Biomedical subjects

M Kawakami

Publications and source records attributed to M Kawakami.

At least 181 records · Page 10Linked to original sources

PubMed1997

Detection of prostate cancer cells circulating in peripheral blood by reverse transcription-PCR for hKLK2.

Two of the human tissue kallikrein family, hK2 and hK3 (prostate-specific antigen), are primarily produced by the prostatic epithelium under the regulation of androgens. In this study, we detected prostate cancer cells that expressed hKLK2 or hKLK3 mRNA in the peripheral blood of patients with prostate cancer using reverse transcription-PCR (RT-PCR). We then demonstrated some differences in characteristics, such as differentiation of cancer cells and response to antiandrogen therapy, between hKLK2 and hKLK3 mRNA-expressing prostate cancer cells. Total RNA was isolated from 41 patients with known prostate cancer, 7 patients with benign prostatic hyperplasia, and 20 normal volunteers. By RT-PCR, hKLK2 mRNA was detected in 7 patients (33%), and hKLK3 mRNA was detected in 17 (81%) of 21 stage D prostate cancer patients. In contrast, all patients with benign prostatic hyperplasia and healthy volunteers were negative. From comparison of the background of the patients positive for hKLK2 and/or hKLK3 mRNA, it became evident that the response to antiandrogen therapy and the expression of hKLK2 mRNA were reciprocally correlated, in contrast with the expression of hKLK3 mRNA. Additionally, our study clearly demonstrated that the detection of hKLK2 mRNA in the peripheral blood was useful for screening patients with certain prostate cancers that did not express hK3. We conclude that taking advantage of the difference between hKLK2 mRNA and hKLK3 mRNA expression is clinically useful for following up prostate cancer patients.

Adenocarcinoma↗

PubMed1997

Synthesis and evaluation of novel rhodacyanine dyes that exhibit antitumor activity.

Rhodacyanine dyes and several analogous delocalized lipophilic cations (DLCs) were synthesized and evaluated as novel antitumor agents. Rhodacyanine dye consists of two heteroaromatic rings such as thiazoles at both termini of the conjugate systems and 4-oxothiazolidine (rhodanine) in the middle of it. Compounds with such a unique double-conjugate structure were found to inhibit the growth of several tumor cell lines, such as colon carcinoma CX-1, and to exhibit relatively low toxicity against normal kidney cell line CV-1 (e.g., IC50(CX-1) = 50 nM, IC50(CV-1) = 17.3 microM; selectivity index = 346 for compound 5). These compounds were also found to be efficacious in the tumor-bearing nude mice model (e.g., against human melanoma LOX; T/C (%) = 168 for compound 5). Structural modifications on rhodacyanine, including deletion of a heteroaromatic ring involved in the merocyanine conjugate system and replacement of rhodanine with a structurally related moiety such as 4-oxoimidazolidine or 4-oxo-1,3-dithiolane, resulted in a loss of the selectivity and/or the activity. Our current structure-activity studies imply that the double-conjugate system with a rhodanine moiety is essential for the selective activity of rhodacyanine dyes, and we find this class of compounds as unique antitumor agents candidates.

Animals↗

PubMed1997

Enhanced expression of prostate-specific membrane antigen gene in prostate cancer as revealed by in situ hybridization.

Recently, the cDNA encoding a novel candidate for prostate cancer-specific antigen, named prostate-specific membrane antigen (PSM), was cloned from the LNCaP prostate cancer cell line (R. S. Israeli, C. T. Powell, W. R. Fair, and W. D. W. Heston, Cancer Res., 53: 227-230,1993). More recently, they also identified an alternatively spliced variant of PSM in normal prostate tissues (S. L. Su, I-P. Huang, W. R. Fair, C. T. Powell, and W. D. W. Heston, Cancer Res., 55: 1441-1443, 1995). The cDNA of this variant, named PSM', lacks 266 nucleotides present in PSM cDNA, so the transcripts derived from this particular nucleotide sequence can be regarded as PSM-specific transcripts. In this study, we investigated the expression of PSM-specific transcripts in 15 specimens of prostate cancer obtained by needle biopsy using in situ hybridization with a newly developed RNA probe. PSM-specific transcripts were detected in most of the carcinoma cells in all of the specimens examined, and the level of expression was higher in carcinoma cells from hormone-refractory patients than in the cells of those who showed a good response to hormonal therapy. In addition, increased expression of PSM-specific transcripts was also associated with an increased Gleason score. In the normal prostate, on the other hand, PSM-specific transcripts were limited to the basal cells of the prostate glands. These results clearly show that expression of PSM-specific transcripts is closely associated with malignant transformation of the prostate; thus, in situ hybridization for detection of the transcripts is useful for the diagnosis of prostate cancer.

Adenocarcinoma↗

PubMed1997

The role of phospholipase A2 and nitric oxide in pain-related behavior produced by an allograft of intervertebral disc material to the sciatic nerve of the rat.

STUDY DESIGN: To elucidate the pathomechanisms of radicular pain secondary to lumbar disc herniation. OBJECTIVES: To evaluate whether intervertebral disc material applied to the sciatic nerve produces hyperalgesia, and if the hyperalgesia in influenced by inhibitors of phospholipase A2 and nitric oxide synthase. SUMMARY OF BACKGROUND DATA: Previously, the authors reported that application of nucleus pulposus and anulus fibrosus material to the lumbar epidural space produces different forms of hyperalgesia (mechanical versus thermal), with different and distinct histologic changes. Additional pharmacologic studies showed that phospholipase A2 and nitric oxide are involved in the mechanisms that produce the mechanical and thermal hyperalgesia, respectively, N omega-nitro-L-arginine methyl ester and mepacrine are relatively selective inhibitors of nitric oxide synthase and phospholipase A2, respectively. However, it is not known what the relation is between the hyperalgesia produced and the activation and involvement of phospholipase A2 and production of nitric oxide, or why the application of nucleus pulposus and nucleus pulposus with anulus fibrosus produces different types of hyperalgesia. METHODS: Experiments were performed in five groups of rats: The control group (no treatment), the sham group (exposure of the sciatic nerve only), the fat group (allografted fat on the sciatic nerve), the nucleus pulposus group (allografted nucleus pulposus) and the nucleus pulposus + anulus fibrosus group (allografted nucleus pulposus and anulus fibrosus). Withdrawal threshold and latency from mechanical pressure and a radiant heat to hind paws were measured preoperatively and postoperatively. After local sciatic nerve administration of N theta-nitro-L-arginine methyl ester or mepacrine into the operated site, sensitivities to noxious stimuli were reevaluated after treatment. RESULTS: Only rats in the nucleus pulposus group showed evidence of mechanical hyperalgesia. However, injection of N theta-nitro-L-arginine methyl ester resulted in evidence of mechanical hyperalgesia in the nucleus pulposus + anulus fibrosus group. Mechanical hyperalgesia was produced in the nucleus pulposus group and after injection of N theta-nitro-L-arginine methyl ester in the nucleus pulposus+anulus fibrosus group, both of which returned to normal after mepacrine injection. There were no significant changes in sensitivity to thermal stimuli in any of the experimental groups. CONCLUSION: It appears that phospholipase A2 and nitric oxide play important but different roles in pathomechanisms of radicular pain in lumbar disc herniation.

Animals↗

PubMed1997

Histochemical demonstration of nitric oxide in herniated lumbar discs. A clinical and animal model study.

STUDY DESIGN: This study was designed to localize the cells that produce nitric oxide in a lumbar disc herniation by histochemical method, including in situ hybridization. OBJECTIVE: To clarify which cells in herniated lumbar discs produce nitric oxide. SUMMARY OF BACKGROUND DATA: It was reported that herniated lumbar intervertebral disc specimens in culture are capable of producing nitric oxide. METHODS: Surgical specimens from lumbar disc herniation were examined to determine nitric oxide synthase histologically using nicotinamide adenine dinucleotide phosphate diaphorase histochemistry. Allografts of intervertebral disc materials were placed on the epidural space at L6 level in the rat. Nitric oxide synthase was examined in the applied tissues using nicotinamide adenine dinucleotide phosphate diaphorase histochemistry and in situ hybridization histochemistry. RESULTS: Nicotinamide adenine dinucleotide phosphate diaphorase (nitric oxide synthase) positive cells were observed in 2 (40%) of 5 herniated disc materials in patients. The positive cells were mainly in granulation tissue around intervertebral disc materials. In animal models, nitric oxide synthase-positive cells were observed in all specimens at 1 and 2 weeks postoperatively. Newly formed vessels and small round cells in granulation tissue around the grafted intervertebral disc showed positive reaction. In situ hybridization demonstrated the expression of inducible isoform of nitric oxide synthase messenger RNA (mRNA) identical to small round cells around the applied intervertebral disc. CONCLUSION: Nitric oxide in a lumbar disc herniation is mainly produced by cells in granulation tissue around the herniated intervertebral disc.

Adult↗

PubMed1997

Prevention of adenocarcinoma colon 26-induced cachexia by interleukin 10 gene transfer.

A s.c. injection of a mouse colon adenocarcinoma cell line, colon 26 clone 20, induced cachexia, as evidenced by progressive weight loss and severe hypoglycemia. Several lines of evidence indicate that a pro-inflammatory cytokine, interleukin 6 (IL-6), plays a major role, albeit partially, in the establishment of cachexia in this model. Because IL-10 can potentially inhibit the production of pro-inflammatory cytokines including IL-6, we evaluated the effects of IL-10 gene transfer on the establishment of cachexia. IL-6 transcript was detected at tumor sites of mice inoculated with parental or control vector transfectant cells, and serum IL-6 levels were markedly increased in these mice. The injection of parental cells into IL-6-deficient mice induced cachexia with elevated serum IL-6 levels comparable to wild-type mice, indicating that tumor cells are a major source of IL-6. The inoculation of IL-10-transfectant cells kept IL-10 mRNA expression at tumor sites and induced the elevation in serum IL-10 levels without affecting the growth rates of colon 26 cells both in vitro and in vivo. However, the implantation with IL-10-transfectant cells reduced the expression of IL-6 mRNA at the tumor sites and the elevation in serum IL-6 levels. Concomitantly, mice inoculated with IL-10-transfectant cells did not exhibit progressive weight loss, a reduction in food intake, or severe hypoglycemia, which was observed in mice inoculated with parental or control vector-transfectant cells. Collectively, these results suggest that IL-10 gene transfer prevented the occurrence of cachexia with a concomitant inhibition of IL-6 production at the tumor sites.

Animals↗

PubMed1997

Secreted proteophosphoglycan of Leishmania mexicana amastigotes activates complement by triggering the mannan binding lectin pathway.

Cutaneous lesions induced by infection of mice with the protozoan parasite, Leishmania mexicana, contain abundant amounts of a high molecular mass proteophosphoglycan (PPG), which is secreted by the amastigote stage residing in phagolysosomes of macrophages and can then be released into the tissue upon rupture of the infected cells. Amastigote PPG forms sausage-shaped but soluble particles and belongs to a novel class of serine-rich proteins that are extensively O-glycosylated by phosphooligosaccharides capped by mannooligosaccharides. The purified molecule is shown here to efficiently activate complement (C) and deplete hemolytic activity of normal serum and may prevent the opsonization of L. mexicana amastigotes. Complement activation is Ca2+ dependent but does not depend on antibodies or the complement component C1. PPG binds to serum mannan binding protein (MBP), thus activating the MBP-associated serine protease, P100. Subsequently, the C cascade is triggered through C4 leading to covalent modification probably of carbohydrate hydroxyls of PPG by C3 fragments. Thus, PPG is able to activate C via the mannan binding lectin pathway which is unusual for secreted, soluble products of microbial origin. The proteophosphoglycan-induced complement activation is postulated to contribute to the lesion development and pathology caused by the parasite.

Animals↗

PubMed1997

Clinicopathologic study of angiogenesis in Japanese patients with breast cancer.

To evaluate the clinicopathologic significance of angiogenesis as a prognostic factor and the objective methods for evaluating angiogenesis, we immunohistochemically stained a representative section of breast tumors with factor VIII-related antigen staining. There were 109 patients with primary breast cancer from 1971 to 1979. The two methods of identifying angiogenesis were the average microvessel count per square millimeter (AMC) and the highest microvessel count per square millimeter (HMC). There was no relation between microvessel count (AMC or HMC) or age, menopausal status, clinical tumor size (T), histologic classification, nuclear grade, node status, histologic grade (HG), mitosis index, or lymphatic invasion (LI). There was a relation between microvessel count and blood vessel invasion (BVI) (HMC:p = 0.0007) and tumor necrosis (TN) (HMC:p = 0.0050). Univariate analysis showed that AMC or HMC was a statistically significant predictor of overall survival in all patients (p = 0.0086 and p = 0.0307, respectively). Multivariate analysis showed that AMC was an independent predictor of node status when we fitted a model with node status, BVI, and either AMC or HMC; but HMC was not independent. However, when we fitted a model including all 11 of the other indicators and AMC or HMC, the node status, HG, and LI were independent predictors, but AMC and HMC were not. Although AMC was a better method than HMC for evaluating angiogenesis, we cannot confirm angiogenesis as a significant independent prognostic factor associated with long-term survival in Japanese breast cancer patients.

Adult↗

PubMed1997

Measurement of interleukin-6, interleukin-10, and tumor necrosis factor-alpha levels in tissues and plasma after thermal injury in mice.

BACKGROUND: Cytokines are important modulators of physiologic alterations after thermal injury. Indeed, an increase in the level of circulating cytokines has been documented after thermal injury. However, the mechanism of the increase has not been clarified. We determined cytokine levels in local tissue after thermal injury to identify the tissues responsible for the increase. METHODS: Female C57BL/6 mice each received a 20% full-thickness burn injury. Blood, burned skin, unburned skin, muscle underlying the burn, and muscle of the thigh, liver, spleen, and mesenteric lymph node were sampled at 1, 2, 4, 8, and 24 hours after injury. Uninjured control mice were treated similarly. The samples were cultured, and concentrations of tumor necrosis factor-alpha, interleukin-6 (IL-6), and IL-10 in the culture media were measured by using an enzyme-linked immunosorbent assay. RESULTS: IL-6 levels in unburned skin were significantly increased at 1 hour and decreased at 24 hours, compared with the control. IL-6 levels in muscle underlying the burn were significantly decreased at 8 hours. No elevation of plasma IL-6 levels was observed after injury. Neither tumor necrosis factor-alpha IL-10 was detected in any tissue. CONCLUSIONS: Results indicate that unburned skin may be a major source of IL-6 production after thermal injury and may contribute to the physiologic alterations occurring after such injury.

Animals↗

PubMed1997

Simple diagnosis of graft-versus-host disease.

BACKGROUND: Among patients undergoing allogeneic bone marrow transplantation, we previously detected an increase of CD8+S6F1+ and CD8+CD57- cells with the onset of acute graft-versus-host disease. OBJECTIVE: This study was an attempt to develop a simple laboratory test for graft-versus-host disease. METHODS: We analyzed the percentage of the two lymphocyte subsets in the peripheral blood mononuclear cells of healthy volunteers, patients with posttransfusion graft-versus-host disease, and recipients of allogeneic bone marrow transplants. RESULTS: Two patients with posttransfusion graft-versus-host disease showed a high percentage of both subsets. When the graft-versus-host disease pattern was defined as 45% or more CD8+S6F1+ cells and 35% or more CD8+CD57- cells, it was found in none of 17 recipients without acute graft-versus-host disease, 9 of 16 recipients with grade I disease, and 8 of 9 recipients with grade II or worse disease had this pattern. CONCLUSIONS: Our test may be useful for the laboratory diagnosis of acute graft-versus-host disease.

Acute Disease↗

PubMed1997

Purification of aminopeptidase from Australian classified barley flour.

Barley is one of the major crops cultivated in the world. A new milling system, which removes successive layers of the grain has been developed, the preparation being called a classified flour. We have detected aminopeptidase activity in the flour obtained from the near surface zone. Barley was the Weeah species cultivated in Australia. Our aim in this paper is to describe the complete purification of aminopeptidase from barley classified flour. Aminopeptidase activity was determined using L-leucine-p-nitroanilide in 10 mM sodium phosphate buffer, pH 7.0. Aminopeptidase was extracted in 20 mM sodium acetate buffer, pH 5.5. Fractions (HP-1 and HP-2) were obtained upon chromatography using an HI-propyl hydrophobic interaction column in 20 mM acetate buffer, pH 5.5, with a linear gradient of ammonium sulfate from 15 to 0% saturation after the ammonium sulfate fractionation (from 40 to 60% saturation) of the extract. The final purified preparation A-1-I-G was obtained from HP-1 by gel filtration, hydroxylapatite chromatography, diethylaminomethyl-ion exchange chromatography, and re-chromatography on a Sephacryl S-100HR gel column. It was pure as assessed by native and sodium dodecylsulfate-polyacrylamide gel electrophoreses. The specific activity of A-1-I-G was 64.8 fold that of the crude extract. A K(m) value of 0.138 mM when using L-leucine-p-nitroanilide was calculated. A-1-I-G is active over a wide pH range and has a strong affinity for its substrate. The classification process is effective as a step of enzyme purification. Also, the results with metal ions suggest that the enzyme is a metalloenzyme. It was concluded that complete purification of an aminopeptidase from barley was achieved.

Aminopeptidases↗

PubMed1997

Vidarabine therapy for virus-associated cystitis after allogeneic bone marrow transplantation.

We describe a method of diagnosing virus-associated cystitis after allogeneic bone marrow transplantation (BMT) and treatment with vidarabine therapy. At 7-10 days post-BMT when cystitis was suspected, we observed urinary sediments by the Papanicolaou stain to detect virus inclusion bodies. When positive, we examined urinary sediments by transmission electron microscope and measured the diameter of viral particles to determine the families. This process needed only 4 days. Among 16 consecutive cases, adenovirus and polyomavirus were each detected in three. Adenovirus caused hemorrhagic cystitis in two cases and cystitis without macroscopic hematuria in one case. Polyomavirus caused cystitis without macroscopic hematuria in one case. Polyomavirus was also detected in two cases without any symptoms. Vidarabine (10 mg/kg/day i.v.) was administered for 5 days as one course. Soon after one course of vidarabine, most symptoms subsided and virus inclusion bodies disappeared in all cases except for one with severe hemorrhagic cystitis. From these experiences, vidarabine reduces excretion of adenovirus and polyomavirus in the urine of BMT recipients and improves clinical symptoms in some cases of cystitis associated with these viruses.

Adenoviridae Infections↗

PubMed1997

Treatment of minute medullary thyroid carcinoma in multiple endocrine neoplasia 2A families first diagnosed by DNA analysis of RET proto-oncogene mutations: a case report.

Multiple endocrine neoplasia (MEN) 2A is an inherited disease characterized by the development of medullary thyroid carcinoma, pheochromocytoma and hyperparathyroidism. It has recently been shown to be associated with germ-line mutations in the RET proto-oncogene. We describe a 21-year-old man from a MEN 2A family who was found by DNA analysis to be a gene carrier of MEN 2A and then was diagnosed, using a stimulated calcitonin test, as having presymptomatic medullary thyroid carcinoma. His morbidity seems to have been cured by total thyroidectomy as postoperative calcitonin levels after stimulation are normal. It is concluded that direct genetic analysis for mutations in the RET proto-oncogene should be the diagnostic test of choice for identifying family members at risk for MEN 2A.

Adrenal Gland Neoplasms↗

PubMed1997

Immunohistochemical study of sulfatide expression in gastric carcinoma: alteration of sulfatide expression.

Immunohistochemical staining using a specific monoclonal antibody against sulfatide was performed to examine cellular localization of sulfatides in normal human gastric mucosa and in various types of gastric carcinoma. In normal gastric mucosa without Helicobacter pylori infection, both epithelial and glandular cells were densely stained with anti-sulfatide antibody. Sulfatide staining was more abundant in the apical area of normal epithelium compared with cytosol or basolateral areas. This tendency was stronger in the antrum than the gastric body and was more intensified in glandular cells of the pyloric glands. The levels of sulfatide expression were decreased in papillary and well-differentiated adenocarcinomas compared with normal mucosa, were markedly attenuated in moderately differentiated adenocarcinomas, and were very low in poorly differentiated adenocarcinomas. The polarity of the stains was preserved in gastric cancers that exhibited differentiated tissue organization. The levels of sulfatide expression were highly variable in signet ring carcinoma cells. The cancer cells that expressed sulfatides did not show any polarity of staining.

Adenocarcinoma↗

PubMed1997

Shear stress as an inhibitor of vascular smooth muscle cell proliferation. Role of transforming growth factor-beta 1 and tissue-type plasminogen activator.

We examined whether shear stress can inhibit vascular smooth muscle cell (VSMC) proliferation in vitro directly. Human VSMCs were exposed to fluid flow for 24 hours using a cone-plate apparatus, and their proliferation was inhibited significantly by shear stresses of 1.4 and 2.8 Pa (14 and 28 dyne/cm2), according to the magnitude. Next, we investigated whether transforming growth factor-beta 1 (TGF beta 1), which is known to be an important cytokine that suppresses VSMC proliferation, is the predominant mediator of shear-induced inhibition of VSMC growth. After exposure of VSMCs to shear stress (2.8 Pa) for 24 hours, gene expression of TGF beta 1 and, interestingly, tissue-type plasminogen activator, which converts plasminogen to plasmin, an activator of TGF beta 1, increased twofold and fivefold, respectively. The levels of both latent and active forms of TGF beta 1 in conditioned media of VSMCs exposed to fluid flow increased significantly. An anti-TGF beta 1 antibody reversed shear-induced inhibition of VSMC growth significantly. We concluded that shear stress inhibited VSMC proliferation in vitro and this inhibition was mediated predominantly by TGF beta 1 in an autocrine manner. These data suggest that shear stress plays an important role as an inhibitor of atherogenesis in endothelium-desquamated lesions.

Antibodies↗

PubMed1997

Blood flow in common carotid and vertebral arteries in patients with sudden deafness.

Blood flow was measured in the common carotid artery (CCA) and the vertebral artery (VA) by the ultrasonic Doppler method in 14 male patients with sudden deafness and 70 normal adults. In the patients, blood flow on the affected side was slower than that on the normal side or that of the control group. Although these differences were not statistically significant in the CCA or in the VA, significant differences in the blood flow were noted between the group with a hearing loss of greater than 50 dB and the group with a loss of less than 50 dB. A negative correlation was found between blood viscosity and blood flow in both CCAs and both VAs. After stellate ganglion block (SGB), the blood flow of the CCA and VA increased on the side of the SGB and decreased on the opposite side. The changes in blood flow after SGB decreased with age, presumably because of changes in the blood vessel walls and a weaker response to sympathetic nerve receptors in the arterial wall.

Adult↗

PubMed1997

Measuring serum thyroglobulin in patients with follicular thyroid nodule: its diagnostic implications.

To determine the diagnostic implications of measuring the serum thyroglobulin level in patients with a solitary follicular thyroid tumor, a retrospective study was conducted on 122 consecutive patients with a solitary follicular thyroid nodule who underwent thyroidectomy. Data for eight variables were collected: the serum thyroglobulin (Tg) level (microgram/l), age, maximum diameter of the nodule, gender, histopathologic type, presence or absence of metastases, macroscopic characteristics of the cut surface of the resected tumor, and smoking habit. Multiple regression analyses were used to investigate the relationships between the serum Tg level and the seven other variables. The diagnostic value of serum Tg was examined by means of receiver operating characteristic (ROC) curves. There were significant correlations between the serum Tg level and the maximum diameter of the nodule, the macroscopic characteristics, and the smoking habit. The sensitivity and specificity of the serum Tg level with a cut-off value of 1,000 micrograms/l were 57% and 86%, respectively. The likelihood ratio favouring follicular carcinoma associated with the serum Tg > 1,000 micrograms/l was 4.41. Measuring the level of serum Tg may be useful in discriminating follicular carcinoma from follicular adenoma, but since there may be some biases in this retrospective study, the results are less definitive. Further research activities are mandatory to obtain valid evidence.

Adenocarcinoma, Follicular↗

PubMed1997

Relation between smoking status of physicians and their enthusiasm to offer smoking cessation advice.

Are nonsmoking physicians more likely to give smoking cessation advice to their patients? To determine this, we sent a questionnaire individually to physicians in Tokyo. The average age of the 323 respondents was 59.8 +/- 12.9 (mean +/- SD); 84.8% of them were male and 21.1% were smokers. Among the respondents, 88.8% asked their patients about their smoking status, 79.9% advised smoking patients to stop, and 93.5% believed smoking cessation interventions to be necessary. Nonsmoking physicians were more likely to advise patients to stop smoking (85.6%) than smoking physicians (70.1%); the smoking physicians who themselves wished to reduce cigarette consumption or stop smoking were more likely to do so (85.0%) than those who did not wish to reduce or stop (43.5%). Moreover, more nonsmoking physicians seriously felt that smoking cessation interventions are necessary (31.2%) than did smoking physicians (6.5%). In conclusion, the smoking status and attitude towards smoking of physicians influences their enthusiasm to give advice to their patients against smoking.

Attitude of Health Personnel↗