Research review: DNA polymerases as molecular markers of the regenerating capacity of hepatocytes

Hepatocyte regeneration has been widely investigated, with the mitotic index and the incorporation of [³H]thymidine being used as regeneration markers. We focused on the induction of DNA replication enzymes, particularly DNA polymerases (pol) α, δ, and ε. Using rat models, we have shown that the activity of pol α in crude liver extract well represents the regenerating capacity of hepatocytes. Using pol α as an indicator, we analyzed liver regeneration in rat models under various conditions: obstructive jaundice, external or internal biliary drainage, and the obstruction of portal vein branches. It has been revealed that the ligation of the common bile duct alone induces a certain amount of hepatocyte proliferation. It was striking that external biliary drainage suppressed regeneration capacity in cholestatic rat liver after partial hepatectomy. The strong regeneration in nonligated lobes induced by portal branch ligation was similar to the liver regeneration seen after partial hepatectomy with respect to the induction of DNA polymerases. Taken together, the aspects of DNA replication, particularly the induction of DNA polymerases, may contribute to shedding new light on the regeneration of human liver. This work was supported in part by a Grant-in-Aid for General Scientific Research and for Cancer Research from the Ministry of Education, Science and Culture, Japan, and by grants from the Uehara Memorial Foundation     

Radiographic study of osteoarthritic elbows in professional basebal pitchers

We examined radiographs of the elbows of the pitching arms of 79 professional baseball pitchers (mean age, 25.1 years; mean duration of professional career, 4.7 years) and noted the frequency and size of spurs, bone fragments, and intra-articular loose bodies according to site. The influence of duration of professional baseball career on these osteoarthritic changes was also investigated. The olecranon tip was the most frequent site of spurs (62/79; 78.5%), and fragmentation of the spur was detected in 17 joints. The frequency of spurs was also high at the medial margin of the olecranon, the tip of the coronoid process, the medial margin of the sigmoid notch, the medial margin of the trochlea and the olecranon fossa. In 38 subjects, spurs were observed at the distal portion of the radial notch of the ulna. However, few pitchers had osteoarthritic changes in the humeral capitellum or radial head. Intra-articular loose bodies were detected in 4 of 79 joints (5.1%), and bone fragments were present below the medial humeral epicondyle in 25 of 79 joints (31.6%). Osteoarthritic changes in the elbow joint appeared to be attributable mainly to traction stress and impingement associated with extension and valgus strain. Significant osteoarthritic changes were often found in professional pitchers whose careers exceeded 5 years.     

Coagulopathy in disseminated intravascular coagulation due to abdominal sepsis: determination of prothrombin fragment 1 + 2 and other markers.

To estimate the degree of coagulopathy in abdominal sepsis, we measured the plasma levels of prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin III complex (TAT) and plasmin-alpha 2-plasmin inhibitor complex (PIC) by the enzyme-linked immunosorbent assay in 38 patients with disseminated intravascular coagulation (DIC). In 20 patients with DIC due to abdominal sepsis, plasma levels of F1 + 2, TAT and PIC were 2.6 nmol/l, 27.9 micrograms/l and 1.5 micrograms/ml, respectively, with a mean antithrombin III (AT III) activity of 41.7%. F1 + 2, TAT, PIC and AT III levels were 4.7 nmol/l, 75.8 micrograms/l, 8.8 micrograms/ml and 70.9% in 18 patients with DIC as the result of malignancy. Though AT III levels in DIC due to sepsis were lower than those in DIC due to malignancy, the levels of F1 + 2, TAT and PIC in the former were not significantly more increased than those in the latter. The plasma levels of F1 + 2 were positively correlated with TAT and PIC in DIC patients with malignancy; however, there was no correlation between F1 + 2 and TAT or PIC in DIC patients with sepsis. In addition, the levels of serum albumin in the two groups were similar. These results suggest that activation of coagulation and fibrinolytic systems may not be so prominent in cases of DIC due to abdominal sepsis, compared to related events in DIC due to malignancy. It is also suggested that the depletion of AT III in cases of sepsis is not only caused by a consumption related to intravascular coagulation or to an alternate distribution of protein.(ABSTRACT TRUNCATED AT 250 WORDS)     

Granular cell tumors of the breast: A report of two cases

Granular cell tumors (GCT) are rare neoplasms, and only 173 cases of benign GCT of the breast have been documented. We report herein the cases of two patients with this tumor and discuss the methods of diagnosis and treatment. The first patient was a 60-year-old woman who presented with a firm ill-defined mass in her left breast. Mammography showed a dense shadow with spicula and skin thickness, and ultrasonography revealed a hypoechoic mass with an irregular border. Radical mastectomy was performed under the wrong preoperative diagnosis of breast cancer. The second patient was a 31-year-old woman who presented with an elastic-hard mass in her left breast. Mammography showed a well-demarcated dense mass, and ultrasonography revealed a well-defined hypoechoic mass with a large depth-width ratio. Fine-needle aspiration cytology (FNAC) showed a large number of histiocytic cells with abundant granular cytoplasm. An excisional biopsy was performed, and histological examination confirmed a diagnosis of GCT. GCT is benign, but often misdiagnosed as breast cancer both clinically and radiologically. Therefore, histological examination is essential for making a correct diagnosis, while FNAC is also useful. Local resection is still the treatment of choice, and surgeons should do their utmost to avoid performing needless radical mastectomy.     

Development of an animal model for neuroleptic malignant syndrome: heat-exposed rabbits with haloperidol and atropine administration exhibit increased muscle activity, hyperthermia, and high serum creatine phosphokinase level

The neuroleptic malignant syndrome (NMS) is a life-threatening complication of neuroleptic treatment. To elucidate the pathogenesis of NMS, an animal model has been developed. Experimental rabbits treated with haloperidol (1 mg/kg) by intramuscular injection, were studied for the diagnostic symptoms of increased muscle rigidity, elevated body temperature, and high serum creatine phosphokinase (CPK) level. Administration of haloperidol (1 mg/kg) and atropine (0.4 mg/kg), and exposure to high ambient temperature (35°C) induced a significant increase in electromyographic activity with muscle rigidity similar to that observed in patients with NMS. Such rabbits also showed elevated body temperature and serum CPK value. In addition to the similarity of the signs and symptoms, all parameters measured (muscle rigidity, body temperature, and serum CPK level) were normalized by dantrolene treatment. The effectiveness of dantrolene in the experimental animal partially confirms the validity of this animal model for NMS. This experimental animal model for NMS may be useful to elucidate the pathogenesis of NMS.     

Normal stomach wall and gastric cancer: evaluation with high-resolution operative US

Operative ultrasound examinations were performed using a 7.5-MHz transducer during nine operations for advanced gastric cancers and during six for early cancers. Normal stomach wall showed five layers that corresponded to histologic structures. Fourteen of 15 tumors, including nonpalpable early cancers, were localized with ultrasonography. In addition, both depth of penetration and lateral wall extension of the gastric cancers were precisely determined with this technique. Our preliminary results indicate that high-resolution operative ultrasonography may become a diagnostic aid during gastric cancer operations.     

Clinical experience with cefodizime in bacterial infection of children

Clinical studies were performed on cefodizime (THR-221, CDZM), a new cephem antibiotic as described below. CDZM was administered to 13 patients in dose levels ranging from 55 to 96 mg/kg/day t.i.d. for 3-7 days (5.5 days on average). These patients included 8 with pneumonia, 2 with tonsillitis, 1 each with bronchitis, phlegmon and urinary tract infection. The overall efficacy rate was 92.3%, i.e., efficacy was excellent in 8, good in 4 and poor in 1. Bacteriological efficacy was 83.3%, i.e., 5 strains of bacteria (Streptococcus pneumoniae 1, Haemophilus influenzae 3, Haemophilus parainfluenzae 1) were eradicated and 1 was unchanged (Enterobacter cloacae, MIC greater than 100 micrograms/ml). Clinical side effect was not observed during the treatment. Laboratory abnormalities were observed in 2 cases, i.e., a slight elevation of GPT and a mild eosinophilia. The above results suggest that CDZM is a useful antibiotic for treating pediatric bacterial infections.