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Biomedical subjects

Ken Yamaguchi

Publications and source records attributed to Ken Yamaguchi.

52 records · Page 3Linked to original sources

Prospective trial of unilateral surgery for nonhereditary medullary thyroid carcinoma in patients without germline RET mutations.

Although sporadic medullary thyroid carcinoma (MTC) tends to be unicentric and confined to one lobe, total thyroidectomy is usually performed because of the risk of a hereditary or bilateral process. Germline RET mutation analysis can discriminate hereditary MTC and truly sporadic, nonhereditary MTC. We analyzed 72 of 94 patients with MTC to establish the genetic nature and the clinical features of nonhereditary MTC. Since 1996 we have prospectively treated 15 patients with nonhereditary MTC (prospective study group, or PSG) according to a unilateral surgery policy. A group of 22 previously operated patients in whom the nonhereditary nature was established served as controls (retrospective study group, or RSG). Systematic central and ipsilateral neck dissection was performed in both groups. Outcome was assessed using postoperative stimulated serum calcitonin levels; a normal value was considered a biochemical cure. All 24 hereditary MTC patients carried germline RET mutations: 8 of 48 patients with apparently sporadic MTC had the mutations, and 6 of the 8 had bilateral MTC. All 40 patients without mutations had a unilateral tumor. In the RSG group 15 of 22 (68%) patients underwent total thyroidectomy, and the biochemical cure rate was 68%. Although only 3 of 15 (20%) of the PSG patients underwent total thyroidectomy, 12 of the 15 (80%) achieved biochemical cure. Univariate analyses revealed that pathologic node involvement- high T and N stages-was adversely related to biochemical cure. The extent of thyroid resection was not related to biochemical cure. Of 20 patients with node involvement, 10 achieved biochemical cure, indicating the importance of systematic neck dissection. Hemithyroidectomy with systematic central and ipsilateral neck dissection is appropriate surgery for nonhereditary MTC.

Adult↗

Peptide differential display of serum-free conditioned medium from cancer cell lines.

Conditioned medium (CM) from cultured cells is a source for screening small peptides of therapeutic or diagnostic value in cancer research. Mass spectrometry has recently enabled the profiling of peptides present in biological samples. We report a single-step extraction method to increase a chance to discover small peptides with a starting volume of 750 microl of serum-free CM. In combination with protein chip mass spectrometry, our protocol will contribute to the discovery of target peptides.

Chromatography, Ion Exchange↗

Geometric analysis of selected press fit prosthetic systems for proximal humeral replacement.

The ability of a prosthetic system to replicate a wide range of normal anatomy appears dependent in part to its capacity to produce variable prosthetic geometries. Several modern designs have recently been developed in order to provide multiple prosthetic options. The purpose of this study was to compare the geometry of select press fit prosthetic systems in terms of their ability to match normal three-dimensional geometry of the proximal humerus. The anatomy of 60 humeral specimens from 30 cadavers known from CT data and computer-aided design (CAD) analysis was compared to a 1996 database of four conventional shoulder prosthetic systems (fixed inclination angle, one medial-lateral offset position per head) and one so-called anatomic system (variable inclination angles, multiple head offset positions). The prosthetic system with greatest geometric options allowed for a significantly better replication of the anatomy. Average displacement of the center of rotation was 2.1 mm compared to 9.7 mm for the other systems combined. Reduction in surface arc was 12 degrees compared to 32 degrees. The most problematic feature of conventional prosthetic systems in terms of replicating normal humeral anatomy is the gap created by the prosthetic collar and Morse taper.

Algorithms↗

Arthroscopic release of the rotator interval and coracohumeral ligament: An anatomic study in cadavers.

PURPOSE: The purpose of this cadaveric study was to examine the anatomy of the normal glenohumeral joint relevant to an arthroscopic rotator interval release and define both the endpoints of a complete release of the coracohumeral ligament and the relationship to surrounding tendons and nerves. TYPE OF STUDY: An anatomic cadaveric study. METHODS: Fifteen fresh-frozen cadaveric specimens were studied with 5 specimens in group I and 10 specimens in group II. Group I specimens were used to examine the relevant anatomy, including the structures at risk, the dimensions of the rotator interval, and potential endpoints for release of the coracohumeral ligament. Measurements included (1) the supraspinatus to the subscapularis distance, (2) the distance from the rotator interval to the deep surface of the coracoid process, and (3) the distance from the rotator interval to the coracoacromial ligament at the level of the glenoid. Group II specimens underwent arthroscopic release of the rotator interval using the appearance of the coracoacromial ligament as the superficial endpoint. Dissection was then performed to examine for complete release of the coracohumeral ligament and to assess the structures at risk of injury. RESULTS: The distance from the anterior edge of supraspinatus to the superior edge of subscapularis at the glenoid rim was 21.6 mm, which increased to 27.8 mm with joint distention. The minimum distance from the rotator interval to the deep surface of the coracoid process was 11.4 mm. Before distention, the coracoacromial ligament was an average of 6.2 mm from the rotator interval capsule. Arthroscopic release from the supraspinatus to the subscapularis resulted in complete resection of the coracohumeral ligament in all 15 specimens. There were no specimens with evidence of injury to the biceps tendon, supraspinatus, subscapularis, or the conjoint tendon. CONCLUSIONS: This study confirms that intra-articularly directed arthroscopic release of the rotator interval can safely lead to complete release of the coracohumeral ligament if dissection is taken superficially to the level of the coracoacromial ligament.

Arthroscopy↗

Postoperative pain control following arthroscopic release of adhesive capsulitis: a short-term retrospective review study of the use of an intra-articular pain catheter.

PURPOSE: The purpose of this study was to examine the effectiveness of an arthroscopically placed intra-articular pain catheter for controlling postoperative pain and also review the results following arthroscopic release of refractor adhesive capsulitis. TYPE OF STUDY: Retrospective clinical trial. METHODS: Twenty-three consecutive cases (20 patients) of arthroscopic adhesive capsulitis release in which an intra-articular pain catheter was used were reviewed. Follow-up ranged from 12 to 37 months (average, 22.4 months). An intra-articular catheter was placed under direct arthroscopic visualization from a superior approach into the glenohumeral joint. Postoperatively, patients were injected with 10 mL of 0.5% bupivacaine every 6 hours as needed. Preoperatively, all patients had filled out a questionnaire based on the American Shoulder and Elbow Surgeons (ASES) outcome guidelines and examined for range of motion. Postoperatively, patients were asked for their precatheter and postcatheter injection pain level based on the visual analog scale (1 to 10 points, 1 = no pain). Patients were then examined for range of motion and retested with the outcome questionnaire. An ASES Shoulder Score Index was calculated for each patient before and after the procedure. RESULTS: The average forward elevation preoperatively was 102 degrees and external rotation at the side was 4.5 degrees. At most recent follow-up, average forward elevation was 169 degrees with external rotation at the side 47 degrees. The Shoulder Score Index increased from an average of 37.1 out of 100 to 90.9 (P <.001). Before being injected with anesthetic through the catheter, patients had an average visual analog scale score of 8.1. Postinjection average pain level was 1.2 (P <.001) and all patients indicated that the pain catheter significantly reduced postoperative pain. Nineteen of 20 patients were satisfied with the procedure. CONCLUSIONS: Placement of an intra-articular pain catheter for delivery of bupivacaine was highly effective in controlling postoperative pain. In all cases, postoperative pain was essentially eliminated and this substantially assisted with range of motion exercises. Near complete restoration of range of motion without pain was achieved in 95% of the patients.

Anesthetics, Local↗

Overview of cancer control programs in Japan.

Japan has a population of about 127 million, with an average life expectancy that is one of the highest in the world. Cancer has been the leading cause of death in Japan since 1981. The incidence of cancer for all sites in 1994 was estimated to be 440 000; crude incidence rates per 100 000 for males and females were 416.3 and 299.4, respectively. In 1997, the number of cancer deaths was 275 413; crude death rates for males and females per 100 000 were 273.0 and 169.9, respectively. Projections for 2015 indicate that 890 000 people will develop cancer and 450 000 will die as a result. It is not too much to say that Japan is now amid a 'Cancer Era'. Meanwhile, the progress in medical sciences is improving survival in cancer patients; in cancer patients diagnosed during 1987-89, relative 5-year survival was reported to be 41.2% for all sites and cancer survivorship research estimated the number of cancer survivors for all sites in 1998 who have lived for between 5 and 24 years after diagnosis to be 1.5 million. The Ministry of Health and Welfare is focusing on five different measures in the implementation of its cancer control programs: public health education, nationwide cancer screening programs, development and support of specialized medical institutions, training of specialists and promotion of basic and clinical cancer research. As a tool for public health education, the Ministry published in 2000 a 10-year health promotion program entitled 'Healthy Japanese in the 21st Century'. In the plan, seven particular goals are enumerated with regard to cancer. In practice, issues of concern include the development of new modalities, telling the truth to cancer patients, clinical trials and bioethical issues.

Female↗

A family of autosomal dominant hypocalcemia with a positive correlation between serum calcium and magnesium: identification of a novel gain of function mutation (Ser(820)Phe) in the calcium-sensing receptor.

To date about 20 activating mutations in the calcium-sensing receptor (CaR) gene have been identified to cause autosomal dominant hypocalcemia (ADH) or sporadic hypoparathyroidism. We report a novel activating mutation in the CaR gene in a Japanese family with ADH. The proband, a 15-yr-old boy, and 5 other patients in 3 generations were asymptomatic, except for the proband's grandmother who had a history of seizures. They showed mild hypocalcemia (1.68-1.98 mmol/liter) with normal urinary calcium excretion and low normal serum PTH levels. Their serum magnesium concentrations were below normal in 3 adults and within the normal range in 3 teenagers. There was a significant positive correlation (r = 0.90; P < 0.05) between the serum calcium and magnesium concentrations of 6 affected members. Nucleotide sequencing revealed that the proband had a known polymorphism (Gly(990)Arg) and a novel heterozygous mutation substituting phenylalanine for serine at codon 820 (Ser(820)Phe) in the sixth transmembrane helix of the CaR. In other family members, the Ser(820)Phe mutation cosegregated with hypocalcemia. The mutation was not detected in 50 control subjects. The Gly(990)Arg polymorphism was observed in 8 of 9 family members with or without hypocalcemia and in 36 of 50 controls. The sensitivity of the Ser(820)Phe mutant CaR to calcium was assessed using transiently transfected HEK293 cells and measuring the increases in intracellular Ca(2+) concentrations in response to the changes in extracellular Ca(2+). The concentration-response curve of the mutant receptor was left-shifted, and its EC(50) (2.5 mM) was significantly (P < 0.05) lower than that of the wild-type CaR (3.3 mM). We conclude that the Ser(820)Phe mutation in the CaR caused ADH in this family. The positive correlation between serum calcium and magnesium levels observed in this family may support the concept that renal CaR acts as a magnesium sensor as well as a calcium sensor.

Adolescent↗

Elbow instability: treatment strategies and emerging concepts.

Elbow stability relies on a complex interaction between the bony articulations of the elbow joint, the capsuloligamentous structures, and dynamic muscle restraints. Understanding the functional anatomy of the elbow and the relative contribution of the various elements to elbow stability is important in developing a strategy for diagnosis and management. Elbow instability presents a spectrum from minor subluxation to dislocation. The treatment of an acute dislocation is determined by the stability of the elbow after reduction and the fixation of associated fractures. Isolated acute tears of the LCL are uncommon and are generally treated nonsurgically. On the medial side, augmented repair is required for return to throwing sports. Chronic MCL insufficiency results in valgus instability, which usually is a problem only for the throwing athlete. Chronic LCL insufficiency may lead to symptomatic posterolateral joint subluxation. Free tendon graft reconstruction can be successful on both sides of the joint, with a return of stability and improved elbow function.

Arthroplasty↗

Retroviral-mediated IL-12 gene transduction into human CD34+ cell-derived dendritic cells.

Genetically modified dendritic cells (DCs) with Th1 type cytokine genes are useful for activating anti-tumor immune response. We made human interleukin (IL)-12 p70 gene-transduced DCs generated from CD34+ progenitor cells using a retrovirus system and investigated the function of IL-12-producing DCs. We used the pMX retroviral vector and made cytokine gene-containing viral vectors referred to as GFP pMX and hIL-12 pMX. Supernatants from BOSC23 cells transfected with GFP pMX and hIL-12 pMX were harvested and used for transfection of DC. Cord blood CD34+ cells were incubated with supernatants containing retrovirus for 48 h with cytokines such as IL-3, IL-6, SCF, Flt3 ligand (FL), bFGF and IGF-I. The cells were cultured for 12 days in the presence of GM-CSF, SCF, FL, IL-4 and TNF-alpha to get mature DC-enriched population. Analysis of surface marker on DCs and allogeneic MLR assay were also performed. After a 14-day culture, 60-70% of cultured CD34+ cells were DC marker (CD1a, DEC205) positive. The IL-12 p70 protein levels in supernatant of DC-GFP and DC-hIL-12 were 0.2 ng/ml and 53 ng/ml/5 x 10(5) DCs for 72 h, respectively. The addition of CH296 fibronectin fragment (FN) increased 3-fold IL-12 gene transduction efficiency into DCs. MLR assay showed that IL-12-producing DC exhibited more potent T cell growth-stimulating activity compared with GFP-DC. These results suggested that genetically modified CD34+ cell-derived DCs with human IL-12 gene are fully efficient in T cell priming, and could be a good tool for effective cancer immunotherapy.

Antigens, CD1↗

The EWS/NOR1 fusion gene product gains a novel activity affecting pre-mRNA splicing.

In extraskeletal myxoid chondrosarcoma, chromosomal translocation creates a gene fusion between EWS and the orphan nuclear receptor NOR1. The resulting fusion gene product, EWS/NOR1, has been believed to lead to malignant transformation by functioning as a transcriptional activator, but an alternative mechanism may also be involved. Here, using a newly developed functional complementation screening in yeast, we found that EWS/NOR1, but not EWS or NOR1, complemented the loss of function of the small nuclear ribonucleoprotein Snu23p, an essential factor for pre-mRNA splicing in yeast. To verify the potential function of EWS/NOR1 in mammalian cells, we next showed that overexpression of EWS/NOR1 caused increased usage of the distal 5'-splice site of pre-mRNA splicing and that EWS/NOR1 interacted with the human splicing protein U1C; neither EWS nor NOR1 had the same activity or interaction as EWS/NOR1. Altogether, our findings reveal that EWS/NOR1 gains a novel activity affecting pre-mRNA splicing.

Adenovirus E1A Proteins↗

The efficacy of ultrasound in the diagnosis of long head of the biceps tendon pathology.

The use of shoulder ultrasound as an imaging modality has recently gained widespread attention; however, the ability of ultrasound to diagnose long head of the biceps tendon pathology accurately still remains unclear. The biceps tendons in 71 patients were prospectively evaluated by comparison of standard ultrasonographic and arthroscopic examinations. Arthroscopic examination was used as the gold standard comparison. Ultrasound showed a 100% specificity and 96% sensitivity for subluxation or dislocation. Ultrasound detected all complete ruptures of the biceps tendon but detected none of the 23 partial-thickness tears. Overall, ultrasound diagnosed 35 of 36 normal biceps tendons (specificity, 97%) and 17 of 35 abnormal biceps tendons (sensitivity, 49%). Ultrasound can reliably diagnose complete rupture, subluxation, or dislocation of the biceps tendon. It is not reliable for detecting intraarticular partial-thickness tears.

Adult↗

Virtual hydrocarbon and combinatorial databases for use with CAVEAT.

Three new virtual databases have been developed for use with the bond-orientation-based database searching program CAVEAT. These consist of a database of trisubstituted monocyclic hydrocarbons having ethyl, vinyl, and phenyl substituents; a database of unsubstituted bicyclic hydrocarbons; and a database of core structures from established combinatorial synthetic methods having hydrogen, ethyl, vinyl, and phenyl substituents at the readily varied positions. Each collection of molecules was subjected to a batch conformational search, minimization, and conversion to a vector database for use with CAVEAT.

Bridged Bicyclo Compounds↗

Arthroscopic treatment of post-traumatic elbow contracture.

The purpose of this study was to evaluate range of motion and patient-reported outcome after complete arthroscopic release of post-traumatic elbow contracture. Fourteen consecutive patients who underwent elbow arthroscopy and capsular release were reviewed retrospectively at a minimum follow-up of 1 year. Pain and range of motion were measured. Patient outcome was assessed with the American Shoulder and Elbow Surgeons Elbow Assessment Form. Mean self-reported satisfaction on a visual analog scale was 8.4 out of 10. Only 6 patients continued to have pain, with a mean maximum pain score of 4.6 out of 10. Flexion increased from a mean of 117.5 degrees to 133 degrees, and extension improved from a mean of 35.4 degrees to 9.3 degrees. In those patients with a preoperative arc of motion less than 100 degrees (10 patients), the mean arc of motion improved from 69 degrees to 119 degrees. All patients had improved function after the procedure, with a mean self-reported functional ability score of 28.3 out of 30. There were no neurovascular complications. The improvement in range of motion and functional outcome compares favorably with open-release procedures. Combined with the potential benefits of improved joint visualization and low surgical morbidity, arthroscopic release of post-traumatic elbow contracture appears to be a reasonable alternative to open techniques.

Adolescent↗

Pectoralis major transfer for anterior-superior subluxation in massive rotator cuff insufficiency.

The purpose of this study was to evaluate the outcome after subcoracoid pectoralis major transfer for anterior-superior shoulder instability in massive rotator cuff insufficiency. Fourteen patients underwent subcoracoid pectoralis major transfer for this debilitating surgical complication. At a mean 17.5-month follow-up, there were 11 satisfactory and 3 unsatisfactory results. Nine of the patients were satisfied with the procedure and would repeat the operation under similar circumstances. Pain scores, as measured on a visual analog scale, decreased from 6.9 to 3.2 postoperatively. Mean forward flexion increased from 24.4 degrees to 60.8 degrees. American Shoulder and Elbow Society functional outcome score increased from 27.2 preoperatively to 47.7 postoperatively. Thirteen of the fourteen patients had improved humeral head containment and improved ability to perform activities of daily living at waist level. A subcoracoid pectoralis major muscle transfer has a low complication rate and is a viable option in this difficult patient population, with better results than those previously reported.

Activities of Daily Living↗

Cytotoxic T cell induction against human malignant melanoma cells using HLA-A24-restricted melanoma peptide cocktail.

Many human leukocyte antigen (HLA)-class I (mainly A*0201)-restricted peptide-specific cytotoxic T cells (CTLs) have been derived from peripheral blood lymphocytes (PBLs) of melanoma patients. However, few studies regarding HLA-A*2402-restricted melanoma-associated peptides have been performed, because HLA-A24 is not a common allele in Caucasians. In this study, we investigated the specific CTL-inducing activity of 5 HLA-A*2402-restricted peptides derived from gp100, tyrosinase, MAGE1, MAGE2 and MAGE3. A CTL induction culture was performed using PBLs and cultured dendritic cell (DC) pulsed with HLA-A*2402-restricted melanoma peptide cocktail. The CTLs derived from volunteers killed the A24 peptide-pulsed TISI cells and even HLA-A*2402-positive melanoma cells, but not HLA-A*0201-positive cells. IFN-gamma levels produced by the melanoma patients' CTLs were obviously low in each peptide group compared with those produced by the volunteers' CTLs, which indicated the presence of immunosuppressive factors in metastatic melanoma. These results suggested that polyvalent immunotherapy using multiple epitopes from melanoma antigens might be a better way of improving the efficacy of treatment.

Antigens, Neoplasm↗

Bilateral anterior cerebral artery territory infarction associated with unilateral hypoplasia of the A1 segment: report of two cases.

We report two cases of bilateral anterior cerebral artery (ACA) territory infarction. On magnetic resonance (MR) angiograms, the A1 segment of the ACA was unilaterally hypoplastic in both cases, suggesting that unilateral hypoplasia of A1 is a significant predisposing factor for this rare type of cerebral infarction. When the contralateral A1 is dominant, embolic materials may enter into it more easily.

Aged↗