Biomedical subjects
K Niimi
Publications and source records attributed to K Niimi.
The effect of growth hormone on the growth failure of chronic renal failure.
To investigate the effects of growth hormone (GH) on the reversal of growth failure in uremia, recombinant human GH (rhGH) was administered to rats with chronic renal failure (CRF). The dosage of rhGH was 3 IU/day (i.p.) for 13 days after the induction of CRF by 5/6 nephrectomy. Animals were classified into four groups: untreated nephrectomized rats (NX, n = 40), GH-treated nephrectomized rats (NX+GH, n = 18), sham-operated rats fed ad libitum (SHAMAL, n = 27), and sham-operated rats pair-fed with 10 NX rats (SHAMPF, n = 10). NX and NX+GH rats developed a similar and moderate degree of CRF, serum urea nitrogen being (mean +/- SEM) 49 +/- 3 and 54 +/- 4 mg/dl, respectively, compared with 16 +/- 4 and 19 +/- 0 mg/dl in SHAMAL and SHAMPF groups. Weight (56.0 +/- 3.3 g) and length (3.5 +/- 0.1 cm) gains of NX rats were lower than those of SHAMAL rats (94.2 +/- 4.0 g, P less than or equal to 0.0001 and 4.1 +/- 0.2 cm, P less than or equal to 0.01). Growth of the SHAMPF group and the matched NX rats was not significantly different. Weight (56.2 +/- 5.0 g) and length (3.4 +/- 0.2 cm) gains of NX+GH and NX rats were similar, the beneficial effect of GH therapy on growth being observed in only those animals with more severe degrees of uremia. This growth-promoting action resulted from greater food efficiency and not from stimulated food intake. The hypercholesterolemia seen in NX rats, 81 +/- 2 mg/dl versus 55 +/- 3 mg/dl in SHAMAL (P less than or equal to 0.0001), was not increased in the NX+GH group, 87 +/- 3 mg/dl. There was a positive and significant correlation between serum cholesterol and serum urea nitrogen values in NX and NX+GH animals. This study suggests that growth impairment of mild CRF is mainly due to malnutrition and is refractory to GH administration. GH therapy improves the growth rate of animals with advanced CRF without aggravating their lipid abnormalities.
Growth hormone secretion from pituitary cells in chronic renal insufficiency.
To examine whether growth hormone (GH) secretion is adversely affected by chronic renal insufficiency (CRI), the GH secretory response of dispersed anterior pituitary cells perifused with GH-releasing hormone (GHRH) was investigated in 5/6 nephrectomized (CRI, N = 18) and sham-operated (N = 18) rats. Two weeks after nephrectomy, during a period of stable uremia, CRI rats had significantly higher serum concentrations (mean +/- SEM) of urea nitrogen and creatinine than sham rats, 16.8 +/- 1.4 mmol/liter (47 +/- 4 mg/dl) and 79.6 +/- 0.0 mumol/liter (0.9 +/- 0.0 mg/dl) versus 6.1 +/- 0.4 mmol/liter (17 +/- 1 mg/dl) and 35.4 +/- 0.0 mumol/liter (0.4 +/- 0.0 mg/dl), respectively (P less than 0.0001). Incremental gains in body weight and nose to tail-tip length of CRI rats over two weeks were also significantly depressed, 53.3 +/- 5.38 g (CRI) versus 87.0 +/- 3.78 g (sham; P less than 0.0001) and 3.2 +/- 0.2 cm (CRI) versus 3.6 +/- 0.1 cm (sham; P less than 0.05). The cumulative food intake as well as food efficiency (g food consumed/g weight gain) were also adversely influenced by the uremic state: food intake 304 +/- 1 g (CRI) versus 397 +/- 6 g (sham; P less than 0.0001) and food efficiency 0.173 +/- 0.013 g/g of weight gain (CRI) versus 0.219 +/- 0.008 g/g of weight gain (sham). No significant difference in GH secretory rate (ng/min/10(7) cells) was found between the uremic and sham animals under basal conditions, 65.2 +/- 2.1 (CRI) and 67.9 +/- 2.2 (sham) or in response to GH-releasing hormone, 282.8 +/- 42.4 (CRI) versus 306.2 +/- 42.6 (sham).(ABSTRACT TRUNCATED AT 250 WORDS)
Growth hormone secretory capacity of individual somatotropes in rats with chronic renal insufficiency.
Growth failure is a common consequence of chronic renal insufficiency (CRI) in children and may be due to a number of factors. With regard to growth hormone (GH), regulation is often abnormal in CRI patients. The present study investigated the effect of CRI on the GH secretory responsiveness to GH-releasing hormone in individual rat pituitary somatotropes. Male Sprague-Dawley rats underwent a 5/6 nephrectomy to produce CRI. Control rats (SHAM) received sham operations, which included kidney decapsulation but not removal. Two wk later, during a period of stable uremia, serum creatinine [CRI: 1.1 +/- 0.08 mg/dL (97 +/- 7 mumol/L); SHAM: 0.4 +/- 0.04 mg/dL (35 +/- 4 mumol/L)] and serum urea nitrogen [CRI: 60.7 +/- 8.3 mg/dL (21.7 +/- 3.0 mmol/L); SHAM: 15.8 +/- 1.2 mg/dL (5.6 +/- 0.4 mmol/L)] were significantly elevated in the CRI rats (p less than 0.0005). Weight gain (p less than 0.0005), length gain (p less than 0.0005), food intake (p less than 0.0005), and food efficiency (p less than 0.005) were all significantly lower in the CRI rats. The GH secretory capacity of individual somatotropes was determined using the reverse hemolytic plaque assay technique. Plaque areas were measured to assess relative amounts of GH secreted. The total number of pituitary cells per rat, the percentage of somatotropes, and the mean plaque areas were similar for the two groups. These findings compare favorably with our in vitro study of GH responsiveness in perifused rat pituitary cells under conditions of mild uremia.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypercholesterolemia in rats with chronic renal insufficiency not aggravated by recombinant human growth hormone.
The lipid metabolic disorders in chronic renal insufficiency (CRI) are related to increased hepatic lipid synthesis, reduced triglyceride removal coupled with insulin insensitivity and impaired lipoprotein lipase activity. Growth hormone is lipolytic, and the effects of recombinant human growth hormone (rhGH) on the hypercholesterolemia of CRI are unsettled. To test this question, we gave rhGH for 14 days at a dosage of 3 units/day intraperitoneally to two-stage, 5/6 nephrectomized, male Sprague-Dawley rats (n = 18) compared to sex- and age-matched control (n = 27) and CRI (n = 40) rats. At the end of the study, CRI rats and those treated with rhGH had a similar degree of renal impairment, as assessed by serum concentrations (mean +/- SEM) of urea nitrogen (49 +/- 3 vs. 54 +/- 4 mg/dl), creatinine (0.9 +/- 0.0 vs. 1.0 +/- 0.1 mg/dl) and cumulative food intake (311 +/- 8 vs. 290 +/- 12 g). Serum urea nitrogen (16 +/- 4 mg/dl) and creatinine (0.4 +/- 0.1 mg/dl) concentrations as well as food intake (412 +/- 9 g) of control rats were significantly (p < 0.0001) different. Serum cholesterol concentration of CRI rats treated with rhGH (87 +/- 3 mg/dl) was not higher than those of CRI rats (81 +/- 2 mg/dl, p < 0.1338) but was significantly higher than in control rats (55 +/- 3 mg/dl, p < 0.0001). CRI rats treated with rhGH showed a similar serum albumin concentration and lower serum glucose than CRI rats (0.9 +/- 0.1 vs. 0.9 +/- 0.0 g/dl and 144 +/- 4 vs. 163 +/- 3 mg/dl, p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)
X-linked hypophosphatemia. Genetic and clinical correlates.
X-linked hypophosphatemia is a hereditary form of rickets that results from an isolated renal tubular wasting of phosphate. The clinical features unique to this disorder, and the recent advances in our understanding of vitamin D metabolism and molecular genetics in X-linked hypophosphatemia are reviewed. Finally, a succinct critique of the controversial treatment modalities round up this review.
Peutz-Jeghers syndrome associated with adenocarcinoma of the cecum and focal carcinomas in hamartomatous polyps of the colon: a case report.
We report herein a case of Peutz-Jeghers syndrome associated with an adenocarcinoma of the cecum and four focal cancers arising in hamartomatous polyps of the colon. There were a total 27 polyps in the intestine; 4 in the small intestine and the rest in the large intestine. The hamartomatous polyps in which the 4 focal cancers were found showed no component of adenoma, and the other polyps removed from the colon and small intestine at the same time were all hamartomas with no evidence of dysplasia or malignancy. This case was rare in that multiple focal cancers may have arisen directly from the hamartomous polyps of the colon.
Cortisone effects on growth, food efficiency, and in vitro growth hormone release.
These studies were designed to investigate the cause of growth retardation during glucocorticoid treatment in rats. In young animals, body weights and amounts of food consumed were measured at two-day intervals, beginning at 29 days of age. Average food intake and food efficiency were calculated. Animals were treated with cortisone (CORT, 5 mg/rat/day, s.c.) or saline (SAL) for eight days between 37 and 44 days. Growth hormone (GH) release by dispersed pituitary cells in response to nine concentrations of GH-releasing hormone (GHRH) were tested by in vitro perifusion at 45 and 73 days. As previously shown, CORT caused a cessation of growth during the treatment period, and body weight failed to catch up. Food efficiency was decreased during CORT treatment. All parameters of in vitro GH release including basal GH secretory rate, overall GH response to GHRH, and the GHRH concentration-response curves were significantly increased by CORT in the 45-day-old animals. An age-related increase in GH release was also observed between the 45 and 73 day saline-treated animals. These results support the hypothesis that glucocorticoids inhibit growth by induction of changes in food metabolism and GH secretion. The effect on the pituitary gland itself paradoxically involves an increase in GH secretory capacity in response to GHRH.
[A calcified mucinous adenocarcinoma of the stomach--case report].
The paper discusses the case of a 44-year-old woman with an epigastric discomfort at Hiroshima University Hospital. A barium study of the stomach showed rigidity and a giant fold. A subsequent abdominal roentgenogram and CT disclosed calcification throughout the stomach wall. Thus, is hopes of effecting a cure, a total gastrectomy, a partial resection of transverse colon, a splenectomy and a pancreatic tail resection were performed. A surgical specimen macroscopically presented an inelastic and thickened wall of the entire stomach, and deposits of whitish calcium were visible within the gastric wall. The pathological diagnosis indicated a mucinous adenocarcinoma, se, INF alpha, v2, ly3, n4 (No. 221), with calcification of this mucinous adenocarcinoma in the stomach.
Brainstem afferents to the intralaminar nuclei of the cat thalamus studied by the horseradish peroxidase method.
Brainstem afferents to the intralaminar thalamic nuclei of the cat have been studied by retrograde axonal transport of horseradish peroxidase (HRP) or wheat germ agglutinin conjugated to HRP (WGA-HRP). Injections of HRP or WGA-HRP into the lateral central and paracentral nuclei led to labeling of cells in various diencephalic structures of the injected side. Some cells were labeled in the intralaminar and medial pulvinar nuclei. A large number of labeled cells were detected in the thalamic reticular and ventral lateral geniculate nuclei. The zona incerta and field of Forel contained a few labeled cells. Occasional labeled cells were seen in the dorsomedial, ventromedial, posterior and lateral hypothalamic nuclei. Labeling of cells in the more caudal brainstem structures was found bilaterally, mostly with ipsilateral predominance. Some labeled cells were detected in the pretectal nuclei, the periaductal gray and the pars reticulata of the substantia nigra as well. The nuclei of Darkschewitsch and Cajal contained occasional labeled cells. Numerous cells were labeled in the superior colliculus, mainly in layers 3 and 4. A number of labeled cells were distributed in almost the entire extent of the brainstem reticular formation. It should be mentioned that the gigantocellular reticular nucleus contained labeled cells bilaterally with contralateral predominance. Very few labeled cells were encountered in the ipsilateral dorsal tegmental and parabrachial nuclei. A few cells were labeled in the vestibular nuclei and nucleus prepositus hypoglossi bilaterally. Some labeled cells were detected mainly contralaterally in three cerebellar nuclei; the fastigial, the interposed and the dentate. Injections of WGA-HRP into the medial central nucleus showed a different pattern of labeling. It is noteworthy that no labeled cells were found in the dorsal thalamus, the hypothalamus (except for the lateral mamillary nucleus), the superior colliculus or the cerebellar nuclei.
Substance P-like immunoreactive projection to the hippocampal formation from the posterior hypothalamus in the cat.
Following the injection of the fluorescent tracer, 4',6-diamidino-2-phenylindol-2HCl (DAPI) or Fluoro-Gold (FG), into the hippocampal formation of the cat, retrogradely-labeled cells were seen mainly in the supramammillary nucleus and the posterior hypothalamic area. Some of these labeled cells contain substance P-like immunoreactivity (SP-LI). When wheat germ agglutinin conjugated with horseradish peroxidase (WGA-HRP) was injected into the supramammillary nucleus and its adjacent regions, anterogradely-labeled terminals were detected, for the most part, in the granular layer and the supragranular molecular layer of the dentate gyrus as well as in the pyramidal layers of the hippocampus and subiculum. All of these layers were included within the terminal areas containing the SP-like immunoreactivity.
Thalamic projections to the cortical gustatory area in the cat studied by retrograde axonal transport of horseradish peroxidase.
The thalamic projections to the cortical gustatory area in the cat were studied using the horseradish peroxidase (HRP) method. The gustatory area extends from the lateral lip of the presylvian sulcus (posterior two-thirds) to the posterior part of the orbital gyrus. It is bounded anteriorly by area 6a beta, laterally by the first somatosensory area, medially by the fundus and medial bank of the presylvian sulcus (prefrontal area), and posteriorly by the insular area. The cortical gustatory area receives fibers mainly from the medial smaller-celled part of the posteromedial ventral nucleus (VPMM). Cortical projections of the VPMM are organized topically; the anterior part of the gustatory cortex receives fibers from the anterodorsal and posteroventral portions of the anterior two-thirds of the VPMM, whereas the posterior gustatory cortex receives fibers from the anteroventral, posterodorsal and posterior portions of the posterior two-thirds of the VPMM. In addition, there appears to be a mediolateral organization of the cortical projections of the VPMM to the gustatory area. The cortical gustatory area receives a few projections from the ventral lateral, ventral medial, submedial, paracentral, lateral central, parafascicular and medial central nuclei.
[A case of systemic lupus erythematosus associated with meningitis, myelitis, and bilateral optic neuritis].
A 16-year-old girl was admitted to our hospital in August 23, 1986, for headache, nausea and low grade fever. Marked increases in immunoglobulin indices were found in the cerebrospinal fluid. When she was 13, she was diagnosed as having SLE and lupus nephritis. On September 9, 1986, she complained of urinary retention, and pathological reflexes were elicited bilaterally. On September 13, she complained of a sudden loss of vision (count fingers) in the right eye which worsened to a visual acuity of light perception over the next 48 hours. A visual evoked response potentials (VEP) to flash stimulation gave a loss of amplitude and an increase in latency. On September 16, she complained of a similar loss of vision in the left eye. Leakage of dye around the left optic disc was found by a fluorescein angiogram on September 26. These results indicated a diagnosis of bilateral optic neuritis. Both visual acuity returned rapidly over the following month following oral prednisolone treatment. Optic neuritis is an exceedingly rare complication in SLE. Although the visual prognosis have been fairly good in the reported cases, some have resulted in various states of blindness. As for etiology of optic neuritis in our patient, ischemic change of optic nerves due to microvasculopathy as well as slight demyelinating process were speculated by the VEP pattern.
Combined effects of UFT with other anticancer agents using in vivo chemosensitivity tests.
In order to estimate the combined effects of UFT with other anticancer agents, a nude mouse experimental system (NMES), and a subrenal capsule assay (SRCA) were investigated. Three human tumor xenografts were serially transplanted into nude mice and examined. These were; EH-1 established from esophageal cancer, SH-6 from gastric cancer and CH-3 from colon cancer. The antiproliferative effects were estimated in accordance with the NCI therapeutic protocol. Significant antiproliferative effects were obtained only in NMES and a positive relationship was observed between the two assays (p less than 0.05). In the groups which were treated with a single agent, positive tumor responses were observed against mitomycin C in SH-6, against cis-DD platinum in SH-6 and EH-1, and against adriamycin in EH-1, respectively. On this study the synergistic, additive and subadditive effects were defined as the positive combined effects. The combination of MMC and UFT produced positive combined effects for all xenografts in both assays.
The indications of chemosensitivity tests against various anticancer agents.
In order to determine the indications of chemosensitivity tests against various anticancer agents, clinical trials of 4 different assays, namely; nude mouse isotope assay (NMIA), subrenal capsule assay (SRCA), human tumor clonogenic assay (HTCA) and adenosine triphosphate inhibition assay (ATPA), were performed on 391 patients. Analysis of the correlation between assay results and clinical effects presented the possibility of determining the indications as follows; (1) The positive clinical response of mitomycin C (MMC) should be predicted by ATPA; (2) The clinical tumor resistance against MMC should be predicted by SRCA; (3) Concerning 5-fluorouracil (5-FU) the chemosensitivity test (ATPA) should only be used for the detection of tumor resistance in the assay; (4) The poor results of this study indicated the difficulty of correctly estimating the effects of cyclophosphamide (CPM); (5) The perfect prediction of clinical effects in this trial indicated that cis-DDPlatinum (CDDP) should be estimated by SRCA; (6) The positive clinical tumor response against adriamycin (ADM) should be predicted by SRCA, while the negative one should be predicted by HTCA; and (7) ATPA showed good potential for estimating not only time dependent drugs such as 5-FU, but also cytotoxic drugs.
Macroconidial development and germination in Trichophyton mentagrophytes.
Trichophyton Mentagrophytes was investigated for macroconidial development with particular emphasis on the conidial ageing by light and scanning electron microscopy. Macroconidial germination was also studied under various conditions. Sabouraud glucose agar supplemented with 3% NaCl was used to enhance production of macroconidia. After a long-term cultivation macroconidial compartments changed to spherical thick-walled structure. Some 12-month-old macroconidia were still capable of germination. A wide range of temperature (15-37 degrees C), and inoculum of less than 1 X 10(5) conidia per ml of rich media were appropriate for macroconidial germination. The germination process of macroconidia was highly tolerant to NaCl. A small fraction of the conidia were able to germinate even in distilled water without activation. Effect of freeze-thaw or ultraviolet irradiation on macroconidial germination was determined.
[Combined effects of interferon alpha-A/D with fluoropyrimidine derivatives in the subrenal capsule assay].
The combined effects of interferon alpha-A/D (IFN alpha-A/D) with 5-fluorouracil and fluoropyrimidine derivatives such as 1-(2-tetrahydrofuryl)-5-fluorouracil (tegafur), UFT, 1-hexylcarbamoyl-5-fluorouracil (HCFU) and 5'-deoxy-5-fluorouracil (5'-DFUR), were examined by 4-day subrenal capsule assay. Four human tumor xenografts serially transplanted in athymic mice, H-111, SH-10 established from gastric cancers, CH-4 and CH-5 from colon cancers, were used. In this experiment, the adequate dose of each agent was estimated as 50 mg/kg for 5-FU, 473 mg/kg for tegafur, 433 mg/kg for UFT, 50 mg/kg for HCFU, 185 mg/kg for 5'-DFUR and 1 x 10(5) IU for IFN alpha-A/D, respectively. When synergistic, additive and subadditive effects were defined as positive combined effects, all combinations produced positive combined effects against H-111 and CH-5, while negative ones were observed for all combinations against CH-4. The combinations of 5-FU, HCFU and 5'-DFUR with IFN alpha-A/D produced synergistic effects against SH-10. These results indicate that the combination therapy of 5-FU and fluoropyrimidine derivatives with IFN alpha-A/D would be useful.