Differential effects of acetaminophen pretreatment on hepatic aflatoxin B(1)-DNA binding, cellular proliferation, and aflatoxin B1-induced hepatic foci in rats and hamsters.

Effects of acetaminophen (AAP) pretreatment on hepatic aflatoxin B1 (AFB(1))-DNA binding, cellular proliferation, and AFB(1)-induced glutathione S-transferase placental form (GST-P) positive hepatocytes and foci have been examined in young male rats and hamsters. Intraperitoneal (i.p.) dosing of 600mg AAP 3h before AFB(1) i.p. injection showed three-fold more AFB(1)-DNA binding in hamsters and 40% less binding in rats. Cell proliferation analyzed by bromodeoxyuridine incorporation was not significant (0.4-0.6%) 24-96h after AAP (600mg) treatment of rats; however, proliferation was stimulated and was maximum (11%) in hamsters at 72h after AAP treatment. Dosing of rats with AFB(1) alone at 0.5 or 2.5mg level gave an appreciable number of GST-P positive minifoci (two to nine cells) with a few foci larger than 100 microm; pretreatment with AAP (300 or 600mg) 48h before 0.5 or 2.5mg AFB(1) had no effect on the number and focal area of foci. In hamsters, 1 or 2mg AFB(1) alone yielded GST-P positive hepatocytes without any minifoci. Pretreatment with AAP (600mg) 48 or 72h before 1 or 2mg AFB(1) produced increases in both GST-P positive hepatocytes and minifoci. Thus, marked changes are observed after AAP pretreatment in hamsters compared to rats.

Malignant gastrointestinal stromal tumor showing remarkable whorl formations.

A case of malignant gastrointestinal stromal tumor (GIST) is reported. Histologically, spindle cell proliferation with remarkable whorl formations was predominant in the tumor. Immunohistochemically, the tumor cells were diffusely positive for CD117 (c-Kit) and vimentin and partially positive for CD34. Ultrastructurally, the desmosome-like structures and interdigitations occurred much more frequently in the areas with whorl formations. These organelles were considered to be closely associated with the whorl formations. Various kinds of cellular arrangements are revealed in GISTs, but remarkable whorl formations, such as in our case, are a rare variant pattern. Herein, we discuss the histopathologic differences between this and other tumors showing whorl formations and describe the meaning of this unique arrangement. GISTs are thought to be immature tumors, and, therefore, variations in histopathologic findings are recognized. Finally, the ultrastructural study of GISTs is useful for understanding the mechanisms forming whorl formations and the differentiation or pathogenesis of GISTs.

Histochemical study of human cremaster in varicocele patients.

Despite the cremaster's important role in thermoregulation, few morphological and biochemical studies of this muscle in humans have been reported, probably due to limitation of sampling. To gain further insight into the pathology of varicocele, the authors studied the histochemical changes of the cremaster from patients with varicocele. Cremaster was obtained from patients with male infertility and varicocele, grades 1-3. The samples were studied using routine histochemical stains. Fiber size variability and type I predominance were observed in all varicocele cases regardless of the grade, and also in control specimens. Muscle from patients with grades 2 and 3 varicocele showed small group atrophy. It would appear that the hemostasis associated with local tissue edema and hypoxemia may lead to nerve damage and denervation of the cremaster. If denervation of the cremaster persists despite the correction of varicocele, thermoregulation would remain disrupted.

Relationship between the states of spinal impact injuries and magnetically evoked EMGs in rats.

The relationship between the states of spinal impact injuries and magnetically evoked electromyograms (EMGs) were studied in rats. Impact injuries to the spinal cord were induced at a depth of 0.25-2.0 mm by insertion of a cylinder tip measuring 2 mm in diameter into the lumbar vertebrae L1-L2. Magnetically induced electromyograms for the brain and lumbar vertebrae L4-L5 were recorded from the tibialis anticus and the gastrocnemius muscles. H-reflex was not induced by the spinal cord injury (SCI) at a depth of 0.25 mm, although motor evoked potential (MEP) was observed. Continuous waves following the M-response were observed in the SCI at a depth of 0.25 mm. Elevation of the threshold, reduction of its latency and decrease in amplitude of the M-responses were observed at an injury depth of 0.5 mm or deeper. With SCI magnitude from mild (0.5 mm depth) to severe (1.0 mm depth), the amplitudes of the M-response were decreased, and the latency of the M-response was shorter than that of the control. The F-response was accelerated in severe SCI. Our results indicated that there was a relationship between extensive injury legions and the H-reflex F- and M-responses in magnetically evoked EMGs. Magnetically evoked EMGs are useful for monitoring the states of SCI.

Changes in spinal cord function caused by injuries at different levels of the lumbar spinal cord.

We examined the impact of spinal cord injury to a depth of 0.5 mm at L1-L2 (upper lumbar cord injury) and in L6-S1 (lower cord injury) in Wistar rats. Upper lumbar cord injury resulted in the disappearance of the motor evoked potential (MEP) of the gastrocnemius muscle during transcranial magnetic stimulation, while the threshold was decreased in rats with lower cord injury. During magnetic stimulation of L4-L5, the M-response threshold was decreased in rats with upper lumbar cord injury, while the amplitude was increased. In lower cord injury, the pattern of H-response recruitment curves differed from that in controls. Our results indicated that MEP and the spinal reflex are influenced not only by upper lumbar cord injury but also by lower cord injury.

[A case of glomangioma of the stomach].

Glomus tumor of the stomach is still a rare disease. In Japan, till now, only 78 cases have been reported as far as we look over the literatures. We report a case of glomangioma of the stomach. The patient is a 44-years old female who underwent a medical examination and pointed out a gastric submucosal tumor, but she had no symptoms and admitted for operation. The endoscopical finding was a submucosal tumor as large as 4 cm, and the result of biopsy was chronic atrophic gastritis. So typical gastrectomy was performed without a definite diagnosis. In the cross section, the tumor was clearly bounded gastric mucosa by a white membrane, and the center of the tumor was spongy. By patho-histological and electro-microscopic study, we diagnosed that the tumor was glomangioma in the classification of Weiss & Enzinger. The patient was getting on well after the operation and left the hospital on the 29th day.

Sensorimotor polyneuropathy associated with chronic lymphocytic leukemia, IgM antigangliosides antibody and human T-cell leukemia virus I infection.

A 65-year-old man presented with a sensorimotor polyneuropathy associated with B-cell chronic lymphocytic leukemia (CLL) and immunoglobulin M (IgM) antibody to various gangliosides. Electrophysiological studies denoted significant abnormalities of motor and sensory nerve conduction. Although the pathology of sural nerve biopsy looked minimally affected, immunohistochemical studies showed specific binding of IgM to the human peripheral nerve. Our patient also had high titer of antibody to human T-cell leukemia virus I (HTLV-I) in both serum and cerebrospinal fluid (CSF), which might activate B-cell-mediated immunity and facilitate the production of IgM antibody. The other unique feature is the reactivity of antibody to gangliosides. The patient had IgM antibody reactivities to gangliosides with disialosyl residue such as GT1b, GQ1b and GD3, but not to GD1b. IgM antibody to gangliosides with disialosyl residue has been reported in ataxic symptoms, but our patient failed to demonstrate ataxia. Without reactivity to GD1b, sensory ataxic neuropathy might not develop even in the presence of antibody reactive to other gangliosides with disialosyl residue.

Simple and reproducible model of rat spinal cord injury induced by a controlled cortical impact device.

Consistently reproducible experimental trauma was inflicted on the rat spinal cord (L3-L4) employing a controlled cortical impact device. The spinal cord was injured with one of three sizes of chips; thick (3 mm diameter), medium (2 mm diameter), thin (1 mm diameter). Each chip was applied at 1, 2 and 3 mm deformation depths. The correlations of the magnitude of the primary trauma were examined histopathologically. It was found that the extent and intensity of the trauma could be changed by altering the depth of deformation and the chip diameter at a fixed velocity of 4.6 m per sec. The injury caused by the 2 mm diameter chip at 0.5 mm-deformation damaged one to two segments of the perifocal spinal cord. In the surviving animals, the histological changes could be classified as primary, secondary, and late phase changes, and finally the lesion became a cavity. This study reports the application of a controlled cortical impact device to morphological research on a spinal cord injury. We found that the injury by the 2 mm chip at 0.5 mm deformation was the most advantageous and reproducible model for further investigations.

Magnetically induced motor evoked potentials and H-reflex during nembutal and ketamine anesthesia administration in rats.

The effects of nembutal and ketamine anesthesia on motor evoked potentials (MEPs) and spinal segment reflex (H-response, F and M waves) were investigated in rats by magnetic stimulation. These potentials were generated by magnetic stimulation of the motor cortex and the spinal cord (L4-L5). After application of nembutal, MEP and H-response decreased in amplitude, eventually disappearing. The amplitudes of F and M waves increased and persisted at the increased levels during anesthesia. The latencies of F and M waves were constant before and after anesthesia. Following ketamine administration, the threshold, latency and amplitude of the magnetically induced MEPs, and M, F and H responses were not influenced systematically. The results suggested that MEPs and H-response depression and/or disappearance due to synaptic site suppression after nembutal anesthesia, and the increase and persistence of increased F and M waves amplitudes were all due to the increasing motoneuron excitability, whereas ketamine did not affect synaptic sites subjected to magnetic stimulation.

[The immunoreactivity studies of the idiopathic inflammatory myopathy over the past three years in our laboratory].

Biopsied skeletal muscles from patients with inflammatory myopathy (6 cases of polymyositis (PM), 2 cases of dermatomyositis (DM), 5 cases of collagen disease with polymyositis and a case of allergic granulomatous angitis) were examined by comparing immunostained infiltrated cells at perivascular, perimysial and the endomysial sites as well as examining the histochemical findings on serial frozen sections from cases examined by our laboratory over the past three years. CD68 was used for macrophage, L26 for B lymphocytes, CD4 and CD8 for T lymphocytes. Expression of HLA-ABC was examined for Class I antigen and HLA-DR for Class II antigen on the muscle fibers. Many macrophages and CD8-positive T lymphocytes had infiltrated the endomysium in PM. Many CD4-positive T lymphocytes and L26-positive B lymphocytes had infiltrated perivascular sites in DM. These results were almost the same as those in many other reports. HLA-ABC was positive on the muscle sarcolemma in all cases. However, the expression of HLA-DR was not identical in all cases. It is useful to determine the diagnosis and consider a pathogenesis of inflammatory muscle diseases to analyze the infiltrated cells and the site of infiltration even in case showing few of infiltrating cells and necrotic fibers.

[An experience of treatment of double positive myeloperoxidase-antineutrophil cytoplasmic antibodies (MPO-ANCA) and anti-glomerular basement membrane antibodies in Goodpasture's syndrome onset of crescentic glomerulonephritis].

A 68-year-old woman was admitted to Kinki University Hospital because of progressive renal failure. She had been well until two months before admission. Laboratory data were as follows: serum creatinine 4.1 mg/dl, BUN 69 mg/dl, MPO-ANCA 33 EU, anti-glomerular basement membrane antibodies (AGBMA) 118 U. Histological findings showed cellular and fibrocellular crescents in many glomeruli. Therefore, we diagnosed rapidly progressive glomerulonephritis (RPGN) due to MPO-ANCA and anti-GBM associated renal disease. The patient was started on prednisolone and double filtration plasmapheresis (DFPP) therapy. Subsequently, the values of MPO-ANCA and AGBMA decreased. However, the patient's condition suddenly worsened and she died of interstitial pneumonia. Autopsy examination revealed crescentic glomerulonephritis and alveolar hemorrhage with linear deposition of IgG along the glomerular and alveolar capillary walls by immunofluorescence studies. We considered this to be a rare case of Goodpasture's syndrome associated with not only anti-GBM antibodies, but also MPO-ANCA.

Nemaline bodies of skeletal muscle fibers of the neck in a case of pharyngeal cancer.

Nemaline bodies were found in the regenerating muscle fibers of the neck of a 74-year-old Japanese male with pharyngeal cancer. Histologically, the nemaline bodies were needle-shaped structures and hematoxophilic with phosphotungstic acid-hematoxylin stain. Electron microscopic examination suggested that they arise as extensions of the Z bands. Although nemaline bodies occur in a variety of pathological conditions other than nemaline myopathy, their occurrence in regenerating skeletal muscle fibers invaded by cancer has not been reported previously. The pathogenesis of the nemaline body formation in the present case is discussed.

Ciliary neurotrophic factor immunoreactivity in rat intramuscular nerve during reinnervation through a silicone tube after severing of the rat sciatic nerve.

The immunoreactivity of ciliary neurotrophic factor (CNTF) and S100 was studied in the degenerating and regenerating intramuscular nerves after the sciatic nerve was severed. The sciatic nerves of male Wistar rats were transected at the midpoint of the thigh, and silicone tubing was used to obtain effective reinnervation. The strong immunoreactivity of CNTF and S100 was observed in the Schwann cell cytoplasm of intramuscular nerves (IMN) and at the neuromuscular junction (NMJ) on the control sections. The CNTF immunoreactivity gradually became weak and indistinct in the Schwann cell cytoplasm after the operation. However, it was recognized again in the IMN at 4 weeks after the operation. On the other hand, the S100 immunoreactivity was continuously observed except at the NMJ through the denervating and reinnervating period. At 12 weeks after the operation, the strong immunoreactivity of both CNTF and S100 was observed again. These findings suggest that the amount of CNTF protein decreased in Schwann cells of the IMN and NMJ during the denervating period and increased during the reinnervating period in proportion to the number of remyelinated Schwann cells after severing of the sciatic nerve. They also suggest that CNTF was more highly correlated than the S100 protein with the reinnervation activity of Schwann cells.

Potentiation of aflatoxin B1-induced hepatocarcinogenesis in the rat by pretreatment with buthionine sulfoximine.

A single i.p. dose of aflatoxin B1 (AFB1) (1.0 and 2.0 mg/kg body wt)-induced hepatocarcinogenesis with phenobarbital as a promoter has been examined in young male Fischer rats. Immunohistochemical method has been employed to detect AFB1-induced glutathione S-transferase placental form (GST-P)-positive hepatic foci observed from 3 week and 10 week to 40-48 week periods. With 2.0 mg AFB1 dosing, the number, area and volume occupied by GST-P-positive hepatic foci increased significantly and progressively from 3 week, 10 week and 48 week periods. In long term studies (40-48 weeks), 1.0 mg and 2.0 mg AFB1 dose levels yielded linear response in area and volume occupied by AFB1-induced hepatic foci. Pretreatment of rats with L-buthionine sulfoximine (BSO), a GSH depleter, at a dose of 4 mmol/kg body wt 4 and 2 h before 1.0 or 2.0 mg AFB1 treatment enhanced the number, area and volume of GST-P-positive hepatic foci, increases being the largest at shorter time periods (3 and 10 weeks) compared to longer time periods (40 and 48 weeks). This report appears to be the first example of an enhanced chemical induced hepatocarcinogenesis in a long term study in any experimental animals species by a GSH depleting agent.

[Assistance to enhance the use of home helper services for the cancer patient].

For the end-stage cancer patient to live at home with his or her quality of life (QOL) sustained, Home Helper Services are considered effective. In fact, however, many do not avail themselves of such services. Since the disease situation is apt to change dramatically, it is difficult to predict the length of time of care at home, and the patient's family does not tend to utilize such services unless the patient is completely bedridden. Short-term use or the difficulty or rapid response of such services has been among the reasons given of this. Given this background, there appears to be a need for suitable assessment in dealing quickly with possible disabilities which might occur and a number of occupations. Also, when considering home medical care for the cancer patient, an administrative system capable of a rapid response when problems of this kind occur is indispensable. Working on the administration to fulfill this need is also the task of the professionals in this field.

[Psychosocial support to improve quality of life (QOL) in home terminal carcinoma patients].

There are numerous psychosocial problems with home care for terminal cancer patients. We studied one case from the viewpoint of providing support for cancer patients and their families. Psychosocial problems are important for the life of cancer patients and their families. The cancer diagnosis and the terminal stage have different levels of psychosocial concerns. We must consider effective intervention with such psychosocial support. (1) The team delivery of health care in oncology is more crucial than ever. (2) Social work plays a key role. (3) We should strive to understand the roles of other members of teams. (4) Members of a support team should take turns in providing care according to the psychosocial conditions of the patients. (5) Sympathy and a broad social outlook are required of medical staff members.

Effect of cell proliferation on initiation of aflatoxin B1-induced enzyme altered hepatic foci in rats and hamsters.

Rat is susceptible whereas hamster is resistant to aflatoxin B1 (AFB1) hepatocarcinogenesis. Effect of cell proliferation on AFB1-induced glutathione S-transferase placental form (GST-P) positive foci has been examined in these two species after a single i.p. dose of AFB1 and phenobarbital (PB) as a promoter in a 3 week period. Bromodeoxyuridine incorporation as a measure of cell proliferation and GST-P hepatic foci were analyzed by immunohistochemical methods. Hepatic cell proliferation was maximum at 24 h after either partial hepatectomy (PH) or CCl4 (4 mmol/kg) pretreatment of rats whereas cell proliferation was maximum at 48 h after PH or CCl4 (1 mmol/kg) treatment of hamsters. Enhanced number of GST-P positive hepatic minifoci (two to nine cells) and foci (>100 microns) and focal area were observed in rats with either AFB1 (0.5 mg/kg) given 24 h after PH or AFB1 (0.5 or 2.5 mg/kg) given 48 h after CCl4 dosing. In hamsters, 1 or 2 mg AFB1 treatment produced only GST-P positive single hepatocytes without presence of any minifoci whereas 3 or 6 mg AFB1 produced minifoci consisting only of doublets. Pretreatment with CCl4 48 or 72 h before 1 mg AFB1 dose level increased GST-P positive single cells and minifoci several fold. PH 24 or 48 h before 1 or 2 mg AFB1 dose level increased minifoci. However, increase in minifoci was higher in PH hamsters at 48 h compared with those at 24 h. These results indicate that even though maximum initiation occurs in both speices when AFB1 is administered at the peak of DNA synthesis, rats are more responsive than hamsters to cellular proliferation in the initiation phase of AFB1-induced hepatocarcinogenesis.

[Support system for long-term morphine administration to terminal cancer patients at home--verification from three patients at home with terminal cancer].

The nursing department at the Saitama Prefectural Cancer Center established a Nursing Consultation Section in April 1993 and a Visiting Nursing Program in May 1993 with the purpose of supporting cancer patients who desired home care. From these dates through March 1994, 1,021 patients were instructed in home care methods and visiting nursing was provided in 98 cases. Of these, three patients with terminal cancer received long-term ameliorative treatment using orally administered morphine and were able to maintain satisfactory QOL through their terminal periods. The results are reported herein.

Effect of glutathione levels on aflatoxin B1-DNA binding in livers and kidneys of male rats and hamsters pretreated with buthionine sulfoximine and dimethylmaleate.

The effects of pretreatment of buthionine sulfoximine (BSO) alone or in combination with diethylmaleate (DEM) on glutathione (GSH) levels and aflatoxin B1 (AFB1)-DNA binding have been examined in livers and kidneys of young male Fischer rats and Syrian golden hamsters 2 h after an intraperitoneal injection of [3H]AFB1 (0.4 mg/kg body wt.). Animals were treated with BSO (4 mmol/kg body wt.) alone at 4 h and 2 h or with DEM (3 mmol/kg body wt.) at 4 h and BSO at 2 h before AFB1 injection. Hepatic AFB1-DNA binding was about 29.0 and 6.0 pmol/mg DNA in rats and hamsters, respectively. In rats, BSO increased AFB1-DNA binding by about 40% with a drop in GSH by 70%. Treatment with DEM-BSO increased AFB1-DNA binding by about 80% with a concomitant drop in GSH in both species. In hamsters, BSO increased AFB1-DNA binding by only 10% with a 50% drop in GSH. The kidneys of both species have lower GSH levels and AFB1-DNA binding than their respective liver tissues. The effect of BSO alone or in combination with DEM on both GSH levels and AFB1-DNA binding are comparable even though BSO alone is less effective in both species. The role of modulation of GSH levels on AFB1-DNA binding and hence biological effects of AFB1 in these two species is discussed.