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Biomedical subjects

J M Hirsch

Publications and source records attributed to J M Hirsch.

At least 37 records · Page 2Linked to original sources
PubMed1996

Immunohistochemical detection of p53 in non-malignant and malignant oral lesions associated with snuff dipping in the Sudan and Sweden.

Immunohistochemistry was used to examine the expression of p53 in pre-malignant oral lesions and oral squamous-cell carcinomas (SCCs) from Swedish and Sudanese snuff-dippers, as well as in pre-malignant oral lesions and oral SCCs from non-snuff-dippers from the Sudan, Sweden and Norway. Of the 14 SCCs from Sudanese snuff-dippers, 21% (3/14) expressed p53. Of the 14, 60 and 41 SCCs from non-snuff-dippers from the Sudan, Sweden and Norway, 64% (9/14), 65% (39/60) and 68% (28/41) expressed p53, respectively. A statistically significant difference in expression of p53 was found in SCCs from Sudanese snuff-dippers compared to those from non-snuff-dippers from all/or any of the 3 countries. None of the suspected pre-malignant oral lesions from Sudanese snuff dippers or non-snuff-dippers expressed p53. Only 2 out of the 15 oral fibro-epithelial hyperplastic lesions from Swedish snuff-dippers expressed p53. Some of the oral epithelial dysplastic lesions, as well as the carcinoma in situ lesions from Norwegian non-snuff-dippers, expressed p53, while the oral fibro-epithelial hyperplastic lesions did not. The low relative frequency of p53 expression found in oral SCCs from snuff-dippers compared to those from non-snuff-dippers might suggest differences in mechanisms of oncogenic action induced by snuff. Alternatively, the pathogenesis of malignant oral lesions from snuff-dippers may follow a p53-independent pathway. In view of the unusually high levels of the tobacco-specific nitrosamines (TSNA) found in the type of snuff used in the Sudan, investigations of p53 mutations or oncogenes are needed.

Adolescent↗
PubMed1996

Assessment of p53 and Ki-67 expression in snuff-induced lesions.

An immunohistochemical study of snuff-induced lesions with a monoclonal antibody (DO-7) specific to p53 mutant and wildtype antioncogene product demonstrated nuclear overexpression of the mutant protein in 45.9 nuclear profiles/mm2 epithelium (SEM 10.8; n = 15) compared with only 0.18 positively stained nuclear profiles/mm2 in the control group (SEM 0.18; n = 4). Furthermore, the biopsy material was also stained with the antibody Ki-67, which has been shown to be excellent for the estimation of the growth fraction in both normal and malignant human tissues. Ki-67 stained positive in 566.1 nuclear profiles/mm2 epithelium (SEM 85.0; n = 15) in the snuff-group compared with 20.2 nuclear profiles/mm2 (SEM 4.9; n = 4) in the control group. To the best of our knowledge, this is the first study showing overexpression of p53 protein and Ki-67 in snuff-induced lesions. The results may indicate that the p53 gene is involved in the initial events leading to subsequent malignant transformation of oral mucosa exposed to snuff. Furthermore, mutations of the p53 gene have been associated with increased cellular proliferation with greater risk of perpetuation of mutations and malignant transformation.

Adult↗
PubMed1995

Fixture stability and nerve function after transposition and lateralization of the inferior alveolar nerve and fixture installation.

Twenty-four posterior mandibular segments in 18 patients were operated on placing implants after mobilisation of the neurovascular bundle. Two different surgical techniques, transposition and lateralization was used. The overall survival rate of fixtures was 92.1%. Performing lateralization resulted in 100% success, while transposition resulted in 80% stable fixtures in the involved segments. The mean time to full restoration of nerve function was 3.8 weeks after lateralization and 5.7 weeks after tranposing the nerve. Three patients exhibited persisting slight hyposthesia, but all, subjectively negligible disturbances in nerve function.

Dental Implantation, Endosseous↗
PubMed1993

Reactivated herpes simplex virus infection as a possible cause of dry socket after tooth extraction.

This study was designed to evaluate a possible association between reactivated herpes simplex virus type 1 (HSV-1) infection after lower third molar extraction and development of dry socket (DS). The HSV-1 antibody response was analyzed before and after tooth removal by enzyme-linked immunosorbent assay and immunoblotting in 208 patients. History of previous possible oral herpes reactivation was evaluated by a questionnaire that was based on self-rated frequency of oral cold sores. Tobacco users were identified. The anatomic proximity of the root apex to the mandibular nerve canal was classified radiographically before extraction. Fifteen patients (7%) developed DS after tooth extraction. Eleven of the 15 DS patients (73%) were HSV seropositive as compared with 7 of 15 (47%) in the matched control group. Seven of the 11 seropositive DS patients have shown HSV-1 reactivation by an increase of specific polypeptides, predominantly gB, gC, gD and ICP 4 and 6, in the immunoblot test. No change in HSV-1 reactivity was observed in control sera. DS patients reported a high frequency of oral cold sores (64%) compared with the controls (33%). Tobacco use was not found to influence the frequency of cold sores or the development of DS. A close radiographic proximity between the mandibular canal and root apex was more common (P < .05) in DS patients. The results indicate that extraction of a mandibular third molar could be a possible cause of reactivation and recurrence of an HSV-1 infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Recrudescence of herpes simplex virus type 1 in latently infected rats after trauma to oral tissues.

Tooth extraction in rats was used to trigger a latent HSV-1 infection. HSV-1 was inoculated unilaterally in the rat palates. Eight weeks later two molars were removed bilaterally. The trigeminal ganglia were co-cultivated and HSV-1 was isolated from 63% of the ganglia on the infected sides but from only 11% on control sides. The immune response pattern was analysed by immunoblotting of rat serum, and strong reactivity to HSV-1 specific cell polypeptides and glycoproteins (ICP6, gC, pgC, gD) was seen after reactivation. The extraction sockets were histopathologically evaluated and showed healing on the infected side in 26% compared to 63% in contralateral control sockets. The effect of acyclovir (ACV) treatment was elucidated and was found to influence the subsequent development of antibodies and to promote healing of the sockets. Vesiculation in intra- and subepithelial tissue was present on the infected side in 58% but in only 12% of ACV-treated animals. The present study in rats has shown that a latent HSV-1 infection can be established and reactivated by tooth extraction. Reactivation resulted in delayed healing of sockets on the latently infected side but not on the contralateral control side. HSV-1 reactivation was demonstrated serologically by immunoblotting. Healing was significantly promoted by administration of ACV, which also supports the contention that HSV-1 interferes with the healing process.

Acyclovir↗
PubMed1993

Measures of dental beliefs and attitudes: their relationships with measures of fear.

Emergency dental and fearful dental patients were questioned in order to investigate the relationship between dental fear and different dental beliefs. The instruments used were the dental anxiety scale and the dental beliefs survey. The study also evaluated a Swedish version of the beliefs survey. The mean anxiety scale scores were 9.4 for emergency and 16.8 for fearful patients. The average beliefs survey item values ranged from 1.6 to 2.6 and 1.7 to 3.8 among the two groups respectively. There were clinical meaningful and statistically significant correlations between the anxiety scale and the beliefs survey. Each of the four dimensions of the beliefs survey (communication, control, belittlement and trust), also correlated with the anxiety scale of which the most clearly defined was belittlement.

Adult↗
PubMed1992

Inhibition of herpes simplex virus replication and protein synthesis by non-smoked tobacco, tobacco alkaloids and nitrosamines.

Inhibitory effects of snuff extract and the tobacco chemicals nicotine, anabasine, diethyl-N-nitrosamine (DEN), and the tobacco-specific nitrosamines (TSNA), N-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) on herpes simplex virus type 1 (HSV-1) replication in vitro and on HSV-1 protein synthesis in infected cells were analysed. Snuff extract and nicotine caused a significant reduction of HSV-1 attachment to cell membranes whereas anabasine, DEN, NNN and NNK did not affect adsorption of HSV-1. Virus production assays in the presence of snuff added after virus adsorption resulted in a significantly reduced production of virus at low multiplicities of infection (MOI), but at high MOI the inhibitory effect of snuff extract was less pronounced. DEN, NNN and NNK only affected virus production at toxic concentrations. Nicotine and anabasine reduced virus production in non-toxic doses but not at the concentrations present in snuff extract. In HSV-infected cells exposed to snuff extract, the immediate early (alpha-) infected cell proteins (ICPs) 4 and 27 (as well as the early (beta-) ICPs 6 and 8) were markedly increased, whereas the late (gamma-) ICPs 5, 11 and 29 were reduced. Nicotine had a less pronounced stimulating effect on the production of alpha-proteins but no detectable effect on production of beta- or gamma-proteins. Anabasine, DEN, NNN and NNK did not affect HSV protein synthesis at non-toxic concentrations. Synthesis of thymidine kinase and DNA polymerase was significantly reduced by snuff extract. Also nicotine and anabasine affected thymidine kinase and DNA polymerase but only at toxic concentrations. The production of the cellular protein actin, which almost disappears a few hours after HSV-1 infection, remained at a significant level in HSV-infected cells exposed to snuff. Thus snuff extract blocks the replicative cycle of HSV at an early stage, which results in an increased production of alpha-proteins in the infected cells and in prolonged maintenance of cellular functions. This may be of importance for HSV-induced transformation and the development of HSV-associated tumours.

Alkaloids↗
PubMed1992

Hemodynamic effects of the use of oral snuff.

The hemodynamic effects during rest and exercise of oral snuff were investigated in an open, placebo-controlled study of nine habitual users of oral snuff. Blood pressure, heart rate, and central hemodynamics were measured noninvasively. Plasma concentrations of nicotine, cotinine, norepinephrine, and epinephrine, as well as neuropeptide Y-like immunoreactivity were measured before and after snuff intake during rest and exercise. Snuff intake induced a significant increase in heart rate and blood pressure and a decrease in stroke volume during rest. Hemodynamic changes were unrelated to nicotine or cotinine concentrations. Resting levels of norepinephrine and neuropeptide Y-like immunoreactivity were similar with or without snuff, whereas epinephrine was slightly increased 30 minutes after snuff intake. The exercise-induced increase in norepinephrine and neuropeptide Y-like immunoreactivity did not differ between the days subjects received snuff and the days they received placebo. In contrast, maximum work load was associated with a slight increase in circulating epinephrine after snuff intake. The findings suggest that snuff intake is associated with significant hemodynamic effects during rest but not during exercise. These effects could not be readily explained by activation of the sympathetic nervous system.

Adult↗
PubMed1991

Reactivity against herpes simplex virus in patients with head and neck cancer.

The relation between herpes simplex virus (HSV) and head and neck cancer was examined. A total of ninety patients were analyzed for IgG antibodies against HSV. Antibody titers were established with an enzyme-linked immunosorbent assay and antibodies against specific HSV-antigens were analyzed by Western blot. These patients' seroreactivity was compared to that of an age-matched control group of patients with arteriosclerotic disease in their lower limbs, a disease also closely related to heavy tobacco consumption. Prevalence of antibodies against HSV was around 90% and did not differ significantly between cancer patients and controls, but antibody titers against HSV were significantly higher in the cancer patients. The cancer patients also reacted more constantly (80%) in Western blot analysis against the early immediate protein, ICP-4, than controls (50%). This suggests a different course of an earlier herpetic infection in these patients with a prolonged exposure to early immediate HSV-proteins which may be related to an increased risk of developing head and neck cancer. We propose that heavy smoking may contribute to this phenomenon.

Antibodies, Viral↗
PubMed1991

Association between development of lower lip cancer and tobacco habits.

Tobacco use is considered to increase the risk of tumor induction. The purpose of this case-controlled investigation was to assess the association of tobacco habits and development of squamous cell carcinoma of the lower lip. Sixty-one patients treated for lower lip cancer, aged between 42 and 90 years, were studied. Age- and sex-matched healthy controls showed a similar exposure to tobacco in years and a comparable distribution of tobacco habits. Although the mean exposure factor (duration times exposure) was greater in the tumor group, no intimate correlation between lip cancer and tobacco was demonstrated. However, an increased, although small, occurrence of herpes labialis lesions was found in cancer patients. The hypothesis is presented that smokers experiencing recurrent herpes simplex virus 1 (HSV-1) infections are more liable to tumor initiation, which issue will be subjected to a future study.

Adult↗
PubMed1991

Tobacco habits among teenagers in the city of Göteborg, Sweden, and possible association with dental caries.

Frome nine dental clinics within the Public Dental Service in the City of Göteborg, 2145 patients aged 14 to 19 answered a questionnaire concerning their tobacco habits. Tobacco was used in some form by 27 per cent of the patients and use increased with age. Smoking was more common among girls than among boys: 24 and 12 per cent, respectively. The statistical analyses showed that smoking as a habit and an increased number of cigarettes smoked per day are positively correlated with increases in the number of decayed, missing and filled teeth and the number of initially decayed proximal surfaces. Further, all caries epidemiological data were significantly higher among patients with tobacco habits compared to non-users. It can be concluded that there is a correlation between the tobacco habit and increased caries prevalence. However, dietary and oral habits have to be further elucidated before any definite conclusions can be made regarding the effect of the tobacco habit per se on the development of caries.

Adolescent↗
PubMed1991

Lack of promoting ability of snuff in rats initiated with 4-nitroquinoline-N-oxide.

In an experiment to evaluate the carcinogenicity and promoting capacity of snuff, a reservoir was created in the lower lip of male Sprague-Dawley rats. Groups of 30 rats were treated with snuff only (twice a day on five days a week), propylene glycol (solvent) three times weekly for four weeks, painting of the hard palate with 4-nitroquinoline-N-oxide (4-NQO) three times weekly for four weeks followed by snuff, 4-NQO only for four weeks, or cotton pellets only (twice a day on five days a week). The experiment was continued up to 108 weeks. High levels of tobacco-specific nitrosamines were found in the snuff (a commercial US brand). Rats treated with snuff only, 4-NQO followed by snuff and 4-NQO only had a significantly higher number of squamous-cell tumours and hyperplastic squamous lesions of the lip, oral and nasal cavity and forestomach than solvent or untreated controls. The total number of neoplasms was significantly higher in rats treated with snuff only and with 4-NQO followed by snuff in comparison to the other groups. Thus, snuff and 4-NQO by themselves can induce benign and malignant tumours. Snuff appears to have a general tumorigenic effect but lacked promoting ability after initiation with 4-NQO.

4-Nitroquinoline-1-oxide↗
PubMed1990

Primary herpes simplex virus (type 1) infection delays healing of oral excisional and extraction wounds in the rat.

The effect of acute herpes simplex virus type 1 (HSV-1) infection on the healing process of intraoral wounds and tooth extraction sockets in the rat was studied. A standardized size of the buccal mucosa was excised and molars were extracted and a HSV-1 suspension was topically applied. The virus infected wounds were clinically characterized by erythema and swelling and histologically by heavy inflammation cell infiltrate and abscesses during the first week. The acute HSV-1 infection was found to significantly delay healing of both types of wounds by 3 days. Antiviral treatment with acyclovir (ACV) decreased the degree of inflammation and improved healing of the infected wounds. The present results indicate a delayed and disturbed healing of wounds in the oral cavity in the presence of HSV-1. The findings may have a clinical significance for primary or latent HSV-1 infections in conjunction with surgical intervention in the oral cavity.

Acyclovir↗
PubMed1989

Snuff-induced carcinogenesis: effect of snuff in rats initiated with 4-nitroquinoline N-oxide.

A canal in the lower lip to function as a reservoir for snuff was surgically created in 150 male Sprague-Dawley rats. The animals were randomized into five groups of 30 each: Group I received snuff twice a day, 5 days a wk; Group II was painted with propylene glycol (solvent control) on the hard palate 3 times a wk during 4 wk; Group III underwent painting on the hard palate with 4-nitroquinoline N-oxide (4-NQO) dissolved in propylene glycol, 3 times a wk for 4 wk; Group IV received 4-NQO as in Group III followed by snuff application as in Group I; and Group V received a cotton pellet dipped in saline twice a day, 5 days a wk. Treatment continued for up to 108 wk. There was no significant difference in mean survival time between the groups. Squamous cell tumors of the lip, oral and nasal cavities, esophagus, and forestomach were seen only in Groups I, III, and IV. Nine tumors of these organs were found in Group I (six carcinomas and three papillomas), nine in Group III (seven carcinomas and two papillomas), and ten in Group IV (eight carcinomas and two papillomas). The difference between each of these groups and the control groups (II and V) with regard to tumor incidence is statistically significant (P less than 0.05). In Group I, four oral cavity or lip carcinomas were found in 29 rats, a significant difference in relation to control rats (P less than 0.05). In addition, hyperplastic lesions of the lip, palate, and forestomach were significantly more common in Groups I and IV compared with Groups II, III, and V. The study has shown that snuff and 4-NQO by themselves have the potential to induce malignant tumors. Initiation with 4-NQO followed by snuff did not significantly enhance tumor formation.

4-Nitroquinoline-1-oxide↗
PubMed1989

Effects of acyclovir on herpes simplex virus type 1 infection in mice treated with 12-O-tetradecanoylphorbol 13-acetate.

The purpose of this study was to determine whether infectious herpes simplex virus type 1 (HSV-1) has tumorigenic properties and, if so, whether inhibition of the cytolytic replicative cycle of the virus after infection enhances tumour development. Eighty mice were subjected to repeated inoculation of HSV-1 on their upper lips after scarification, and systemic administration of acyclovir (ACV). 12-O-tetradecanoylphorbol 13-acetate (TPA) was used as the tumour promoter. The tumour incidence was compared to control groups each of 40 mice that were either not treated with ACV, not treated with TPA, not infected with HSV or only scarified. In the virus-infected group treated with ACV and TPA, 25% of the animals developed tumours. In the HSV-infected group treated with TPA only, 25% of the animals also developed tumours. The uninfected animals which were not treated with TPA developed tumours to a significantly lesser degree. In conclusion, the combined effects of HSV-1 and TPA, with or without ACV treatment, resulted in a significant increase in the number of tumours in comparison to the control groups.

Acyclovir↗
PubMed1989

Snuff tumorigenesis: effects of long-term snuff administration after initiation with 4-nitroquinoline-N-oxide and herpes simplex virus type 1.

The tumor promoting effects of snuff was studied in Lewis rats initiated with 4-nitroquinoline-N-oxide (4-NQO) and Sprague Dawley rats repeatedly inoculated with herpes simplex virus type 1 (HSV-1). The test substances were administered in a surgically created canal in the lower lips of the rats. There were 15 rats in each test group and 10 rats in the control group. In the groups treated with 4-NQO and 4-NQO + snuff, 8 and 12 tumors (5 and 9 malignant) were found, respectively. In the group subjected to HSV-1 only, 3 tumors were found (2 malignant), in the group subjected to snuff only, 4 tumors were found (3 malignant) and in the group subjected to the combination of HSV-1 and snuff, 13 tumors were found (7 malignant). In the control group only one malignancy was found. The study did not show any promoting effects of snuff in the oral cavity after initiation with 4-NQO. Neither was there any increase in the number of oral tumors in rats treated with HSV-1 and snuff. However, there was a marked increase in the number of malignant tumors outside the oral cavity in the group treated with HSV-1 and snuff, underlining the importance of interactions between these two agents in the development of malignant lesions.

4-Nitroquinoline-1-oxide↗