A case of Hashimoto's thyroiditis with antibodies to thyroid hormone analogues.
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Biomedical subjects
Publications and source records attributed to S Wada.
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The potential reversibility of glandular stomach lesions induced by the clastogen, catechol, was examined in groups of male F344 rats treated continuously with 0.8% catechol in the diet for 12, 24, 48, 72, or 96 weeks. After a return to basal diet for 84, 72, 48, 24, and 0 weeks, respectively, the animals were killed for histopathological examination. Incidences of submucosal hyperplasia, adenomas and adenocarcinomas, average number of tumors per rat, and the size of tumors in rats treated with catechol for 12, 24, 48, 72, and 96 weeks increased time dependently. After cessation of catechol treatment, although average number of tumors per rat slightly decreased, the size of tumors tended to increase. Labeling indices in both tumorous and nontumorous areas decreased after cessation of catechol treatment. The results thus indicate that whereas some submucosal hyperplasias or adenomas may regress, others have the potential to develop into adenomas or adenocarcinomas. However, tumor growth does depend to a certain extent on continued catechol treatment.
The authors examined interleukin-2 (IL-2) production and interferon gamma (IFN gamma) production of peripheral blood mononuclear cells in 28 patients with renal cell carcinoma and 17 control subjects. The peripheral blood was obtained prior to the initiation of therapeutic procedures. The patients were divided into two groups according to tumor size, less than or equal to 5 cm and greater than 5 cm. The production of IL-2 and IFN gamma was measured by immunoradiometric assay. As a result, in the patients with tumors greater than 5 cm, IL-2 and IFN gamma production was impaired. However, in the patients with tumors less than or equal to 5 cm, IFN gamma production was enhanced, though IL-2 production was not significantly different from that of the control subjects. There was no significant correlation between IL-2 production and IFN gamma production.
We investigated the effect of combination therapy with interleukin 2 (IL-2) and cyclophosphamide (CPM) in C3H/HeN mice implanted with mouse bladder tumor cells (MBT2). MBT2-bearing mice were treated with a single intraperitoneal injection of 120 mg/kg CPM on day 10 and/or subcutaneous administration of 5 x 10(4) units IL-2/day from day 11 to day 20. As a result, the growth of tumor in mice treated with IL-2 alone was slightly suppressed. On the other hand, regression was observed in all mice treated with CPM alone, although regrowth of tumor was seen in all of them. However, when IL-2 was administered with CPM, regrowth of tumor was completely suppressed. An immunologic study was done that showed cytotoxicity against YAC-1 and P815 in the spleen cells was suppressed in mice treated with CPM alone, but that both recovered to control levels when IL-2 was administered with CPM. Cytotoxicity against MBT2 in the spleen cells was most elevated in mice treated with both IL-2 and CPM. These findings suggested that clinical evaluation of combination therapy with IL-2 and CPM may be worthwhile.
A two-dimensional electrophoretic system using SDS-polyacrylamide gel electrophoresis (SDS-PAGE) in the first dimension and isoelectric focusing (IEF) in the second dimension was devised. In spite of its simplicity, this method could show a markedly high resolution for tubulin isoforms and moreover could classify them into alpha- or beta-tubulin as a two-dimensional profile. With this method, seven alpha- and four beta-tubulin isoforms could be detected within axoneme from Tetrahymena cilia. Moreover this method could also resolve tubulin isoforms from the rabbit brain. These results indicate that the present two-dimensional gel electrophoresis is a useful tool for the electrophoretic analysis of tubulin isoforms from various sources.
Thymus lymphocyte subsets in uraemic rats were studied using monoclonal antibodies. Severe and moderate uraemia was induced in rats, and sham-operated and normal rats were used as the controls. As a result, the weight of the thymus decreased in uraemic rats. As for lymphocyte subsets, the frequency of W3/25+OX8+ decreased and those of W3/25-OX8-, W3/25+OX8- and W3/25- OX8+ relatively increased in uraemic rats. All these changes were more significant in severely uraemic than in moderately uraemic rats. When thymosin fraction 5 (TF5) was administered to severely uraemic rats, the weight of the thymus increased and the lymphocytes subsets normalized. These results suggest that uraemia may cause a maturational impairment of thymus lymphocytes by the depression of thymic hormone secretion.
A 16-year-old girl with anorexia nervosa first presented with malnutrition, liver dysfunction, and rhabdomyolysis. Administration of fluid and nutrition saved her from the initial critical state, but acute renal failure followed. Laboratory examination revealed intrinsic renal failure induced by rhabdomyolysis. Latent phosphate depletion and refeeding-induced hypophosphatemia was implicated as the cause of rhabdomyolysis; however coexisting hypotension, dehydration, and liver dysfunction may have contributed to the renal failure. The patient recovered from azotemia by hemodialysis. This is the first reported case of anorexia nervosa with acute renal failure resulting from rhabdomyolysis induced by hypophosphatemia or phosphate depletion.
Hypercalcemia occurred in a patient with non-Hodgkin's (B-cell type) lymphoma when generalized lymphadenopathy developed. Despite low normal plasma parathyroid hormone (PTH), nephrogenous cAMP (NcAMP) was not suppressed, and serum and urine PTH-related protein (PTH-rP) levels were elevated. The plasma level of 1,25(OH)2D was within normal range. The combined chemotherapies successfully reduced the tumor size, serum Ca, PTH-rP, and lactic dehydrogenase. Serum osteocalcin was suppressed while the patient was hypercalcemic, and increased after chemotherapy. In the extract of the tumor tissue obtained post mortem, bioactivity stimulating the production of cAMP in osteoblasts was demonstrated along with the immunoreactive PTH-rP. This is the first report of a B-cell lymphoma producing PTH-rP and its association with humoral hypercalcemia of malignancy.
The case of a brain-dead patient with complex movements of the extremities (Lazarus' sign) is reported. This is the first description in the literature of short-latency somatosensory evoked potentials (SSEP's) following median-nerve stimulation by a noncephalic reference method. The scalp P14 wave (a far-field positivity with a peak latency around 14 msec that originates from the cervicomedullary junction) disappeared, and the spinal N13 wave (a near-field negativity with a 13-msec peak recorded on the posterior neck and generated by the cervical dorsal horn) was preserved. Respiratory-like movement was also seen in this case. The SSEP. findings support the hypothesis that both Lazarus' sign and respiratory-like movement have a spinal origin.
Bladder tumors were induced in rats by the oral administration of 0.025% N-butyl-N-(hydroxybutyl) nitrosamine (BBN). In order to study the suppressive effects of rat interferon-alpha (IFN-alpha) on induction of carcinogenesis in vivo, rats were treated with IFN-alpha i.m. twice a week. The treatment began at 5th week of BBN administration. The bladder mucosa was observed macroscopically and microscopically, and NK activity was examined. The results were as follows. 1) There was no significant difference in the bladder to body weight ratio between the BBN + IFN-alpha and BBN groups in during stage A (10th-14th week when changes in the mucous membrane such as hypertrophy in the bladder wall or vascular formation are observed). This ratio in the BBN + IFN-alpha group was less than that in the BBN group in during stages B and C (15th-19th week and 20th-30th week respectively when tumors are visually recognizable). 2) The rate of carcinogenesis in the BBN + IFN-alpha group was less than that in the BBN group in stages A and C. 3) The pathological grade and stage of the bladder cancer in the BBN + IFN-alpha group were lower than those in the BBN group in stages B and C. 4) There was no significant difference in NK activity between the two groups in stage A, but NK activity of the BBN + IFN-alpha group was higher than that of the BBN group in stage B. 5) These findings substantiated the hypothesis that IFN-alpha can suppress tumor-growth in BBN induced bladder carcinoma.
A very rare case of gliosarcoma with von Recklinghausen's disease is presented. A 51-year-old man was admitted to our hospital in March 1990, because of a 2-month history of personality change and left hemiparesis. Multiple neurofibroma over his whole body with many café au lait spots had been present since early childhood. His mother, brothers and children also had café au lait spots. Neurological examination on admission revealed memory disturbance, left homonymous hemianopsia and left hemiparesis. CT scan showed a large lobular lesion in the right temporoparietal region. The medial hypodense part was sharply demarcated by a ring-like enhancement, while the lateral isodense part was homogeneously enhanced. MRI showed a sharply demarcated high intensity lesion with Gd-EDTA enhancement corresponding to the enhanced area on CT. Faint staining on angiography revealed that the blood supply to the tumor was predominantly dural. At surgery, the tumor was solid and highly vascular, and adhered tightly to the dura. The superficial part of the tumor was well demarcated from the brain tissue, but the demarcation was obscure in the deeper part. Histological findings showed two clearly defined neoplastic components: a gliomatous component that was stained for GFAP, and a sarcomatous component that had spindle-shaped nuclei and eosinophilic fibers. The patient underwent radiotherapy after surgery, but the tumor soon recurred. A second operation was performed, but the tumor had infiltrated into the scalp and he died 10 months after the first operation. This combination is very rare and has not been reported previously.
A 74-year-old male with the chief complaint of painless enlargement of a mass in the scrotum was diagnosed as having a giant epidermoid cyst on July 8, 1991. He had no past history of injury or pain of the scrotum. Magnetic resonance imaging (MRI) of the scrotum demonstrated a well-circumscribed homogeneous mass, and was distinguished from both normal testes. Under the diagnosis of intrascrotal epidermoid cyst, the mass was resected surgically. The mass measured 23 x 15 x 15 cm, and it contained liquids. The pathological diagnosis was epidermoid cyst of the scrotum.
A clinical trial using interferon alpha 2b (IFN alpha-2b) for prophylactic therapy was done on 44 patients who had received nephrectomy for renal cell carcinoma. Principally, the daily intramuscular injection of 3 of 6 million units of IFN alpha-2b was done for 4 consecutive weeks after 2 weeks postoperatively and thereafter followed by injection once every 2 weeks. The clinical evaluation was done for the recurrence rate, the survival rate, the IFN alpha and IFN gamma producing ability, the activity of 2',5' oligoadenylate synthetase (2-5AS) and the side effect. Out of 44 cases entered, 42 were completely evaluable and recurrence was observed in 5 (11.9%) of the 42 cases. The recurrence rate was 5.5% and 16.4%, at the first and second year, respectively. Three (7.1%) of the 42 patients died. The survival rate was 97.6% at the first year, 89.7% at the second year for the followup study. The IFN alpha producing capacity was low in all of the 4 evaluable cases. The IFN gamma producing capacity was high in 3 cases and normal in 1 case. 2-5AS, the enzyme produced by IFN, was activated by IFN alpha-2b administration in all of the 4 evaluable cases. Side effects were observed in 24 (54.5%) of the 44 cases. The main side effect was fever. Leucopenia, general fatigue, appetite loss, temporary elevation of liver transaminase were also observed. However, there were only 5 cases (11.4%) in which administration of IFN alpha-2b had to be discontinued.
The antitumor activity of combination therapy of recombinant human tumor necrosis factor alpha (rHu-TNF alpha) and chemotherapeutic agents against murine bladder tumor (MBT-2) was studied. Tumors were intradermally transplanted into the hind leg of C3H-HeN mice and allowed to grow until they reached a diameter of 8 to 10 mm 10 days after transplantation. TNF (3,000 units) was given intraperitoneally from day 10 to day 19, and the chemotherapeutic agents, 5-FU (60 mg/kg), CPM (100 mg/kg), CDDP (10 mg/kg) and ADM (5 mg/kg), were applied once intraperitoneally on day 10. The antitumor effects were evaluated based on tumor volume on day 20. 5-FU, CPM and ADM enhanced the antitumor effect when combined with TNF, but CDDP did not. These findings suggest that combination therapy of TNF and certain antitumor chemotherapeutic agents is effective cancer treatment.
To treat superficial bladder cancer or invasive bladder cancer presenting as a solitary tumor, conservative therapy such as transurethral resection of bladder tumor or partial cystectomy has long been carried out. We studied the effect of 1-hexylcarbamoyl-5-fluorouracil (HCFU), and the effects of the combination of HCFU and 2.5-di-O-acetyl-D-glucaro-(1-4)(6-3) dilactone (SLA) which is an anti-beta-glucuronidase agent, for preventive therapy. In the patients treated with HCFU, the recurrence rate was 3.6% and 26.6% one year and two years, respectively, after conservative operation. In the patients treated with both SLA and HCFU, the recurrence rate was lower than in those treated with HCFU one year or more after conservative operation, and a long-term preventive effect was expected for nondrinkers.
Hyperbaric chamber dives at 19 ATA with helium-oxygen were performed at the Japan Marine Science Technology Center, Yokosuka, from January 31 to February 2 in 1990. During simulated underwater experiments, event-related potentials were recorded in 2 divers for assessment of the cognitive function. Although the P300 amplitude of the potentials did not show any significant change, its latency was clearly prolongated and this prolongation continued to when the decompression reached to 70 m below sea level. These findings indicated that the hyperbaric environment corresponding to 180 m below sea level or less must cause some cognitive dysfunctions and that P300 is useful for early detection of those dysfunctions or HPNS.
The effect of prostaglandin F2 alpha (PGF2 alpha) was investigated in MC3T3E1 cells on the succeeding cAMP response to parathyroid hormone (PTH). PGF2 alpha increased the membrane-associated protein kinase C (PKC) activity, indicating the activation of this enzyme. The effect of PTH to increase cAMP production was enhanced by pretreatment with PGF2 alpha. Phorbol 12-myristate 13-acetate also enhanced cAMP production stimulated by PTH, and PKC inhibitor H7 attenuated the enhancement of PGF2 alpha. A23187 did not reproduce the PGF2 alpha effect, and this effect was not antagonized by the calmodulin antagonist W7. PGF2 alpha did not change the ED50 nor the maximally responsive dose of PTH in stimulating cAMP production. The effect of PGF2 alpha was not affected by pertussis toxin, and PGF2 alpha also enhanced cholera toxin- or forskolin-stimulated cAMP production. In accordance with the response of cAMP to PTH, the resorption of mouse limb bones stimulated submaximally by PTH was enhanced by the concomitant presence of PGF2 alpha. These results indicate that PGF2 alpha modulates cAMP response through the activation of PKC, the target of which might be the catalytic unit of adenylate cyclase. Such interaction between signal transduction systems may have significance in modulating the effect of PTH on bone, i.e., bone resorption.
Inhibitory activity on renal membrane adenylate cyclase (AC) has previously been found in the extract of a pancreatic cancer associated with humoral hypercalcemia of malignancy (HHM). AC inhibitor was purified employing inhibition of AC activity of renal membrane stimulated by forskolin as its index. N-terminal 9 residues and a digested fragment of purified protein (14 residues) were completely consistent with that of histones H1b and H1d. Not only histone H1 but also histones H2A, H2B and H3 from calf thymus inhibited AC activity. These results indicate that the AC inhibitor in the pancreatic cancer extract is histone H1b or H1d and histones H2A, H2B and H3 also have an AC inhibitory activity.