[Significance of interferon alpha therapy for advanced renal cell carcinoma. Fukushima Renal Cancer Study Group].

We ranked prognostic factors to retrospectively evaluate the clinical significance of interferon alpha (IFN-alpha) therapy in patients with Robson stage IVB renal cell carcinoma. A total of 44 Robson stage IVB renal cancer patients were divided into 2 groups, one with more than 6 months administration of IFN-alpha (3-7 times a week: group A) and another without any IFN-alpha administration. The distribution of these 2 groups was not randomized. In addition to IFN-alpha therapy, survival was analyzed with respect to performance status (PS), mass reductive nephrectomy, concomitant use of other cytotoxic therapies, the number of metastatic organs, growth type, site of metastasis and the period of diagnosis, using a multivariate method with Cox proportional hazards regression. The multivariate analysis showed administration of IFN-alpha to be the most significant factor influencing a good prognosis. Improved survival was also significantly correlated with slow growing type and good PS. Among group A, a significant favorable prognosis was obtained in patients with the responses of no change (NC), partial response (PR) and complete remission (CR) 6 months after initiating administration of IFN-alpha, as well as with good PS and a slow growing type carcinoma. We conclude that IFN-alpha therapy might improve the prognosis of patients with Robson stage IVB renal cell carcinoma, especially, in cases when a greater than NC response is obtained after 6 months administration of IFN-alpha.

Clinicopathological observations on thoroughbred foals with enlarged thyroid gland.

Seven cases of thoroughbred foals kept on a farm in the Hidaka district of Hokkaido showed bilateral thyroid enlargement from 3 or 4 months after birth. Their serum T4 levels were remarkably low, whereas T3 levels were in the normal range. Serum T4 levels were also low in the other clinically normal foals and their dams kept together. Since the iodine content in pasture soil and grass was very low, iodine deficiency was supposed to be the cause of the disease.

[A case of adult mature nephroblastic tumor].

A 22-year-old woman had a well differentiated nephroblastic tumor. The tumor was composed of mesenchymal elements with mature tubules and occasionally smooth muscle elements. None of the cellular elements showed any feature indicative of malignancy. Histologically this was similar to congenital mesoblastic nephroma, but the tumor showed an evidence of a uniform expansile growth. It was considered to be a form of mature nephroblastoma.

Effects of active egg white product on neutrophil function in calves.

The effects of an active egg white product (AEWP) on neutrophil function in calves were investigated. Calves were administered AEWP orally at doses of 250 mg and 500 mg/kg either once or twice, with an interval of 5 days between doses in the latter case. The peripheral blood neutrophils of calves receiving a single 500 mg/kg dose displayed increased nitroblue tetrazolium reducing activity and increased intracellular killing of Staphylococcus aureus from 1 day after administration, with maximum levels being attained on the 3rd day. However, no such increase of these activities was observed after administration of 250 mg/kg. Calves receiving two doses of 500 mg/kg displayed the same changes as seen in the corresponding one-dose group, while the neutrophil activity of calves receiving 250 mg/kg also increased after the second dose. However, no increase in the peripheral blood neutrophil count was observed after AEWP administration. Thus, AEWP enhanced the nonspecific antibacterial activity of neutrophils when given to calves by the oral route.

Isolation of Trichophyton verrucosum from lesional and non-lesional skin in calves.

Trichophyton verrucosum, a causative agent of bovine dermatophytosis in Japan is considered to transfer easily from infected cattle to other healthy ones. No studies have ever tried to elucidate the distribution of T. verrucosum in breeding environment. In this study, we investigated the distribution of T. verrucosum in infected young calf skin and healthy skin. Hairs or scale samples were collected from 29 lesional skin, and 46 non-lesional skin of the 19 and 34 infected calves, respectively, both varying in age 2 to 6 months old, and 35 hair samples from the 29 healthy ones. They were directly inoculated on medium. The detection rates of T. verrucosum-positive were 58.6% from the lesional parts, 34.8% from the non-lesional parts and 17.1% from the healthy parts. The isolation of T. verrucosum from the calves with no skin lesion due to dermatophytosis implied that this infection might be easily transmitted by the contact with the infected calves. T. verrucosum infection in cattle poses a serious problem in animal husbandry. It is also important for public health to take preventive measures against the infection.

[Cytologic atypical grade of exfoliative cytology versus histologic differentiation degree in prostatic carcinoma].

Our method of exfoliative cytology using a prostatic fluid collecting catheter is effective in detecting prostatic carcinoma. To presume histological diagnosis by means of the cytology we analyzed cytological findings of 62 cases of prostatic carcinoma in relation with their biopsy findings, clinical stages and clinical courses. In cases in which cellular atypism was low in the cytology the carcinoma was mostly well or moderately differentiated. Conversely, in cases in which the carcinoma was well differentiated atypism was mostly low in the cytology. In cases in which the cellular atypism was high the carcinoma was poorly differentiated, and vice versa. The poorer histological differentiation and the higher cytological atypism, the more advanced carcinoma and the higher death rate from the carcinoma. The tendency seemed to be more related with the cellular atypism than with the histological differentiation. Thus the cytological findings reflect the histology well and the degree of the histological differentiation can be presumed by the cytological atypism. The cellular atypism is not a less important factor than the histologic differentiation degree for determining the clinical stage and the prognosis.

Efficacy of colostral immunoglobulins for therapeutic and preventive treatments of calf diarrhea.

Pooled colostral milk samples were collected from apparently healthy Holstein cows. Immunoglobulin (Ig) was partially purified from the colostral milk and concentrated by freeze drying. The Ig powders had neutralizing antibody titers of 1:6,250 to 1:31,250 against bovine rotavirus (RV), and reacted with four RV proteins of VP2, VP4, VP6, and VP7. No therapeutic effect of Ig powder showed on clinically serious diarrhea with RV in dairy and beef calves. However, the Ig powder had a preventive effect on the diarrhea in beef calves when it was given soon after calving.

Studies on serum tocopherol and selenium levels and blood glutathione peroxidase activities in lambs with white muscle disease.

For the investigation of the cause of white muscle disease (WMD), tocopherol (Toc) and selenium (Se) levels and blood glutathione peroxidase (GSH-Px) activities were examined using lambs with WMD and their ewes. Serum Se levels of 4 lambs with WMD were low under 30 ppb, lambs showing very low levels below 15 ppb. The serum Se level was correlated with blood GSH-Px activity showing remarkably low activities in the lambs with WMD. Se contents in the organs of lambs with WMD were lower than those of control lambs, and particularly liver Se contents were deficient levels below 50 ppb. Serum Toc levels were normal, but alpha-Toc contents in organs showed very low levels, especially in the liver. The serum Toc and Se levels and blood GSH-Px activities of their ewes and other sheep kept in the same farm revealed similar results to those of lambs with WMD. Feedstuffs supplied on the farm showed the deficient level of the Se content below 50 ppb and a very low level of alpha-Toc. It was concluded that WMD of lambs in Hokkaido was nutritional muscular dystrophy resulted from deficiencies of Toc and Se to their ewes.

Primary structure of bovine lactate dehydrogenase-A isozyme and its synthesis in Escherichia coli.

Eleven cDNA clones encoding lactate dehydrogenase(LDH)-A isozyme were isolated from a bovine lymphocyte cDNA library, and the nucleotide sequences of three of the clones (pLDH5, pLDH9 and pLDH12) were determined. With the exception of variation in the 5' portion, two cDNA clones (pLDH9 and pLDH12) appeared to contain the full-length cDNA of 1786 bp, consisting of the protein-coding sequence (996 bp), the 5'- and the 3'-untranslated regions and the poly(dA) tail. The predicted amino acid (aa) sequence of bovine LDH-A (332 aa) showed 96.7% homology with that of pig LDH-A. The protein-coding cDNA region (1650 bp) was inserted into an Escherichia coli expression vector ptac11 and expressed. The protein synthesized in E. coli showed enzyme activity of LDH and was identified by cellogel electrophoresis as LDH-5 isozyme whose subunit M chain is the product of the LDH-A gene.

[Cytological changes in endocrine therapies of prostatic carcinoma].

We studied cytological changes by endocrine therapies of prostatic carcinoma in 31 cases. We originated a method of cytology, in which a prostatic fluid collecting catheter was used. This has been already reported in previous papers. By the therapies, carcinoma cells usually became edematous, swollen, squamous and finally keratinized and in the cytoplasm hematoxylin-stained granules often appeared. These findings were usually seen in two weeks after the onset of the endocrine therapy. But the degree of the changes differed among the cases and among the therapies. In some there was no response or only squamous metaplasia was found. Most of the carcinoma cells were viable. In these cases the therapies were thought to be ineffective and their mortality was high. On the contrary, in those with only keratinized cells, the therapies were thought to be effective and the mortality was low. We conclude that the cytological methods were useful for evaluating the therapies.

Origin of abomasum gas in the cows with displaced abomasum.

The gas composition of the rumen and the abomasum were investigated in 71 cows including 25 cows with displaced abomasum. The ratio of methane (CH4) to CO2 in the abomasum gas was higher than that in the rumen. In the incubated mixtures of fresh rumen fluid, CH4 was detected at a high concentration, while a small amount of CO2 and CH4 was found in incubated mixtures of fresh abomasum fluids. Hence, it was suggested that the gas in the abomasum originated not from the abomasum itself but from the rumen. In cows fed with mixed roughages and concentrates, the rumen CO2:CH4 ratio was higher compared with cows fed with roughages alone. Marked changes in rumen gas composition were presumed to be associated with changes in abomasum gas composition. Consequently, it is possible that feeding a large quantity of concentrates may increase the flow rate of the ingesta through the forestomach, so that the return rate of gas separated from the ingesta in the abomasum to the forestomach may also increase. Therefore, the frequent accumulation of a large amount of gas with concomitant changes in the total volatile fatty acid (VFA) concentration in the abomasum caused abomasal atony and subsequently displaced abomasum.

Effects of dihydroheptaprenol on neutrophil functions in calves.

Microemulsified dihydroheptaprenol (DHP) was administered intramuscularly to clinically healthy calves at doses of 4, 6 and 8 mg/kg body weight. Marked increase of neutrophil counts was observed 0.5, 1 and 2 days after the injection at a dose of 6 mg/kg. Nitroblue tetrazolium reducing activity of neutrophils was also obviously enhanced 1, 2 and 3 days after DHP administration. Phagocytic killing of Staphylococcus aureus by neutrophils was further enhanced markedly 1, 2 and 3 days after the drug injection at 6 mg/kg.

Studies on serum tocopherol, selenium levels and blood glutathione peroxidase activities in calves with white muscle disease.

For the purpose of clarifying the cause of white muscle disease (WMD) in calves, tocopherol and selenium levels and blood glutathione peroxidase (GSH-Px) activity were measured on 10 calves with WMD and nine of their dams. The main clinical symptoms of the 10 calves with WMD were motor disturbances including recumbency and stiffness. Serum enzyme activities (GOT, GPT, CPK, LDH) in calves with WMD increased markedly, and this increase was also observed in some of their dams. Serum tocopherol levels of calves with WMD were low, 70% of which showing deficient levels of less than 70 micrograms/100 ml. Serum selenium levels of all the calves were lower than 35 ppb, indicating a deficiency, and were accompanied by low blood GSH-Px activity. alpha-Tocopherol and selenium concentrations in organs were very low. Dams of calves with WMD showed low serum tocopherol levels, 22% of which indicating deficient levels below 150 micrograms/100 ml. Serum selenium levels in dams showed a marked decrease to under 20 ppb, and also low blood GSH-Px activity. Feedstuffs supplied in the farms to affected calves indicated very low alpha-tocopherol contents (below 3 mg/100g DM) and low selenium concentrations below 50 ppb in DM. It was concluded that WMD in calves was attributable to nutritional muscular dystrophy caused by deficiencies in tocopherol and selenium in feedstuffs supplied to their dams.

Studies on serum selenium and tocopherol in white muscle disease of foal.

In order to clarify the cause of white muscle disease (W.M.D.) in foals, tocopherol and selenium concentrations in serum and glutathione peroxidase activities in blood were measured. Examination was made on the samples from horses affected with W.M.D., the foal kept with them in the same stable, the foals kept in the stables without affected foals, and respective mares. The heavy-breed horses in Fukuoka prefecture and Tokachi district were also examined for comparison. Serum tocopherol levels of these foals were normal because after intake of colostrum. Mares of affected foals showed lower tocopherol levels than other examined mares (p less than 0.01). Serum selenium levels of all foals were below 65 ppb, showing deficient levels. The mares of affected foals had lower selenium levels than other mares (p less than 0.01). There was a good correlation between serum selenium concentration and blood glutathione peroxidase activity (r = 0.81). Selenium levels in the liver of affected foals were lower than the foals which succumbed with other diseases. Diet supplied in the stables with affected foals showed low alpha-tocopherol and selenium contents. These findings suggest that W.M.D. in foals is attributed to nutritional muscular dystrophy caused by tocopherol and selenium deficiency of their mares in late gestation period.

Clinical and biochemical findings in bovine cerebrocortical necrosis produced by oral administration of amprolium.

Purposing to get some hints on cause and early diagnosis for cerebrocortical necrosis (CCN), CCN was produced in three healthy calves by the oral administration of amprolium. All three calves showed central nervous signs characterized by ataxic gait, clonic spasm, astasia and opisthotonus, from 24 to 49 days after the start of daily administration of 321-418 mg/kg amprolium. They showed bradycardia from about 20 days before the appearance of the nervous signs, which was supposed to be a finding of primary change and to be useful for early diagnosis of CCN. At necropsy of the two calves, large necrotic lesion was found in the cerebral cortex, and tissue thiamine levels decreased significantly, especially in cerebrum and cerebellum. In the other calf, injection with 25 mg thiamine tetrahydrofurfuryl disulfide (TTFD) was proved to be effective for the recovery of clinical signs. No significant changes in thiamine level were recorded in the whole blood, but those in erythrocytes decreased slightly at about a week before the appearance of the clinical signs. No significant alteration of thiamine excretion was observed in urine. Those findings suggest that CCN in calves is caused by thiamine deficiency and that the blood thiamine levels cannot be used for diagnosis of CCN.