Lipid analysis of normal dermis and hypertrophic scars

Hypertrophic scars (HS) are a consequence of abnormal wound healing. We examined fatty acids that are contained within, and participate in, every reaction through the membrane; then, we analyzed the percentage composition of the fatty acids in deepithelialized normal dermis (ND) and HS. In vivo HS samples were obtained from six patients undergoing surgical excision, and ND samples from five patients undergoing skin grafting surgery for excess. In vitro, cultured fibroblasts from HS and ND were also analyzed. The percentage composition of fatty acids extracted from all the samples was analyzed. In vivo, arachidonic acid (20:4) was significantly more abundant in HS than in ND, in the phospholipids from both whole tissue and cell membranes. In vitro, there were no significant differences among ND, HS, and 10% fetal calf serum. The results suggest that HS formation does not necessarily involve simple excess of 20:4; however, there are considerable differences in the percentage composition of 20:4 between ND and HS. Arachidonic acid probably participates in the formation and maintenance of HS, whereas in vitro cultured fibroblasts are affected largely by fetal calf serum.     

Repair of skin defect after extensive resection for penile cancer: report of two cases, and clinical observation of patients with penile cancer at Mie University hospital]

Case 1: A 48-year-old male with stage 4 penile cancer is reported. We used peplomycin (PEP) and cisplatinum (CDDP) for preoperative chemotherapy. Chemotherapy was effective. Radical surgery with bilateral inguinal lymphadenectomy was done and skin defect was covered with a skin flap. Case 2: A 61-year-old male with stage 4 penile cancer underwent radical surgery after modified MBD therapy with methotrexate (MTX), PEP and CDDP. Emasculation with skin resection and inguinal and pelvic lymphadenectomy were performed. The skin defect was deep and wide. It was covered with a glacilis myocutaneous skin flap. Distal end of the flap became necrotic. It was covered with tensor fascia lata myocutaneous flap. Seventeen patients with penile cancer were treated between 1972 and 1990 at Mie University Hospital. Nine patients were in stage 1, 4 stage 2, 1 stage 3, 3 stage 4. Treatment consisted of surgery (3), surgery+chemotherapy (10), surgery+chemotherapy+irradiation (2), chemotherapy+irradiation (1), and surgery+irradiation(1). Cancer death was observed in 2 cases (stage 2), 2 patients died of other diseases, 10 are alive, and 3 patients were lost to follow up.     

Clinical study on low body temperature in health subjects

During last year, 931 men aged 51.0 +/- 9.5 years participated in our hospital's 3-day health screening. Their axillary temperature were taken 3 times per day (twice each, at 6:00 a.m., 2:00 p.m. and 6:00 p.m.) during their 3-day stay and the mean axillary temperature was determined for each subject. In 72 among all subjects, the mean axillary temperature was below 36 degrees C. These 72 subjects were classified as low-temperature individuals with normal temperature below 36 degrees C. This study was designed to compare low-temperature subjects with mean axillary temperature, on various factors, such as age, degree of obesity, liver function, renal function, lipids, electrolytes, and biochemical data (blood glucose, serum amylase, and CPK). This study also included seasonal changes in these low-temperature subjects. The following results were obtained. 1) Age was most closely related to low-axillary temperature, and the degree of obesity (modified Broca-Katsura method) had second significant relation. The low-axillary temperature was in common in subjects over 60 years and was also common in obese subjects, regardless of their age. 2) No seasonal effect was observed with low-temperature subjects. 3) Only the age and the degree of obesity (modified Broca-Katsura method) showed negative correlation independently with the mean axillary temperature. (For age, the correlation coefficient was Y = -0.006539X + 36.491, while for obesity it was Y = -0.004536X + 36.203.) Therefore the older and the more obese the subjects, the lower the mean axillary temperature.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of zinc and other divalent metals on deoxyribonucleic acid binding and hormone-binding activity of human alpha 1 thyroid hormone receptor expressed in Escherichia coli

Full-length human thyroid hormone receptor alpha 1 (hTR alpha 1) was expressed in Escherichia coli using a T7 expression system. While present in large amounts, the receptor was highly enriched in the insoluble fraction after cell lysis. We describe here the successful solubilization and refolding of the expressed receptor in a functional form in the presence of Zn2+. Using a DNA-cellulose binding assay and gel shift assay, we found that treatment of expressed receptor with 1 mM EDTA in the denaturing agent (5 M guanidine-HCl) results in the formation of aporeceptor that does not specifically recognize target DNA, while it does retain T3-binding activity. This aporeceptor recovered DNA-binding activity by adding Zn2+ during refolding. Zinc-induced restoration of DNA-binding activity occurred in a dose- and time-dependent manner. Moreover, once recovered, this DNA-binding activity persisted without Zn2+, even in the presence of 1 mM EDTA. These data indicate that the hTR alpha 1 molecule has a high affinity for Zn2+, and this metal coordination is essential for proper folding of TR protein into its native active structure.     

A case of renal schwannoma

A case of renal schwannoma is presented. A 51-year-old female was admitted to our hospital because of a left renal mass on April, 16, 1987. A drip infusion pyelogram showed encasement of the lower and medial calyx. An abdominal CT-scan showed a 2.5 cm mass with irregular density. Selective left renal arteriography showed the hypovascular tumor of the left kidney. Transperitoneal radical nephrectomy was performed on May, 1, 1987. Histological diagnosis was renal schwannoma arising from renal pelvis. The patient was well without recurrence 20 months after operation. Our present case is the 12th case of renal schwannoma reported in the English and Japanese literature.     

Concentration of cefotaxime and its metabolite in human bone marrow blood

Cefotaxime (CTX) was intravenously administered in an amount of 2.0 g to each of 34 adult patients before the surgery mainly of the hip joint. Samples of the blood from the bone marrow around the trochanter were taken at the time of the operation. At the same time blood samples were taken from peripheral veins. The sample was centrifuged and the supernatant was analyzed for CTX and desacetyl-CTX. The concentration of CTX in the marrow blood was 150.9 micrograms/ml and that in the blood was 182.5 micrograms/ml in the earliest samples taken at 20 minutes after injection. In the 44 pairs of samples, the concentration of CTX in the marrow blood was lower than that in the peripheral blood in all the cases except 4. The concentration of desacetyl-CTX (Des-CTX), however, in the marrow blood was higher than in the peripheral blood in 33 of the 44 pairs of specimens. Since the degradation of the drug progresses with time, the ratio of Des-CTX to CTX increased with time. This trend was particularly marked in the bone marrow blood and can be expressed as Y = 113.0 + 0.32 t, when Y is the ratio percentage (Des-CTX/CTX) and t is time after the injection of the drug in minute. Thus, CTX transferred into the bone marrow tends to remain there and transformed into the desacetyl form.     

Regulation of the acid-labile subunit of the insulin-like growth factor ternary complex in patients with insulin-dependent diabetes mellitus and severe burns

OBJECTIVE Little information is available regarding the regulation of serum acid-labile subunit (ALS) in human disease. We have studied alterations in serum ALS of the insulin-like growth factor (IGF) ternary complex in children with untreated insulin-dependent diabetes mellitus (IDDM) and subjects with severe burns before and after insulin therapy. In addition, we have investigated the effect of insulin plus GH on serum ALS in burn patients. DESIGN Serum samples were obtained from children with newly diagnosed and untreated IDDM before the initiation of insulin therapy and 1 month thereafter. Serum samples were also obtained from adult patients with severe burns who were on a continuous infusion of a carbohydrate-rich enteral diet via nasogastric and duodenal catheters under basal conditions, after a 1-week period of continuous insulin infusion, and after an additional week of insulin plus recombinant GH. PATIENTS Twenty children and adolescents with untreated IDDM, aged 1.2–16 years, and 6 young adult patients with severe burns aged 17–28 years were studied longitudinally. Control sera were obtained from age, sex and pubertal status matched subjects (for children with IDDM) and from fed healthy adults. MEASUREMENTS Serum insulin, GH, cortisol and IGF-I were measured by radioimmunoassay, and serum ALS levels were assessed by Western immunoblot before and after treatment periods. RESULTS Serum ALS levels were lower in untreated children with IDDM (69 ± 6% of control children). Insulin therapy significantly increased serum ALS (79 ± 5%, P<0.05) in these children. Patients with severe burns also had lower serum ALS levels (79 ± 10% of control adults). After one week of insulin therapy serum ALS levels increased to 90 ± 15% of control values (P<0.05). Addition of GH to insulin therapy for another week did not significantly further increase serum ALS levels (95 ± 27%). Serum IGF-I concentrations increased nearly 2.5-fold in diabetic subjects and fourfold in burn subjects at the end of the study periods. There were no proteolytic fragments of ALS in the sera studied. The deglycosylation pattern of ALS did not differ between diabetic and control sera. CONCLUSION Serum ALS levels were diminished in children with untreated IDDM and were partially restored after the initiation of insulin therapy. Serum ALS levels were also diminished in patients with severe burn injury and restored by insulin treatment. Addition of GH to insulin therapy did not significantly increase serum ALS levels over levels obtained during insulin therapy alone. These decreases in serum ALS were smaller than the decrease in serum IGF-I concentrations in both conditions, suggesting that IGF-I is the limiting factor for the ternary complex formation in the catabolic states. Insulin may regulate circulating ALS levels in catabolic states and helps to restore the IGF system.     

Responsiveness of human gastric tumors implanted in nude mice to clinically equivalent doses of various antitumor agents

To reproduce clinical effects of various antitumor agents in the human tumor/nude mouse model, we investigated the responsiveness of 11 lines of human gastric tumor xenografts to doses of the agents pharmacokinetically equivalent to the respective clinical doses, which we designated the "rational dose" (RD). We found that the response rates to mitomycin C, 3-[(4-amino-2-methyl-5-pyrimidinyl]methyl-1-[2-chloroethyl]-1- nitrosourea (ACNU), adriamycin, 5-fluorouracil were 18%, and that to vinblastine was 30%; on the other hand, those to vincristine, methotrexate, and cyclophosphamide were poor. In contrast, in our previous study using the maximum tolerated doses, response rates to mitomycin C, ACNU, and vinblastine were as high as 64-82%, and those to adriamycin and 5-fluorouracil were 18%. When these results were compared with the clinical response rates of gastric tumors, as a whole, the results with RD's exhibited much better coincidence with the clinical data in terms of relative therapeutic potency, indicating the validity of the use of clinically equivalent doses instead of maximum tolerated doses in the human tumor model.