Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In December 1993, a 76-year-old Japanese male presented with general fatigue. Peripheral blood (PB) examination indicated marked leukocytosis (WBC count, 19.8 x 10(4)/microliter; leukemic blast differential, 89.5%). Leukemic blasts were positive for CD33, and negative for lymphoid antigens, with 2% of the blasts being positive for myeloperoxidase staining. On admission, chromosome analysis of leukemic cells in PB showed 45, X,-Y, t (9;22) [12/15]/46, XY, t (9;22) [3/15]. Southern blot analysis of the DNA from PB showed a rearrangement at the M-BCR region and germline configurations of both TCR beta and IgH chain genes. The patient was diagnosed as Philadelphia-positive chronic myelogenous leukemia (CML) in blast crisis. We commenced treatment with daunorubicin (DNR; 20 mg/day x 1 IV) and daily prednisolone (PSL; 60 mg/day PO). Leukemic blasts disappeared rapidly from PB, while the promyelocytes showed a transient increase, peaked 7 days after the start of therapy, and then disappeared. Myelocytes and metamyelocytes also showed transient increases. Without a period of severe myelosuppression, the patient reverted to the chronic phase of CML and karyotypic analysis of bone marrow cells showed 45, X,-Y, t (9;22) [33/35]/46, XY, [2/35]. Consolidation chemotherapy with DNR and BHAC was started, but the patient's condition deteriorated due to bacterial infection and he died of hepatic failure on March 1994. In this case, reversion to the chronic phase of CML in blast crisis may be accomplished by the cytodifferentiating effects of small-dose DNR and oral PSL to the leukemic blasts.
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PMID:[Reversion to chronic phase of chronic myelogenous leukemia in blast crisis with small-dose daunorubicin and oral prednisolone]. 858 71

CPT-11 (irinotecan) is a promising anticancer agent with a novel mechanism of action dependent on the inhibition of the DNA eukaryotic enzyme, topoisomerase I. The clinical utility of CPT-11 in advanced colorectal cancer has been documented in more than 400 patients recruited in phase II clinical trials in Europe, Japan, and United States. Among 178 eligible patients in a multicenter European study, the overall response rate to CPT-11 on a once-every-3-weeks regimen was 18%, and the median duration of response was 9.1 months. Thirty-two percent of the patients had no evidence of disease progression at 6 months. These results were similar in chemotherapy-naive and pretreated patients. These findings are consistent with the results of other studies conducted in Japan and the United States in which a weekly CPT-11 regimen was associated with response rates of 15% to 32% in chemotherapy-naive or pretreated patients. The principal adverse events of CPT-11 are neutropenia and delayed diarrhea, which in the European studies developed as grade 3 or 4 toxicity in 21% and 12% of the cycles (47% and 38% of patients), respectively. Neutropenia did not appear to be cumulative, with total recovery by day 22 in most cases. Loperamide was considered the most effective agent for controlling delayed diarrhea. Other adverse events included an early cholinergic-like syndrome (consisting of diaphoresis, early diarrhea, and abdominal cramps), nausea and vomiting, fatigue, and alopecia. In conclusion, CPT-11 has shown promising antitumor activity in the treatment of patients with advanced colorectal cancer, including those refractory to 5-fluorouracil (5-FU)-based regimens, suggesting no cross-resistance to 5-FU. CPT-11 appears to have activity similar to that of 5-FU in first-line treatment and, moreover, remains active after failure of 5-FU therapy. The specific gastrointestinal toxicity is manageable, and a better control of this type of toxicity is expected in the future. CPT-11 would therefore appear a welcome addition to the oncology armamentarium for this difficult-to-treat malignancy.
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PMID:CPT-11 in the treatment of colorectal cancer: clinical efficacy and safety profile. 863 52

We describe a rare example of inflammatory pseudotumor of the pancreas in a 42-yr-old woman, which developed following chemotherapy for lymphoma of the uterine cervix. The patient had developed fatigue, weight loss, abdominal pain, and anemia; abdominal CT scan showed a large mass in the pancreas. Examination of the resected specimen revealed a fleshy, well-circumscribed, 7-cm mass. Histologically, there was a hypocellular to moderately hypercellular, bland spindle-cell proliferation admixed with a prominent infiltrate of lymphocytes, histiocytes, and plasma cells. The spindle cells were vimentin positive but negative for muscle markers; electron microscopy revealed only fibroblastic cells. DNA analysis revealed a diploid population with low S-phase fraction. The patient was well at 6-mo follow-up. It is important for the pathologist to be aware of the existence of this entity in unusual locations such as the pancreas so as to avoid a mistaken diagnosis of malignancy.
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PMID:Inflammatory pseudotumor of the pancreas. 870 1

1. Chronic fatigue syndrome is characterized by muscle fatigue and pain at rest, symptoms which are usually exacerbated with exercise. Although various studies have shown minor, non-specific morphological and biochemical changes in muscle of patients with chronic fatigue syndrome, no consistent defect has been identified. Some have suggested that an enteroviral infection in muscle may cause the chronic muscle fatigue seen in patients with chronic fatigue syndrome, with acute infection directly and irreversibly impairing mitochondrial function, and persistent infection depressing muscle protein synthesis and metabolism. 2. To clarify the involvement of enterovirus infection in chronic fatigue syndrome, muscle biopsies from a group of patients with chronic fatigue syndrome were examined for the presence of enteroviral RNA by reverse transcriptase-polymerase chain reaction techniques in relation to functional studies of muscle mitochondria and the muscle RNA/DNA ratio. 3. Fifty-eight percent of patients reported an uncharacterized 'viral infection' before the onset of their illness, but none of the muscle samples from 34 patients contained detectable amounts of enteroviral RNA. Muscle tissue had a general reduction in the RNA/DNA ratio and mitochondrial enzyme activities with no specific abnormality in the activity of enzymes encoded partially on the mitochondrial genome (cytochrome-c oxidase) or nuclear genome (citrate synthase, succinate reductase). 4. These data provide no evidence of an enteroviral infection in muscle of patients with chronic fatigue syndrome, although this does not exclude a role of enterovirus in initiating the disease process. The general reduction in RNA/DNA ratio and mitochondrial enzyme activities is consistent with a general reduction in habitual activity.
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PMID:Investigation by polymerase chain reaction of enteroviral infection in patients with chronic fatigue syndrome. 877 36

Patients with chronic fatigue syndrome (CFS) mainly complain of symptoms in the musculoskeletal domain (myalgias, fatigue). In 21 CFS patients the deep (muscle) versus superficial (skin, subcutis) sensitivity to pain was explored by measuring pain thresholds to electrical stimulation unilaterally in the deltoid, trapezius and quadriceps and overlying skin and subcutis in comparison with normal subjects. Thresholds in patients were normal in skin and subcutis but significantly lower than normal (hyperalgesia) in muscles (P < 0.001) in all sites. The selective muscle hypersensitivity corresponded also to fiber abnormalities at muscle biopsy (quadriceps) performed in nine patients which were absent in normal subjects (four cases): morphostructural alterations of the sarchomere, fatty degeneration and fibrous regeneration, inversion of the cytochrome oxidase/succinate dehydrogenase ratio, pleio/polymorphism and monstruosity of mitochondria, reduction of some mitochondrial enzymatic activities and increments of common deletion of 4977 bp of mitochondrial DNA 150-3000 times the normal values. By showing both sensory (diffuse hyperalgesia) and anatomical (degenerative picture) changes at muscle level, the results suggest a role played by peripberal mechanisms in the genesis of CFS symptoms. They would exclude the heightened perception of physiological signals from all districts hypothesized by some authors, especially as the hyperalgesia is absent in skin/subcutis.
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PMID:Sensory characterization of somatic parietal tissues in humans with chronic fatigue syndrome. 885 4

The mutations in one-third of both Duchenne and Becker muscular dystrophy patients remain unknown because they do not involve gross rearrangements of the dystrophin gene. Here we report the first example of multiple exon skipping during the splicing of dystrophin mRNA precursor encoded by an apparently normal dystrophin gene. A 9-year-old Japanese boy exhibiting excessive fatigue and high serum creatine kinase activity was examined for dystrophinopathy. An immunohistochemical study of muscle tissue biopsy disclosed faint and discontinuous staining of the N-terminal and rod domains of dystrophin but no staining at all of the C-terminal domain of dystrophin. The dystrophin transcript from muscle tissue was analyzed by the reverse transcriptase polymerase chain reaction. An amplified product encompassing exons 67-79 of dystrophin cDNA was found to be smaller than that of the wild-type product. Sequence analysis of this fragment showed that the 3' end of exon 70 was directly connected to the 5' end of exon 75 and, thus, that exons 71-74 were completely absent. As a result, a truncated dystrophin protein lacking 110 amino acids from the C-terminal domain should result from translation of this truncated mRNA, and the patient was diagnosed as having Becker muscular dystrophy at the molecular level. Genomic DNA was analyzed to identify the cause of the disappearance of these exons. Every exon-encompassing region could be amplified from genomic DNA, indicating that the dystrophin gene is intact. Furthermore, sequencing of these amplified products did not disclose any particular nucleotide change that could be responsible for the multiple exon skipping observed. Considering that exons 71-74 are spliced out alternatively in some tissue-specific isoforms, to suppose that the alternative splicing machinery is present in the muscle tissue of the index case and that it is activated by an undetermined mechanism is reasonable. These results illustrate a novel genetic anomaly that results in dystrophinopathy.
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PMID:A case of Becker muscular dystrophy resulting from the skipping of four contiguous exons (71-74) of the dystrophin gene during mRNA maturation. 886 44

Phosphofructokinase (PFK) is the key regulatory enzyme of glycolysis. Patients lacking the muscular isoform of PFK typically present with myopathy and compensated hemolysis (glycogenosis type VII or Tarui's disease). Since 1965 about 30 cases of muscular PFK deficiency have been reported. In most cases family history suggests a recessive inherited trait. We describe a family of Ashkenazi Jewish origin with two members in subsequent generations suffering from muscular PFK deficiency. The propositus, a 19-year-old male patient presented with weakness, myalgias and exercise intolerance since early infancy. His father also had early fatigue on exercise with myalgias; the mother and a 12-year-old brother were asymptomatic. Muscle biopsy of both the propositus and his father showed increased glycogen storage and absent histochemical stain for PFK. Biochemical studies of muscle revealed a markedly decreased PFK activity and DNA analysis of the muscle PFK gene revealed compound heterozygosity in both cases. This is the first description of proven muscle PFK deficiency (glycogenosis type VII) in two subsequent generations.
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PMID:Muscle phosphofructokinase deficiency in two generations. 888 Jun 99

A 42 year old patient was admitted for evaluation of a febrile state and left thoracic pain. Chest-X-ray revealed a left-sided pleural effusion nonresponsive to a trial antibiotic treatment. The subsequent punction yielded sterile exudate without microorganisms or malignant cells. Tuberculostatic treatment for suspected tuberculosis lead to exacerbation and hospitalization. Antibodies against native DNA first became detectable during the further course. Together with anamnestic information about fatigue, hair loss and the family history revealing two sisters touched by the disease, the diagnosis of systemic lupus erythematodes was made. Corticosteroids led to rapid improvement with complete resolution of the pleural effusion.
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PMID:[Febrile state and pleural effusion]. 892 82

Epididymal sperm counts, a common measurement in male reproductive toxicity studies, are routinely determined using a hemacytometer. Recently, computer assisted methods for automated sperm counts have been developed. In the present study we evaluated an automated system, the TOX IVOS (Hamilton Thorne Research, Beverly, MA) HTM-IDENT option, that utilizes a DNA-specific stain and fluorescence illumination to identify sperm for enumeration. Cauda and caput epididymal sperm counts were determined in 48 adult male Sprague-Dawley rats, using both the hemacytometer and HTM-IDENT. The mean hemacytometer and HTM-IDENT counts (+/- SD) were 250 +/- 43 and 254 +/- 52 million, respectively, for cauda sperm, and 123 +/- 13 and 127 +/- 18 million, respectively, for caput sperm. The average coefficient of variation using the hemacytometer was 13.8% as compared to 17.3% for the HTM-IDENT. Comparison of the machine count and a visual count from the Display Statics screen of the HTM-IDENT indicated that when two or more sperm heads touched or overlapped, the machine counted them as one. Manual (visual) and machine counts when compared over a range of nine concentrations from 3.7 to 47.8 million/mL differed by 4 to 12% at the lowest to highest concentration. The concentration of epididymal sperm samples used in comparing the two counting methods ranged from 5.8 to 17.7 million/mL. Therefore, the HTM-IDENT undercounting error attributable to sperm heads touching was less than 6%. Overall the data indicate good agreement between the HTM-IDENT and the hemacytometer counts. Furthermore, both counting time and technician fatigue were markedly reduced. Thus the HTM-IDENT option improves the efficiency of epididymal sperm counting without loss of precision.
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PMID:Comparison of rat epididymal sperm counts by IVOS HTM-IDENT and hemacytometer. 894 67

Uric acid is the end product of purine metabolism in human. Then, the enzymatic abnormalities, concerning purine metabolism, cause disorders of uric acid metabolism including hyperuricemia and hypouricemia. The superactivity of 5-phosphoribosyl-pyrophosphate (PRPP) synthetase and deficiency of hypoxanthine-guanine phosphoribosyltransferase (HGPRT) caused hyperuricemia. In glycogen storage diseases of type I, III, V, and VII, decreased energy supply induces hyperuricemia by accelerating ATP degradation. Deficiencies of xanthine oxidase (XO), purine nucleoside phosphorylase (PNP), and PRPP were reported causing hypouricemia. Many methods for DNA-diagnosis were developed including Southern blot, Northern blot, PCR-SSCP (polymerase chain reaction-single strand conformation polymorphism), PCR-RFLP (restriction fragment length polymorphism), and allele specific oligonucleotide hybridization etc.
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PMID:[Inherited disorders of uric acid metabolism--classification, enzymatic- and DNA-diagnosis]. 897 10


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