beginning. The author could have been inspired by the following reasons to have a non oath related doctor let done the medical operation: the removal of a bladder stone by an operation, which was outfitted with many complications, was one of the most difficult surgical interventions in the antique. Celsus (1st century A. D.) mentioned "severe fever, urine fistula and deadly inflammations" after lithotomy. Since the operation was done perineally, presumably a negative sexual potency was feared. No doctor engaged to help and not to harm his patients was allowed to make this kind of operation, which was often followed by many complications. Nevertheless sometimes patients were "tantalised to death by suffering dreadful pain" through those bladder stone diseases. Consequently "practising men" (the term "surgeon" was created at a later date), those who had been specialised in that operation and had not been linked to the oath, were allowed to make this kind of dangerous operation. Due to a greater experience of those specialists (named as "Lithotomos" by Celsus ih the 1st century A. D.) the danger of this kind of operation was reduced. The prohibition of lithotomy could be interpreted as a commitment to realize the limits of ones own medical actions.

Cystostomy↗
PubMed2002

[Wound management with coconut oil in Indonesian folk medicine].

The medical plants which are used to treat wounds and injuries by the ethnic group of Ngada on Flores, an Eastern Indonesian island, will be presented. Additionally, the coconut oil used to treat wounds and to conserve medicinal plants will be analysed biochemically. The people of Ngada use the following plants for wound treatment: seeds of the betel nut (Areca catechu L.), fruits of papaya (Carica papaya L.), leaves of the Indian Hydrocotyle (Centelle asiatica L.), the rhizome of turmeric (Curcuma domestica Val. and Curcumara xanthorrhiza Roxb.), leaves of betel (Piper betel L.). Coconut oil is particularly useful because of its biochemical structure: unlike olive oil and animal fatty tissue, it consists of short-chained and saturated fatty acids. These qualities in coconut oil prevent it from becoming oxidized and rancid, thus making it suitable for the preservation of medicinal plants and for wound treatment.

Coconut Oil↗
PubMed2001

Novel p62dok family members, dok-4 and dok-5, are substrates of the c-Ret receptor tyrosine kinase and mediate neuronal differentiation.

Docking proteins are substrates of tyrosine kinases and function in the recruitment and assembly of specific signal transduction molecules. Here we found that p62dok family members act as substrates for the c-Ret receptor tyrosine kinase. In addition to dok-1, dok-2, and dok-3, we identified two new family members, dok-4 and dok-5, that can directly associate with Y1062 of c-Ret. Dok-4 and dok-5 constitute a subgroup of dok family members that is coexpressed with c-Ret in various neuronal tissues. Activated c-Ret promotes neurite outgrowth of PC12 cells; for this activity, Y1062 in c-Ret is essential. c-Ret/dok fusion proteins, in which Y1062 of c-Ret is deleted and replaced by the sequences of dok-4 or dok-5, induce ligand-dependent axonal outgrowth of PC12 cells, whereas a c-Ret fusion containing dok-2 sequences does not elicit this response. Dok-4 and dok-5 do not associate with rasGAP or Nck, in contrast to p62dok and dok-2. Moreover, dok-4 and dok-5 enhance c-Ret-dependent activation of mitogen-activated protein kinase. Thus, we have identified a subclass of p62dok proteins that are putative links with downstream effectors of c-Ret in neuronal differentiation.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Serum and urine markers of bone metabolism during the year after hip fracture.

OBJECTIVE: As part of a larger study to describe indices of recovery during the year after hip fracture, the current prospective study investigated longitudinal changes in serum and urine markers of bone metabolism for the year after hip fracture and related them to bone mineral density (BMD). DESIGN: A representative subset of participants provided serum and urine samples and had bone density measured at 3, 10, 60, 180, and 365 days postfracture. SETTING: Two Baltimore hospitals. PARTICIPANTS: The subjects were 205 community-dwelling, white women age 65 and older with fresh proximal femur fractures. MEASUREMENTS: Samples were assayed for specific bone-related proteins and bone turnover markers, including serum osteocalcin (OC), procollagen type 1 carboxy-terminal extension peptide (PICP), bone-specific alkaline phosphatase (BAP), and urinary deoxypyridinoline (DPD) cross-links. Selected hormonal regulators of bone metabolism, including parathyroid hormone (PTH), calcitonin (CT), 1,25-dihydroxy vitamin D(3) (1,25 (OH)(2)D), and estrone (E(1)) were measured from serum samples. Repeated measures analyses were used to evaluate postfracture changes in each of the markers. RESULTS: BAP, OC, and PICP were most active during the early postfracture period (3-60 days). BAP and OC remained elevated at 365 days compared with 3 days. DPD rose 48% from 3 days to 60 days, but this difference was not statistically significant. PTH and 1,25 (OH)(2)D increased steadily and significantly from 3 to 365 days. E(1) was highest at baseline and decreased at each time point, whereas CT showed no significant changes. When subjects were stratified into high-, medium-, and low-BMD groups based on their measurement at 3 days, both osteoclastic and osteoblastic markers in the low-BMD group displayed exaggerated and different patterns over time compared with the other groups. CONCLUSION: Currently, the standard treatment of care for hip fractures still results in high morbidity and mortality and failure to regain prefracture quality of life. Gaining an understanding of bone cell activity in these patients after hip fracture, derived by measuring markers longitudinally during recovery, provides a baseline by which to measure the effectiveness of new interventions to improve recovery from hip fracture.

Absorptiometry, Photon↗
PubMed2000

Essential role of Gab1 for signaling by the c-Met receptor in vivo.

The docking protein Gab1 binds phosphorylated c-Met receptor tyrosine kinase directly and mediates signals of c-Met in cell culture. Gab1 is phosphorylated by c-Met and by other receptor and nonreceptor tyrosine kinases. Here, we report the functional analysis of Gab1 by targeted mutagenesis in the mouse, and compare the phenotypes of the Gab1 and c-Met mutations. Gab1 is essential for several steps in development: migration of myogenic precursor cells into the limb anlage is impaired in Gab1-/- embryos. As a consequence, extensor muscle groups of the forelimbs are virtually absent, and the flexor muscles reach less far. Fewer hindlimb muscles exist, which are smaller and disorganized. Muscles in the diaphragm, which also originate from migratory precursors, are missing. Moreover, Gab1-/- embryos die in a broad time window between E13.5 and E18.5, and display reduced liver size and placental defects. The labyrinth layer, but not the spongiotrophoblast layer, of the placenta is severely reduced, resulting in impaired communication between maternal and fetal circulation. Thus, extensive similarities between the phenotypes of c-Met and HGF/SF mutant mice exist, and the muscle migration phenotype is even more pronounced in Gab1-/-:c-Met+/- embryos. This is genetic evidence that Gab1 is essential for c-Met signaling in vivo. Analogy exists to signal transmission by insulin receptors, which require IRS1 and IRS2 as specific docking proteins.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Coupling of Gab1 to c-Met, Grb2, and Shp2 mediates biological responses.

Gab1 is a substrate of the receptor tyrosine kinase c-Met and involved in c-Met-specific branching morphogenesis. It associates directly with c-Met via the c-Met-binding domain, which is not related to known phosphotyrosine-binding domains. In addition, Gab1 is engaged in a constitutive complex with the adaptor protein Grb2. We have now mapped the c-Met and Grb2 interaction sites using reverse yeast two-hybrid technology. The c-Met-binding site is localized to a 13-amino acid region unique to Gab1. Insertion of this site into the Gab1-related protein p97/Gab2 was sufficient to confer c-Met-binding activity. Association with Grb2 was mapped to two sites: a classical SH3-binding site (PXXP) and a novel Grb2 SH3 consensus-binding motif (PX(V/I)(D/N)RXXKP). To detect phosphorylation-dependent interactions of Gab1 with downstream substrates, we developed a modified yeast two-hybrid assay and identified PI(3)K, Shc, Shp2, and CRKL as interaction partners of Gab1. In a trk-met-Gab1-specific branching morphogenesis assay, association of Gab1 with Shp2, but not PI(3)K, CRKL, or Shc was essential to induce a biological response in MDCK cells. Overexpression of a Gab1 mutant deficient in Shp2 interaction could also block HGF/SF-induced activation of the MAPK pathway, suggesting that Shp2 is critical for c-Met/Gab1-specific signaling.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Signaling of hepatocyte growth factor/scatter factor (HGF) to the small GTPase Rap1 via the large docking protein Gab1 and the adapter protein CRKL.

Hepatocyte growth factor (HGF; scatter factor) is a multipotent protein with mitogenic, motogenic, and developmental functions. Upon activation, the HGF-receptor c-Met binds and phosphorylates the multisite docking protein Gab1. Besides binding motifs for phosphatidylinositol 3-kinase and Grb2, Gab 1 contains multiple Tyr-X-X-Pro (YXXP) motifs which, when phosphorylated, are potential binding sites for the adapter proteins c-Crk and Crk-like (CRKL). Stimulation of human embryonic kidney cells (HEK293) with HGF leads to Gab1 association with CRKL. The Gab1-CRKL interaction requires both, the SH2 domain of CRKL and the region containing the YXXP motifs in Gab1. CRKL binds via its first SH3 domain to several downstream signal transducers, including C3G an activator of the small GTPase Rap1. Indeed, Rap1 was rapidly activated after HGF stimulation of HEK293 cells. Rap1 activation through HGF was suppressed through transfection of a truncated C3G protein which only contains the SH3-binding motifs of C3G. Transfection of nonmutated Gab1 led to a strong increase of Rap1.GTP in the absence of HGF. In contrast, transfection of the GabDeltaYXXP mutant abolished the elevation of Rap1.GTP by HGF. A replating assay indicated that HGF decreases the adhesion of HEK293 cells. The results presented here delineate a novel signaling pathway from HGF to the GTPase Rap1 which depends on the interaction of the adapter protein CRKL with the exchange factor C3G and could be linked to cell migration.

Adaptor Proteins, Signal Transducing↗
PubMed2000

[Observations on traditional healers ("medicine men") of Indonesian aborigines].

The observations were done during expeditions to tribes of Indonesian aborigines on the islands of New Guinea/Irian Jaya (Korowai-tribe) and Borneo/Kalimantan (Benuaq-tribe). Neither the Korowai people, who are still living under stone age-like circumstances in up to 30 m high tree-houses, nor the Benuaq people of Borneo, being already influenced by missionary men, do treat injuries or wounds by traditional healers. All the "internal" disorders, not being suffered by injuries, are diagnosed and treated in certain ceremonies, during which the healer tries to get in contact to the spirits triggering the disease. The idea is to know the reason of the disorder caused by demons, though the patient can be treated with bringing offerings or confirmations. This way of treating is due to the image of a magic-demoniac relationship between patient and his disease.

Borneo↗
PubMed1999

Historical evolution of limb amputation.

The amputation of a limb is one of the oldest surgical procedures. In the course of medical history operative techniques and surgical instruments have been improved continuously. As early as the first century Celsus described an amputation. A major step in the development of the operative technique was the introduction of an artery forceps by Paré during the sixteenth century. Nevertheless, due to a lack of analgesics and narcotics the operation had to take only a few minutes. Therefore the amputation was completed in one cut (i.e., detachment of the skin, muscles, and bone at the same level). This technique, known as "classic circular cut," was modified several times in the following period: to reduce suture tension Petit recommended that we transect the skin first and the muscles and bone more proximally ("two-stage circular cut," 1718), and Bromfield approved that the skin be cut first, the muscles more proximally and the bone most proximal ("three-stage circular cut," 1773). Lowdham (1679), Verduyn (1696), and Langenbeck (1810) changed the operative technique in that they used a soft-tissue flap to cover the bone without tension ("flap amputation").

Amputation, Surgical↗
PubMed1999

SF/HGF is a mediator between limb patterning and muscle development.

Scatter factor/hepatocyte growth factor (SF/HGF) is known to be involved in the detachment of myogenic precursor cells from the lateral dermomyotomes and their subsequent migration into the newly formed limb buds. As yet, however, nothing has been known about the role of the persistent expression of SF/HGF in the limb bud mesenchyme during later stages of limb bud development. To test for a potential role of SF/HGF in early limb muscle patterning, we examined the regulation of SF/HGF expression in the limb bud as well as the influence of SF/HGF on direction control of myogenic precursor cells in limb bud mesenchyme. We demonstrate that SF/HGF expression is controlled by signals involved in limb bud patterning. In the absence of an apical ectodermal ridge (AER), no expression of SF/HGF in the limb bud is observed. However, FGF-2 application can rescue SF/HGF expression. Excision of the zone of polarizing activity (ZPA) results in ectopic and enhanced SF/HGF expression in the posterior limb bud mesenchyme. We could identify BMP-2 as a potential inhibitor of SF/HGF expression in the posterior limb bud mesenchyme. We further demonstrate that ZPA excision results in a shift of Pax-3-positive cells towards the posterior limb bud mesenchyme, indicating a role of the ZPA in positioning of the premuscle masses. Moreover, we present evidence that, in the limb bud mesenchyme, SF/HGF increases the motility of myogenic precursor cells and has a role in maintaining their undifferentiated state during migration. We present a model for a crucial role of SF/HGF during migration and early patterning of muscle precursor cells in the vertebrate limb.

Animals↗