RESUMEN
We compared the clinical outcomes of post-trapeziectomy protocols according to their duration. The main hypothesis was that there would be no significant difference in postoperative function whether immobilization duration was 2 or 4 weeks. The secondary hypotheses were that there would be no significant difference in postoperative pain, motion, or strength. 40 trapeziectomies were reviewed. Two weeks' postoperative commissural immobilization was systematic. Patients were then divided in two groups. For the first 20 patients (group I), immobilization stopped at 2 weeks. For the next 20 patients (group II) it was replaced by a splint for further 2 weeks. We compared mean pre- and post-operative (10-20 weeks) function (QuickDASH score), pain (visual analog scale - VAS), thumb opposition (Kapandji score) and strength (palmar pinch test) between the two groups. There was no significant difference between groups in postoperative values or in pre- to post-operative progression. The main hypothesis was confirmed: there was no significant difference in the postoperative function whether the immobilization was for 2 or 4 weeks. The secondary hypotheses regarding postoperative pain, motion and strength were also confirmed.
Asunto(s)
Articulaciones Carpometacarpianas , Osteoartritis , Hueso Trapecio , Articulaciones Carpometacarpianas/cirugía , Humanos , Osteoartritis/cirugía , Rango del Movimiento Articular , Pulgar/cirugía , Hueso Trapecio/cirugíaRESUMEN
The aim of this work was to analyze the results of a percutaneous drainage technique with 2 catheters during surgical treatment of phlegmons of the finger flexor tendon sheath. Our series included 32 patients with a phlegmon of flexor tendon sheaths, including 19 men and 13 women, mean age 43.4years. The first 16 patients (group I) were treated by a conventional open technique for the lavage and drainage of the affected tendon sheath. The last 16 (group II) were treated by an ultrasound-guided percutaneous lavage technique with 2 catheters: one proximal and one distal. In the case of impermeability of the digital canal, conversion by open technique was carried out. In group II, the ultrasound-guided percutaneous lavage was 5 times successful. Failure of the proximal catheter alone was noted once, whereas failure of the distal catheter alone was noted 7 times. The failure of both catheters was noted 3 times. At a mean follow-up of 19.7 days, mean handgrip strength was 56.5% compared to the contralateral side in group I and 82% in group II (P<0.05). However, there was no significant difference for pain, QuickDASH, total active mobility between group I and group II. Pain was at 1.4/10 for group I and 1.4/10 for group II. QuickDASH was measured at 27/100 for group I and 22.27/100 for group II. Total active mobility was 227° for group I and 243° for group II. In conclusion, surgical treatment of the phlegmons of the finger flexor tendon sheath with an ultrasound-guided percutaneous lavage technique gives significantly better short-term grip strength than the conventional open technique.
Asunto(s)
Celulitis (Flemón)/cirugía , Drenaje/métodos , Tendones/cirugía , Adolescente , Adulto , Anciano , Catéteres , Drenaje/instrumentación , Femenino , Dedos , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Irrigación Terapéutica/métodos , Resultado del Tratamiento , Ultrasonografía Intervencional , Adulto JovenRESUMEN
Arthrodesis of the thumb metacarpophalangeal (MCP) joint usually leads to satisfying results when performed with an open technique. The main complication is adhesion of the extensor tendons that sometimes requires hardware removal associated with tenolysis. The goal of this study was to assess whether a minimally invasive technique could reduce the risk of this complication. Arthrodesis of the thumb MCP was performed using an open technique with a locking plate or compression pins in 12 cases (group I) and using a minimally invasive technique with compression pins or screws in 12 cases, for a total of 24 patients aged 48.9 years on average, among which 15 were women. At the last follow-up, the average pain level was rated at 2/10 in group I and 2.3/10 in group II. The QuickDASH was 40.70/100 in group I and 36.24 in group II, grip strength was 79% of the contralateral side in group I and 51% in group II. Pinch strength was 81% of the contralateral side in group I and 45% in group II. Fusion was achieved in all cases in group I and in 7 of 12 cases in group II. Surgical revision for non-union was needed in 5 cases in group II, with hardware removal and tenolysis performed in 2 cases. The non-unions were observed in non-rheumatoid cases. While the two groups were not identical, arthrodesis of the thumb MCP using a minimally invasive technique with compression pins or screws seems to give satisfying results for rheumatoid cases in which no cartilage remains.
Asunto(s)
Artritis/cirugía , Artrodesis/métodos , Clavos Ortopédicos , Placas Óseas , Articulación Metacarpofalángica/cirugía , Procedimientos Quirúrgicos Mínimamente Invasivos , Adulto , Anciano , Artritis/fisiopatología , Artrodesis/instrumentación , Evaluación de la Discapacidad , Femenino , Estudios de Seguimiento , Fuerza de la Mano , Humanos , Masculino , Articulación Metacarpofalángica/fisiopatología , Persona de Mediana Edad , Osteogénesis , Reoperación/estadística & datos numéricos , Estudios Retrospectivos , Pulgar/fisiopatología , Pulgar/cirugíaRESUMEN
The goal of this study was to develop a minimally-invasive, ultrasound-guided percutaneous flexor tendon sheath lavage technique on cadaver model. Two catheters were inserted using ultrasound guidance at the proximal and distal ends of the tendon sheath in 20 fingers from cadaveric forearms. Percutaneous injection of a saline solution colored with methylene blue resulted in anterograde lavage of the flexor tendon sheath. The technique was successful in 13 out of 20 cases. The proximal catheter was in the correct position in 17 cases and the distal catheter was correctly positioned in 15 cases. The flexor tendons were continuous in all cases and had puncture wounds in 9 cases. Based on our study, this minimally-invasive, ultrasound-guided percutaneous lavage of the flexor tendon sheath was effective in 65% of cases and safe in 100% of cases in the index, middle and ring fingers. If this percutaneous lavage fails, it is always possible to switch to a conventional open technique.
Asunto(s)
Tendones/diagnóstico por imagen , Irrigación Terapéutica/métodos , Cadáver , Catéteres , Humanos , Azul de Metileno , Ultrasonografía IntervencionalRESUMEN
The aim of our study was to demonstrate the benefits of combining the Canaletto® implant with carboxymethylcellulose/polyethylene oxide gel in the surgical treatment of carpal tunnel syndrome (CTS) recurrences. Our case series included 39 patients (40 hands, one bilateral case) who underwent revision surgery for recurrent CTS (28 cases) or resistant CTS (12 cases). The mean age of the patients was 56 years. The Canaletto® only was implanted in the first 21 cases (group I). In the following 19 cases (group II), Dynavisc® gel was added to the protocol and applied around the median nerve when the Canaletto® was implanted. At 12 months' follow-up (group I) and 11 months' follow-up (group II), the pre-versus post-operative difference between the average values of the DN4 neuropathic Pain Score was 0.55/10 in group I and 2.25/10 in group II; the Pain Score was 2.23/10 (in group I) and 2.52/10 (in group II); the Quick DASH Score was 18.98/100 (group I) and 19.06/100 (in group II); the hand grip strength was 19.55% (group I) and 28.53% (group II); the sensory nerve conduction velocity was 8.67 m/s (group I) and 10.27 m/s (group II); the distal motor latency was 1.05 m/s (group I) and 1.75 m/s (group II). Nine patients recovered from hypoesthesia in both groups, 5 patients regained satisfactory trophism of the thenar muscles in group I and 3 patients in group II. No improvement whatsoever was noted in 2 patients in group II, despite the electromyogram being normal. One patient from group II suffered an infection that required revision surgery to remove the Canaletto®; this led to a moderate improvement. Our results show that when resistant or recurrent CTS is diagnosed, the combined treatment of an anti-adhesion gel such as Dynavics® around the median nerve with the Canaletto® implant after performing secondary neurolysis leads to satisfactory post-operative outcomes. Compared to other techniques described in the current literature, our technique is less invasive, quicker and associated with minimal morbidity of the surgical site.
Asunto(s)
Síndrome del Túnel Carpiano/cirugía , Geles , Prótesis e Implantes , Adulto , Anciano , Anciano de 80 o más Años , Carboximetilcelulosa de Sodio , Evaluación de la Discapacidad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Conducción Nerviosa , Polietilenglicoles , Recurrencia , Reoperación , Estudios Retrospectivos , Escala Visual AnalógicaRESUMEN
Radiolucent foreign bodies of the hand are frequent and may lead to pain, infection, hematoma and/or migration. Their diagnosis and removal can be difficult. The goal of this study was to assess the usefulness of intraoperative ultrasound imaging for detecting translucent foreign bodies in the hand to facilitate their removal. Our single-center retrospective study included 19 patients with preoperatively radiolucent but echogenic foreign bodies. An intraoperative ultrasound was performed to assist with and confirm the removal of the foreign body. The foreign bodies were vegetal in 15 cases, made of glass in 2 cases, rock in 1 case and undetermined in 1 case. The average length was 4.65 mm (min 1, max 16) and the average width 1.02 mm. All foreign bodies were visible during the intraoperative ultrasound and were no longer visible after their removal. Because intraoperative ultrasound imaging was able to guide the removal of all radiolucent foreign bodies in our study, it can be a useful tool for the removal of radiolucent foreign bodies.
Asunto(s)
Cuerpos Extraños/diagnóstico por imagen , Cuerpos Extraños/cirugía , Mano/diagnóstico por imagen , Mano/cirugía , Ultrasonografía , Humanos , Cuidados Intraoperatorios , Estudios RetrospectivosRESUMEN
The aim of this retrospective study was to compare the results of arthroscopic dorsal capsulodesis performed with or without temporary K-wiring to treat patients who had sustained scapholunate ligament injuries. Our case series included 30 patients with an average age of 37 years (range: 19-55) of whom 12 were female. Dorsal scapholunate capsulodesis was carried out in all patients. In 15 patients, splint immobilization only was used (group I). For the remaining 15 patients, supplementary scapholunate and scaphocapitate K-wiring was performed (group II). The outcomes, whether K-wiring was used or not, were not as good as the outcomes of other published studies. In our study, the reported QuickDASH score was on average higher than 20/100, pain score was higher than 2/10, grip strength was less than 70% of the contralateral side. There was one postoperative complication in the first group and three complications in the second group; five cases of DISI were reported in the first group and three in the second group. There were no significant differences between the two groups. Based on our findings, supplementary K-wiring is not necessary when a dorsal scapholunate capsulodesis is performed. The outcomes of our study were not as good as those of other published series, potentially due to a shorter follow-up and the more severe ligament injuries in our case series.
Asunto(s)
Artroscopía , Hilos Ortopédicos , Hueso Grande del Carpo/cirugía , Inmovilización/métodos , Hueso Semilunar/cirugía , Hueso Escafoides/cirugía , Férulas (Fijadores) , Adulto , Evaluación de la Discapacidad , Femenino , Estudios de Seguimiento , Fuerza de la Mano , Humanos , Cápsula Articular/cirugía , Ligamentos Articulares/lesiones , Ligamentos Articulares/cirugía , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Cuidados Posoperatorios , Complicaciones Posoperatorias , Estudios Retrospectivos , Adulto JovenRESUMEN
The purpose of this work was to determine whether the Cochet-Bonnet (CB) corneal sensitivity test has a lower cutaneous pulp sensitivity threshold than the Semmes-Weinstein (SW) monofilament test. Tactile sensitivity thresholds for the radial hemi-pulp of the index finger of 25 healthy adult subjects aged 30 years on average were measured using SW and CB esthesiometers. The sensitivity threshold of the radial hemi-pulp of the index was lower with the CB test than with the SW test. The sensitivity and specificity of the CB test on palm wounds still needs to be determined to rule out nerve damage.
Asunto(s)
Dedos/inervación , Examen Neurológico/instrumentación , Umbral Sensorial/fisiología , Tacto/fisiología , Adulto , Femenino , Dedos/fisiología , Voluntarios Sanos , Humanos , Masculino , Examen Neurológico/métodos , Adulto JovenRESUMEN
The usefulness of ultrasound for making the diagnosis of pyogenic flexor tenosynovitis (PFTS) has been demonstrated. The primary goal of this study was to show that the diameter of the flexor sheath near the A2 pulley was larger when PFTS was present compared to the healthy contralateral finger. The secondary goal was to determine the reproducibility of these ultrasound measurements. Our series included 20 patients (12 men and 8 women) operated due to PFTS. The average age was 41.7 years old. The average diameter of the digital sheath measured near the A2 pulley on transverse and longitudinal ultrasound sections was 5.01mm (transverse 5mm, longitudinal 5.03mm) on infected fingers, and 4.17mm on healthy contralateral fingers. Reproducibility, as measured by the intraclass coefficient between transverse and longitudinal values, was 0.910 for infected fingers and 0.928 for contralateral fingers, thus was excellent. Our hypothesis was confirmed. A unilateral increase of more than 20% in diameter of the flexor sheath measured in transverse or longitudinal ultrasound sections near the pulley A2 contributes to the surgical indication when a patient presents with PFTS.
RESUMEN
PURPOSE: Animal bite injuries are often encountered in daily practice. In particular, these injuries of the upper limbs can result in severe functional impairment. We have performed early debridement of contaminated tissue and primary closure for these injuries. METHODS: The subjects consisted of 15 patients (6 males and 9 females) aged 1-91 years (mean 53.6 years) who visited our hospital due to animal bite injuries (dog in 9 patients, cat in 6). The bite site was the forearm in 5 patients and the hand in 10. In the operating room, contaminated tissue was removed, and primary wound closure was performed after irrigation. RESULTS: The bite penetrated to the muscle layer in 6 patients, tendon sheath in 5, joint in 1, bone in 1, and involved only the subcutaneous tissue in 3 patients. The mean period until the completion of wound treatment was 19.8 ± 8.4 days. As complications, numbness of finger, metaphalangeal joint contracture and superficial radial nerve injury were observed in each one case. In a patient with bite injury of the palmar and dorsal sides of the thumb reaching the bone, additional debridement was necessary. At the final observation, the visual analog scale was 1.2 ± 1.4, and the Quick Disabilities of the Arm, Shoulder, and Hand score was 9.7 ± 12.2. CONCLUSIONS: Debridement to achieve wound closure is indispensable in patients with animal bite injuries of the upper limbs. The results of our study suggest that thorough debridement allows primary closure, even for animal bite injuries.
Asunto(s)
Mordeduras y Picaduras , Huesos de la Extremidad Superior/lesiones , Contractura , Desbridamiento , Traumatismos de los Tejidos Blandos , Extremidad Superior/lesiones , Técnicas de Cierre de Heridas/efectos adversos , Infección de Heridas , Animales , Antibacterianos/uso terapéutico , Mordeduras y Picaduras/complicaciones , Mordeduras y Picaduras/diagnóstico , Mordeduras y Picaduras/terapia , Gatos , Contractura/diagnóstico , Contractura/etiología , Contractura/prevención & control , Desbridamiento/efectos adversos , Desbridamiento/métodos , Perros , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad , Traumatismos de los Tejidos Blandos/complicaciones , Traumatismos de los Tejidos Blandos/etiología , Traumatismos de los Tejidos Blandos/cirugía , Irrigación Terapéutica/métodos , Resultado del Tratamiento , Infección de Heridas/diagnóstico , Infección de Heridas/etiología , Infección de Heridas/prevención & controlRESUMEN
Deciduous oak dieback in Japan has been known since the 1930s, but in the last ten years epidemics have intensified and spread to the island's western coastal areas. The symbiotic ambrosia fungus Raffaelea sp. is the causal agent of oak dieback, and is vectored by Platypus quercivorus (Murayama). This is the first example of an ambrosia beetle fungus that kills vigorous trees. Mortality of Quercus crispula was approximately 40% but much lower for associated species of Fagaceae, even though each species had a similar number of beetle attacks. It is likely that other oaks resistant to the fungus evolved under a stable relationship between the tree, fungus and beetle during a long evolutionary process. Quercus crispula was probably not part of this coevolution. This hypothesis was supported by the fact that P. quercivorus showed the least preference for Q. crispula yet exhibited highest reproductive success in this species. Therefore, P. quercivorus could spread more rapidly in stands with a high composition of Q. crispula. The present oak dieback epidemic in Japan probably resulted from the warmer climate that occurred from the late 1980s which made possible the fateful encounter of P. quercivorus with Q. cripsula by allowing the beetle to extend its distribution to more northerly latitudes and higher altitudes. Future global warming will possibly accelerate the overlapping of the distributions of P. quercivorus and Q. crispula with the result that oak dieback in Q. crispula will become more prevalent in Japan.
Asunto(s)
Ascomicetos/fisiología , Escarabajos/microbiología , Efecto Invernadero , Enfermedades de las Plantas/microbiología , Quercus/microbiología , Animales , Japón , Quercus/crecimiento & desarrolloRESUMEN
Autoantibodies against glutamic acid decarboxylase (GAD) have been found in stiff-man syndrome, insulin dependent diabetes mellitus, and progressive cerebellar ataxia. A patient with progressive cerebellar ataxia is described who was positive for GAD autoantibodies, and had Sjögren's syndrome. Immunohistochemical studies using CSF and serum samples from the patient showed immunoreactivities in axon terminals of cerebellar GABAergic neurons. A whole cell patch clamp technique recording from rat cerebellar slices showed that the CSF, presumably through GAD autoantibodies, presynaptically inhibited GABAergic transmission. Intravenous administration of immunoglobulin failed to improve clinical symptoms and immunoreactivities examined after therapy. The findings suggest that GAD autoantibodies play a pathogenic part in reducing GABA release in in vitro slices.
Asunto(s)
Autoanticuerpos/inmunología , Ataxia Cerebelosa/inmunología , Ataxia Cerebelosa/patología , Glutamato Descarboxilasa/inmunología , Terminales Presinápticos/inmunología , Transmisión Sináptica/inmunología , Anciano , Femenino , Humanos , InmunohistoquímicaRESUMEN
To clarify the role of presenilin-1 (PS-1) in the pathology of Alzheimer's disease (AD), we tested four antisera to PS-1. The specific antisera to the N-terminus (HSN-2) and C-terminus (HS-C) of PS-1 detected a 44/40kD holoprotein, a 25kD N-terminal fragment (NTF) and a 16kD C-terminal fragment (CTF) of PS-1 in COS-7 cells. The 25kD NTF and 16kD CTF were observed in human brains, and their amounts were not significantly different between the control and AD brains. The antibody HS-C labeled extensive neurofibrillary tangles, dystrophic neurites and curly fibers in the AD brains. In the paired helical filament (PHF) fraction containing A68 protein from AD brains, a smear pattern of CTFs was revealed. Antisera (HS-L292 and HS-L300) to cleavage sites of PS-1 also revealed immunoreactive neurofibrillary tangles in the AD brain sections and the smear pattern of CTFs of A68 protein fraction. The CTFs of PS-1 accumulate with PHF tau, suggesting a close relationship between PS-1 and cytoskeletal abnormalities in AD brains.
Asunto(s)
Enfermedad de Alzheimer/patología , Encéfalo/patología , Citoesqueleto/patología , Proteínas de la Membrana/metabolismo , Fragmentos de Péptidos/metabolismo , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/metabolismo , Animales , Western Blotting , Encéfalo/metabolismo , Células COS , Citoesqueleto/inmunología , Citoesqueleto/metabolismo , Dimerización , Humanos , Sueros Inmunes/inmunología , Inmunohistoquímica , Proteínas de la Membrana/química , Proteínas de la Membrana/inmunología , Peso Molecular , Neuritas/metabolismo , Neuritas/patología , Ovillos Neurofibrilares/inmunología , Ovillos Neurofibrilares/metabolismo , Ovillos Neurofibrilares/patología , Fragmentos de Péptidos/química , Fragmentos de Péptidos/inmunología , Placa Amiloide/inmunología , Placa Amiloide/metabolismo , Placa Amiloide/patología , Presenilina-1 , Estructura Secundaria de Proteína , Solubilidad , Proteínas tau/inmunología , Proteínas tau/metabolismoRESUMEN
Cerebrospinal fluid samples from a total of 157 subjects consisting of 55 patients with sporadic Alzheimer's disease (AD), 34 normal controls, 23 patients with non-AD dementia, and 45 with other neurological diseases were examined by ELISA of tau, A beta 1-40, and A beta 1-42(43). The AD group had a significantly higher level of tau than the normal control group (P < 0.001), and the diagnostic sensitivity was 31% and specificity was 94%. CSF A beta 1-40 levels did not show any significant differences. Although the level of A beta 1-42(43) was decreased significantly in the AD group compared to the control group (P < 0.005), the overlap of A beta 1-42(43) levels among all groups meant that none of the AD samples exceeded the cut-off value, the mean 2SD of normal control subjects. Reduction of A beta 1-42(43) levels in AD resulted in a significant increase in the ratio of A beta 1-40 to A beta 1-42(43) (A beta ratio) as an improved marker. The diagnostic sensitivity and specificity of A beta ratio were 51% and 82% respectively. The three indexes, using the tau level and A beta ratio (tau or A beta ratio, deviation score and tau x A beta ratio), showed better sensitivity (58%, 67%, 69%) and specificity (82%, 86%, 88%) than previously reported methods. Combination assay for CSF tau, A beta 1-40 and A beta 1-42(43) in CSF is a biological marker of AD and may be useful to biochemically monitor subjects under treatment.
Asunto(s)
Enfermedad de Alzheimer/líquido cefalorraquídeo , Péptidos beta-Amiloides/líquido cefalorraquídeo , Fragmentos de Péptidos/líquido cefalorraquídeo , Proteínas tau/líquido cefalorraquídeo , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores , Demencia/líquido cefalorraquídeo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedades del Sistema Nervioso/líquido cefalorraquídeo , Valores de ReferenciaRESUMEN
To clarify the alterations of tau, amyloid beta protein (A beta) 1-40 and A beta1-42(43) in the cerebrospinal fluid (CSF) that accompany normal aging and the progression of Alzheimer's disease (AD), CSF samples of 93 AD patients, 32 longitudinal subjects among these 93 AD patients, 33 patients with non-AD dementia, 56 with other neurological diseases, and 54 normal control subjects from three independent institutes were analyzed by sensitive enzyme-linked immunosorbent assays. Although the tau levels increased with aging, a significant elevation of tau and a correlation between the tau levels and the clinical progression were observed in the AD patients. A significant decrease of the A beta1-42(43) levels and a significant increase of the ratio of A beta1-40 to A beta1-42(43) were observed in the AD patients. The longitudinal AD study showed continuous low A beta1-42(43) levels and an increase of the ratio of A beta1-40 to A beta1-42(43) before the onset of AD. These findings suggest that CSF tau may increase with the clinical progression of dementia and that the alteration of the CSF level of A beta1-42(43) and the ratio of A beta1-40 to A beta1-42(43) may start at early stages in AD. The assays of CSF tau, A beta1-40, and A beta1-42(43) provided efficient diagnostic sensitivity (71%) and specificity (83%) by using the production of tau levels and the ratio of A beta1-40 to A beta1-42(43), and an improvement in sensitivity (to 91%) was obtained in the longitudinal evaluation.
Asunto(s)
Enfermedad de Alzheimer/líquido cefalorraquídeo , Péptidos beta-Amiloides/líquido cefalorraquídeo , Fragmentos de Péptidos/líquido cefalorraquídeo , Proteínas tau/líquido cefalorraquídeo , Anciano , Anciano de 80 o más Años , Envejecimiento/fisiología , Enfermedad de Alzheimer/diagnóstico , Biomarcadores/líquido cefalorraquídeo , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Curva ROC , Sensibilidad y Especificidad , Caracteres SexualesRESUMEN
Carboxyl-terminal fragments of beta amyloid precursor protein (betaAPP) were expressed in mice under the transcriptional control of an ubiquitous promoter system, based upon a chicken beta-actin (betaA) promoter combined with cytomegalovirus (CMV) enhancer to obtain a systemic overproduction of amyloid beta protein (Abeta). Three transgene constructs were designed to encode signal peptide and carboxyl-terminal 99 amino acid residues to betaAPP (NOR-beta), methionine and C-terminal 103 amino acid residues of betaAPP (deltaNOR-beta), and methionine and C-terminal 103 amino acid residues with KM-NL substitution of betaAPP (deltaNL-beta). Although the transcriptional mRNA level and post-translational protein level from transgenes showed the same expression pattern, both the expression of Abeta and distribution of Abeta deposits were completely different among these strains. In NOR-beta mice, considerable amounts of Abeta were detected in plasma and Abeta deposits were observed in the pancreas. Brain Abeta deposits and small amounts of plasma Abeta were recognized in deltaNL-beta. These findings indicate that tissue specific processing and transgene constructs are major factors to determine the distribution of Abeta deposits.
Asunto(s)
Péptidos beta-Amiloides/genética , Péptidos beta-Amiloides/metabolismo , Química Encefálica/genética , Actinas/metabolismo , Animales , Northern Blotting , Pollos/genética , Citomegalovirus/genética , Ensayo de Inmunoadsorción Enzimática , Exones , Vectores Genéticos , Inmunohistoquímica , Ratones , Ratones Transgénicos , Biosíntesis de Proteínas/genética , Transcripción Genética/genéticaRESUMEN
To study the role of apolipoprotein E (apoE) in vivo in deposits of amyloid beta protein (A beta), a major component of senile plaque amyloid in the brain of patients with Alzheimer disease, the transgenic mice were examined by apoE immunostaining. The mice were systemically overexpressing signal peptide and 99 amino acid residues of the carboxy-terminal fragment of human amyloid beta protein precursor (betaAPP) under control of the powerful cytomegalovirus enhancer/chicken beta-actin promotor. A beta deposits appeared at 4 months and increased with aging in the acinar cells of the transgenic pancreas. Similarly, apoE deposits appeared in the pancreatic acinar cells at 4 months old. The number and size of apoE deposits increased with aging and correlated with the progression of A beta deposits. Interstitial macrophages labeled by apoE immunostaining appeared at 8 months after birth and their number increased with aging. On serial section of the pancreata of 24-month-old mice, approximately 70% of A beta deposits were labeled with the apoE antiserum. ApoE was detected in the highly insoluble formic acid fraction of the transgenic pancreas by an immunoblot study. The Northern blot study revealed no increase in synthesis of endogenous apoE mRNA. These findings indicate that apoE is closely related to progression of A beta deposits with aging and suggest that A beta deposition in the transgenic pancreas is similar to that in the senile plaque of Alzheimer brains. Therefore, our experimental system using transgenic mice will provide a useful tool to analyze the molecular mechanism of A beta deposition in association with apoE in vivo.
Asunto(s)
Péptidos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/genética , Apolipoproteínas E/metabolismo , Ratones Transgénicos/genética , Ratones Transgénicos/metabolismo , Envejecimiento/metabolismo , Animales , Humanos , Immunoblotting , Ratones , Páncreas/metabolismo , ARN Mensajero/biosíntesis , SolubilidadRESUMEN
Soluble amyloid beta protein (A beta)1-40 and highly amyloidogenic A beta 1-42/43 were immunocytochemically labeled in lysosomes of acinar cells and macrophages in the pancreas of transgenic mice systemically expressing a C-terminal fragment of the A beta precursor. A beta 1-42/43 and long A beta species extending their C-termini were detected in the detergent-insoluble fraction. Immunoreactivity of cathepsin D was markedly increased in lysosomes filled with A beta fibrils. These findings indicated that A beta 1-40, A beta 1-42, A beta 1-43 and longer A beta species were generated in the lysosomes of the transgenic pancreas, and suggested that the activation of cathepsin D, a candidate gamma-secretase, leads to acceleration of A beta amyloid formation.
Asunto(s)
Precursor de Proteína beta-Amiloide/metabolismo , Lisosomas/metabolismo , Ratones Transgénicos/metabolismo , Animales , Inmunohistoquímica , Ratones , Páncreas/metabolismoAsunto(s)
Hidrocefalia/etiología , Enfermedades Hipotalámicas/etiología , Hipotermia/etiología , Tuberculosis Meníngea/complicaciones , Antiinflamatorios/administración & dosificación , Antituberculosos/administración & dosificación , Drenaje , Femenino , Humanos , Hidrocefalia/terapia , Hidrocortisona/administración & dosificación , Enfermedades Hipotalámicas/cirugía , Hipotermia/terapia , Persona de Mediana Edad , Tuberculosis Meníngea/terapia , Derivación VentriculoperitonealRESUMEN
Serial extraction study of Alzheimer's disease (AD) and control brains revealed 4, 3.7 and 3 kD amyloid beta protein (A beta) species accumulated in AD brains. In the fractions extracted with TBS, 10% SDS and formic acid, considerable amounts of A beta species were recovered in SDS fractions besides TBS and formic acid fractions. Immunoblotting with several site-specific antibodies confirmed not only the presence of 4 kD A beta starting at the first amino acid of A beta but also 2 smaller A beta species with modification of their amino-termini in the highly resolutional Tris/Tricine gel system. A beta solubility using these solvents was associated with both modification of the amino-terminus and length of carboxyl-terminus of A beta. Especially, a large amount of modified A beta was found to be accumulated as forms with different solubility in AD brains.