Biomedical subjects
Publications and source records attributed to H Takami.
Traumatic rupture of the flexor tendons at the musculotendinous junction is rare. A case of flexor pollicis longus tendon rupture at the musculotendinous junction is described. The mechanism of the tendon injury appears to be longitudinal traction on the contracted muscle during delivery of a bowling ball.
In the pathology of simple complete dislocation involving the metacarpophalangeal joint of the thumb, whether or not the palmar plate is interposed within the joint is controversial. Nine cases of complete dorsal dislocation of the joint were reviewed, and cadaver dissection was performed to study the pathology of this injury. Eight of the nine patients were seen within 4 days of injury and treated successfully by closed manipulation. One patient treated 7 days after the injury required open reduction. We were able to reproduce the pathological anatomy of the dislocation, wedging of the palmar plate in the joint of the cadaver. In this cadaver and in all clinical cases, radiographs showed a complete dislocation with an increased distance between the palmar edge of the base of the proximal phalanx and the metacarpal head, indicating an interposition of the palmar plate. Our study suggests that in simple complete dislocations of this joint, the palmar plate is interposed between the displaced bones.
An avulsion fracture of the insertion of the extensor carpi radialis longus tendon is rare. There have been only five reports of this injury in the literature [1, 2, 4]. We describe an additional case in which open reduction with internal fixation gave a satisfactory result.
A toluene-resistant variant of Pseudomonas putida KT2442, strain TOL, was isolated after liquid cultivation under xylene followed by toluene for 1 month in each condition. Almost all the populations of the variant strain formed small but readily visible colonies under toluene within 24 h at 30 degrees C. The toluene-resistant strain also showed an increase in resistance to some unrelated antibiotics. Several toluene-sensitive Tn5 mutants have been isolated from the toluene-resistant strain and showed various levels of sensitivity. Most of these mutations did not cause significant changes in antibiotic resistance; however, one of the mutants (TOL-4) was highly susceptible to both organic solvents and various antibiotics, especially beta-lactams. Sequencing analysis revealed that the mutation in TOL-4 had been introduced into a gene that may encode a transporter protein of an efflux system. This efflux system is very similar to one of the multidrug efflux systems of Pseudomonas aeruginosa. These observations indicate that a multidrug efflux system plays a major role in the organic solvent resistance of P. putida TOL. However, several other genes may also be involved.
We have isolated a Pseudomonas-like amylase producer, the strain MS300, which displayed a large halo on starch medium, from the deepest site of the Mariana Trench. The strain MS300 produced two major and two minor alpha-maltotetraohydrolases (G4-amylase). The two major G4-amylases share the same molecular weight of 55,000 but had different pI values, 5.0 and 4.7, respectively. The optimum temperature for activity of both major G4-amylases is 40 degrees C, and the optimum pH is 6.8 for one and 8.9 for the other. MS300 produced more amylase under high hydrostatic pressure than under atmospheric pressure. Strain MS300 may be active in the deep sea at a depth of 10,897 m.
Multiple endocrine neoplasia types 2A and 2B (MEN2A and MEN2B) and familial medullary thyroid carcinomas (FMTC) are caused by germline mutations in the RET proto-oncogene. To investigate the spectrum of RET mutations among Japanese patients, we screened the RET gene in 71 patients with thyroid carcinomas. The panel included representatives of 44 families carrying FMTC or MEN2, 22 sporadic medullary thyroid carcinomas (MTCs), and five MTCs without familial information. Mutations in nucleotide sequences encoding one of three specific cysteine residues in the extracellular domain of the RET protein were found in 33 of the 34 MEN2A patients and in five of the six FMTC patients examined. A mutation at codon 918, causing the substitution of threonine for methionine in the tyrosine kinase domain of the protein, was found in germline DNAs of all four patients with MEN2B and in two of the 22 patients with sporadic MTCs; codon 918 was mutated somatically in tumor DNAs from three other sporadic cases. Germline mutations of codon 768, GAG to GAC (Glu to Asp), were detected in one FMTC, in one patient with sporadic MTC, and in one of the patients without familial information. Two somatic mutations, an Asp to Gly substitution at codon 631 and a Cys to Arg substitution at codon 634, had not been reported previously. Of five germline mutations found among the 22 sporadic cases, four were confirmed as de novo mutations since in each case neither parent carried the mutation. As nearly one-fourth of the patients with sporadic MTCs carried germline mutations and 50% of their children are expected to develop MTC and other endocrine tumors, these results indicated the importance of careful clinical surveillance of family members of any patient with MTC.
A 30-year-old man presenting with Cushing's syndrome was admitted in 1995. A diagnosis of ectopically ACTH-secreting, primary-unknown abdominal carcinoid tumour was made. The patient's plasma ACTH and cortisol levels failed to decrease after short-term treatment with octreotide, and somatostatin-receptor scintigraphy did not show any accumulation in the tumour. The patient died 1 year after admission. This is a relatively rare somatostatin-receptor-negative case of this disease and it appears necessary to test for the presence of somatostatin receptors before treating with octreotide.
A second nationwide survey was conducted to determine the outcome of pregnancy in long-term survivors of acute leukemia and to clarify the influence of treatment on the offspring of long-term survivors. In July 1996, 336 survey responses were received from the 498 Japanese institutions surveyed. A total of 89 cases (39 spouses of male patients and 50 female patients) who had babies during their first remission were analyzed, including 43 patients from the first survey in 1991. Median age at the birth of first baby was 30.7 years for male patients and 28.6 years for female patients. A total of 109 of the 117 pregnancies resulted in live births and eight resulted in abortions. A total of 58 cases had single children and 23 cases had two or more, generally from separate pregnancies, but including two pairs of twins. The infant was male in 59 cases, female in 37 and gender was not reported in 13 cases. Ages of children ranged from 2 months to 20 years at the time of this study and all children were in good health. There were two minor anomalies, both of which were surgically corrected. Of the 81 parents bearing live infants, 75 remained in complete remission. Five fathers died (four of relapse and one of another disease). In conclusion, there was no apparent increase in pregnancy complications or congenital anomalies in the children of long-term survivors with acute leukemia.
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A novel series of indole and benzimidazole derivatives were synthesized and evaluated for their inhibitory activity of rat prostatic 5alpha-reductase. Among these compounds, 4-¿2-[1-(4,4'-dipropylbenzhydryl)indole-5-carboxamido]phenoxy¿buty ric acid (15) and its benzimidazole analogue 25 showed potent inhibitory activities for rat prostatic 5alpha-reductase (IC50 values of 9.6+/-1.0 and 13+/-1.5 nM, respectively), with the potency very close to that of finasteride. Compound 30, in which the moiety between the benzene ring and amide bond was replaced by quinolin-4-one ring, showed almost equipotent activity (IC50= 19+/-6.2nM) with the correspondent amide derivative 13. This result was consistent with the previous observation that the coplanarity of this moiety might contribute to the potent inhibitory activity.
We describe the occurrence of autoimmune haemolytic anaemia (AIHA) in a patient who had had both idiopathic thrombocytopenic purpura (ITP) and bullous pemphigoid (BP) for about 10 years. All of these diseases worsened rapidly, and the patient's clinical condition became critical after an episode of acute pneumonia. His AIHA, ITP and BP were responsive to combination chemotherapy consisting of cyclophosphamide, vincristine and prednisolone (CVP therapy).
We present a case report of a 55-year-old male patient with hypoplastic myelodysplastic syndrome (MDS, refractory anemia) in which a good response to recombinant human erythropoietin (rhEPO) has been maintained for more than 60 months. There is with no evidence of progression to high risk MDS or acute leukemia, although he was predicted to be a low-responder to rhEPO therapy because of very high serum EPO levels (5,260 mU/ml), a history of multiple transfusions, chromosomal abnormalities (47,XY,+8) and severe thrombocytopenia. Since he received rhEPO with no adverse effects, it may be valuable to try rhEPO treatment at least one time for low-risk MDS patients, depending on red cell transfusion requirements.
We have developed a new computerized system for measurement of quantitative bleeding time (QBT) to detect subtle abnormalities of primary hemostasis that are difficult to detect with the standard bleeding time determination. This new apparatus can simultaneously measure the bleeding time (BT; sec), amount of total blood loss (Tv; microl), maximum bleeding rate (Rmax; microl/sec) and bleeding pattern from the bleeding time incision. We have also developed a new holder for the Simplate that enables more consistent incisions and thus improves the reproducibility of the BT test. In this study, the newly developed QBT test was performed in 137 normal healthy volunteers and 10 patients having defined abnormalities of either primary or secondary hemostasis. Comparisons of the standard BT test and our QBT were made in 5 normal subjects and 7 thrombocytopenic patients. Additionally, 6 normal subjects were examined with both tests before and after administration of aspirin. Those results show that our QBT appears to be a more sensitive indicator of primary hemostasis than the standard BT method.
Phase III clinical study in 78 patients with hyperparathyroidism was performed to determine clinical utility of 99mTc-MIBI in the localization of hyperfunctioning parathyroid lesions. Except slight tremor in one patient, no adverse events were reported. No abnormal changes in clinical laboratories or vital signs were noted. The clinical utility of the agent was evaluated in 70 patients. Out of 108 hyperfunctioning glands, 93 (86%) were detected with 99mTc-MIBI regardless of their histology, numbers, or location. Specifically, single or ectopic lesions were detected with high sensitivity (97% and 100%, respectively). Sensitivity in 53 glands with weight data was 79%, while 94% in 36 glands above 200 mg, which is extremely high compared to the 201T1-99mTc subtraction method. Specificity in a group of PHP patients with single adenoma who underwent surgery was 100% (63/63), though in case of coexistent thyroid disease obviously interfered parathyroid images. Our study indicates that 99mTc-MIBI is a safe and excellent agent for the localization of hyperfunctioning parathyroid tissues. Especially, the fact that 99mTc-MIBI detected ectopic glands with high specificity is a great advantage over the ultrasound or 201Tl-99mTc subtraction method.
Phase III clinical study in 136 patients diagnosed or strongly suspected of thyroid, lung/mediastinum or breast cancer was performed to determine clinical utility of 99mTc-MIBI in the localization of tumors, and the results in 135 were evaluated. Except taste peculiar in 43 patients and nausea in one, no adverse events were reported. Seven abnormal changes in vital signs and 27 in clinical laboratories were noted, which were all judged as having no or unlikely relationship to the agent. Out of 177 malignant lesions, 156 (88%) were detected with 99mTc-MIBI regardless of their histology or location. Of 6 benign tumors, 3 were detected. Fifteen sites of false positive in 11 malignant tumor patients and 5 sites in 6 patients with non-tumor disease were observed. Our study indicates that 99mTc-MIBI is a safe and excellent agent for the localization of tumors. Especially, the fact that 99mTc-MIBI detected remote metastatic lesions with high sensitivity is a great advantage over the other conventional imaging modalities.
In an attempt to characterize the microbial flora on the deepest sea floor, we isolated thousands of microbes from a mud sample collected from the Mariana Trench. The microbial flora found at a depth of 10897 m was composed of actinomycetes, fungi, non-extremophilic bacteria, and various extremophilic bacteria such as alkaliphiles, thermophiles, and psychrophiles. Phylogenetic analysis of Mariana isolates based on 16S rDNA sequences revealed that a wide range of taxa were represented.
Germ-like and somatic mutations in the RET proto-oncogene are associated with inherited and sporadic medullary thyroid carcinoma (MTC). The majority of patients with multiple endocrine neoplasia type 2A (MEN2A) and familial medullary thyroid carcinoma (FMTC) carry germ-line point mutations that result in the substitution of one of five cysteine residues. We investigated exons 10, 11, 13, 14 and 16 of the RET proto-oncogene in 33 unrelated Japanese patients with MTC. Eleven of the 33 cases (33%) were found to have germ-line mutations. Three previously unreported mutations in exon 10 and 11 were identified: one in codon 620, (TGC-->GGC), resulting in a cysteine to glycine substitution, and two in codon 630, (TGC-->TCC) and (TGC-->TAC), resulting in cysteine to serine and cysteine to tyrosine changes, respectively. The new mutations were present in the germ-line DNA of four unrelated patients for whom a family history of MTC had not been documented. Because the new RET alleles described here involve cysteine residues in a region of protein previously associated with FMTC and MEN2A, it is very likely that they represent mutations that predispose to the development of MTC.
DNA topoisomerases are major defined targets for a large variety of clinically important anticancer agents, including etoposide, adriamycin, and mitoxantrone. Mutations at amino acids 439, 450 and 803 of DNA topoisomerase II were examined in multiple anticancer drug-resistant anaplastic thyroid carcinomas (ten cell lines and three cancerous tissues) by reverse transcriptase-polymerase chain reaction (RT-PCR) and subsequent DNA sequencing. No mutation was found in these cell lines and tissues, but mdr1, mrp and/or lrp mRNA were expressed to a varying degree, and there was no significant difference in DNA topoisomerase IIalpha content among the cell lines and tissues as evaluated by Western blotting. Our experimental data indicate that overexpression of multidrug resistance-related mRNA is sufficient to confer drug resistance.